StemCell Therapy

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

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

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

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

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Bone Marrow Segment to Dominate Market

Neurology Segment to be Highly Lucrative Segment

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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.

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

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?

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

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

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.

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

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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.

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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.

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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.

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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.

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

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

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

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.

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

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]

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

Already known for their shape-shifting abilities, stem cells can now add death-defying to their list of remarkable qualities.

A new study shows how stem cells which can contribute to creating many parts of the body, not just one organ or body part are able to postpone their own death in order to respond to an injury that needs their attention. The study was done in planarians, which are tiny worms used as model organisms to study regeneration because of their ability to recover from any injury using stem cells.

Planarian stem cells, even when challenged and under a lot of duress, will still respond to an injury by delaying death, said Divya Shiroor, first author and a graduate student in Dr. Carolyn Adlers lab, in the College of Veterinary Medicine.

The study, published May 7 in Current Biology, is the first to demonstrate this reaction in planarians.

The research team exposed planarians to radiation, then subjected half of them to injury. Radiated worms that had not been injured experienced predicted levels of stem cell death. Stem cells of the injured worms, however, survived, gathering around the site of the wound and postponing their deaths to mount a response.

We show that this inevitable radiation-induced cell death can be significantly delayed if animals are injured soon after radiation exposure, said Shiroor.

This could have important implications for cancer research and therapies, particularly when examining chemotherapy and surgery options for patients.

By understanding how injury prompts planarian stem cells to withstand radiation, Shiroor said, we hope to identify genes that, if shared with mammals, could perhaps help hone existing therapies.

Planarians are commonly used in basic research because of their similarities to humans. Like humans, planarians have stem cells, similar organs and similar genes, but are much more adept at responding to injury, thanks to their higher volume of stem cells and lack of a developed immune system, which in humans complicates the healing process.

This really simplifies the process of understanding the effects of both injury and radiation on stem cells, and allows us to study it directly without being hampered by parallel processes integral to wound healing, such as inflammation, that get simultaneously triggered in mammals, Shiroor said.

By uncovering the mechanisms that govern stem cells after wounding in a system like planarians, researchers could also apply this knowledge when engineering stem cells to respond similarly in the human body.

Labs have many ways to understand how planarians use stem cells to successfully recover and regenerate, but the Adler labs combination of radiation and injury to identify a novel stem cell response is unique. The researchers plan on digging deeper to understand how the stressed stem cells know that there is an injury and what role other cells may play in their response.

We have identified a key gene that is required for stem cell persistence after radiation and injury, Shiroor said, and we plan on using this as a stepping stone for further exploration.

Melanie Greaver Cordova is managing editor at the College of Veterinary Medicine.

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Stem cells shown to delay their own death to aid healing ...

DetailsCategory: DNA RNA and CellsPublished on Tuesday, 25 August 2020 10:13Hits: 244

ATLANTA, GA, USA I August 24, 2020 I Primary HLH is a family of devastating primary immune deficiencies with limited treatment options and no gene therapies under clinical testing. Expression Therapeutics has developed a promising and potentially curative gene therapy candidate for familial hemophagocytic lymphohistiocytosis (HLH) type 3 (FHL3). Untreated, FHL3 presents as a hyper-inflammatory state with multi-organ damage leading to premature death. Expression Therapeutics expects to rapidly progress candidates for other common forms of primary HLH as well.

"We are excited to announce this expansion of our gene and cell therapy pipeline beyond our lead stem cell lentiviral gene therapy candidate for hemophilia A that is entering Phase 1 clinical testing. Through ongoing research and development incorporating our core technology platforms, Expression Therapeutics has been able to rapidly generate promising therapeutic candidates for our HLH portfolio and several other critical disease areas with significant unmet clinical need," said Christopher Doering, Ph.D., Chief Scientific Officer of Expression Therapeutics.

Proof of concept for stem cell lentiviral gene therapy of FHL3 was demonstrated using primary patient cells and a genetic mouse model of FHL3. A key component in this success was the integration of one of Expression Therapeutics' core technology platforms that facilitates the rapid generation of transgenes with superior potency. Our lead candidate successfully restored exocytosis and cytolytic function to primary patient cells as well as a murine disease model strongly supporting the advancement of this pipeline product candidate.

"We believe there are three key aspects to FHL3 that make it a strong candidate for hematopoietic stem and progenitor cell (HSPC) lentiviral vector (LV) gene therapy. First, preclinical and clinical studies suggest that less than 20% genetically corrected cells are required to reverse most FHL3 disease symptoms. Second, because of the autologous nature of stem cell-based lentiviral gene therapy, the grave risk of graft vs host disease is eliminated. Third, with stem cell-based lentiviral gene therapy there will be no wait time to find a sufficiently human leukocyte antigen-matched donor," said Trent Spencer, Ph.D., President of Expression Therapeutics.

According to Deanna Fournier, Executive Director of the Histiocytosis Association, "We are very excited about the possibilities this work offers. Our HLH community, and the entire histiocytosis community, is very hopeful and excited about the future!"

Expression Therapeutics is a biotechnology company based in Atlanta and Cincinnati. The current therapeutic pipeline includes advanced gene therapies for hemophilia, neuroblastoma, T-cell leukemia/lymphoma, acute myeloid leukemia (AML), and primary immunodeficiencies such as hemophagocytic lymphohistiocytosis (HLH).

SOURCE: Expression Therapeutics

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Expression Therapeutics Announces Success in Developing a Stem Cell Lentiviral Gene Therapy for Hemophagocytic Lymphohistiocytosis (HLH) | DNA RNA and...

Despite significant progress in treating cancer in recent years, the need for further improvements has persisted particularly for some of the most challenging forms of the disease, such as lung cancer. Lung cancer is one of the most common cancers, and is the leading cause of cancer death in both men and women.

The majority of lung cancer cases are non-small cell lung cancer (NSCLC), a complex disease that can affect each patient differently. Most cases of NSCLC are not diagnosed until the disease is advanced meaning it has metastasized or spread which can make it more challenging to treat.

The impact of lung cancer, and advanced NSCLC in particular, continues to be felt across our communities, explained Andrea Ferris, president and chairman of LUNGevity Foundation. While every persons experience with the disease is unique, many patients hope they can retain a sense of normalcy in their lives and are seeking more treatment options that offer a chance at a longer life.

Research Driving New Progress for Certain Patients

Researchers have accelerated their pursuit of new and differentiated approaches that address this critical unmet need, focusing on options that may offer patients a chance at a longer life. One area of research that has shown potential is combining treatments, such as immunotherapies, for certain patients with previously untreated advanced disease.

Hossein Borghaei, D.O., chief of thoracic medical oncology at Fox Chase Cancer Center in Philadelphia explains, Progress in treating advanced lung cancer has led to more options for patients with newly diagnosed advanced NSCLC. Some of the most recent developments in the field of immunotherapy are particularly exciting.

