Page 11234..1020..»

Archive for the ‘Death by Stem Cells’ Category

Study: Poverty Linked to Higher Risk of Death Among Children with Cancer Undergoing Stem Cell Transplantation – PRNewswire

Wednesday, October 28th, 2020

WASHINGTON, Oct. 26, 2020 /PRNewswire/ --Despite the increasing use and promise of hematopoietic cell transplantation (HCT) as curative therapy for children with cancer and other life-threatening diseases, new research suggests that children transplanted for cancer are more likely to die from treatment-related complications if they live in poorer neighborhoods. The study, published today in the journal Blood, also found that having Medicaid versus private insurance, another marker of poverty, was associated with a higher chance of dying. Researchers say the results underscore the need to better understand and mitigate the effects of poverty and other social determinants of health on pediatric cancer care.

Hematopoietic cell transplantation, also called stem cell or bone marrow transplantation, is a treatment option for patients with blood cancers such as leukemia or lymphoma, as well as certain non-malignant conditions such as sickle cell disease or immunodeficiencies. It is only accessible at some medical centers. Together with radiation therapy or chemotherapy, HCT is designed to increase the chance of eliminating the cancerous or abnormal blood cells, and of restoring normal blood cell production.

The data revealed that children under the age of 18 with cancer who live in communities with high poverty rates had a 34% greater risk of treatment-related mortality following HCT compared with children in low-poverty areas. Even after adjusting for a child's disease and transplant-related factors, the data revealed children on Medicaid had a 23% greater risk of dying from any cause within five years of undergoing HCT and a 28% greater risk of treatment-related mortality when compared to children with private insurance.

"Our study shows that even after children with cancer have successfully accessed this high-resource treatment at specialized medical centers, those who are exposed to poverty are still at higher risk of dying of complications after treatment and of dying overall," said lead author Kira Bona, MD, MPH, Attending Physician, Dana-Farber/Boston Children's Cancer and Blood Disorders Center. "Simply providing the highest quality complex medical care to children who are vulnerable from a social perspective is inadequate if our goal is to cure every child with cancer."

One in five children in the U.S. lives in a household with an income below the federal poverty level. While previous studies have shown an association between household poverty and poorer outcomes in HCT procedures generally, there are limited data on how poverty influences the success of HCT in children specifically.

Dr. Bona and her team sought to fill this gap by reviewing outcomes data for pediatric allogeneic transplant recipients from the Center for International Blood and Marrow Transplant Research Database, the largest available repository of HCT outcomes. The researchers looked at two cohorts of patients: 2,053 children with malignant disease and 1,696 children with non-malignant disease, who underwent a first HCT between 2006 and 2015. Neighborhood poverty exposure was defined according to U.S. Census definitions as living within a ZIP code in which 20% or more of the residents live below 100% of the Federal Poverty Level. They also stratified patients by type of insurance and used Medicaid as a proxy measure for household level poverty. The researchers looked at pediatric patients' overall survival defined as the time from HCT until death from any cause, as well as relapse, transplant-related mortality, acute and chronic graft-versus-host disease, and infection in the first 100 days following HCT.

Interestingly, neighborhood poverty or having Medicaid insurance did not seem to affect outcomes, including overall survival, relapse, or infection, among children transplanted for non-malignant diseases such as sickle cell disease. Dr. Bona said the study does not explain why this might be and more research is needed; however, it is possible that physicians and families of children with non-malignant conditions who face social health challenges may elect to avoid intensive HCT procedures.

One study limitation is its reliance on proxy measures of household poverty (ZIP code and Medicaid insurance) that do not provide insight into specific aspects of an individual child's socioeconomic exposures and the home environment in which they live that may interfere with their ability to navigate the health care system. Dr. Bona says researchers and clinicians have historically not considered social determinants of health as being as important as biological variables in specialized cancer care and so have not collected data on these factors as part of research. She says this is a missed opportunity.

"We as a field need to recognize that non-biological variables such as your exposure to poverty and other social determinants of health matter just as much as many of the biological variables we pay close attention to when thinking about outcomes for children, and these variables must be collected systematically for research if we want to optimize the care and outcomes of the children we serve," Dr. Bona said.

If future studies could collect more nuanced measures of poverty such as household material hardship (e.g., food insecurity, access to heat and electricity, housing insecurity, transportation insecurity) or language barriers, targeted interventions in the form of assistance programs could potentially help mitigate social hardships and improve the overall care of children with cancer.

Blood(www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is a journal of the American Society of Hematology (ASH) (www.hematology.org).

SOURCE American Society of Hematology/Blood Journal

http://www.bloodjournal.org

Continue reading here:
Study: Poverty Linked to Higher Risk of Death Among Children with Cancer Undergoing Stem Cell Transplantation - PRNewswire

Read More...

Exclusive: "Ending Disease" Documentary Explores How Stem Cell Therapy Aims to Cure the Incurable – Prevention.com

Wednesday, October 28th, 2020

Ending Disease, a forthcoming documentary directed by Emmy award-winning filmmaker Joe Gantz, explores the controversial world of stem cell researchand why it's on the frontlines of combatting incurable disease.

The four-part series follows 10 patients who suffer from debilitating illnesses including paralysis, blindness, and terminal cancer. Each patient participated in the first FDA-approved clinical trials using stem cell and CAR T-cell therapy to treat conditions that were previously deemed incurable.

Stem cells are cells with the ability to develop into other cells, allowing them to repair damaged areas of the body. Stem cell therapy, also known as regenerative medicine, involves using these cells to heal diseased, injured, or dysfunctional tissue. CAR T-cell therapy, on the other hand, is a form of immunotherapy in which a patient's T cells are collected from the blood and modified into chimeric antigen receptors (CARs).

In this exclusive Ending Disease trailer, a high school senior becomes paralyzed after suffering a neck injury during a basketball game. His parents view stem cell therapy as their son's only option to recovery:

Another woman learns that her cancer has returned, after an MRI shows lesions on her breast and lungs. "It seemed like it was a death sentence," she says in the video, and then she begins the process of CAR T-cell therapy.

"I became legally blind when I was 26; this could potentially restore my vision," a second woman shares of the revolutionary clinical trial.

Later, the documentary shows the teenage boy regaining his strength in a wheelchair, while the formerly blind woman goes rock climbing. The woman with cancer is seen playing soccer with young children.

"We have in our own bodies the cells that know how to regenerate our own bodies, so this is a real medical revolution," a healthcare worker says.

The documentary promises to be an exciting look at an ambitious clinical trial that aims to change lives for the better. Ending Disease is set to release on Friday, November 13.

You can catch a virtual screening by purchasing tickets at one of the following local participating cinemas: Gathr Films, Laemmle Virtual Cinema (Los Angeles, C.A.), The Lark (Marin County, C.A.), Tampa Theater (Tampa, F.L.), Grail Movie House (Asheville, N.C.), Cinema Art Theater (Lewes, D.E.), Real Art Ways (Hartford, C.T.), The Neon (Dayton, O.H.), Oxford Film Society (Oxford, M.S.).

Support from readers like you helps us do our best work. Go here to subscribe to Prevention and get 12 FREE gifts. And sign up for our FREE newsletter here for daily health, nutrition, and fitness advice.

This content is created and maintained by a third party, and imported onto this page to help users provide their email addresses. You may be able to find more information about this and similar content at piano.io

Continued here:
Exclusive: "Ending Disease" Documentary Explores How Stem Cell Therapy Aims to Cure the Incurable - Prevention.com

Read More...

Lab-Grown Mini-Lungs Mimic the Real Thing Right Down to Covid Infection – Duke Today

Wednesday, October 28th, 2020

DURHAM, N.C. -- A team of Duke University researchers has developed a lab-grown living lung model that mimics the tiny air sacs of the lungs where coronavirus infection and serious lung damage take place. This advance has enabled them to watch the battle between the SARS-CoV-2 coronavirus and lung cells at the finest molecular scale.

The virus damages the delicate, balloon-like air sacs, known as alveoli, leading to pneumonia and acute respiratory distress, the leading cause of death in Covid-19 patients. But scientists have been hampered in Covid-19 studies by the lack of experimental models that mimic human lung tissues.

Now, a team led by Duke cell biologist Purushothama Rao Tata has developed a model using lung organoids, also dubbed mini-lungs in a dish. The organoids are grown from alveolar epithelial type-2 cells (AT2s) which are the stem cells that repair the deepest portions of the lungs where SARS-CoV-2 attacks.

Earlier research at Duke had shown that just one AT2 cell, isolated into tiny dishes, could multiply to produce millions of cells that assemble themselves into balloon-like organoids that look just like alveoli. However, the soup in which the cells were grown contained complex ingredients such as serum from cows that is not completely defined.

Tatas group took on the big challenge of predicting and testing many combinations of chemically pure factors that would do the job just as well, a problem that required close co-operation with Dukes shared computing cluster.

The result is a purely human organoid without any helper cells. Mini-lungs grown in tiny wells will enable high throughput science, in which hundreds of experiments can be run simultaneously to screen for new drug candidates or to identify self-defense chemicals produced by lung cells in response to infection.

This is a versatile model system that allows us to study not only SARS-CoV-2, but any respiratory virus that targets these cells, including influenza, Tata said. A paper describing the development of the mini-lungs and some early experiments with coronavirus infection appeared early online Oct. 21 in the journal Cell Stem Cell.

In using mini-lungs to study SARS-CoV-2 infection, Tatas team collaborated with virology colleagues at Duke and the University of North Carolina in Chapel Hill. To safely handle these deadly viruses, the researchers utilized state-of-the art biosafety level 3 facilities at Duke and UNC-CH to infect lung organoids. The researchers watched the gene activity and chemical signals that are produced by the lung cells after infection.

This is a major breakthrough for the field because we were using cells that didnt have purified cultures, said Ralph Baric, a co-author on the paper who is a distinguished professor of epidemiology, microbiology and immunology at UNC and world authority on coronaviruses. The Duke mini-lungs are 100 percent human with no supporting cells that could confuse findings. This is incredibly elegant work to figure out how to purify and grow AT2 cells in culture in pure form, Baric said.

Barics lab is capable of changing any nucleotide of the Covid-19 viruss genetic code at will, so it produced a glowing version that would reveal where it went in the mini-lungs, confirming that it did indeed home in on the crucial ACE2 cell surface receptor, leading to infection.

When infected with the virus, the organoids were shown to launch an inflammatory response mediated by interferons. The researchers have also witnessed the cytokine storm of immune molecules the lungs launch in response to the virus.

It was thought cytokine storm happened due to the large influx of immune cells, but we can see it also happens in the lung stem cells themselves, Tata said.

Tatas lab found the cells produced interferons and experienced self-destructive cell death, just as samples from Covid-19 patients have shown. The signal for cell suicide was sometimes triggered in uninfected neighboring lung cells as well, as the cells struggled to get ahead of the virus. The researchers also compared the gene activity patterns between the mini-lungs and samples from six severe Covid-19 patients and found they agreed with striking similarity.

Weve only been able to see this from autopsies until now, Tata said. Now we have a way to figure out how to energize the cells to fight against this deadly virus.

In another series of experiments, mini-lungs treated with low doses of interferons before infection were able to slow viral copying. But suppressing interferon activity before infection led to increased viral replication.

Tata, who is a part of Dukes regenerative medicine initiative, Regeneration Next, said his lab was working on growing the mini lungs in mid-2019 and had achieved a working model just as the coronavirus pandemic emerged. He said his group will be working with both academic and industry partners to use these cells for cell-based therapies and eventually to try to grow a complete lung for transplantation.

Baric said his lab will probably be using the mini-lungs to better understand a new strain of SARS-CoV-2 called D614G that has become the dominant version of the virus. This strain, which emerged in Italy, has a spike protein that is apparently more efficient at recognizing the ACE2 receptor on lung cells, making it even more infectious.

This research was performed with support from the Chan Zuckerberg Foundation, the U.S. National Institutes of Health (UC6-AI058607, AI132178, AI149644, R00HL127181, R01HL146557, R01HL153375, R21GM1311279, F30HL143911, DK065988), Duke University and United Therapeutics Corporation.

CITATION: Human Lung Alveolospheres Provide Insights Into SARS-Cov-2 Mediated Interferon Responses and Pneumocyte Dysfunction, Hiroaki Katsura*, Vishwaraj Sontake*, Aleksandra Tata*, Yoshihiko Kobayashi*, Caitlin E. Edwards*, Brook E. Heaton, Arvind Konkimalla, Takanori Asakura, Yu Mikami, Ethan J. Fritch, Patty J. Lee, Nicholas S. Heaton, Richard C. Boucher, Scott H. Randell, Ralph S. Baric, Purushothama Rao Tata.* indicates co-first authors. Cell Stem Cell, early online Oct. 21, 2020. DOI: 10.1016/j.stem.2020.10.005

View original post here:
Lab-Grown Mini-Lungs Mimic the Real Thing Right Down to Covid Infection - Duke Today

Read More...

J&J’s Darzalex Proves Effective in Yet Another Multiple Myeloma Indication – BioSpace

Wednesday, October 28th, 2020

Denmark-based Genmab A/S announced positive topline data from the second part of the Phase III CASSIOPEIA trial. The study is evaluating daratumumab monotherapy as maintenance treatment compared to observation, in other words, no treatment, for patients with newly diagnosed multiple myeloma that are eligible for autologous stem cell transplant (ASCT).

The second part of the trial is being conducted by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen Research & Development, a Johnson & Johnson company.

The trials primary endpoint was improved progression free survival (PFS), which the trial met at a pre-planned interim analysis. It demonstrated a 47% decrease in the risk of progression or death in the patients receiving daratumumab. The safety profile was consistent with previous studies and no new safety signals were seen.

An Independent Data Monitoring Committee (IDMC) has recommended the study results be unblinded. Janssen Biotech licensed the drug from Genmab in 2012 and indicates it plans to meet with regulators to discuss a possible submission for this indication. It also plans to present the data at an upcoming medical conference and submit it for a peer-reviewed scientific journal.

Following the positive data from the first part of the CASSIOPEIA study, we are very pleased to see this benefit, said Jan van de Winkel, chief executive officer of Genmab. We are appreciative of the efforts of the IFM, of HOVON and of Janssen for their work on this study.

Darzalex (daratumumab) is indicated for treatment of adults in the U.S. in combination with carfilzomib and dexamethasone for relapsed/refractory multiple myeloma patients who have received one to three earlier lines of therapy; in combination with bortezomib, thalidomide and dexamethasone for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant, and for several other combinations and as a monotherapy for various stages of multiple myeloma.

The drug is a human IgG1k monoclonal antibody. It binds strongly to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. The drug causes an individuals own immune system to attack the cancer cells, causing rapid tumor cell death via multiple immune-mediated mechanisms of action and through immunomodulatory effects, as well as direct tumor cell death by way of apoptosis.

Net sales of Darzalex in the first quarter of 2020 totaled $937 million, with $463 million in the U.S. and $474 in the rest of the world.