One example is the U.S. Food and Drug Administrations approval of the first and only dual immunotherapy approach for newly diagnosed patients. Opdivo (nivolumab) is a prescription medicine used in combination with Yervoy (ipilimumab) for adults with advanced stage NSCLC that has spread to other parts of your body (metastatic) and tests positive for PD-L1 and do not have an abnormal EGFR or ALK gene.

Opdivo can cause problems that can sometimes become serious or life threatening and can lead to death. Serious side effects may include lung problems (pneumonitis); intestinal problems (colitis) that can lead to tears or holes in your intestine; liver problems (hepatitis); hormone gland problems (especially the thyroid, pituitary, adrenal glands, and pancreas); kidney problems, including nephritis and kidney failure; skin problems; inflammation of the brain (encephalitis); problems in other organs; and severe infusion reactions; and complications of stem-cell transplant that uses donor stem cells (allogeneic). Additional serious side effects of Yervoy alone include: nerve problems that can lead to paralysis; eye problems; and complications of stem-cell transplant that uses donor stem cells (allogeneic). Please see Important Facts about side effects for Opdivo and Yervoy below.

Opdivo and Yervoy work with your immune system to help fight cancer in two ways. Yervoy stimulates the kind of cells that help fight cancer, while Opdivo may help these cells to find and fight the cancer cells again. While doing so, Opdivo and Yervoy can also affect healthy cells. These problems can sometimes become serious or life threatening and can lead to death. These problems may happen anytime during treatment or even after treatment has ended. Some of these problems may happen more often when Opdivo is used in combination with Yervoy.

Clinical Trial Findings: A Chance to Live Longer

Opdivo + Yervoy was studied in a clinical trial and compared to platinum-based chemotherapy among certain patients with previously untreated, advanced NSCLC that tested positive for PD-L1.

In the trial, 396 patients received Opdivo + Yervoy and 397 patients received platinum-based chemotherapy. Patients who were treated with Opdivo + Yervoy lived longer than those treated with platinum-based chemotherapy:

In the trial, 396 patients received Opdivo + Yervoy and 397 patients received platinum-based chemotherapy. Patients who were treated with Opdivo + Yervoy lived longer than those treated with platinum-based chemotherapy:

An additional analysis showed:

The data supporting this dual immunotherapy approach are encouraging, particularly as one third of the patients who responded to treatment with Opdivo + Yervoy were still alive at three years, said Dr. Borghaei. Further, Opdivo + Yervoy offers a non-chemotherapy option, which can be important to some patients.

The most common side effects of Opdivo, when used in combination with Yervoy, include: feeling tired; diarrhea; rash; itching; nausea; pain in muscles, bones, and joints; fever; cough; decreased appetite; vomiting; stomach-area (abdominal) pain; shortness of breath; upper respiratory tract infection; headache; low thyroid hormone levels (hypothyroidism); decreased weight; and dizziness. Please see Important Facts about side effects for Opdivo and Yervoy below.

Evolving Outlooks and Adapting Support for Patients

Facing a lung cancer diagnosis and beginning treatment can be life-altering in many ways and todays unique environment as a result of the coronavirus has brought about additional considerations for patients, caregivers and the broader healthcare community, with telemedicine and other forms of remote support playing an increasingly vital role.

Patients should know there are resources available and ways to stay connected, even during times when maintaining physical distance from others is important, said Ferris. We have transformed many of our patient support and education offerings into virtual formats, which we are updating frequently to provide the most recent information and reach and connect as many people as possible.

Dr. Borghaei also urges patients to reach out to their doctor or care team to learn about and take advantage of available remote support offerings. Advances in cancer research are still happening every day, with Opdivo + Yervoy being one example. Its as important as ever that people diagnosed with lung cancer speak with their doctor to fully understand their treatment options. While how we deliver care might look different now in some ways, our commitment to helping patients live longer hasnt changed.

To learn more about Opdivo + Yervoy, please visit http://www.Opdivo.com.

INDICATION

OPDIVO (nivolumab) is a prescription medicine used in combination with YERVOY (ipilimumab) as a first treatment for adults with a type of advanced stage lung cancer (called non-small cell lung cancer) when your lung cancer has spread to other parts of your body (metastatic) and your tumors are positive for PD-L1, but do not have an abnormal EGFR or ALK gene.

It is not known if OPDIVO is safe and effective in children younger than 18 years of age.

OPDIVO (10 mg/mL) and YERVOY (5 mg/mL) are injections for intravenous (IV) use.

ImportantSafetyInformationforOPDIVO(nivolumab) + YERVOY (ipilimumab)

OPDIVO is a medicine that may treat certain cancers by working with your immune system. OPDIVO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become serious or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended. Some of these problems may happen more often when OPDIVO is used in combination with YERVOY.

YERVOY can cause serious side effects in many parts of your body which can lead to death. These problems may happen anytime during treatment with YERVOY or after you have completed treatment.

Serious side effects may include:Lung problems (pneumonitis). Symptoms of pneumonitis may include: new or worsening cough; chest pain; and shortness of breath. Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include: diarrhea (loose stools) or more bowel movements than usual; blood in your stools or dark, tarry, sticky stools; and severe stomach area (abdomen) pain or tenderness. Liver problems (hepatitis). Signs and symptoms of hepatitis may include: yellowing of your skin or the whites of your eyes; severe nausea or vomiting; pain on the right side of your stomach area (abdomen); drowsiness; dark urine (tea colored); bleeding or bruising more easily than normal; feeling less hungry than usual; and decreased energy.Hormone gland problems (especially the thyroid, pituitary, adrenal glands, and pancreas). Signs and symptoms that your hormone glands are not working properly may include: headaches that will not go away or unusual headaches; extreme tiredness; weight gain or weight loss; dizziness or fainting; changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness; hair loss; feeling cold; constipation; voice gets deeper; and excessive thirst or lots of urine. Kidney problems, including nephritis and kidney failure.Signs of kidney problems may include: decrease in the amount of urine; blood in your urine; swelling in your ankles; and loss of appetite. Skin problems.Signs of these problems may include: rash; itching; skin blistering; and ulcers in the mouth or other mucous membranes. Inflammation of the brain (encephalitis). Signs and symptoms of encephalitis may include: headache; fever; tiredness or weakness; confusion; memory problems; sleepiness; seeing or hearing things that are not really there (hallucinations); seizures; and stiff neck. Problems in other organs. Signs of these problems may include: changes in eyesight; severe or persistent muscle or joint pains; severe muscle weakness; and chest pain.

Additional serious side effects observed during a separate study of YERVOY alone include: Nerve problems that can lead to paralysis. Symptoms of nerve problems may include: unusual weakness of legs, arms, or face; and numbness or tingling in hands or feet. Eye problems.Symptoms may include: blurry vision, double vision, or other vision problems; and eye pain or redness.

Get medical help immediatelyif you develop any of these symptoms or they get worse. It may keep these problems from becoming more serious. Your healthcare team will check you for side effects during treatment and may treat you with corticosteroid or hormone replacement medicines. If you have a serious side effect, your healthcare team may also need to delay or completely stop your treatment.

OPDIVO and OPDIVO + YERVOY can cause serious side effects, including: Severe infusion reactions. Tell your doctor or nurse right away if you get these symptoms during an infusion: chills or shaking; itching or rash; flushing; difficulty breathing; dizziness; fever; and feeling like passing out.Graft-versus-host disease, a complication that can happen after receiving a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic), may be severe, and can lead to death, if you receive YERVOY either before or after transplant. Your healthcare provider will monitor you for the following signs and symptoms: skin rash, liver inflammation, stomach-area (abdominal) pain, and diarrhea.

Pregnancy and Nursing: Tell your healthcare provider if you are pregnant or plan to become pregnant. OPDIVO and YERVOY can harm your unborn baby. If you are a female who is able to become pregnant, your healthcare provider should do a pregnancy test before you start receiving OPDIVO. Females who are able to become pregnant should use an effective method of birth control duringtreatmentand for at least 5 months after the last dose. Talk to your healthcare provider about birth control methods that you can use during this time. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment. You or your healthcare provider should contact Bristol Myers Squibb at 1-800-721-5072 as soon as you become aware of the pregnancy. Pregnancy Safety Surveillance Study: Females who become pregnant during treatment with YERVOY are encouraged to enroll in a Pregnancy Safety Surveillance Study. The purpose of this study is to collect information about the health of you and your baby. You or your healthcare provider can enroll in the Pregnancy Safety Surveillance Study by calling 1-844-593-7869. Before receiving treatment, tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if either treatment passes into your breast milk. Do not breastfeed during treatment and for 5 months after the last dose.

Tell your healthcare provider about: Your health problems or concerns if you: have immune system problems such as autoimmune disease, Crohns disease, ulcerative colitis, lupus, or sarcoidosis; have had an organ transplant; have lung or breathing problems; have liver problems; or have any other medical conditions. All the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of OPDIVO, when used in combination with YERVOY, include: feeling tired; diarrhea; rash; itching; nausea; pain in muscles, bones, and joints; fever; cough; decreased appetite; vomiting; stomach-area (abdominal) pain; shortness of breath; upper respiratory tract infection;headache; low thyroid hormone levels (hypothyroidism); decreased weight; and dizziness.

These are not all the possible side effects. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatchor call 1-800-FDA-1088.

Please see U.S. Full Prescribing Information and Medication Guide forOPDIVO and YERVOY.

2020 Bristol-Myers Squibb Company.

OPDIVO and YERVOY are registered trademarks of Bristol-Myers Squibb Company.

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The Science of Survival: Evolving Research in Advanced Non-Small Cell Lung Cancer - Reuters

When Eimear Smyth passed away, her family promised her that they'd raise awareness for stem cell donation in the most fun way possible.

The West Belfast woman was 22 when she was diagnosed with Hodgkins Lymphoma and died just three years later after complications from a Donor Stem Cell transplant.

Today, Eimear's family and friends continue to raise awareness for stem cell donation, organ donation and blood cancer as part of Eimear's Wish.

From fundraisers to pink glazed donuts, everything the Smyth's have done in memory of Eimear has been fun, so they decided to take things up a notch and create a Gin brand named after the woman who taught them so much in life and death.

Speaking to Belfast Live, Eimear's dad Sean said the Gin has proved popular from across Ireland and beyond.

"Eimear's Wish Gin has taken a life of its own, people are really interested. We are getting requests from all over, and then when people try it they're asking for me. And the Wolf and Whistle in West Belfast are actually going to run a cocktail for us too.

"Our Eimear loved lemon and strawberry sherbet so they have agreed to run a pink lemon sherbet cocktail in memory of Eimear, and it launched on September 4 so we are looking forward to that.

"Everything we want to do, and have done in the past has been fun. See standing and shaking a bucket saying 'give me your money,' we don't want to do that. And we don't want to make it sad, because there is enough sadness in the world.

Eimear just loved dancing, and her social life. She loved coffee and donuts and now and again would take a wee Gin. She wasn't a big drinker but she would love having a Gin named after her.

"And the idea is to create a legacy for Eimear and to get people talking about stem cell donation, blood cancer and organ donation."

Eimear's Wish are asking for a 30 charitable donation which will be divided equally between Action Cancer, Cancer Fund for Children and Anthony Nolan Stem Cell - and in turn you'll get a bottle of Eimear's Gin.

All three charitable groups have helped Eimear and the Smyth family throughout their darkest days.

"Action Cancer was very, very good to us. Cancer Fund for Children looked out for Eimear and Anthony Nolan are helping to raise that awareness," said Sean.

"There are not enough people in Northern Ireland on the stem cell list, especially from the BAME community. If you are a white European, there's a 70% chance that you will find a match, but if you are from the Black, Asian, Minority Ethnic community that chance is 20% because your tissue is more difficult to match. So we need more people from those backgrounds to join.

"Before Eimear, I didn't know much about stem cell donation, I didn't know that stem cell and bone marrow was the same thing. I always thought it was two separate things.

"Our problem was that Eimear was only 22. She had just graduated and was taking the year out to get the money to go on to do a PGCE to become a teacher. She didn't smoke and rarely drank, she had a good healthy lifestyle. No cancer in my side of the family or Eimear's mummy's side. If that can happen to Eimear, it can happen to anyone, and that was really frightening.

"Awareness if one part of it, but the other part is to get better facilities, more age appropriate facilities for our young people who are going through this."

Throughout her illness, Eimear was treated in the City Hospital.

Hailing the medical care his daughter received, Sean says he would like to see more "age appropriate settings" for young adults for treatment.

"Eimear couldn't open the window to feel air on her skin when she was there. The TVs don't work. There's nowhere for relatives to sleep and there is one small fridge for 24 people. The facilities are from 1986. It is a horrible place to die.

"People have got to understand that we do not have age appropriate care for teenagers and young adults. They're sitting beside a 70-year-old man who is also ill, it's not fair on either patient to be in that situation.

"Eimear lived in Leeds and was treated in St James' Hospital and the unit she was in was brilliant. It was for patients aged 17-24. You walk in and there's a fully stocked kitchen for parents. The wards are a four people maximum. The far end of the ward is a youth club, it has snooker tables, jukeboxes, all the games consoles.

"The outpatients come for their chemo and their friends come with them for company. It is brilliant but we have nothing here. If we hadn't been in England we wouldn't have known the difference, we would have just thought it was the norm.