The CASSIOPEIA Phase III trial included 1,085 newly diagnosed patients with previously untreated symptomatic multiple myeloma who were eligible for high-dose chemotherapy and ASCT. In the first part of the trial, patients received induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide and dexamethasone (VTd) or VTd alone. The primary endpoint was the number of patients that achieved a stringent complete response (sCR).

In the second part of the study, which is what is being reported on today, patients that achieved a response in the first part underwent a second randomization to receive either maintenance treatment of 1i6 mg/kg every eight weeks for up to two years of daratumumab, or no further treatment. The primary endpoint was progression-free survival.

Read the original:
J&J's Darzalex Proves Effective in Yet Another Multiple Myeloma Indication - BioSpace

Read More...

Man accused of killing Greeley musician Scott Sessions, ex-girlfriend likely going to trial – Coloradoan

Wednesday, October 28th, 2020

The Patio Patrol program allows residents with home security systems register their devices to help police investigate crimes in their area more efficiently. Fort Collins Coloradoan

A Colorado man will likely go to trial formurder in the deaths of his ex-girlfriend and her new love interest ina double homicide that spanned one week andtwo Colorado counties earlier this year.

Kevin Eastman, 48, will appear in court in Weld County on Dec. 7 for an arraignment on 2 charges each of first-degree murder, tampering with a deceased human body and tampering withphysical evidence. He also faces on charge of possession of a weapon by a previous offender.

The charges seven in all stem from the early February death of 53-year-old Greeley musician Scott Sessions and, later, the death of Eastman's on-again, off-again ex-girlfriendHeatherFrank, also of Greeley.

In interviews with investigators, Eastman denied involvement in Frank's and Sessions' deaths,Eastman's defense attorney Ashley Morriss argued during the conclusion of Eastman's preliminary hearingMonday.

Sessions' body was found Feb. 10 wrapped in plastic and burned near a smoldering log along Old Flowers and Pingree Park roads about 40miles west of Fort Collins in Larimer County. He haddied from sharp force injuries to the back of his neck, Larimer County Sheriff's Office Investigator Justin Atwoodtestified during a preliminary hearing in the case.

Frank's body was foundFeb. 16 wrapped in plastic and bound with baling wire on the rural Weld County property of Eastman's former employer, Troy Bonnell. She had been shot twice in the chest at close range.

Investigators determined Sessions was last heard from by his father in a phone call around 6:12 p.m. Feb. 8. Sessions told his father he wasdriving to meet an unknown person. Facebook messages and location data from his cell phoneindicate thatSessions met Frank, 48, at her Greeley apartment that night, according to testimony from Eastman's hybrid in-person and virtual preliminary hearing, which concluded Monday.The first portion of the preliminary hearing was held Oct. 15.

Eastman later told investigators he showed up to Frank's apartment unannounced on Feb.8 to discuss the possibility of the two getting back together. Frank told Eastman he had to leave because she had a date, according to investigators'testimony.

Facebook messages between Frank and Sessions indicate they met on Jan. 22 at a Wednesday night blues jam concert and that there had later been at least one date before they made plans to meet up again on Feb. 8, Weld County Chief DeputyDistrict AttorneySteveWrenn said.

Sessions, a well-known singer and trumpet player in Denver bandThe Movers & Shakers, had recently returned from a music contest in Memphis, Tennessee, when he and Frank agreed to reconnect, Wrenn added.

COVID-19 in Colorado tracker: Larimer and state case, death and hospital data for October

Tracking the location data of their cellphones, investigators determined Sessions, Frank and Eastman were all in the same area of Greeley near Frank's apartment around 20th Street and 35th Avenue on the night of Feb. 8.

Using that same phone tracking data, investigators determined Scott Sessions' phone went dead or was turned off around 5 a.m. Feb. 9. It was last recorded in the area of Frank's apartment.

Eastman's and Frank's phonesremained active into Feb. 9, and location data showsthe phonestraveled in the area of Ted's Place in Laporte and up the Poudre Canyon that morning.

Surveillance footage at the Mishawaka Amphitheatre also showed a Subaru Crosstrek matching the description of Eastman's passing by the venue twiceonce when it was traveling westbound up the canyon and again as it traveled east down the canyon,Atwood testified.

Sessions' Ford Escape was later seen in surveillance footagebeing driven from Frank's cul-de-sac and left by an unknown person at a nearby King Soopers grocery store on Feb. 11.

A camera placed outside of Frank's cul-de-sac showed her and Eastman leaving her apartment and getting into Eastman's vehicle on Feb. 15, Larimer County Sheriff's Office Sgt. Donald Robbins testified Monday.

A GPS trackerplaced on Eastman's vehicle indicates it then traveled, without stopping, to Bonnell's property that afternoon leaving and coming back three times until early the next morning, when it returned again, Robbins said.

Robbins said he observed Eastman tending to a fireon the property the morning of Feb. 16. By that time, there were active warrants forEastman and Frankon suspicion of first-degree murder in Sessions' case.

From Fort Collins: Police make arrest in downtown stabbing incident

Robbins later followed Eastman to a Kersey gas station, where Eastman was arrested while trying to fill up a portable gasoline tank.

He was found in possession of a sheathed, fixed-blade knife as well as three live rounds and two spent rounds of .22 caliber shell casings, according to Wrenn.

Frank's body was found wrapped in plastic on the Bonnell property after Eastman's arrest onFeb. 16 as law enforcement searched the area where he had previously been spotted by Robbins.

Investigators have not found the gun used in Frank's death.

Investigators later found a large pool of suspected blood near the front entryway of Frank's apartment. As Eastman's preliminary hearing concluded Monday,Wrenn theorized the blood belonged to Sessions and was the result of anambush-style killing by Eastman on Feb. 8.

Wrenn theorized that Eastman then shot and killed Frank the only witness to Sessions'death, Wrenn surmised just over a week later on Feb. 15. Eastmanwas taking steps to burn her body when arrested by law enforcement, Wrenn alleged.

Weld District Court Judge Marcelo Kopcow ruled Monday to bind over all of Eastman's charges for trial. An arraignment of those charges was set for 9 a.m. Dec. 7 in Weld County. Eastman will remain in custodywith no possibility of bond.

All suspects are innocent until proven guilty in court. Arrests and charges are merelyaccusations by law enforcement until, and unless, a suspect is convicted of a crime.

Erin Udell reports on news, culture, history and more for the Coloradoan. Contact her at ErinUdell@coloradoan.com. The only way she can keep doing what she does is with your support. If you subscribe, thank you. If not, sign up for a subscription to the Coloradoan today.

Read or Share this story: https://www.coloradoan.com/story/news/2020/10/27/kevin-eastman-likely-going-trial-murders-heather-frank-greeley-musician-scott-sessions/6043488002/

Follow this link:
Man accused of killing Greeley musician Scott Sessions, ex-girlfriend likely going to trial - Coloradoan

Read More...

How air pollution is making COVID-19 worse – Fast Company

Wednesday, October 28th, 2020

Even before the spread of COVID-19, scientists had declared we were in the midst of an air pollution pandemic, with bad air responsible for 8.8 million premature deaths every year. Now, researchers better understand how these two crises are converging. Across the world, more than 1.1 million people have died of COVID-19, and 15% of those deaths, researchers estimate, could be attributed to long-term air pollution exposure.

The study, conducted by experts at the Max Planck Institute for Chemistry, the German Center for Cardiovascular Research, and more, builds on a previous report from Harvard University that found that someone living in an area with high pollution levels for decades is 8% more likely to die from COVID-19 than someone living with less pollution.

That Harvard study accounted for other mortality factors, such as the number of hospital beds available or comorbidities such as obesity and smoking, and looked at more than 3,000 counties across the U.S, comparing air pollution levels and coronavirus deaths in each area. The authors of this most recent study, published in the journal Cardiovascular Research, applied that same relationship to the rest of the world, using satellite data on global particulate matter exposure and epidemiological data gathered up to June 2020.

Globally, the study found that air pollution exposure may account for 15% of COVID-19 deaths. At the country level, the impact is even more pronounced. In the Czech Republic, researchers estimated that air pollution contributed to 29% of coronavirus deaths; in China, 27%; and in Germany, 26%. In the U.S., 18% of all COVID-19 deaths could be attributed to air pollution. In countries with lower levels of air pollution, the effect was smaller; in Australia, for instance, only 3% of COVID-19 deaths could be attributed to air pollution, researchers estimated.

This doesnt mean theres a direct cause-and-effect relationship between air pollution and COVID-19 deaths, the researchers write; rather, there is some relationship between the two that affects health outcomes. People that have a precondition in terms of lung diseases or heart diseases have a much higher risk of dying from COVID-19. Air pollution affects the same types of mortality and the same diseases, says Jos Lelieveld, an atmospheric chemist at the Max Planck Institute and one of the authors of this latest study. Its not coincidental that these effects are sort of enhancing each other.

When we breathe polluted air, PM2.5particulate matter 2.5 micrometers or less in sizecan enter into our lungs and travel through our bloodstream, damaging our arteries and causing inflammation and oxidative stress, which has been linked to cancer, diabetes, high blood pressure, asthma, and other health impacts. SARS-CoV-2, the coronavirus that causes the disease COVID-19, does the same: entering our bodies through our lungs, traveling through our bloodstream, and damaging our arteries.

Air pollution also makes receptors on our cells called ACE-2 more active. Those receptors are involved in the way COVID-19 infects our bodies. What happens then is a double hit, the researchers explain: Air pollution damages the lungs and increases the activity of those receptors, which then take even more of the SARS-CoV-2 virus into the lungs and bloodstream.

Its important that people realize that air pollution really plays an important role in determining your overall level of health, Lelieveld says. Even though you may not immediately notice that theres something wrong when youre exposed to high levels of air pollution, it causes conditions that make you more sensitive to disease and dying from these diseases.

Lelieveld hopes this research supports that realization and pushes people to do more to stem air pollution. While soon there may be a COVID-19 vaccine, theres no vaccine for poor air or the effects of climate change. When the COVID-19 pandemic has passed, and the next pandemic comes, we may be at risk of more deaths again if we havent addressed pollution. Its extremely important that these vaccines and better cures are being developed, he says. But its also important that people realize that some of the factors that affect your health can only be dealt with if we start realizing that the way were treating our planet is not sustainable.

Follow this link:
How air pollution is making COVID-19 worse - Fast Company

Read More...

Role of Trop-2 as an Actionable Biomarker in Solid Tumors – OncLive

Wednesday, October 28th, 2020

Trophoblast cell surface antigen 2 (Trop-2) is a glycoprotein that spans the epithelial membrane surface and plays a role in cell self-renewal, proliferation, and transformation.1,2 Encoded by the TACSTD2 gene, Trop-2 is a 35-kDa protein composed of a large extracellular domain, a single transmembrane domain, and a short intracellular tail that is the functionally dominant part of the protein.1-4

Under physiological conditions, Trop-2 plays an essential role in embryonic development, placental tissue formation, embryo implantation, stem cell proliferation, and organ development.2 A low basal expression level of Trop-2 is found on the surface of multiple normal epithelial tissues, including skin and oral mucosa.1,3 Trop-2 can promote tumor growth and its overexpression is common in many types of malignant epithelial tumors.1,2,4

Expression of Trop-2 is regulated by several pro-oncogenic transcription factors (eg, CREB1, nuclear factor [NF]B, and HOXA10) via positive feedback relationships.2 Trop-2 expression may be upregulated because of the inactivation of several transcription factors (eg, HNF4A, TP63/TP53L, ERG, HNF1A/TCF-1, and FOXP3).1,2 Overexpression of Trop-2 accelerates the cancer cell cycle and drives cancer growth. Knocking out the TACSTD2 gene disturbs the proliferation of tumor cells, further validating the role of Trop-2 in tumorigenesis.1

Trop-2 was first elucidated as a transducer of intracellular calcium signals; however, it is now known to function in a variety of cell signaling pathways associated with tumorigenesis (Figure 1).1,2,4 Expression of Trop-2, as a calcium signal transducer, causes calcium to be mobilized from internal stores. Increased intracellular calcium levels activate MAPK, which in turn increases levels of phosphorylated ERK1 and ERK2.2,4 ERK1 and ERK2 are important mediators of cell cycle progression, angiogenesis, cell proliferation, cell invasion, and metastasis.2,4 Intracellular calcium also activates the NF-B pathway, which is involved in stimulation of cell growth, and the RAF pathway, which is essential for the upregulation of FOXM1, one of the most commonly overexpressed genes in human solid tumors.2

In addition to stimulating calcium release and MAPK signaling, Trop-2 is involved in several other pro-oncogenic signaling pathways, leading to tumor cell growth and proliferation. Activation of cyclin E and D further promotes cell cycle progression.4Alteration of the Notch, Hedgehog, and Wnt pathways may discourage appropriate stem cell proliferation and differentiation.2,4 Trop-2 signaling also appears to be dependent on -catenin.5 Direct interaction between -catenin and the intracellular domain of Trop-2, through -catenin signaling, enhances stem celllike properties (eg, self-renewal and transformation) of cancer cells.5 Attenuation of IGF-1 receptor signaling by Trop-2 encourages cancer growth and malignancy, particularly in lung cancers.2

Trop-2 is inextricably linked to cancer progression and metastasis because of its role as a key regulator of the hallmarks of cancer, including cell growth, proliferation, migration, invasion, and survival.4 A variety of human epithelial cancer cells are characterized by Trop-2 overexpression, including breast, lung, urothelial, gastric, colorectal, pancreatic, prostatic, cervical, head and neck, and ovarian carcinomas.2,3 In an analysis of 702 tissue samples from patients with breast cancer, Trop-2 expression was detected via immunohistochemistry (IHC) across a wide range of breast cancer subtypes.6 Trop-2 expression is substantially higher in hormone receptorpositive/HER2-negative (HR+/HER2-) disease and triple-negative breast cancer (TNBC) compared with other breast cancer subtypes, including HER2-positive disease.7

Trop-2 overexpression is also common in nonsmall cell lung cancer (NSCLC).8 Using IHC on tissues collected from the tumors of 68 patients with NSCLC, Trop-2 expression was significantly higher in NSCLC tissues compared with matched healthy tissues (P < .05). Moreover, its overexpression was associated with worse tumor, node, metastasis stage (P = .012), lymph node metastasis (P = .038), and histologic grade (P = .013).9

Bladder cancer, the most common urothelial cancer, is also marked by elevated Trop-2 expression.10,11 In a study of 102 transitional cell bladder cancer samples, IHC staining for Trop-2 demonstrated increased Trop-2 expression compared with noncancerous samples, and this expression pattern was significantly associated with worsened tumor grade (P = .001), stage (P < .0 01), and bladder cancer recurrence (P = .0 3).11

Molecular markers that influence the biological progress of tumors often serve as important prognostic indicators. Overexpression of Trop-2 has been associated with more aggressive disease, poorer overall survival (OS), and worse disease-free survival in patients with solid tumors.4 A meta-analysis conducted in 2016 explored the association of Trop-2 expression and prognosis in patients with a variety of solid tumors (N = 2569). Results from the study showed that high Trop-2 expression negatively affected OS (hazard ratio, 1.896; 95% CI, 1.599-2.247; P < .001) and disease-free survival (pooled hazard ratio, 2.336; 95% CI, 1.596-3.419; P < .0 01).12

Specific to breast cancers, increased Trop-2 mRNA is a strong predictor of lymph node involvement, distant metastasis, and poor OS.13,14 Trop-2 is expressed across all breast cancer subtypes; however, overexpression appears more common in aggressive disease subtypes, including HR+/HER2- disease and TNBC.7

Trop-2 overexpression is also associated with poor outcomes in patients with urothelial cancer. In an analysis of 102 tissue samples collected from patients with noninvasive bladder cancer, Trop-2 expression was higher in samples from patients who experienced disease recurrence compared with those who did not have recurrent disease (P = .0 3). Additionally, patients with Trop-2 overexpression had significantly lower rates of recurrence-free survival (P = .0 01).11 In a separate study, high Trop-2 expression analyzed by IHC was strongly correlated with bladder cancer severity and worsened disease prognosis, with particularly strong Trop-2 expression in muscle-invasive bladder cancer tissues compared with normal bladder tissues (P < .0 01).15

Taken together, the data indicate that Trop-2 is a potentially valuable therapeutic target, given the connection between its overexpression and poor prognosis in various solid tumors.4,15 Its value as a prognostic indicator and potential target for therapeutic development is particularly evident in advanced cancers that have limited or few treatment options available, such as TNBC and metastatic urothelial cancers.