"The environment isn't nice at all. These are our kids. They're told those three words 'you've got cancer' and that is heartbreaking. The only thing I want is for the young people to be able to look at something other than beige colour walls. They deserve better.

"Nothing will ever bring my daughter back, but if we can make it a bit easy for another family or child, then we'll do that - it was Eimear's Wish."

For more information on how to donate, how to order a bottle or Eimear's Wish Gin or to stock it in your premises CLICK HERE.

You can register as a stem cell donor with the Anthony Nolan Trust or DKMS.

More:
Eimear's Wish Gin helping Belfast family pay tribute to daughter and raise awareness for Stem Cell Donation - Belfast Live

About 40 Maryland life sciences organizations are working on creating and assembling COVID-19 vaccines and therapeutics, improving diagnostic tests, and giving clinical examination and technical support to guarantee safe and viable health care delivery.

The University System of Maryland and Johns Hopkins University have likewise committed a great many dollars toward examination, testing, and clinical preliminaries. The University of Maryland School of Medicine recently started stage three testing of a COVID-19 immunization.

Up to now, Marylands life sciences companies have secured more than $3 billion for the advancement of a vaccine for SARS-CoV-2, the infection that causes COVID-19.

Gaithersburg-based Novavax was granted $1.6 billion through Operation Warp Speed to finish late-stage clinical developments, set up large scale manufacturing, and deliver 100 million vaccine dosages as early as the end of 2020. It has also secured $388 million from the international Coalition for Epidemic Preparedness Innovations and $60 million through a U.S. Department of Defense contract to support vaccine creation.

Rising BioSolutions, headquartered in Gaithersburg with three manufacturing facilities in Baltimore and Rockville, has agreements with AstraZeneca, Johnson and Johnson, Novavax, and Vaxart and also with Operation Warp Speed for the sum of $1.5 billion to help COVID-19 vaccine development and production.

Bethesda-based Longhorn Vaccines and Diagnostics won a $225 million Department of Homeland Security contract to transport clinical examples to testing labs.

Altimmune, headquartered in Gaithersburg, has a $4.7 million contract with the U.S. Army Medical Research and Development Command and is working with Rockville-based Vigene Biosciences on a single-dose intranasal COVID-19 vaccine.

The University System of Maryland and Johns Hopkins University have been working from the start of the pandemic on medical responses to combat COVID-19. Johns Hopkins has devoted $6 million in support of about 260 scientists and researchers working on more than two dozen projects involving COVID-19. In addition, Hopkins School of Medicine is conducting more than 100 clinical studies to develop COVID-19 diagnostics and, with $35 million from the U.S. Department of Defense, is working with the Bloomberg School of Public Health to test the efficacy of blood plasma from COVID-19 survivors as a viable treatment alternative.

The University System of Maryland faculty are working to develop a rapid COVID-19 test and are conducting a clinical trial of experimental stem cell therapy to reduce death in the sickest patients. The University of Maryland School of Medicine will receive up to $3.6 million over the next year from the Defense Advanced Research Projects Agency to test hundreds of drugs, approved and marketed for other conditions, to see whether any can be repurposed to forestall and treat COVID-19.

On the day of our first coronavirus cases, I said that Maryland was home to some of the top health research facilities in the world, and vowed that we would be a part of developing treatments and perhaps even a vaccine for this deadly virus, said Governor Larry Hogan in a statement. I want to commend our world-class life sciences community, our universities, and federal research labs for working together to fight this unprecedented global pandemic. Our state will continue to lead on the road to recovery.

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Nearly 40 Maryland companies are working to beat COVID-19 - Baltimore Fishbowl

to her legions of fans, Lynn Gunn Gunnulfsen made the jump from star to icon years ago.

As the vocalist of dark pop-rock purveyors PVRIS, she spent the bands first two albums, 2014s White Noise and 2017s All We Know of Heaven, All We Need Of Hell, speaking frankly about her own battles with depression, turning reflections of self-doubt and the complexities of relationships into arena-sized slices of electronic fizz. Shes campaigned for LGBTQ+ rights and become a figurehead for countless devotees who have adopted her songs as anthems of bravery and resilience.

The only person who doesnt seem to have grasped the pull of her star power is Gunn herself although thats changing with the release of PVRIS fearless new record, Use Me.

When she announced the album back in March, Gunn revealed that, from day one, shes consistently downplayed her true role as PVRIS sole creative force. Shes been responsible for everything from the bands sound to songwriting, visuals and driving production, but has preferred to share the spotlight with her bandmates, bassist Brian Macdonald and lead guitarist and keyboardist Alex Babinski. With Use Me, though, she says shes finally allowing herself to take credit for PVRIS ever-growing list of achievements.

It feels so good, she says on the phone line from her home in LA, referring to her unmasking as a lifting of the veil. She adds: This had to happen for me to continue wanting to do this. With all the work I was putting into this next record, it felt really weird and uncomfortable to be giving equal credit to everyone. Brian and Alex have always been incredibly supportive of my vision over the years, but I never felt comfortable opening up and owning that role. It made me feel apathetic towards the project.

You need only look at the promotional photos for Use Me, in which Gunn stands defiantly alone, without her bandmates, to see that newfound confidence in action, but she baulks at the suggestion that this is her going solo. Its quite similar to Tame impala and Florence + The Machine; were still very much a band, she says. Everythings operating the same as it always has, its just being presented differently. Her sense of empowerment is plastered all over Use Me.

Wide awake. Just cut the head off of a snake, she sings on the opening line of euphoric, disco-influenced first track, Gimme a Minute, a lyric that finds her looking forward to the future, having let go of the anxieties that plagued her career until now. The new music is also a break with the past, leaning more heavily on the PVRIS lustrous pop inclinations than its predecessors. The bands trademark brooding darkness still bubbles underfoot, but this time its buried beneath slick, vivid production and playful, clubby electronica.

Use Me was originally slated to arrive back in May, but as Covid-19 tightened its grip across the world, the bands label, Reprise/Warner Records, pushed the release to July. After the death of George Floyd in police custody in May, and the subsequent outpouring of shock and revolt and global renewal of the Black Lives Matter movement, Gunn decided that releasing new music would be a distraction from the bigger issues at hand.

In a statement posted to the bands Twitter account in July, she announced that the album would be further delayed: Self-promotion can wait for now and I want to make room and hold space for the conversation and message of the Black Lives Matter movement to continue.

She tells NME today: This moment in time is a paradigm shift and awakening for a lot of people. But theres so much work to do. It has to be lifelong commitment in order to see change.

Gunn recognises that healing the divisions of a splintered America will be a mountainous challenge, but shes inspired by the passion shes seen fighting for change online and out on the streets. In this, shes inspired by the tireless efforts of Gen-Z. We want a better future and are down and willing to be part of that shift, she says. Its so palpable and intense and real. I think the best thing you can do right now, instead of being apathetic and pretending that you dont care, is do care. Youve got to give a shit, you know?