Metastatic TNBC

TNBC is an aggressive form of invasive breast cancer that accounts for 15% to 20% of all breast cancers and a disproportionate number of deaths due to breast cancer.16-18 Its prevalence is particularly high in premenopausal women and those of African American and Hispanic descents.17,19 TNBC is characterized by a lack of estrogen and progesterone receptors and a low expression of HER2; therefore, TNBC cannot be effectively treated with standard hormone-based therapies and HER2-targeted agents.16, 20Although chemotherapy has shown promising results in early TNBC, the majority of patients relapse and progress to metastatic TNBC within the first 3 to 5 years after initial treatment.18 The treatment of metastatic TNBC remains a clinical challenge, as no standard-of-care chemotherapy exists for previously treated patients.17,18 There is an urgent unmet need for effective treatment options in patients with metastatic TNBC.18

Metastatic Urothelial Cancer

In the United States, an estimated 81,400 new cases of urothelial cancer will be diagnosed in 2020, and approximately 18,000 Americans will die from the disease.21 The majority of urothelial cancers arise in the bladder, and established risk factors for bladder cancer include older age, male gender, Caucasian race, family history, and smoking.22,23 Muscle-invasive and meta-static urothelial cancers represent 25% of urothelial carcinoma cases and are characterized by substantially worse prognostic outcomes.23,24 Current chemotherapeutic options for metastatic disease offer a modest median OS of 15 months and a 5-year survival of less than 5%.23,24 Long-term survival is infrequent, and newer treatment modalities that target distinct molecular biomarkers are warranted.24,25

As Trop-2 is a clinically relevant cell surface antigen among several solid tumor types, its overexpression on cancer cells makes it an ideal candidate for targeting by specific therapies.26 One targeted approach involves the use of antibody-drug conjugates (ADCs), a technology that has revolutionized the approach to cancer chemo-therapy over the past 2 decades.26

An ADC is designed to contain 3 components: a monoclonal antibody (mAb), a cytotoxic drug called a payload, and a linker that connects the mAb to the cytotoxin. The mAb binds specifically to its tumor-associated antigen (eg, Trop-2), thereby delivering the cytotoxin to the surface of the tumor cell. Once bound, the ADC is internalized through receptor-mediated endocytosis. Lysosomal degradation of the ADC ensues, facilitating the release of the cytotoxin and enabling it to bind to its intracellular target and induce apoptotic cell death (Figure 2).26,27 The targeted nature of ADCs allows potent therapy to be delivered to the cancer cell itself, limiting systemic exposure. The result is fewer adverse effects (AEs), a wider therapeutic window, and reduced exposure of the drug to efflux mechanisms that can increase drug resistance.26,27

Sacituzumab govitecan-hziy is the only FDA-approved Trop-2targeted ADC, and several other agents are under preclinical and clinical development.28

Sacituzumab govitecan-hziy is an ADC that binds to Trop-2 and delivers a potent cytotoxic drug into tumor cells.29,30 The FDA recently granted it accelerated approval for the treatment of metastatic TNBC, and it has also received fast track designation for metastatic urothelial carcinoma, NSCLC, and small cell lung cancer.28,30-32

The composition of sacituzumab govitecan-hziy has been optimized to effectively target tumors expressing Trop-2. A humanized monoclonal antibody (hRS7) binds to Trop-2 and delivers govitecan (SN-38) to the cell surface. SN-38 is the active metabolite of irinotecan and functions as a DNA topoisomerase I inhibitor. A hydrolysable CL2a linker covalently binds SN-38 to h R S 7.30 When released intracellularly, SN-38 causes double-stranded DNA breaks that lead to apoptosis.29 Additionally, the hydrolysable linker allows a portion of the SN-38 payload to be released into the tumor microenvironment, leading adjacent tumor cells to be killed via a bystander effect.31,32

Sacituzumab govitecan-hziy delivers SN-38 in its most active nonglucuronidated form. Because of its moderate toxicity profile, SN-38 is conjugated to hRS7 at a high drug-to-antibody ratio of up to 8 SN-38 molecules per antibody, allowing for greater drug delivery than systemic irinotecan can achieve.29,32 Irinotecan causes grade 3 to 4 diarrhea in approximately one-third of patients, whereas the lower toxicity of SN-38 may confer an improved therapeutic index.29,30 This high level of drug delivery may overcome the ability of Trop-2expressing tumors to repair DNA breaks.30

On April 22, 2020, sacituzumab govitecan-hziy received accelerated approval from the FDA for the treatment of adult patients with metastatic TNBC who have received at least 2 prior therapies for metastatic disease.28 Approval was based on findings of the phase 1/2, single-arm, multicenter IM-T-IMMU-132-01 trial (NCT01631552), in which sacituzumab govitecan-hziy produced durable responses in a subset of patients with heavily pretreated metastatic TNBC.31,33

The IM-T-IMMU-132-01 trial enrolled 108 patients with metastatic TNBC who had received at least 2 prior treatments for metastatic disease. In the study population, the median number of prior systemic therapies in the metastatic setting was 3, and the majority of patients received prior taxanes (98%) and anthracyclines (86%) in the neoadjuvant or metastatic setting. The median age of study patients was 55 years (range 31-80); 99% were female, and 76% were Caucasian.31Brain metastases were present in 23% of patients, and visceral metastases were present in 77% of patients; these included metastases in the lung/pleura (57%), the liver (42%), and other visceral organs (adrenal glands, pancreas, and kidney; 7%).31

Patients received sacituzumab govitecan-hziy 10 mg/kg administered intravenously on days 1 and 8 of 21-day cycles. Treatment continued until disease progression or unacceptable toxicity. The primary efficacy end point was objective response rate (ORR) assessed according to RECIST 1.1 tumor criteria. The secondary efficacy end points included time to response, duration of response, clinical benefit rate (defined as a complete or partial response or stable disease for 6 months), progression-free survival (PFS), and OS.31

After a median follow-up duration of 9.7 months, an objective response occurred in 36 of 108 patients (ORR, 33.3%; 95% CI, 24.6%-43.1%), including a complete response in 3 patients.31 The median time to response was 2 months (range 1.6-13.5). The median response duration was 7.7 months (95% CI, 4.9-10.8), with 55.6% of patients responding at 6 months and 16.7% of patients still responding at 12 months.31,34 An independent central review of the data found a similar ORR and median response duration (34.3% and 9.1 months, respectively).31 The clinical benefit rate, including stable disease for at least 6 months, was 45.4%. Median PFS was 5.5 months; the estimated probability of PFS at 6 and 12 months was 41.9% and 15.1%, respectively. Median OS was 13 months (95% CI, 11.2-13.7); the estimated probability of survival at 6 and 12 months was 78.5% and 51.3%, respectively.31

The most common AEs of any grade were nausea (67%), neutropenia (64%), diarrhea (62%, predominantly grade 1), and fatigue (55%). Of grade 3 or 4 AEs, the most common were neutropenia, decreased white cell count, and anemia (occurring in 42%, 11%, and 11% of patients, respectively).31 Serious AEs occurred in 32% of patients, with the most common being febrile neutropenia (7%), vomiting (6%), nausea (4%), diarrhea (3%), and dyspnea (3%). Occurrence of AEs led to treatment interruption in 44% of patients, dose reductions in 34%, and discontinuation of treatment in 3%.31,34

IM-T-IMMU-132-01 Trial HR+/HER2- Subpopulation Analysis

Treatment with sacituzumab govitecan-hziy showed encouraging results in a prespecified subpopulation of patients with histologically confirmed HR+/HER2- metastatic breast cancer from the IM-T-IMMU-132-01 trial.32

A total of 54 patients with histologically confirmed HR+/HER2- metastatic breast cancer were enrolled. Eligible patients had received at least 1 line of hormone-based therapy and at least 1 prior chemotherapy in the metastatic setting. The median age of enrollees was 54 years (range, 33-79); aside from required prior hormone-based therapy, previous chemotherapies included a taxane (85%), an anthracycline (67%), capecitabine (65%), a CDK4/6 inhibitor (61%), an mTOR inhibitor (44%), and an immune checkpoint inhibitor (1.9%). After a washout period of at least 2 weeks since prior treatment, sacituzumab govitecan-hziy was dosed at 10 mg/kg via intravenous infusion on days 1 and 8 of 21-day cycles.32

The primary efficacy end point was ORR. Of the 54 patients enrolled, 17 patients achieved partial responses during a median follow-up duration of 11.5 months (ORR, 31.5%; 95% CI, 19.5%-45.6%). In the key secondary outcomes, patients experienced a median PFS of 5.5 months (95% CI, 3.6-7.6) and a median OS of 12.0 months (95% CI, 9.0-18.2). The median time to response was 2.1 months (95% CI, 1.4-7.8), and median duration of response was 8.7 months (95% CI, 3.7-12.7). Of the 17 responders, 4 achieved a response lasting more than 12 months (24%). The clinical benefit rate was 44.4% (95% CI, 30.9%-58.6%), with 7 patients showing stable disease for at least 6 months.32

Safety analyses showed a manageable AE profile for sacituzumab govitecan-hziy. There were no reports of cardiac toxicity or severe peripheral neuropathy. The most common grade 3 or higher treatment-related AE was neutropenia, which occurred in 50% of patients. The incidence of diarrhea was 46% and was mild overall. Grade 3 diarrhea was reported in 4 patients, with no reports of grade 4.32 Serious AEs occurred in 2 patients, who experienced febrile neutropenia and 1 case each of neutropenia, viral pneumonia, sepsis, diarrhea, nausea, vomiting, dehydration, and acute respiratory failure.32

ESMO 2020 Data: ASCENTTrial in Metastatic TNBC (NCT02574455)

Final results of the international, multicenter, open-label ASCENT trial (NCT02574455) were presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020. ASCENT was the first phase 3 study of an ADC to show improvement in PFS and OS compared with standard-of-care chemotherapy in patients with previously treated metastatic TNBC.35,36

A total of 529 patients with metastatic TNBC were randomized 1:1 to receive either sacituzumab govitecan-hziy or physicians choice of single-agent chemotherapy (capecitabine, eribulin, vinorelbine, or gemcitabine). The dose of sacituzumab govitecan-hziy was 10 mg/kg intravenously on days 1 and 8 of 21-day cycles. All patients had histologically or cytologically confirmed TNBC refractory to or relapsed after at least 2 prior chemotherapies including a taxane. The median age of the study population was 54 years, and the median number of prior chemotherapies received was 4.

In the primary end point, sacituzumab govitecan-hziy significantly improved median PFS (hazard ratio, 0.41; P< .0001) compared with chemotherapy. The sacituzumab govitecan-hziy treatment group achieved a median PFS of 5.6 months compared with 1.7 months in the chemotherapy treatment group. Compared with chemotherapy, sacituzumab govitecan-hziy treatment also significantly improved key secondary end points of OS (12.1 vs 6.7 months; hazard ratio, 0.48; P < .0001) and ORR (35% vs 5%; P < .0001).35,36

The most common treatment-related grade 3 or higher AEs with sacituzumab govitecan-hziy compared with chemotherapy were neutropenia (51% vs 33%, respectively), diarrhea (10.5% vs < 1.0%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%). No treatment-related deaths were reported, and no cases of neuropathy or interstitial lung disease greater than grade 3 occurred with sacituzumab govitecan-hziy.35

ESMO 2020 Data: Sacituzumab Govitecan-hziy in Combination with Talazoparib for Patients with Metastatic TNBC (NCT04039230)

At the ESMO Virtual Congress 2020, investigators presented the trial design, objectives, and status of a phase 1/2, open-label study that will investigate the efficacy and safety of sacituzumab govitecan-hziy in combination with the PARP inhibitor talazoparib for patients with metastatic TNBC.37 PARP is involved in repairing damaged DNA and is required for clearance of Trop-2 cleavage complexes; thus, PARP inhibitors may be complementary therapeutic partners with sacituzumab govitecan-hziy.37, 38

This study will include a dose escalation in phase 1b followed by a dose expansion in phase 2. Patients will receive sacituzumab govitecan-hziy on days 1 and 8 of 21-day cycles and talazoparib daily on days 15 to 21 of each cycle.38 The primary objective of phase 1b is to assess the dose-limiting toxicity rate and maximum tolerated dose of sacituzumab govitecan-hziy when given in combination with talazoparib. From these data, investigators will determine the recommended phase 2 dose. During phase 2, investigators will assess the ORR, PFS, OS, and clinical benefit rate. As of August 30, 2020, the trial was undergoing active recruitment, and a total of 20 patients were enrolled.37, 38

ESMO 2020 Data: Sacituzumab Govitecan-hziy for Breast Cancer Brain Metastases (NCT03995706)

SN-38, the cytotoxic payload delivered by sacituzumab govitecan-hziy, crosses the blood-brain barrier and is often included in central nervous system (CNS) cancer regimens.39 Investigators hypothesized that sacituzumab govitecan-hziy would yield therapeutically relevant SN-38 concentrations within the CNS of patients under-going craniotomy for breast cancer brain metastases or recurrent glioblastoma.39,40

In this single-center, nonrandomized, phase 0 study (NCT03995706), patients receive a single 10-mg/kg intravenous dose of sacituzumab govitecan-hziy the day prior to craniotomy and then resume therapy (on days 1 and 8 of 21-day cycles) after recovery. To date, 14 patients have been treated. For patients with recurrent glioblastoma (n = 7), the mean SN-38 concentration was 420 nM; for patients with breast cancer brain metastases (n = 7), the mean SN-38 concentration was 626 nM. Among those patients with residual measurable disease, 2 partial intracranial responses have been observed in each group after 12 weeks of treatment (ORR, 28% and 50% for glioblastoma and breast cancer brain metastases, respectively). As of September 2020, recruitment for this trial was ongoing.39,40

The metastatic urothelial cancer cohort of the IM-T-IMMU-132-01 trial reported encouraging activity with sacituzumab govitecan-hziy monotherapy (ORR, 31%; median PFS, 7.3 months; and median OS, 18.9 months).41Sacituzumab govitecan-hziy has FDA fast track desig-nation for metastatic urothelial cancer and is currently under further investigation in the phase 2 TROPHY U-01 trial (NCT03547973) and the upcoming phase 3 TROPiCS-04 trial (NCT04527991).42-45

Final data for cohort 1 and the trial design for cohort 3 were presented at the ESMO Virtual Congress 2020 for the pivotal phase 2, open-label, multicohort TROPHY U-01trial. The TROPHY U-01trial is investigating the safety and efficacy of sacituzumab govitecan-hziy in patients with heavily pretreated metastatic urothelial cancer across several cohorts. The study population across the TROPHY U-01 trial includes patients with disease progression despite treatment with platinum (PLT)-based chemotherapy, checkpoint inhibitors, or both. For all cohorts, the primary efficacy end point is ORR, and key secondary end points include PFS, OS, duration of response, and safety analyses.44,45

Cohort 1

Cohort 1 included a total of 113 patients who were treated with sacituzumab govitecan-hziy. The study population included patients who experienced disease progression after both PLT-based chemotherapy and checkpoint inhibitor therapy.44 Overall, patients in cohort 1 were previously treated with a median of 3 therapies and were a median of 66 years of age. In the results presented at ESMO 2020, a total of 31 patients had achieved an objective response (ORR, 27%; 95% CI, 19%-37%), of which 6 were complete responses and 25 were partial responses. The median duration of response was 5.9 months (95% CI, 4.7-8.6); median PFS and OS were 5.4 months (95% CI, 3.5-6.9) and 10.5 months (95% CI, 8.2-12.3), respectively. Sacituzumab govitecan-hziy demonstrated manageable toxicity. Key grade 3 or higher AEs were neutropenia (35%), anemia (14%), febrile neutropenia (10%), and diarrhea (10%).44

Cohort 3

As of March 2020, cohort 3 had started enrollment and is ongoing. The study plans to enroll a total of 61 patients with metastatic urothelial cancer who are nave to checkpoint inhibitor agents and have experienced disease progression or recurrence after PLT-based chemotherapy.45 As checkpoint inhibitors are the stan-dard-of-care therapy for patients who have failed on PLT-based chemotherapy, this study will investigate combination therapy with sacituzumab govitecan-hziy and the checkpoint inhibitor pembrolizumab. Exclusion criteria include active autoimmune disease or a history of interstitial lung disease, given the coadministration of pembrolizumab. A 10-patient lead-in cohort will determine standard the recommended phase 2 dose of sacituzumab govitecan-hziy (given on days 1 and 8 of 21-day cycles), to be given along with pembrolizumab 200 mg on day 1 of each cycle. The primary end point of ORR and secondary end points of PFS, OS, clinical benefit rate, duration of response, and safety will be assessed.45

The phase 3, global, open-label TROPiCS-04trial aims to enroll 482 patients to investigate the efficacy and safety of sacituzumab govitecan-hziy in patients with metastatic or locally advanced unresectable urothelial cancer who have progressed despite prior therapy with PLT-based chemotherapy and a PD-1 or PD-L1 checkpoint inhibitor. Sacituzumab govitecan-hziy will be compared with physicians choice of chemotherapy (paclitaxel, docetaxel, or vinflunine). The primary outcome measure will be OS; secondary outcomes will include PFS, ORR, safety, and quality of life. As of August 2020, the trial was not yet recruiting patients.43

Evaluation of novel and existing ADCs has revealed that success is not based on the use of any one particular cytotoxic compound or conjugate platform. Factors such as the consistency and level of target-antigen expression, tumor progression, and specific properties of the cancer and stage of disease also play important roles.46 Several additional Trop-2targeted ADCs are currently being investigated in solid tumors (Table).33,36,37,40,42,43,47-51

DS-1062a is a Trop-2directed ADC that contains the cytotoxic compound DXd, a derivative of exatecan that acts as a DNA topoisomerase I inhibitor.52 It is currently being investigated for the treatment of advanced NSCLC in an ongoing phase 1, multicenter, open-label study (NC T 03 401385).48

The study involves a dose-escalation phase and a dose-expansion phase. Dose-limiting toxicity, maximum tolerated dose, and AEs will be explored in both phases.47 Eligible patients have experienced disease progression or recurrence despite previous treatments, have measurable disease per RECIST 1.1 criteria, and are able to provide a sufficient tumor tissue sample for Trop-2 measurement. Patients with multiple primary malignancies or untreated brain metastases are ineligible for the study.48

As of November 2018, a total of 22 patients had been treated with 1 of 3 escalating doses of DS-1062a. Nearly 82% of patients experienced at least 1 treatment-emergent AE, with fatigue being the most common complaint. Fatigue was the only reported grade 3 or higher AE and was reported by 1 patient. Of 18 tumor-evaluable patients, 1 showed a partial response and 8 showed stable disease. Maximum-tolerated dose has not been achieved, and investigators will continue to monitor for safety and disease progression.47, 48

RN927C

RN927C, also known as PF-06664178, is an ADC composed of a Trop-2directed antibody conjugated with the cytotoxic microtubule inhibitor PF-06380101. Release of PF-06380101 leads to mitotic arrest, apoptosis, and cell death.3 Preclinical studies demonstrated the ability of RN927C to induce cell death among various tumor cell lines, including those from the skin, lung, head and neck, breast, ovary, and colon.3

RN927C was investigated in a phase 1, open-label, nonrandomized dose-escalation study (NCT02122146)of patients with advanced or metastatic solid tumors that were unresponsive to current therapies or for whom no standard therapy was available. The primary objective of the study was to determine the maximum tolerated dose and recommended phase 2 dose. Secondary outcomes included safety and preliminary evidence of antitumor activity. A total of 31 patients were enrolled and received treatment with escalating doses of RN927C. Stable disease was noted in 11 patients (39%), but no partial or complete responses were seen. Doses of 3.6 mg/kg, 4.2 mg/kg, and 4.8 mg/kg were considered intolerable, primarily because of skin reactions and development of neutropenia. The next-lower dose of 2.4 mg/kg was well tolerated, but the study was terminated early because of minimal anti-tumor activity and excessive toxicities.50

BAT8003

BAT8003 is an ADC composed of a Trop-2directed antibody conjugated to a potent cytotoxic maytansine derivative. The ADC has been optimized to facilitate site-specific conjugation, which allows for a more controllable drug-antibody ratio. In addition, a fucosylation of the Fc region of the antibody enhances its antibody-dependent cell-mediated cytotoxicity effect. In preclinical xenograft and primate models, BAT8003 demonstrated strong inhibition of tumor growth at doses of 5 mg/kg and 15 mg/kg, with a highest nonseverely toxic dose of 20 mg/kg given once every 3 weeks.51, 53

Given the promising preclinical data, a phase 1 dose-escalation study (NCT03884517) is currently investigating the safety, tolerability, and pharmacokinetics of BAT8003 in patients with advanced epithelial cancer who are either ineligible for standard therapy or have disease refractory to standard therapy.Eligible patients will receive escalating doses of BAT8003 (0.2-10.0 mg/kg) on day 1 of each 21-day cycle. The study will be divided into 3 periods: (1) the first 21-day cycle, which will examine the safety of a single BAT8003 administration, observe for dose-limiting toxicities, and establish preliminary pharmacokinetic parameters; (2) cycles 2 through 8, which will examine safety, immunogenicity, and preliminary efficacy of escalating doses of BAT8003; and (3) an expansion period, which could include an additional 10 to 30 cases to further assess safety and efficacy once a safe and effective dose has been established. As of the last update on March 21, 2019, the trial was actively recruiting patients.51

Trop-2 has established itself as a clinically meaningful biomarker among several types of solid malignancies. Its ability to promote self-renewal, proliferation, and cell invasion makes it an ideal candidate for targeted anti-tumor therapies, including ADCs.

Sacituzumab govitecan-hziy is the first Trop-2directed ADC to receive FDA approval for the treatment of metastatic TNBC. In the pivotal IM-T-IMMU-132-01 trial, sacituzumab govitecan-hziy showed encouraging results in patients with multiple difficult-to-treat solid tumor types, including TNBC, HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer.31,32,41 Sacituzumab govitecan-hziy and other Trop-2directed ADCs represent a novel strategy to improve outcomes among these populations of patients with few therapeutic options. Data from additional trials of sacituzumab govitecan-hziy were presented at the ESMO Virtual Congress 2020. In the ASCENT trial, sacituzumab govitecan improved response rates and survival outcomes in patients with metastatic TNBC compared with standard-of-care therapy.35 Data from a cohort of patients with metastatic urothelial cancer in the TROPHY U-01 trial indicated positive survival impacts with manageable toxicity.44 Additional trials of sacituzumab-govitecan-hziy (as monotherapy or in combination with PARP inhibitors or checkpoint inhibitors) are under way in patients with metastatic TNBC, breast cancer brain metastases, and metastatic or locally advanced urothelial cancer.37,40,43,45 Other Trop-2directed ADCs are under investigation in NSCLC and advanced epithelial cancers.47, 51

See the original post:
Role of Trop-2 as an Actionable Biomarker in Solid Tumors - OncLive

Read More...

Scientists grow mini-lungs in a lab, infect them with coronavirus and watch battle in real time – The Indian Express

Wednesday, October 28th, 2020

Written by Kabir Firaque | New Delhi | Updated: October 25, 2020 11:18:59 amMedical workers check a X-ray photo of a lung of a patient suffering of Covid-19 in the Nouvel Hopital Civil of Strasbourg, eastern France, Thursday, Oct.22, 2020. (AP Photo: Jean-Francois Badias, File)

The novel coronavirus is known to attack primarily the lungs, but how the attack unfolds is still a subject of research. Now, two studies have thrown light on these processes by using the same approach. Scientists have developed lung models in the lab, infected these with SARS-CoV-2, and watched the battle between the lung cells and the virus.

Both papers are published in the journal Cell Stem Press. One study is by South Korean and UK researchers, including from the University of Cambridge; the other is by researchers from Duke University and University of North Carolina.

In both studies, scientists observed how the virus damages the alveoli in the lungs. Alveoli are balloon-like air sacs that take up the oxygen we breathe and release the carbon dioxide we exhale. Damage to alveoli causes pneumonia and acute respiratory distress the leading cause of death in Covid-19.

Both teams developed the model using mini-lungs or lung organoids. The organoids were grown from the stem cells that repair the deepest portions of the lungs where SARS-CoV-2 attacks. These are called AT2 cells. Follow Express Explained on Telegram

The UK and South Korean team reprogramed the AT2 cells back to their earlier stem cell stage. They grew self-organising, alveolar-like 3D structures that mimic the behaviour of key lung tissue. When the 3D models were exposed to SARS-CoV-2, the virus began to replicate rapidly.

In six hours, cells began to produce interferonsproteins that act as warning signals to neighbouring cells. After 48 hours, the cells started fighting back. And after 60 hours from infection, some of the alveolar cells began to disintegrate, leading to cell death and damage to the tissue.

In the other study, led by Duke University cell biologist Purushothama Rao Tata, the team got a single lung cell to multiply into thousands of copies and create a structure that resembles breathing tissues of the human lung. Once infected with the virus, the model showed an inflammatory response.

The team also witnessed the cytokine storm the hyper reaction of immune molecules the lungs launch to fight the infection.

The Indian Express is now on Telegram. Click here to join our channel (@indianexpress) and stay updated with the latest headlines

For all the latest Explained News, download Indian Express App.

The Indian Express (P) Ltd

Read the rest here:
Scientists grow mini-lungs in a lab, infect them with coronavirus and watch battle in real time - The Indian Express

Read More...

Apellis and Sobi Enter Collaboration for Global Co-development and Ex-US Commercialization of Systemic Pegcetacoplan in Rare Diseases with Urgent Need…

Wednesday, October 28th, 2020

DetailsCategory: Proteins and PeptidesPublished on Tuesday, 27 October 2020 18:20Hits: 344

WALTHAM, MA, USA and STOCKHOLM, Sweden I October 27, 2020 I Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) and Swedish Orphan Biovitrum AB (publ) (Sobi) (STO:SOBI) today announced a strategic collaboration to accelerate the advancement of systemic pegcetacoplan, a targeted C3 therapy, for the treatment of multiple rare diseases with high unmet need that impact more than 275,000 patients globally.

Sobi will receive global co-development and exclusive ex-US commercialization rights for systemic pegcetacoplan. Apellis retains U.S. commercialization rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, which is being evaluated by Apellis in two fully enrolled Phase 3 studies in geographic atrophy (GA). Pegcetacoplan targets excessive activation of C3 in the complement cascade, part of the bodys immune system, which can lead to the onset and progression of many serious diseases.

Apellis and Sobi plan to jointly advance the clinical development of systemic pegcetacoplan in five parallel registrational programs across hematology, nephrology, and neurology. These include new registrational programs in cold agglutinin disease (CAD) and hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA), both of which are expected to start in 2021. By controlling complement activation centrally, pegcetacoplan offers the potential to become a transformative new therapy in several rare diseases where patients have few or no treatment options today.

This collaboration enables us to further expand on the broad platform potential of targeting C3 for serious rare diseases that impact hundreds of thousands of patients around the world, said Cedric Francois, M.D., Ph.D., co-founder and chief executive officer of Apellis. We evaluated numerous companies, medium and large, and chose Sobi because of their global leadership in hematology and rare diseases, track record of successful product launches, and deep commitment to patients. Together, we will quickly advance systemic pegcetacoplan in multiple registrational programs across hematology, nephrology, and neurology while also preparing for our first potential U.S. launch in PNH. Financially, this transaction also strengthens our position, with our cash runway expected to extend into the second half of 2022.

We are excited to collaborate with Apellis, a leader in targeted C3 therapies. The collaboration will significantly strengthen and broaden our late-stage R&D portfolio and be a catalyst for further internationalization. The products have an excellent fit with our strategic focus on hematology and immunology, said Guido Oelkers, chief executive officer and president of Sobi. Given the central role of C3 in the complement cascade, pegcetacoplan has the potential to become the foundation for a broader platform in rare diseases. With positive Phase 3 data in PNH, pegcetacoplan can elevate the standard of care for this debilitating blood disorder.