Gunn is now 26, and was only 19 when she wrote the bands debut.When that album was released in 2014, the impact was instant, racking up millions of streams on Spotify and YouTube thanks to gloomy, yet jubilant synth-pop bangers such as St. Patrick and You And I. The record catapulted the band across the globe on a punishing tour schedule, which included high-profile US arena dates with Fall Out Boy, Bring Me The Horizon and Muse. Within three years, they had been booted from clubs onto festival main stages.

The full band, comprise of Gunn, bassist Brian Macdonald and lead guitarist and keyboardist Alex Babinski. Credit: Lindsey Byrnes

Yet success took its toll. By the time Gunn finally sat down to write 2017s All We Know of Heaven, All We Need of Hell, she was knackered and in a dark place, suffering with depression, which shes described as a downward spiral.

Years of constant gigging had damaged her voice, almost leading the band to cancel the tour of their second album while she worked with a vocal coach to retrain herself to sing. In the end, the band ploughed on with the promotion, but Gunns confidence had nosedived and onstage she seemed a reluctant frontwoman, hiding behind a guitar. In later interviews she admitted that she felt exposed and vulnerable.

Around the same time, she was diagnosed with Crohns disease, while in November 2019 it was confirmed that she was also battling an autoimmune disease, ankylosing spondylitis. The diagnoses, she says, came as a strange kind of relief after four years of pain and discomfort.

It has to be lifelong commitment in order to see [social] change

I didnt know what was wrong, she says. I was having a really difficult time getting out and into my bunk every morning and night and waking up with stomach pains. With autoimmune disease, theres a general fatigue and brain fog that comes with chronic inflammation, so a lot of the time Id be really unfocused or really tired. I was hard on myself about it.

Over time, Gunn has found her confidence again. Ive been really on top of my mental and physical health for the last few years, she says. I feel like Ive been in a really good head space for quite a while, which Im really grateful for.

Working with a small team of medical practitioners, including a herbalist, an acupuncture doctor and a womans specialist, who together have slowly but surely helped her to heal and rebalance, she now follows a what she dubs a crazy protocol.

I have up to 20 supplements I need to take, and different droplets, flower essences and plant stem cells, she says. I think theres 16 and you have to take all of them at different points throughout the day. The result has been transformative: Im determined to experience no symptoms in the next five years. Im ready to whoop its ass.

After a few turbulent personal years, Use Me represents a fresh start in many ways. While writing the album she upped sticks to Los Angeles, a move initially borne out of necessity. With an increased focus on protecting her physical and mental health following her Crohns diagnosis, it was clear that her usual approach shuttling back and forth between her home in New York and LA studio sessions had become unworkable. But no-one was more surprised than Gunn to find that her new home city was a genuine source of solace.

Ive always had a love-hate [relationship] with LA, she reveals. Ive had really good things happen here and difficult emotional situations happen here, so for a long time [the city] felt really dark. When I moved here, I was going through a pretty rough time, but I instantly loved it. All my best friends are out here, and I guess it feels like home.

By the time she made the move, she had already written three songs for the album the anthemic Death Of Me, the glossy Old Wounds and the vibrant Hallucinations, which were all released as part of the Hallucinations EP released in October 2019. The latter was penned during writing sessions with hotshot songwriter Amy Allen (whos worked with the likes of Halsey and Harry Styles) and Nashville-based Use Me producer, JT Daly. The remaining songs were finished in Dalys Nashville studio.

If 2017s All We Know of Heaven, All We Need of Hell was a cleansing experience that found Gunn crawling towards the end of the tunnel, its successor captures the moment that she finally emerged from the other end and into the light.

Inner peace is hard to find she sings on the opening line of euphoric, disco-influenced first track, Gimme a Minute, which refers to her overcoming recent emotional and physical upheaval. Over the glassy synths of Deadweight, she discusses walking away from negative mindsets and toxic relationships, sighing, I cant take it over and over / Deadweight hanging off of my shoulders.

[Those songs] capture the chaos of the last two years, she says. Theres so much that Ill never be probably able to share. Youve got to keep changing and growing. If someone or something is attacking you negatively, sometimes youve just got to have the power and the courage to walk away from it.

Is this a reference to long-time drummer Justin Nace, who left the band back in January? At the time the split seemed amicable, but was the shift a result of PVRIS new way of working, with Gunn stepping into the spotlight as band linchpin?

[Our new songs] capture the chaos of the last two years

Sort of, but it was a natural thing that needed to happen, says Gunn hesitantly, seeming reluctant to be drawn on the details. A lot of personal stuff [happened] that Im not going to mention here. Hes never been an official member [of PVRIS] so I dont think its that big a thing to touch on. We love him very much and wish him the best, but now is the time for change and growth for both parties.

The album closes with a reworked version of its titular track, which was put together during lockdown, featuring rising rapper and Kanye West protge 070 Shake. It was such a last-minute blessing from the heavens. I swear, says Gunn. Weve never had a featured artist on an album [before]. Theres never been anyone I was particularly excited about or felt compelled to collab with. I think shes real deal and a really special artist. Her album [070s excellent 2020 record Modus Vivendi] is very experimental, abstract, cool and weird and it takes risks.

Thats something I always want to do with PVRIS so its very aligned creatively. I think shes out in Colorado and as soon as she confirmed it was happening, she ended up having to drive an hour to a studio to track it, sent it over and it was perfect right away. Its a collaboration our fans didnt know they wanted, but hopefully they do now.

PVRIS live in London in February, Credit: India Fleming

Back in February, NME watched the band celebrate their live return to the UK, after two years away, at an intimate London show. As Gunn perched behind a keyboard during Heaven and danced across the stage watched by thousands of adoring eyes, there was no sign of the vocal issues and subsequent nerves that had plagued her in the past. Covid might have stolen that momentum, but Gunn is no longer content to remain trapped inside her inside her chrysalis.

I just want to be real and transparent, she insists. Growing up, I never really had a good example of the artist I am, and the role I take in the band. I just want to show this is an option for anyone who might be a similar position and inspire other people to do the same.

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PVRIS: Sometimes youve got to have the power and the courage to walk away - NME

Company Announcement

Copenhagen, Denmark; August 20, 2020 Genmab A/S (Nasdaq: GMAB) announced today that the U.S. Food and Drug Administration (U.S. FDA) has approved the use of DARZALEX (daratumumab) in combination with carfilzomib and dexamethasone (DKd) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received one to three previous lines of therapy. A supplemental Biologics License Application (sBLA) for this indication was submitted by Genmabs licensing partner, Janssen Biotech, Inc. (Janssen), in February 2020. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

We are extremely pleased that multiple myeloma patients in the U.S. will now have yet another treatment option as this is the eighth overall U.S. FDA approval for DARZALEX and the fifth in the relapsed/refractory setting. In addition, DARZALEX is now the first CD38 antibody approved for use in combination with carfilzomib, said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The combination has been approved in two carfilzomib dosing regimens, 70 mg/m2 once weekly and 56 mg/m2 twice weekly, based on positive results from the Phase 3 CANDOR and Phase 1b EQUULEUS studies. CANDOR was an Amgen-sponsored study, co-funded by Janssen Research & Development, LLC. EQUULEUS was sponsored by Janssen Research & Development, LLC.