As part of the collaboration, Apellis and Sobi will co-develop systemic pegcetacoplan in the following rare diseases:

Hematology Paroxysmal nocturnal hemoglobinuria (PNH), CAD, and HSCT-TMAPNH represents the first potential indication to market for systemic pegcetacoplan. Marketing applications for pegcetacoplan for the treatment of PNH were submitted to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) based on positive results from the Phase 3 PEGASUS study. Top-line results from the Phase 3 PRINCE study, which is evaluating pegcetacoplan in treatment-nave patients with PNH, are expected in the first half of 2021.

Sobi will lead development activities for the Phase 3 study in CAD and a potentially registrational Phase 2 study in HSCT-TMA, both planned to start in 2021.

Nephrology Immune complex membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G)Apellis has initiated and will continue to lead a registrational program in IC-MPGN and C3G, which includes Phase 2 and Phase 3 studies.

Neurology Amyotrophic lateral sclerosis (ALS)Apellis has initiated and will continue to lead a potentially registrational Phase 2 study in ALS. Multiple other neurological conditions are under consideration for future clinical development.

About the TransactionSobi will make an upfront payment of $250 million to Apellis and up to $915 million in other regulatory and commercial milestone payments, and will contribute $80 million in reimbursement payments over a four-year period for research and development to support the initial development plan, which includes ongoing studies in PNH, IC-MPGN/C3G, and ALS and new studies in CAD and HSCT-TMA. Apellis will also be eligible for tiered double-digit royalties on sales ranging from high teens to high twenties. Sobi intends to finance these payments with available funds. Sobi will receive reimbursement payments for the costs incurred by Sobi in connection with the CAD and HSCT-TMA trials that Sobi will conduct. The parties have agreed to split costs 50/50 for any future global studies beyond the initial development plan.

Per the terms of the agreement, Apellis will be responsible for all regulatory and commercial activities in the United States and the ongoing Marketing Authorization Application (MAA) review for PNH in the European Union, which will be subsequently transferred to Sobi. Sobi will be responsible for regulatory and commercial activities for systemic pegcetacoplan in ex-US markets. The co-development of systemic pegcetacoplan will be overseen by a joint development committee, and the commercial strategy will be overseen by a joint commercial committee.

Conference Call and WebcastApellis will host a conference call and webcast to discuss its collaboration with Sobi today, October 27, 2020, at 8:30 a.m. ET. To access the conference call, please dial (866) 774-0323 (local) or (602) 563-8683 (international) at least 10 minutes prior to the start time and refer to conference ID 5774165. A live audio webcast of the event and accompanying slides may also be accessed through the Events and Presentations page of the Investors and Media section of the companys website at http://investors.apellis.com/events-and-presentations. A replay of the webcast will be available for 30 days following the event.

About Pegcetacoplan (APL-2)Pegcetacoplanis an investigational, targeted C3 therapy designed to regulate excessive complement activation, which can lead to the onset and progression of many serious diseases.Pegcetacoplanis a synthetic cyclic peptide conjugated to a polyethylene glycol polymer that binds specifically to C3 and C3b.Apellis is evaluatingpegcetacoplanin several clinical studies across hematology, ophthalmology, nephrology, and neurology.Pegcetacoplanwas granted Fast Track designation by the U.S. Food and Drug Administration (FDA) forthe treatment of PNH and the treatment of geographic atrophy and received orphan drug designation for the treatment of C3G by the FDA and European Medicines Agency.

About Pegcetacoplan for Paroxysmal Nocturnal Hemoglobinuria (PNH)In October, the European Medicines Agency validated the Marketing Authorization Application (MAA) for pegcetacoplan in PNH, and an opinion from the Committee for Medicinal Products for Human Use is expected in 2021. A decision by the U.S. Food and Drug Administration regarding the acceptance of the New Drug Application (NDA) and a Prescription Drug User Fee Act (PDUFA) target action date is expected in the fourth quarter of 2020. Top-line results from the Phase 3 PRINCE study, which is evaluating pegcetacoplan in treatment-nave patients with PNH, are expected in the first half of 2021.

The NDA and MAA submissions for pegcetacoplan for the treatment of PNH are based on positive results from the Phase 3 PEGASUS study (APL2-302; NCT03500549), a multi-center, randomized, active-comparator controlled Phase 3 study in 80 adults with PNH. The primary objective of PEGASUS was to establish the efficacy and safety of pegcetacoplan compared to eculizumab. Pegcetacoplan is also being evaluated in the Phase 3 PRINCE study (APL2-308; NCT04085601), a randomized, multi-center, controlled study evaluating pegcetacoplan in 53 patients with PNH who had not received a complement inhibitor within three months before entering the study.

AboutPNHPNH is a rare, chronic, life-threatening blood disorder characterized by the destruction of oxygen-carrying red blood cells through extravascular and intravascular hemolysis. Persistently low hemoglobin can result in frequent transfusions and debilitating symptoms such as severe fatigue, hemoglobinuria, and difficulty breathing (dyspnea). A retrospective analysis shows that, even on eculizumab, approximately 72% of people with PNH have anemia, a key indicator of ongoing hemolysis.1 The analysis also finds that 36% of patients require one or more transfusions a year and 16% require three or more.1

About Cold Agglutinin Disease (CAD) CAD is a severe, chronic, rare blood disorder2 that currently has no approved therapies and impacts ~10,500 people across the United States and Europe.3 People living with CAD may suffer from chronic anemia, transfusion requirements, and an increased risk of life-threatening thrombotic events such as stroke.4 In people with CAD, immunoglobin M (IgM) autoantibodies cause red blood cells to agglutinate, or clump together, at temperatures below 30oC or as a result of a compromised immune system or infection.5 This activates the complement cascade to destroy healthy red blood cells through extravascular and intravascular hemolysis.6,7

About Hematopoietic Stem Cell Transplantation Thrombotic Microangiopathy (HSCT-TMA)HSCT-TMA is rare blood disease that can be a fatal complication of a bone marrow transplant or HSCT.8 In HSCT-TMA, microscopic blood clots form in small blood vessels, leading to organ damage. The kidneys are commonly affected, although any organ may be involved.8 HSCT-TMA occurs in up to 40% of HSCT recipients;9 every year, there are ~9,000 allogeneic transplants in the United States and ~18,000 in the EU+.10,11 Excessive complement activation is a high-risk feature in patients with HSCT-TMA,12 and C3 is believed to play a critical role in TMA based on proinflammatory and procoagulant properties of C3a and C3b.13

About Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN) and C3 Glomerulopathy (C3G) IC-MPGN and C3G are rare, debilitating kidney diseases that affect ~18,000 people in the United States and Europe.14 There are no approved therapies for the diseases, and symptoms include blood in the urine, dark foamy urine due to the presence of protein, swelling, and high blood pressure.15 Approximately 50% of people living with IC-MPGN and C3G ultimately suffer kidney failure within five to 10 years of diagnosis.16 Although IC-MPGN is considered a distinct disease from C3G, the underlying cause and progression of the two diseases are remarkably similar and include overactivation of the complement cascade, with excessive accumulation of C3 breakdown products in the kidney causing inflammation and damage to the organ. 17,18

About Amyotrophic Lateral Sclerosis (ALS)ALS is a devastating neurodegenerative disease that results in progressive muscle weakness and paralysis due to the death of nerve cells, called motor neurons, in the brain and spinal cord.19, 20 The death of motor neurons leads to theprogressive loss of voluntary muscle movement required forspeaking, walking, swallowing and breathing.19,20In individuals with ALS, high levels of C3 are present at the neuromuscular junction21 where motor neurons communicate directly to muscle cells. Numerous studies suggest that elevated levels of C3 present throughout the motor system of ALS patients are likely to contribute to chronic neuroinflammation and the death of motor neurons.21,22,23 There are no treatments that stop or reverse the progression of ALS, which impacts ~225,000 patients worldwide.24

About ApellisApellis Pharmaceuticals, Inc. is a global biopharmaceutical company that is committed to leveraging courageous science, creativity, and compassion to deliver life-changing therapies. Leaders in targeted C3 therapies, we aim to develop transformative therapies for a broad range of debilitating diseases that are driven by excessive activation of the complement cascade, including those within hematology, ophthalmology, nephrology, and neurology. For more information, please visithttp://apellis.com.

About SobiSobi is a specialized international biopharmaceutical company transforming the lives of people with rare diseases. Sobi is providing sustainable access to innovative therapies in the areas of hematology, immunology and specialty indications. Today, Sobi employs approximately 1,500 people acrossEurope,North America, theMiddle East,RussiaandNorth Africa. In 2019, Sobi's revenue amounted toSEK 14.2 billion. Sobi's share (STO:SOBI) is listed on Nasdaq Stockholm. You can find more information about Sobi atwww.sobi.com.

1 McKinley C. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130:3471.2 Sokol RJ, Hewitt S, Stamps BK. Autoimmune haemolysis: an 18-year study of 865 cases referred to a regional transfusion centre.Br Med J (Clin Res Ed).1981;282(6281):2023-2027.National Institute of Health (NIH), Genetic and Rare Diseases Information Center (GARD) 3 Catenion using physician and literature consensus4 Websitehttps://rarediseases.info.nih.gov/diseases/6130/cold-agglutinin-disease. Accessed November 21, 2019.5 Berentsen S, Ulvestad E, Langholm R, et al. Primary chronic cold agglutinin disease: a population based clinical study of 86 patients.Haematologica.2006;91(4):460-466.6 Cold agglutinin disease. Genetic and Rare Diseases Information Center Web site. https://rarediseases.info.nih.gov/diseases/6130/cold-agglutinin-disease. Accessed November 21, 2019.7 Reynaud Q, Durieu I, Dutertre M, et al. Efficacy and safety of rituximab in auto-immune hemolytic anemia: A meta-analysis of 21 studies.Autoimmun Rev.2015;14(4):304-313.8 Dvorak C, et al. Transplant-Associated Thrombotic Microangiopathy in Pediatric Hematopoietic Cell Transplant Recipients: A Practical Approach to Diagnosis and Management. Frontiers in Pediatrics. Vol 7, article 133. (2019)9 Jodele S, et al. Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults. Blood. 124(4): 645653 (2014)10 Current Uses and Outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR Summary Slides11 Passweg et al, BMT. 2019, 38: 1575158512 Jodele S, et al. Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab. Blood. 135 (13): 10491057. (2020)13 Noris M, et al. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nature Reviews Nephrology. 8, 622633 (2012)14 ClearView Analysis using physician and literature consensus.15 Complement 3 Glomerulopathy (C3G). National Kidney Foundation Website.https://www.kidney.org/atoz/content/complement-3-glomerulopathy-c3g.Accessed November 21, 2019.16 C3 glomerulopathy. National Institute of Health, Genetics Home Reference.https://ghr.nlm.nih.gov/condition/c3-glomerulopathy#resources. Accessed November 21, 2019.17 Noris M, Donadelli R, Remuzzi G. Autoimmune abnormalities of the alternative complement pathway in membranoproliferative glomerulonephritis and C3 glomerulopathy. Pediatr Nephrol. 2019 Aug;34(8):1311-1323.18 Cook HT. Evolving complexity of complement-related diseases: C3 glomerulopathy and atypical haemolytic uremic syndrome. Curr Opin Nephrol Hypertens. 2018 May;27(3):165-170.19 National Institute of Neurological Disorders and Stroke. (2020). Amyotrophic Lateral Sclerosis Fact Sheet. Retrieved from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Amyotrophic-lateral-Sclerosis-ALS-Fact-Sheet20 ALS Association. What is ALS? Retrieved June 2020 from https://www.als.org/understanding-als/what-is-als21 Bahia El Idrissi N, et al. J Neuroinflammation. 2016;13(1):72.4 Sta M, et al. Neurobiol Dis. 2011;42(3):211-220.22 Woodruff, et al., PNASJanuary 7, 2014111(1)E3-E423 Lee, et al Journal of Neuroinflammation volume 15: 171 (2018)25 Arthur K et al. Nat Commun, 2016, Vol 7, article 1240824 Arthur K et al. Nat Commun, 2016, Vol 7, article 12408

SOURCE: Apellis Pharmaceuticals

Read more:
Apellis and Sobi Enter Collaboration for Global Co-development and Ex-US Commercialization of Systemic Pegcetacoplan in Rare Diseases with Urgent Need...

Read More...

Rates of Invasive Pulmonary Aspergillosis in ICU Patients With Influenza Far Lower Than Previously Thought – Contagionlive.com

Wednesday, October 28th, 2020

Despite recent studies identifying invasive pulmonary aspergillosis (IPA) as a common complication of severe influenza, even in hosts who are immunocompetent, a retrospective look at the last 9 influenza seasons at 1 healthcare center in the United States tells a different tale.

In a poster presented virtually at ID Week 2020, investigators at Northwestern Universitys Feinberg School of Medicine determined the incidence of IPA among critically ill patients with influenza over multiple seasons and sought to track outcomes and hone in on predisposing risk factors.

Data were collected at a single healthcare center in Chicago, Illinois, across 9 influenza seasons (March 2009 March 2018), and included patients > age 18 who were admitted to the intensive care unit (ICU) with respiratory distress and had a positive influenza polymerase chain reaction test.

Investigators relied on criteria from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) to define IPA, as well as the revised AspICUcriteria.

The study population comprised 224 patients admitted to the ICU with influenza, and the overall rate of IPA was 3.1% (7/224). History of stem cell transplant was found to be a statistically significant risk factor for IPA (P = .015), with hematologic malignancy (P = .09), lung disease (P = .098), and obesity (P = .051) tending toward significance. Only 1 out of 7 patients with IPA was not immunosuppressed.

Length of hospital stay was significantly increased for patients with IPA (P = .046), but there was no significant difference in need for mechanical ventilation, renal replacement therapy, or death in these patients.

Other coinfections were common in these patients, with 31.3% bacterial, 7.6% viral, and 8.9% non-aspergillosis fungi infections reported.

The incidence of IPA was significantly lower (3.1%) in our study over 9 influenza seasons than has been reported in similar studies, investigators concluded. History of stem cell transplant was a risk factor strongly associated with the development of IPA. IPA did not significantly predict morbidity and mortality among critically ill influenza patients.

The poster, Aspergillosis Complicating Severe Influenza in ICU Patients: A Retrospective Cohort Study, was presented virtually at ID Week 2020.

Link:
Rates of Invasive Pulmonary Aspergillosis in ICU Patients With Influenza Far Lower Than Previously Thought - Contagionlive.com

Read More...

Promising, Early Results for Combined HDAC and mTOR Inhibition in Relapsed/Refractory Hodgkin Lymphoma – Cancer Therapy Advisor

Tuesday, October 20th, 2020

High response rates were observed for patients with relapsed/refractory Hodgkin lymphoma treated with the combination of vorinostat and an mTOR inhibitor, according to findings published in Clinical Cancer Research.1

Although the majority of patients diagnosed with Hodgkin lymphoma are considered to be cured following first-line treatment with standard therapy, 5-year survival rates for those with relapsed/refractory disease following primary treatment can be as low as 30%.2

Despite US Food and Drug Administration (FDA) approvals of brentuximab, a CD30 antibody-drug conjugate, and the programmed cell death 1 (PD-1) inhibitors pembrolizumab and nivolumab for the treatment of patients with relapsed/refractory Hodgkin lymphoma, an unmet need remains for new therapies in this setting.

Based on prior preclinical and early clinical evidence supporting the potential efficacy of dual histone deacetylase (HDAC) and AKT/mTOR inhibition for those with relapsed/refractory Hodgkin lymphoma, the cohort of patients with heavily pretreated Hodgkin lymphoma enrolled in a nonrandomized, open-label, dose-escalation phase 1 study (ClinicalTrials.gov Identifier: NCT01087554) investigating the combination of vorinostat, an HDAC inhibitor, with an mTOR inhibitor in advanced cancer was expanded.

The rationale for such an approach was grounded in evidence implicating HDAC overexpression and associated aberrant gene expression in relapsed/refractory Hodgkin lymphoma, as well as a possible role for mTOR signaling as a pathway for resistance to HDAC inhibition in this setting.2,3

At baseline, the 40 patients included in this analysis were aged at least 18 years; the median patient age was 33 years. Regarding race/ethnicity, 55%, 27.5%, 12.5%, and 5% of these patients were White, Hispanic, Black, and Asian, respectively. Stage IV disease was present in 65% of patients, and Eastern Cooperative Oncology Group (ECOG) performance status was 0 (30%), 1 (50%), and 2 (20%). The median number of prior treatments was 5, with previous therapies including brentuximab vendotin, autologous hematopoietic stem cell transplantation (HSCT), and allogeneic HSCT in 97.5%, 65%, and 30% of patients, respectively.

None of these patients had received prior treatment with a PD-1 inhibitor.

Vorinostat, in combination with either siroliumus and everolimus, was administered to 22 and 18 patients, respectively.

For those patients treated with vorinostat plus siroliumus, the complete response (CR) and partial response (PR) rates were both 27%. At a median follow-up of 43.3 months, median progression-free survival (PFS) was 5.8 months.

In the subgroup receiving vorinostat plus everolimus, the CR and PR rates were 11% and 22%, respectively, and, at a median follow-up of 21 months, the median PFS was 4.8 months. A comparison of median PFS for those treated with either sirolimus or everolimus did not show a significant difference (P =.13)

Of note, responses were seen even in patients who received prior treatment with AKT or HDAC inhibitors, the study authors commented.

Regarding the safety of combination therapy with an HDAC and an mTOR inhibitor, the most commonly reported grade 3/4 adverse events (AEs) in the overall study population were neutropenia, thrombocytopenia, and anemia. However, while the frequencies of grade 4 neutropenia, thrombocytopenia, and anemia for those treated with sirolimus were 9%, 36%, and 0%, respectively, the corresponding rates were 0%, 11%, and 9% for the subgroup receiving everolimus. No treatment-related grade 5 AEs were reported.

In their concluding remarks, the study authors noted that combined HDAC and mTOR inhibition has encouraging activity in patients with relapsed and/or refractory Hodgkin lymphoma and warrants further investigation.

References

Continued here:
Promising, Early Results for Combined HDAC and mTOR Inhibition in Relapsed/Refractory Hodgkin Lymphoma - Cancer Therapy Advisor

Read More...

Autologous Cell Therapy Market is Anticipated to Expand at a CAGR of 18.1% from 2019 to 2027 – Eurowire

Tuesday, October 20th, 2020

Transparency Market Research (TMR) has published a new report titled, Autologous cell therapy Market Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 20192027. According to the report, the global autologous cell therapy market was valued at US$ 7.5 Bn in 2018 and is projected to expand at a CAGR of 18.1% from 2019 to 2027.

Overview

Request a PDF Brochure https://www.transparencymarketresearch.com/sample/sample.php?flag=B&rep_id=715

Rise in Prevalence of Neurological Disorders & Cancer and Others to Drive Market

Request for Analysis of COVID19 Impact on Autologous Cell Therapy Market https://www.transparencymarketresearch.com/sample/sample.php?flag=covid19&rep_id=715

Bone Marrow Segment to Dominate Market

Neurology Segment to be Highly Lucrative Segment

Buy Autologous Cell Therapy Market Report https://www.transparencymarketresearch.com/checkout.php?rep_id=715&ltype=S

Hospitals Segment to be Highly Lucrative Segment

North America to Dominate Global Market

Competitive Landscape

The global autologous cell therapy market is fragmented in terms of number of players. Key players in the global market include Pharmicell Co., Inc., Castle Creek Biosciences, Inc., Vericel Corporation, Lineage Cell Therapeutics, Inc., BrainStorm Cell Therapeutics, Caladrius Biosciences, Inc., Opexa Therapeutics, Inc., Regeneus Ltd., Takeda Pharmaceutical Company Limited., Sangamo Therapeutics, U.S. Stem Cell, Inc. and other prominent players.

More Trending Reports by Transparency Market Research

Genome Engineering Market https://www.prnewswire.com/news-releases/genome-engineering-market-to-clock-cagr-of-10-9-from-2019-to-2027-crispr-gene-edition-tools-present-sizable-revenue-streams-tmr-301073517

Read our Case study at https://www.transparencymarketresearch.com/casestudies/innovative-medical-device-manufacturing-start-up

About Us

Transparency Market Research is a global market intelligence company providing global business information reports and services. Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insight for several decision makers. Our experienced team of analysts, researchers, and consultants use proprietary data sources and various tools and techniques to gather and analyze information.

Our data repository is continuously updated and revised by a team of research experts so that it always reflects latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in developing distinctive data sets and research material for business reports.

Contact

Transparency Market Research,

90 Sate Street, Suite 700,

Albany, NY 12207

Tel: +1-518-618-1030

USA Canada Toll Free: 866-552-3453

Website: https://www.transparencymarketresearch.com/

Read this article:
Autologous Cell Therapy Market is Anticipated to Expand at a CAGR of 18.1% from 2019 to 2027 - Eurowire

Read More...

YOUR HEALTH: Saving an unborn baby breaking apart in the womb – WQAD.com

Tuesday, October 20th, 2020

DENVER A baby broken, inside the womb.

Most doctors gave little unborn Payton Calvillo any hope she would survive. But through strong faith and the help of a team of medical experts, she is thriving today.

"She's a complete miracle baby," said Payton's mother, Ahna Calvillo.

When Ahna was just five months pregnant, she was told her unborn baby would probably not survive birth.

"It was pretty much a death sentence from the beginning."

Payton's bones were breaking and bending inside the womb.

"She likely had a problem where she couldn't make alkaline phosphatase properly," explained Dr. Sunil Nayak, a pediatric endocrinologist at Rocky Mountain Hospital for Children.

Alkaline phosphatase is needed for bones to grow and strengthen and there was little anyone could do.

Nineteen different specialists were on hand for the C-section delivery

"They even asked us the question that morning, how far do you want us to go?" Ahna remembered. "'Do you want a ventilator on her?', you know, 'How far do you want us to prolong her life?' Our ultimate hope and goal was that she would come out and breathe on her own."

"She just came out screaming," said Ahna. "She came out crying. She breathed on her own right away. She was perfect."

Payton was diagnosed with hypophosphatasia, a disorder that weakens bones and was immediately placed on a new FDA-approved medicine.

"Here we are just one year later at one year of age and you see a dramatic difference in the shape," said Dr. Jared Riley, a pediatric orthopedic surgeon at Rocky Mountain Hospital.

Before the medicine, 75% of all patients died by the age of five.

Now there is a 97% chance Payton will live a normal life.

"My baby was broken and that's what I needed God to do was a miracle," said Ahna.

One was also treated with bone fragments and cultured osteoblasts, which are bone-forming cells.

"Cultured" refers to cells that are grown under specific conditions outside of the natural environment (the body) and within a laboratory.

Both patients showed significant, but incomplete improvement, although no more formal studies have been conducted.

Then, the drug teriparatide (parathyroid hormone 1-34) has been given "off-label" to several adults with HPP with metatarsal stress fractures or femoral pseudo fractures, resulting in healing.

The drug is not permitted for use in children.

More research is necessary to determine the long-term safety and effectiveness of teriparatide in the treatment of HPP.

Every year eight million babies are born with genetic disorders passed down from generation to generation.

Payton will stay on the new medication for the next few years and then doctors will re-evaluate whether she needs to continue.

Payton's family didn't even know they carried the problematic HPP gene until an ultrasound revealed it in their unborn baby.

After being genetically tested, Payton's mother and grandfather are positive.

Neither one has ever suffered from weak or broken bones.

If this story has impacted your life or prompted you or someone you know to seek or change treatments, please let us know by contacting Jim Mertens atjim.mertens@wqad.comor Marjorie Bekaert Thomas atmthomas@ivanhoe.com.

Continued here:
YOUR HEALTH: Saving an unborn baby breaking apart in the womb - WQAD.com

Read More...

Cell Therapy: A Potential Treatment for COVID-19? | Roots Analysis – The Think Curiouser

Tuesday, October 20th, 2020

With the success of first vaccine to reach phase I clinical trial and turning out to be safe, well-tolerated, and capable of generating an immune response against the virus in humans, a lot of hope has been created with this vaccine. However, the research is still ongoing to develop novel therapeutic treatments that could aid infected patients in the meantime. One such growing area of interest is the use of cell therapy.

Cell Therapy: A Potential Treatment for COVID-19?

Cell therapies represent highly innovative therapeutic approaches that have revolutionized healthcare practices. Several studies from all over the world has proposed stem-cells based therapy, specifically mesenchymal stem cells, as a suitable remedial approach in the treatment of acute respiratory distress syndrome (ARDS), which is the leading cause of death in COVID-19 patients. Even though there are no approved cell therapy-based approaches for the prevention or treatment of COVID 19, however, many clinical trials have begun, and scientists are trying relentlessly to develop a therapeutic to treat this disease.

Companies Engaged in the Manufacturing of Cell Therapies

Presently, over 100 industry players and 60 non-industry players are involved in the manufacturing of cell therapies; of these, 52% have the required capabilities for manufacturing T-cell therapies.

Satta King

The Key Hubs of Cell Therapy Manufacturing

Majority of the industrial stakeholders (41%) are based in North America, followed by those based in Europe (31%) and the remaining in Asia Pacific. It is worth mentioning that within Asia Pacific, Japan (8) emerged as a popular hub for cell therapy manufacturers.

Demand for Cell Therapies (in terms of number of patients) is Anticipated to Grow at a CAGR of >21%, During 2019-2030

Given that advanced therapeutic medicinal products (ATMPs) is relatively a niche domain, the overall commercial demand for cell therapies is estimated to be more than 18,500 patients in 2019 and this value is likely to grow to close to 0.4 billion patients by 2030.

To get a detailed information on the key players, recent developments, capacity available, demand and the likely market evolution, visit this link

Cell Therapy: A Potential Treatment for COVID-19?

You may also be interested in the following titles:

About Roots Analysis

Roots Analysis is one of the fastest growing market research companies, sharing fresh and independent perspectives in the bio-pharmaceutical industry. The in-depth research, analysis and insights are driven by an experienced leadership team which has gained many years of significant experience in this sector. If youd like help with your growing business needs, get in touch at [emailprotected]

Contact Information

Roots Analysis Private Limited

Gaurav Chaudhary

+1 (415) 800 3415

[emailprotected]

More:
Cell Therapy: A Potential Treatment for COVID-19? | Roots Analysis - The Think Curiouser

Read More...

New ASH Guidelines Highlight a Call to Action for Treatment of Older AML Patients – Targeted Oncology

Tuesday, October 20th, 2020

New guidelines from he American Society of Hematology (ASH) for treating newly diagnosed acute myeloid leukemia (AML) in older patients recommend intensive antileukemic therapies over more conservative approaches, such as less-intensive therapies or supportive care, when treatment is considered tolerable.1

The guideline panel included physicians based in the United States and Canada who represented a variety of subspecialties including frailty, geriatric oncology, and patient-reported outcomes. In an interview with Targeted Therapies in Oncology, primary guidelines author Mikkael A. Sekeres, MD, MS, said the panel selection process was sensitive to gender and geographic distribution and included 3 leaders of cooperative groups in the United States for leukemia, as well as one from the National Cancer Institute of Canadas leukemia group.

These are the first guidelines published by ASH for any hematological malignancy. They are unique in how rigorously developed they were, [as they were] based on stringent standards for guideline development, said Sekeres, a professor in the Department of Medicine at Case Western Reserve University School of Medicine as well as medical director of the Clinical Trials Unit at Taussig Cancer Institute of Cleveland Clinic, both in Ohio.

In weighing multifactorial risks and benefits of initiating potential antileukemic therapy in patients with AML older than aged 65 years, decisions to pursue treatment may be influenced by the physicians or patients reluctance to assume an aggressive treatment strategy. The health care system also may contribute to poor prognoses in this patient subset due to treatment reluctance, as more than half of patients in this AML subgroup received no therapy and were not provided equal access to allogenic transplant once achieving remission.1 Because survival rates for this vulnerable population remain historically low, data regarding best practices are limited.

Methods for Determining Recommendations The recommendations were developed through a systemic review of evidence using the McMaster University Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, allowing the panel to provide recommendations that vary in strength based on certainty of evidence available. Strong to conditional recommendations were based on investigator-assessed certainty of evidence available.1

Patient data included in the review were from patients with newly diagnosed de novo, treatment-related, and secondary AML aged 55 years or older with receipt of less-intensive or intensive antileukemic therapy and treated as part of a clinical trial with 20 or more patients. Patient data from those with acute promyelocytic leukemia, myeloid neoplasms associated with Down syndrome, and studies in which more than 75% of the population did not meet criteria for inclusion were excluded from the review.1

The data reviewed by the panel showed a limited number of randomized studies available for this population. Although a number of retrospective data studies were examined, Sekeres pointed out the potential for high selection bias in [such] studies due to factors like existing serious comorbidities, such as end-stage lung cancer. We made recommendations at different levels based on the quality of supporting data, couching our recommendations in the quality of data that we had, he said, adding that critical outcome factors such as caregiver burden, quality-of-life (QOL) impairment, functional status impairment, and severe toxicity also factored in to the panels decisions. The weight of these factors varied slightly with each clinical question. Sekeres said the panel tailored factors they considered relevant in managing an older adult with AML to each specific clinical question. Unfortunately, often due to poor health or functional status within this population, patients did not participate directly in providing this data.

Although the panel began with approximately 20 clinical questions, Sekeres said they narrowed down the guidelines to 6 key areas of consideration. Clinical questions were determined and prioritized by the panel and are shown below with corresponding recommendations.

With strong evidence based on moderate certainty provided by the clinical data, the panel recommends offering antileukemic therapy to patients over best supportive care whenever possible. The comparison of intensive therapy versus best supportive care suggests a hazard ratio for death of 0.36 (95% CI, 0.26-0.50) based on low quality of evidence.