About the CANDOR studyThe Phase 3 trial (NCT03158688) was a randomized, open-label study that included 466 patients with multiple myeloma who had relapsed after 1 to 3 prior therapies. Patients were randomized to receive either DKd or carfilzomib and dexamethasone (Kd) alone. In the daratumumab treatment arm, patients received 8 milligrams per kilogram (mg/kg) on days 1 and 2 of cycle 1, then 16 mg/kg once weekly for the remaining doses of the first 2 cycles, then every 2 weeks for 4 cycles (cycles 3 to 6), and then every 4 weeks for the remaining cycles or until disease progression. In both treatment arms carfilzomib was dosed twice weekly (20 mg/m2 on cycle 1 days 1 and 2 and 56 mg/m2 beginning on cycle 1 day 8 and thereafter) and dexamethasone was given weekly (40 mg orally or via IV infusion). The primary endpoint of the study was progression free survival (PFS).

About the EQUULEUS (MMY1001) Study The Phase 1b EQUULEUS (NCT01998971) study was an open label, multi-cohort trial that evaluated the safety, tolerability, and dose regimen of daratumumab when administered in combination with various treatment regimens for the treatment of multiple myeloma. Among the regiments evaluated, the combination of DKd compared to Kd alone was studied in 85 patients with relapsed/refractory multiple myeloma who had received one to three prior lines of therapy using a once-weekly dosing regimen. DKd was evaluated at a starting dose of 20 mg/m2, which was increased to 70 mg/m2 on Cycle 1, Day 8 and onward.

About multiple myelomaMultiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX (daratumumab)DARZALEX (daratumumab) has become a backbone therapy in the treatment of multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with carfilzomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma who have received one to three previous lines of therapy; in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX is indicated for the treatment of adult patients in Europe via intravenous infusion or subcutaneous administration: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy7. Daratumumab is the first subcutaneous CD38 antibody approved in Europe for the treatment of multiple myeloma. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit http://www.DARZALEX.com.

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, is approved in the United States for the treatment of adult patients with multiple myeloma: in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for ASCT; in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy; in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and as monotherapy, in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.8 DARZALEX FASPRO is the first subcutaneous CD38 antibody approved in the U.S. for the treatment of multiple myeloma.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a persons own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,9,10,11,12

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis and T-cell acute lymphocytic leukemia (ALL). Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

About Genmab Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer. Founded in 1999, the company is the creator of the following approved antibodies: DARZALEX (daratumumab, under agreement with Janssen Biotech, Inc.) for the treatment of certain multiple myeloma indications in territories including the U.S., Europe and Japan, Kesimpta (subcutaneous ofatumumab, under agreement with Novartis AG), for the treatment of adults with relapsing forms of multiple sclerosis in the U.S. and TEPEZZA (teprotumumab, under agreement with Roche granting sublicense to Horizon Therapeutics plc) for the treatment of thyroid eye disease in the U.S. A subcutaneous formulation of daratumumab, known as DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in the U.S., has been approved in the U.S. and Europe for the treatment of adult patients with certain multiple myeloma indications. The first approved Genmab created therapy, Arzerra (ofatumumab, under agreement with Novartis AG), approved for the treatment of certain chronic lymphocytic leukemia indications, is available in Japan and is also available in other territories via compassionate use or oncology access programs. Daratumumab is in clinical development by Janssen for the treatment of additional multiple myeloma indications, other blood cancers and amyloidosis. Genmab also has a broad clinical and pre-clinical product pipeline. Genmab's technology base consists of validated and proprietary next generation antibody technologies - the DuoBody platform for generation of bispecific antibodies, the HexaBody platform, which creates effector function enhanced antibodies, the HexElect platform, which combines two co-dependently acting HexaBody molecules to introduce selectivity while maximizing therapeutic potency and the DuoHexaBody platform, which enhances the potential potency of bispecific antibodies through hexamerization. The company intends to leverage these technologies to create opportunities for full or co-ownership of future products. Genmab has alliances with top tier pharmaceutical and biotechnology companies. Genmab is headquartered in Copenhagen, Denmark with sites in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan.

Contact: Marisol Peron, Corporate Vice President, Communications & Investor Relations T: +1 609 524 0065; E: mmp@genmab.com

For Investor Relations: Andrew Carlsen, Senior Director, Investor RelationsT: +45 3377 9558; E: acn@genmab.com

This Company Announcement contains forward looking statements. The words believe, expect, anticipate, intend and plan and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmabs most recent financial reports, which are available on http://www.genmab.com and the risk factors included in Genmabs most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at http://www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

Genmab A/S and/or its subsidiaries own the following trademarks: Genmab; the Y-shaped Genmab logo; Genmab in combination with the Y-shaped Genmab logo; HuMax; DuoBody; DuoBody in combination with the DuoBody logo; HexaBody; HexaBody in combination with the HexaBody logo; DuoHexaBody; HexElect; and UniBody. Arzerra and Kesimpta are trademarks of Novartis AG or its affiliates. DARZALEX and DARZALEX FASPRO are trademarks of Janssen Pharmaceutica NV. TEPEZZA is a trademark of Horizon Therapeutics plc.

1 American Cancer Society. "Multiple Myeloma Overview." Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma.Accessed June 2016.2 National Cancer Institute. "A Snapshot of Myeloma." Available at http://www.cancer.gov/research/progress/snapshots/myeloma. Accessed June 2016. 3 Globocan 2018. United States of America Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/840-united-states-of-america-fact-sheets.pdf.4 Globocan 2018. World Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed December 2018.5 American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 20166 DARZALEX Prescribing information, September 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s024lbl.pdf Last accessed September 20197 DARZALEX Summary of Product Characteristics, available at https://www.ema.europa.eu/en/medicines/human/EPAR/darzalex Last accessed June 20208 DARZALEX FASPRO Prescribing information, May 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761145s000lbl.pdf Last accessed May 20209 De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848.10 Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-21.11 Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94.12 Jansen, JH et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking.Blood. 2012; 120(21): abstract 2974.

Company Announcement no. 38CVR no. 2102 3884LEI Code 529900MTJPDPE4MHJ122

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On May 25, 1968, surgeons in Richmond, Virginia, performed a successful heart transplant, one of the world's first, on a white businessman. The heart that they used was taken from a Black patient named Bruce Tucker who had been brought to the hospital the day before, unconscious and with a fractured skull and traumatic brain injury. He was pronounced brain dead less than 24 hours later.