This recommendation may seem incredibly obvious, but when you examine the data in the United States, you realize that a lot of older adults with AML are told to get their affairs in order and seek no treatment, said Sekeres. Lets be clear at the very beginning. If someone wants treatment, you should treat them, and this should be done in alignment with their overall QOL goals.

Level of evidence is of a lower certainty based on the data available, but the panel favors intensive therapybut placed a conditional recommendation on this determination. A review suggested that intensive therapy may produce a lower risk of death versus the alternative (HR, 0.78; 95% CI, 0.69-0.89) and that the risk of death may be lower at 1 year with this strategy (risk ratio [RR], 0.93; 95% CI, 0.85-1.01).1 The [limited available] studies support more intensive antileukemic therapy if it is consistent with the patients individual goals, Sekeres said. That involves the careful balance of potential benefit in terms of getting into remission and survival versus risks of dying. The risks to QOL and of being hospitalized for the first 4 to 6 weeks of diagnosis also weigh heavily on the decision-making process.

Sekeres said certain patients who receive one therapy and achieve remission still need additional intervention. [Remission] is not enough. You need to give more [treatment] or else the chances of long-term survival diminish, he said. Moderate quality evidence supports consolidation therapy for lower mortality (RR, 0.96; 95% CI, 0.89-1.03), longer survival times by a median of 3 months, and longer time to recurrence by a median of 1 month versus no consolidation.

We only know this through indirect evidence. Long-term survivors who are older always receive more than one course of chemotherapy, but there are no randomized trials stating that more...is better than just one course [of treatment] or that a certain number of courses is the ideal amount, Sekeres said. As such, the panel suggests treating patients who are not candidates for allogeneic hematopoietic stem cell transplantation with at least 2 cycles of intensive antileukemic therapy based on low certainty of evidence.

Considering potential treatment planning factors such as age, comorbidities, and patient goals can sometimes lead to a third branch of decision-making for older patients, Sekeres said. For example, some patients with AML are under the initial impression that they likely have 2 options for treatment: intense chemotherapy or no treatment with supportive care only. Sekeres explained that less-intensive therapy is a third option to strongly consider when trying to align care with the patients goals and life experiences. In the United States, this commonly includes hypomethylating agents azacitidine and decitabine.

As such, recommendation 4 is divided into 2 subgroups focusing on less-intensive therapy options using hypomethylating agents. There doesnt seem to be one preference for one hypomethylating agent over another or over other low-dose approaches, said Sekeres. As our guidelines were breaking, we knew of some trials that were going to be published that looked at combination therapy versus monotherapy.

In a phase 1/2 study (NCT02203773) reviewed by the ASH panel, azacitidine plus venetoclax (Venclexta) demonstrated a promising efficacy rate with a tolerable safety profile versus administrations of azacitidine alone. However, the patients in this positive study were subjected to required hospitalization to receive the combination therapy.2 In this case, if you think back to where we started regarding patient goals, you are now mixing goals, Sekeres said. If a patient wants a less-intensive approach, they typically want out of the hospital and to be at home.

As such, the official recommendation from the panel suggests the use of either a hypomethylating agent or low-dose cytarabine as monotherapy based on moderate certainty of evidence in patients who are not eligible for intensive regimens. The second part of the recommendation suggests favoring monotherapy over combination therapy. However, if the patient chooses to move forward with combination treatment, low-dose cytarabine plus glasdegib (Daurismo) or a hypomethylating agent plus venetoclax can be used based on randomized trial data.

A conditional recommendation based on a low level of certainty led to the panel suggesting continuous therapy versus a time-limited approach.

Sekeres said that although this recommendation had limited supporting evidence, the specific amount of time is somewhat irrelevant. [Patients] should continue to receive [the treatment] as long as they are responding, he said. There is currently no study that stops this therapy at a certain point.

The last recommendation is a favorite of Sekeres because this is where we make the very clear statement that if a patient wants blood transfusions while on hospice, that person should be allowed to do so. We consider it to be supportive care and not heroic, he said.

Sekeres also explained the importance of finding a less-intensive approach for patients who have concerns about the effects of intensive therapy but still desire treatment, perhaps because of an expressed wish to live long enough for an upcoming family celebration or other personal reasons. Concerns such as hospitalization time, tolerability, potential adverse effects, overall QOL, and functional status are all incredibly important factors to consider when deciding the best course of action. In some instances, it may be more important to focus on tolerability than overall survival in this fragile population.

The ASH guidelines are not intended to serve or be construed as a standard of care, said Sekeres, but they are intended to assist physicians and educate patients in making decisions about potential diagnostic and treatment alternatives.1 The data herein highlight an unmet need for continued advocacy and research.

Sekeres said his interest in this patient population and corresponding research focus began during his fellowship, where he felt that a set of guidelines were important to address this clinical question with evidence-based treatment support for newly diagnosed AML.

This is an extremely vulnerable population for whom the treatment decision at the very beginning of diagnosis is far from straightforward, Sekeres said. My job is somewhat easy because my decision trees dont have a lot of branches to them. However, its hard because the therapy we are giving has an appreciable mortality itself.

To provide fellow treating physicians with a key takeaway, Sekeres advised, Your most important job as a health care provider working with a patient who has leukemia is making sure you are helping that person identify what his or her goals are and then meeting those goals with the treatments that you are offering.

References:

1. Sekeres MA, Guyatt G, Abel G, et al. American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. Blood Adv. 2020;4(15):3528-3549. doi:10.1182/bloodadvances.2020001920

2. DiNardo CD, Pratz KW, Letai A, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previouslyuntreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018;19(2):216-228.doi:10.1016/S1470-2045(18)30010-X

View original post here:
New ASH Guidelines Highlight a Call to Action for Treatment of Older AML Patients - Targeted Oncology

Read More...

Jeff Bridges is one of the 85,000-plus lymphoma cases expected in the U.S. this year – MarketWatch

Tuesday, October 20th, 2020

Careful, man, theres a beloved actor here.

Jeff Bridges revealed that he has lymphoma, which is the most common type of blood cancer. And this sobering news has spurred celebrities and fans to send their best wishes to the star best known for playing the Dude, the White Russiandrinking bowler and casual-wear icon from the Coen brothers 1998 cult classic, The Big Lebowski.

But the Dude abides, and Bridges suggested that his outlook looks just as promising.

As the Dude would say.. New S**T has come to light, tweeted Bridges, 70, on Monday. I have been diagnosed with Lymphoma. Although it is a serious disease, I feel fortunate that I have a great team of doctors and the prognosis is good.

Celebrities such as Cary Elwes, John Lithgow, Patricia Arquette and George Takei posted encouraging words and prayers to Bridges, who is the son of Lloyd and Dorothy Bridges, and has starred in more than 70 films including Starman, True Grit and The Last Picture Show. He won an Academy Award in 2010 for Crazy Heart, and was honored with the Cecil B. DeMille lifetime-achievement award during the 2019 Golden Globes.

And he is now one of the most high-profile cases of lymphoma, a cancer of the bodys infection-fighting lymphatic system that affects the blood and bone marrow. And more than 85,000 new cases of lymphoma are expected to be diagnosed in the U.S. this year, according to American Cancer Society data shared by the Leukemia & Lymphoma Society, with some 791,550 people currently living with lymphoma or in remission from the disease in the U.S.

Many different types of lymphoma exist, and Bridges did not share any more details about his diagnosis or treatment. But his disclosure is an opportunity to share more information about lymphoma, the risk factors and symptoms to be aware of, as well as treatment options.

What is lymphoma?

Lymphoma is a type of cancer that starts in cells that are part of the bodys immune system, specifically the lymphocytes, which are a type of white blood cell that fights germs. So these cancers can affect the blood and bone marrow, as well as the other tissues and organs that produce, store and carry white blood cells including the spleen.

Doctors still dont know what specifically causes lymphoma, but at some point a lymphocyte mutates and begins to reproduce rapidly. The mutated, abnormal cells live longer than the normal cells would, and in time, the diseased and ineffective lymphocytes outnumber the healthy cells, which causes the lymph nodes, liver and spleen to swell.

There are two main types of lymphoma, the CDC explains, including:

Hodgkin lymphoma (HL), which spreads in an orderly manner from one group of lymph nodes to another.

Non-Hodgkin lymphoma (NHL), which spreads through the lymphatic system in a non-orderly manner.

What are the symptoms?

Signs and symptoms of lymphoma may include:

These symptoms can be signs of other health conditions, of course, so its recommended that anyone experiencing them should see a doctor to determine the cause.

How is it treated?

There are many different types of lymphoma including 90 different types of non-Hodgkin lymphoma and treatment varies depending on the type and severity. Generally, lymphoma treatment involves chemotherapy, radiation therapy and immunotherapy medication. The Mayo Clinic, which is an international authority on lymphoma research, explains that the goal of treatment is to destroy as many cancer cells as possible to bring the disease into remission. A bone marrow or stem cell transplant may be performed in some cases to help rebuild healthy bone marrow after chemo and radiation has suppressed the diseased bone marrow.

Bridges didnt specify his own treatment, only saying that he is beginning treatment and will keep the public posted on his recovery.

Treatment can be very expensive, however, with almost 60% of patients covered by Medicare telling the Leukemia & Lymphoma Society in a 2019 study that they decided to delay or forego treatment, largely due to steep out-of-pocket costs. It noted that some traditional Medicare lymphoma patients getting anti-cancer therapy though infusions experienced out-of-pocket costs of more than $19,000 in their first year. And costs can extend two or three years beyond a blood cancer diagnosis.

Who is most at risk?

While children, teens and adults can all develop lymphoma, some types are more common in certain age groups. The CDC notes that rates of Hodgkin lymphoma are highest among teens and young adults (ages 15 to 39) as well as among older adults (ages 75 and older). But non-Hodgkin lymphoma becomes more common as people get older.

Men are also slightly more likely to develop lymphoma than women, the CDC adds, and white people are more likely than Black people to develop non-Hodgkin lymphoma.

Cases have also been more common in people who are immunocompromised, including those who take drugs to suppress their immune systems. And some infections such as HIV and the Epstein-Barr virus are also associated with an increased lymphoma risk.

And like many other cancers, family history has been linked with a higher risk of Hodgkin lymphoma.

What is the survival rate?

The good news is, Hodgkin lymphoma is now considered to be one of the most curable forms of cancer, according to the Leukemia & Lymphoma Society, with a five-year survival rate of 94.4% among patients younger than 45 at diagnosis. And the five-year relative survival rate for those with Hodgkin lymphoma more than doubled from 40% in whites in 1960 to 1963 (the only data available) to 88.5% for all races from 2009 to 2015.

And the five-year relative survival rate for people with non-Hodgkin lymphoma rose from 31% in whites from 1960 to 1963 (the only data available) to 74.7% for all races from 2009 to 2015.

Still, an estimated 20,910 Americans are expected to die from lymphoma this year, including 19,940 with non-Hodgkin lymphoma and 970 with Hodgkin lymphoma.

How does COVID-19 complicate things?

While the medical community is still learning about COVID-19, the general consensus is that people with cancer, who are in active cancer treatment or have previously been treated for cancer, may be at higher risk of severe illness and death if they get the coronavirus. So its important that these folks lower their risk of exposure to COVID-19 by avoiding large crowds and non-essential travel; working from home, if possible; staying at least six feet away from people outside their household; wearing a face mask when they cant socially distance; as well as washing their hands frequently, and not touching their eyes, nose or mouth.

Where can I find more information or support?

Visit the CDC and American Cancer Society pages on lymphoma.

The Mayo Clinic also outlines its lymphoma research and treatment strategies on its website.

The Leukemia & Lymphoma Society and the Lymphoma Research Foundation also provide valuable information and support.

See original here:
Jeff Bridges is one of the 85,000-plus lymphoma cases expected in the U.S. this year - MarketWatch

Read More...

Induced Pluripotent Stem Cells Market To Grow At 7% YOY In Forecast Years 2026 – The Think Curiouser

Tuesday, October 20th, 2020

Market Report Summary

For Full Information -> Click Here

Read Full Press Release Below

The healthcare industry has been focusing on excessive research and development in the last couple of decades to ensure that the need to address issues related to the availability of drugs and treatments for certain chronic diseases is effectively met. Healthcare researchers and scientists at the Li Ka Shing Faculty of Medicine of the Hong Kong University have successfully demonstrated the utilization of human induced pluripotent stem cells or hiPSCs from the skin cells of the patient for testing therapeutic drugs.

The success of this research suggests that scientists have crossed one more hurdle towards using stem cells in precision medicine for the treatment of patients suffering from sporadic hereditary diseases. iPSCs are the new generation approach towards the prevention and treatment of diseases that takes into account patients on an individual basis considering their genetic makeup, lifestyle, and environment. Along with the capacity to transform into different body cell types and same genetic composition of the donors, hiPSCs have surfaced as a promising cell source to screen and test drugs.

Get Sample Copy of Report @ https://www.persistencemarketresearch.com/samples/17968

Company Profile

Get To Know Methodology of Report @ https://www.persistencemarketresearch.com/methodology/17968

In the present research, hiPSC was synthesized from patients suffering from a rare form of hereditary cardiomyopathy owing to the mutations in Lamin A/C related cardiomyopathy in their distinct families. The affected individuals suffer from sudden death, stroke, and heart failure at a very young age. As on date, there is no exact treatment available for this condition.

This team in Hong Kong tested a drug named PTC124 to suppress specific genetic mutations in other genetic diseases into the iPSC transformed heart muscle cells. While this technology is being considered as a breakthrough in clinical stem cell research, the team at Hong Kong University is collaborating with drug companies regarding its clinical application.

The unique properties of iPS cells provides extensive potential to several biopharmaceutical applications. iPSCs are also used in toxicology testing, high throughput, disease modeling, and target identification. This type of stem cell has the potential to transform drug discovery by offering physiologically relevant cells for tool discovery, compound identification, and target validation.

A new report by Persistence Market Research (PMR) states that the globalinduced pluripotent stem or iPS cell marketis expected to witness a strong CAGR of 7.0% from 2018 to 2026. In 2017, the market was worth US$ 1,254.0 Mn and is expected to reach US$ 2,299.5 Mn by the end of the forecast period in 2026.

Access Full Report @ https://www.persistencemarketresearch.com/checkout/17968

Customization to be the Key Focus of Market Players

Due to the evolving needs of the research community, the demand for specialized cell lines have increased to a certain point where most vendors offering these products cannot depend solely on sales from catalog products. The quality of the products and lead time can determine the choices while requesting custom solutions at the same time. Companies usually focus on establishing a strong distribution network for enabling products to reach customers from the manufacturing units in a short time period.

Entry of Multiple Small Players to be Witnessed in the Coming Years

Several leading players have their presence in the global market; however, many specialized products and services are provided by small and regional vendors. By targeting their marketing strategies towards research institutes and small biotechnology companies, these new players have swiftly established their presence in the market.

Explore Extensive Coverage of PMR`sLife Sciences & Transformational HealthLandscape

Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics and market research methodology to help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

Our client success stories feature a range of clients from Fortune 500 companies to fast-growing startups. PMRs collaborative environment is committed to building industry-specific solutions by transforming data from multiple streams into a strategic asset.