Tucker's still-beating heart was then removed without his family's knowledge or prior permission; their horrified discovery from the local funeral director that Tucker's heart was missing was a devastating blow.

The surgeons' actions, which led to America's first civil suit for wrongful death, are brought to light in the new book "The Organ Thieves: The Shocking Story of the First Heart Transplant in the Segregated South" (Simon and Schuster, 2020) by Pulitzer Prize-nominated journalist Charles "Chip" Jones. Jones raises troubling questions about the ethics of this pioneering transplant, revealing its deep roots in racism and discrimination toward Black people in health care.

Related: 7 Reasons America still needs civil rights movements

The first human organ transplant, a kidney, took place in 1954, and by the late 1960s, "superstar" surgeons were vying to be the first to successfully transplant a human heart, Jones told Live Science.

"In terms of science, it was the medical parallel to the space race," Jones said.

Dr. Richard Lower and Dr. David Hume, surgeons at the Medical College of Virginia (MCV) in Richmond, were at the forefront of that race, but it was South African surgeon Dr. Christiaan Barnard who performed the first heart transplant on Dec. 3, 1967. In May of 1968, MCV admitted to its hospital a patient with severe coronary disease who was a promising candidate for a heart transplant. But Lower and Hume had yet to find a viable heart donor.

And with time running out for their sick patient, they needed one fast.

Tucker, a Richmond factory worker who had sustained a serious head injury in a fall, was brought to the MCV Hospital on May 24, 1968. Though Tucker's personal effects included one of his brother's business cards, officials were unable to locate a family member on behalf of the unconscious man. And because the hospital claimed Tucker had no family and had liquor on his breath (he had been drinking prior to his accident), he was profiled as a "charity patient" and marked as a potential heart donor.

"He was in the wrong place at the wrong time," Jones said.

Tucker was connected to a ventilator, unable to breathe on his own. A junior medical examiner performed an electroencephalogram (EEG) to determine electrical activity in Tucker's brain; the examiner declared that there was none. The surgeons pronounced this to be sufficient evidence of brain death; Tucker was removed from the ventilator, and Hume and Lower removed Tucker's heart for the transplant, Jones wrote.

Related: What happens to your body when you're an organ donor?

Decades later, in 1981, the Uniform Determination of Death Act provided a legal definition of death: "irreversible cessation of circulatory and pulmonary functions" and "irreversible cessation of all functions of the whole brain," which means that the entire brain including the brain stem has ceased to function, according to Johns Hopkins Medicine.

But in 1968, the legal concept of death was not as clearly defined, Jones said.

"There was no statutory framework that would let doctors know how to proceed in a situation like this, where they had a patient that they legitimately thought had no chance of recovery," Jones explained. "And time was of the essence, in their view, to save a very sick man." However, the doctors were also quick to presume that Tucker was indigent and without family a racially motivated judgment, according to Jones.

Related: The 9 most interesting transplants

Tucker's family learned that his heart was missing from the funeral director; they pieced together what had happened from news reports (Tucker's identity was not initially released to the public, Jones wrote). Eventually, Tucker's family would file a civil lawsuit for wrongful death, which went to trial in 1972. Representing them was attorney L. Douglas Wilder, who later became the first elected Black governor in the U.S.

According to Wilder, Lower "willfully, wrongfully, wantonly and intentionally pronounced Bruce O. Tucker dead ahead of his actual death, in violation of the law, well knowing that he was not legally qualified to do so." State law required family notification and waiting for 24 hours before performing surgery.

"They skirted the process that was in place in Virginia because they were so eager to finally do the operation," Jones said.

The famous case of Henrietta Lacks presents a similar collision between medical ethics and racism. Lacks, a Black woman (also from Virginia), was diagnosed in 1951 with cervical cancer. A doctor collected cells from one of her tumors and then reproduced them indefinitely in the lab; after Lacks' death, those cells were then distributed widely among scientists for years without her family's knowledge or permission. Known as the HeLa cell line, they were used in research that led to cancer treatments and to the discovery of the polio vaccine, but decades passed before Lacks' family learned of her medical "immortality."

In 2013, the National Institutes of Health (NIH) reached an agreement with the family for permitting future research involving data from HeLa cells; the new process requires application through a panel that includes descendants and relatives of Lacks, Live Science previously reported.

The injustices experienced by Lacks, Tucker and their families stemmed from racism that is deeply embedded in America's medical infrastructure, Jones noted. In fact, when medical colleges in America adopted a more hands-on approach to anatomical studies during the 19th century, instructors frequently trained their students in human anatomy using cadavers of Black people that were stolen from African American cemeteries, Jones wrote.

Grave robbing was technically illegal, but when Black people were the victims, authorities tended to look the other way, according to Jones. Medical schools would hire a "body man" (also known as a "resurrectionist") to procure bodies; at MCV, the designated grave robber was a Black man named Chris Baker, a janitor at the school who lived in the basement of the college's Egyptian Building.

Most of the country's medical schools abandoned this racist method of procuring cadavers by the mid-1800s, but records suggest that it continued in Virginia until at least 1900, Jones said.

"There were news reports of bodies being 'snatched' from the Virginia state pen, which is about five blocks from the medical college," he said.

Jones unexpectedly discovered a reminder of this crime while researching his book, in a mural displayed in MCV's McGlothlin Medical Education Center. Painted between 1937 and 1947 by Richmond artist George Murrill, the mural celebrates the medical college's history. And it includes the image of a corpse being furtively carried away from a grave in a wheelbarrow.

"It shows how the legacy of racism is literally right under people's noses," Jones said.

"The Organ Thieves" is available to buy on Aug. 18; read an excerpt here .

Originally published on Live Science.

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Landmark transplant in 1960s Virginia performed with heart stolen from a Black man - Live Science

Chemotherapeutic drug resistance is one reason cancer remains an unsolved clinical problem despite the efforts ever since President Nixon declared his "War on Cancer" in 1971. Cancer cells, due in part to the genetic destabilization characteristic of the disease, are capable of expressing genes (normal or aberrant) that permit the cell to avoid the cytotoxic effect of such drugs with the patient providing the situs of selection for and growth of resistant cells. The phenomenon is certain tumor types can have more deleterious consequences than in others, and this is particularly true for glioblastomas (and their non-malignant counterparts, gliomas), cancer of the cells that protect neurons in brain. That organ, confined to the skull, cannot accommodate tumor growth without damaging the brain with which it is confined.