Contact us:

Ashish KoltePersistence Market ResearchAddress 305 Broadway, 7th FloorNew York City,NY 10007 United StatesU.S. Ph. +1-646-568-7751USA-Canada Toll-free +1 800-961-0353Sales[emailprotected]Website https://www.persistencemarketresearch.com

More:
Induced Pluripotent Stem Cells Market To Grow At 7% YOY In Forecast Years 2026 - The Think Curiouser

Read More...

Cell proliferation, mechanisms of Cell Death, types …

Tuesday, September 15th, 2020

Early development is characterized by the rapid proliferation of embryonic cells, which then differentiate to produce the many specialized types of cells that make up the tissues and organs of multicellular animals. As cells differentiate, their rate of proliferation usually decreases, and many cells in adult animals are arrested in the G0 stage of the cell cycle.

Cell proliferation is carefully balanced with cell death to maintain a constant number of cells in adult tissues and organs. Somatic cells in the adult can be grouped into three general categories with respect to cell proliferation:

Static cell population: These are non-dividing permanent cells, thus they would not be replaced if injured or lost. They leave the cell cycle to perform a specialized function. Static cells include cardiac muscle fibers and neurons.

Stable cell population: These are quiescent cells that do not usually divide. They are considered to be in the G0 phase but be they may be stimulated to divide by appropriate signals as injury, thus their renewal occurs by duplication of existing cells. They include smooth muscle fibers and the epithelial cells of most internal organs such as the liver and kidney.

Labile cell population: These are fully differentiated cells that do not themselves proliferate. instead, their continuous renewal is via the proliferation of the less differentiated stem cells. They include all cells that have a short life span as blood cells, epithelial cells of the skin (skin epidermis), and epithelial cells lining the digestive tract.

It is the process by which unspecialized cells (as embryonic or regenerative cells) acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism.

They are primal cells which are the source, or stem for all of the specialized cells that form organs and tissues.

Stem cell possesses two properties:

They have the potential to generate all types of cells and tissues and can construct a complete, viable organism. Totipotent stem cells are derived from the cells produced by the first few divisions of the fertilized ovum ( morula cells).

They are the descendants of totipotent cells, derived from the inner cell mass of the blastocyst. They can differentiate into more than 220 cell types in the adult body, these are the derivatives of the three primary germ layers, ectoderm, endoderm, and mesoderm. Pluripotent stem cells undergo further specialization into multipotent progenitor cells.

They can produce cells of a closely-related family. They include the multipotent hematopoietic stem cells that can differentiate into red blood cells, white blood cells, and platelets.

They can produce mature cells of a single type but still, have the property of self-renewal which distinguishes them from non-stem cells. They include stem cells in the skin epidermis.

The normal cells are able to handle normal physiologic demands. If the cell is exposed to severe stresses, it goes into cellular adaptations. When the adaptive response to a stimulus is exceeded, reversible or irreversible cell injury occurs. If the stimulus persists, the cell reaches a point of no return and ultimately cell death. There are 2 different mechanisms of cell death, necrosis, and apoptosis.

Necrosis = accidental cell death: it is a pathological process due to various unfavorable factors e.g. hypoxia, radiation, or as a result of pathogens such as viruses.

It is a physiological process controlled by several genes, during which loss of mitochondrial function initiates a cascade of reactions that can set on cell death. Apoptosis occurs in many conditions, including:

Cell division types, Mitosis, Meiosis, Reductional division & Equatorial division

Regulation of the cell cycle, DNA synthesis phase, Interphase & Mitosis

Cytoplasmic organelles, Ribosomes & Endoplasmic reticulum function, structure & definition

Cell Structure, the function of Golgi apparatus, Endosomes & Lysosomes

The function of Cytoplasmic organelles, Mitochondria, Peroxisomes & Cytoskeleton

Structure of Cytoplasm, The function of centrosome & Cytoplasmic inclusions

Nucleus components, function, diagram & classification of chromosomes

Importance of Nucleosides, Nucleotides, Purines, Pyrimidines & Sugars of nucleic acids

More:
Cell proliferation, mechanisms of Cell Death, types ...

Read More...

Study identifies therapeutic targets for most lethal pancreatic cancer – Drug Target Review

Tuesday, September 15th, 2020

The detailed analysis of adenosquamous cancer of the pancreas (ASCP) suggested FGFR and RORC were two promising therapeutic targets.

Using preclinical models, researchers have identified two promising therapeutic targets for the most aggressive and lethal form of pancreatic cancer, adenosquamous cancer of the pancreas (ASCP).

The team of researchers led by Mayo Clinic and the Translational Genomics Research Institute (TGen), both US, suggested fibroblast growth factor receptor (FGFR) and Retinoic acidrelated orphan receptor C (RORC) inhibitors that are already available in clinic could be effective against ASCP.

Dr Daniel Von Hoff, Distinguished Professor and TGens Physician-In-Chief, considered one of the nations foremost authorities on pancreatic cancer and one of the studys authors, said: The rarity of ASCP, the scarcity of tissue samples suitable for high resolution genomic analyses and the lack of validated preclinical models, has limited the study of this particularly deadly subtype of pancreatic cancer.

Where pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and the US third leading cause of cancer-related death (according to the American Cancer Society); ASCP is a rare and particularly aggressive form of pancreatic cancer, diagnosed in less than four percent of patients.

ASCP currently has no effective therapies. Unlike PDAC, ASCP is defined by the presence of more than 30 percent squamous (skin-like) epithelial cells in the tumour. The normal pancreas does not contain squamous cells, said the studys senior author, Dr Michael Barrett, who holds a joint research appointment at Mayo Clinic and TGen.

Dr Barrett explained that in their study they discovered ASCPs have novel mutations and deletions in genes that regulate tissue development and growth, alongside those typically evident in PDAC. As a consequence, cells within the tumour have the ability to revert to a stem-cell-like state that includes changes in cell types and appearance, and the activation of signalling pathways that drive the aggressive nature of ASCP.

He added that while the aggressive stem-like state is very resistant to current pancreatic cancer therapies, the study indicated ASCP could be targeted by drugs currently in clinical use.

Using multiple analysis methods, the research team conducted what is believed to be the most in-depth analysis of ASCP tissue samples.

They identified multiple mutations and genomic variants that are common to both PDAC and ASCP, but highlighted two significant therapeutic targets that were unique to ASCP genomes alone: FGFR signalling, inhibition of FGFR signalling had a significant effect on organoids harbouring the FGFR1-ERLIN2 gene fusion; and a pancreatic cancer stem cell regulator known as RORC.

The team concluded in their study: Of significant interest will be clinical trials with FGFR and RORC inhibitors that include correlative studies of genomic and epigenomic lesions in both ASCP and PDAC.

The paper was published in Cancer Research.

Here is the original post:
Study identifies therapeutic targets for most lethal pancreatic cancer - Drug Target Review

Read More...

Cancer Stem Cells Market to witness astonishing growth by 2026 | AbbVie, The Merck KGaA Group, Bionomics, Lonza Group – The PRNews Pulse

Tuesday, September 15th, 2020

Global Cancer Stem Cells Market Insights by Application, Product Type, Competitive Landscape & Regional Forecast 2025 is latest research study released by HTF MI evaluating the market, highlighting opportunities, risk side analysis, and leveraged with strategic and tactical decision-making support. The study provides information on market trends and development, drivers, capacities, technologies, and on the changinginvestment structure of the Global Cancer Stem Cells Market. Some of the key players profiled in the study are Thermo Fisher Scientific, Inc. (United States), AbbVie, Inc.(United States), The Merck KGaA Group (Germany), Bionomics (Australia), Lonza Group (Switzerland), Stemline Therapeutics, Inc.(United States), Fujifilm Irvine Scientific (United States), STEMCELL Technologies Inc. (Canada), Sino Biological Inc. (United States) and BIOTIME, Inc. (United States).

You can get free access to samples from the report here:https://www.htfmarketreport.com/sample-report/2134979-global-cancer-stem-cells-market-2

Market Snapshot:According to the World Health Organization, Cancer is the second leading cause of death globally, and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer. Hence, there is a need for a tremendous research on Cancer Cells. Cancer stem cells (CSCs) refers to the cells which are obtained from tumor that posses potential to reproduce all types of cancer cells found in a cancer sample.These cells are grown in tumors as a separate population and thereby it causes Deterioration and Metastasis of Existing tumor through generation of new tumor. Hence, with the Advancement in Technology Especially in Cancer Stem Cells Research area, Therapies specific to Targeting Cancer Stem Cells are anticipated to drive the Global Cancer Stem Cells Market.

Market DriversIncreasing Prevalence of Cancer leading to rapidly rising burden of the mortality rate of Cancer among PatientsThe Continuous Rise in the number of Research Studies and Development on Cancer Stem Cells (CSCs)The Government initiatives to boost the Cancer Research activities and availability of funds.

Market TrendImprovements in experimental approaches by the Researchers such as, In vitro assay has enabled them to establish a relationship between different cell types in a tumor and their microenvironmentThis has led to the Development of a Broad Therapeutic Portfolio for CSCs and their associated key pathways.

RestraintsHigh Costs related to Cancer Stem Cell Therapeutics may hamper market growth.

Cancer Stem Cells Market: Demand Analysis & Opportunity Outlook 2025

Cancer Stem Cells research study is to define market sizes of various segments & countries by past years and to forecast the values by next 5 years. The report is assembled to comprise each qualitative and quantitative elements of the industry facts including: market share, market size (value and volume 2014-19, and forecast to 2025) which admire each countries concerned in the competitive examination. Further, the study additionally caters the in-depth statistics about the crucial elements which includes drivers & restraining factors that defines future growth outlook of the market.

Important years considered in the study are:Historical year 2014-2019 ; Base year 2019; Forecast period** 2020 to 2025 [** unless otherwise stated]

Enquire for customization in Report @https://www.htfmarketreport.com/enquiry-before-buy/2134979-global-cancer-stem-cells-market-2

The segments and sub-section of Cancer Stem Cells market are shown below:

The Study is segmented by following Product Type: Cell Culturing, Cell Separation, Cell Analysis, Molecular Analysis and Others

Major applications/end-users industry are as follows: Breast Cancer Diagnosis and Treatment , Prostate Cancer Diagnosis and Treatment , Colorectal Cancer Diagnosis and Treatment , Lung Cancer Diagnosis and Treatment and Other Cancers Diagnosis and Treatment

Some of the key players/Manufacturers involved in the Market are Thermo Fisher Scientific, Inc. (United States), AbbVie, Inc.(United States), The Merck KGaA Group (Germany), Bionomics (Australia), Lonza Group (Switzerland), Stemline Therapeutics, Inc.(United States), Fujifilm Irvine Scientific (United States), STEMCELL Technologies Inc. (Canada), Sino Biological Inc. (United States) and BIOTIME, Inc. (United States)

If opting for the Global version of Cancer Stem Cells Market analysis is provided for major regions as follows: North America (USA, Canada and Mexico) Europe (Germany, France, the United Kingdom, Netherlands, Russia , Italy and Rest of Europe) Asia-Pacific (China, Japan, Australia, New Zealand, South Korea, India and Southeast Asia) South America (Brazil, Argentina, Colombia, rest of countries etc.) Middle East and Africa (Saudi Arabia, United Arab Emirates, Israel, Egypt, Nigeria and South Africa)

Buy this research report @https://www.htfmarketreport.com/buy-now?format=1&report=2134979

Key Answers Captured in Study areWhich geography would have better demand for product/services?What strategies of big players help them acquire share in regional market?Countries that may see the steep rise in CAGR & year-on-year (Y-O-Y) growth?How feasible is market for long term investment?What opportunity the country would offer for existing and new players in the Cancer Stem Cells market?Risk side analysis involved with suppliers in specific geography?What influencing factors driving the demand of Cancer Stem Cells near future?What is the impact analysis of various factors in the Global Cancer Stem Cells market growth?What are the recent trends in the regional market and how successful they are?

Read Detailed Index of full Research Study at @https://www.htfmarketreport.com/reports/2134979-global-cancer-stem-cells-market-2

There are 15 Chapters to display the Global Cancer Stem Cells market.Chapter 1, About Executive Summary to describe Definition, Specifications and Classification of Global Cancer Stem Cells market, Applications [Breast Cancer Diagnosis and Treatment , Prostate Cancer Diagnosis and Treatment , Colorectal Cancer Diagnosis and Treatment , Lung Cancer Diagnosis and Treatment and Other Cancers Diagnosis and Treatment], Market Segment by Types Cell Culturing, Cell Separation, Cell Analysis, Molecular Analysis and Others;Chapter 2, objective of the study.Chapter 3, to display Research methodology and techniques.Chapter 4 and 5, to show the Cancer Stem Cells Market Analysis, segmentation analysis, characteristics;Chapter 6 and 7, to show Five forces (bargaining Power of buyers/suppliers), Threats to new entrants and market condition;Chapter 8 and 9, to show analysis by regional segmentation[North America, Europe, Asia-Pacific etc ], comparison, leading countries and opportunities; Regional Marketing Type Analysis, Supply Chain AnalysisChapter 10, to identify major decision framework accumulated through Industry experts and strategic decision makers;Chapter 11 and 12, Global Cancer Stem Cells Market Trend Analysis, Drivers, Challenges by consumer behavior, Marketing ChannelsChapter 13 and 14, about vendor landscape (classification and Market Ranking)Chapter 15, deals with Global Cancer Stem Cells Market sales channel, distributors, Research Findings and Conclusion, appendix and data source.

Thanks for reading this article; you can also get individual chapter wise section or region wise report version like North America, Europe or Asia or Oceania [Australia and New Zealand].

About Author:HTF Market Report is a wholly owned brand of HTF market Intelligence Consulting Private Limited. HTF Market Report global research and market intelligence consulting organization is uniquely positioned to not only identify growth opportunities but to also empower and inspire you to create visionary growth strategies for futures, enabled by our extraordinary depth and breadth of thought leadership, research, tools, events and experience that assist you for making goals into a reality. Our understanding of the interplay between industry convergence, Mega Trends, technologies and market trends provides our clients with new business models and expansion opportunities. We are focused on identifying the Accurate Forecast in every industry we cover so our clients can reap the benefits of being early market entrants and can accomplish their Goals & Objectives.

Contact US :Craig Francis (PR & Marketing Manager)HTF Market Intelligence Consulting Private LimitedUnit No. 429, Parsonage Road Edison, NJNew Jersey USA 08837Phone: +1 (206) 317 1218[emailprotected]

Connect with us atLinkedIn|Facebook|Twitter

Go here to see the original:
Cancer Stem Cells Market to witness astonishing growth by 2026 | AbbVie, The Merck KGaA Group, Bionomics, Lonza Group - The PRNews Pulse

Read More...

Page 11234..1020..»


2020 © StemCell Therapy is proudly powered by WordPress
Entries (RSS) Comments (RSS) | Violinesth by Patrick