The chemotherapeutic drug of choice for treating glioblastomas is temezolomide (TMZ), an oral alkylating agent that had its chemotherapeutic effect by introducing alkyl groups onto nucleotide bases (preferably at the N-7 and O-6 positions of guanine and N-3 position of adenine) in tumor cell DNA preferentially (due to the greater amount of DNA synthesis occurring in these cells) and disrupting the process leading to cell death (the O-6 methylation having the greatest capacity to induce apoptosis or programmed cell death).O-6-methylguanosnine DNA methyltransferase (MGMT) is the cellular enzyme responsible for repairing alkylated bases in DNA and reduced expression of this gene (e.g., by hypermethylation of the MGMT promoter) is a biomarker for TMZ sensitivity in gliomas and glioblastomas. Recently, a multinational team of researchers* reported genetic rearrangements associated with TMZ resistance, in a paper entitled "MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas" published in Nature Communications. This paper shows a subset of gliomas with rearrangements in the MGMT gene that produce overexpression of the gene and resistance as a result. These authors screened 252 TMZ-treated recurrent gliomas by RNA sequencing and found eight different MGMT genetic fusions (designated BTRC-MGMT,CAPZB-MGMT,GLRX3-MGMT,NFYC-MGMT,RPH3A-MGMT, andSAR1A-MGMTin high-grade gliomas, HGG, andCTBP2-MGMTandFAM175B-MGMT in low-grade gliomas, LGG, in the paper) in seven patients (6 females) with recurrent disease, created by chromosomal rearrangement (see Figure 1c from paper; shown below). These individuals' tumors showed "significantly higher" expression of the rearranged MGMT gene product.

Upon further study, the authors report that five of the eight rearranged genes were located on Chromosome 10 in the vicinity of the MGMT gene itself. The breakpoint in the MGMT was uniformly found at the boundary of exon 2 of the MGMT gene, at a point 12 basepairs upstream of the ATG translation "start" codon. In three of the rearrangements, the breakpoint in the partner gene in the genetic fusion was found in the 5' untranslated region (UTR). All fusions were found to be in-frame (i.e., the reading frame of the MGMT transcript was not disrupted) and the functional regions of the MGMT protein (the methyltransferase domain and DNA-binding domain) were intact. A more fine-structure mapping experiment in the genetic rearrangement resulting in FAM175B-MGMTfound that the fusion was the consequence of a deletion of 4.8 Mb.

The effect of these rearrangements on MGMT expression was elucidated using CRIPSR-Cas9 to produce the BTRC-MGMT, NFYC-MGMT, SAR1A-MGMT, and CTBP2-MGMT rearrangements in cells of two glioblastoma cell lines, U251 and U87. When these cells and their untreated counterparts were challenged by growth in vitro with TMZ, only cells bearing the rearrangements (as confirmed by PCR analysis) were shown to be TMZ resistant. Unlike genetic rearrangements in other cancers that produce fusion proteins (such as the abl-bcr gene produced in chronic myelogenous leukemia bearing the diagnostic Philadelphia chromosome), because most of the rearrangements found involving the MGMT gene were located upstream of the initiation codon of the MGMT gene these authors reasoned that these rearrangements produce increased expression of MGMT leading to TMZ resistance because the cells were better able to repair the methylation injury and replicate functionally. This hypothesis was supported by real-time quantitative PCR analysis of MGMT transcripts in cells bearing the rearrangements, that showed a "striking" increase in expression of MGMT-encoding transcripts (an observation also found in tumors from patients whose gliomas or glioblastomas showed these rearrangements), and Western blot analysis confirmed higher expression levels of the MGMT protein. In two of the rearrangements (BTRC-MGMT and NFYC-MGMT), higher molecular weight fusion proteins were detected as predicted from the genetic data. These results were also replicated in patient tumor-derived stem cells for the BTRC-MGMTandSAR1A-MGMT rearrangements.

These results, and the researchers' conclusion that these rearrangements caused TMZ resistance by overexpression of MGMT, were confirmed by re-establishing TMZ sensitivity in these cells in the presence of O6-benzylguanine (O6-BG), an MGMT inhibitor. These results were further confirmed by detection of double-strand breaks in DNA in these cells in the presence of TMZ and O6-BG.

The relevance of these results to TMZ resistance in vivo was demonstrated using nude mouse xenograft models bearing tumors produced using BTRC-MGMT U251 cells and U251 cells without the rearrangement as control; these cells also contained a recombinant luciferase gene. Mice containing the rearrangement showed no significant prolongation of lifespan in the presence or absence of TMZ, indicating tumor cell resistance, whereas TMZ treatment of nave U251 cells showed improved survival.

While hypomethylation of the native MGMT promoter is the most frequently change associated with TMZ resistance, the results presented in this paper illustrate an alternative mechanism for glioblastomas and gliomas to acquire resistance to TMZ, the only current chemotherapeutic drugs for these maladies. Because these rearrangements were found in patients with recurrent tumors, these authors hypothesize that the rearrangements were selected or by TMZ treatment. A similar rearrangement has also been found in another cancer, medulloblastoma, after TMZ relapse. These authors also suggest that detection of these rearrangements can be used clinically to determine appropriate treatment modalities, particularly for recurrent disease.

* Seve Ballesteros Foundation Brain Tumor Group, Molecular Oncology Programme, Spanish National Cancer Research Center; Division of Life Science, Department of Chemical and Biological Engineering, Center of Systems Biology and Human Health and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology; Beijing Neurosurgical Institute, Capital Medical University; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine; Department of Systems Biology, Columbia University; The Jackson Laboratory for Genomic Medicine; and Molecular Cytogenetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Center, CNIO, 28029, Madrid, Spain

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Chromosomal Rearrangements Associated with Chemotherapeutic Drug Resistance | McDonnell Boehnen Hulbert & Berghoff LLP - JD Supra

How worried should we be that the President of the United States recently described as very impressive a woman who claims that doctors make medicine using DNA from aliens? Or that he shows no sign of recognizing the magnitude of the COVID-19 pandemic? Its simply not possible to worry too much.

I thought her voice was an important voice, Donald Trump said, after a reporter asked him why he would retweet the claims of Stella Immanuel, a Houston pediatrician with a long history of bizarre statements about medicine and human sexuality. Immanuel also shares Trumps unfounded enthusiasm for hydroxychloroquine. The drug has been repeatedly discredited as a treatment for this disease. She insists that it is a cure. Its tempting to write off this episode purely as evidence of Trumps disrespect for science. But the problem it represents is much bigger; it is the clearest sign yet that political interests and personal whims have eclipsed the rigor of some of our most important scientific institutions.

Twenty years ago, reporting from South Africa, I saw firsthand what happens when a national leader forces his people to subsist on lies and magic. From 2000 to 2005, according to a definitive study by researchers at the Harvard School of Public Health, Thabo Mbeki, then the President of South Africa, let as many as three hundred and thirty thousand of his fellow-citizens die and thirty-five thousand babies be born with H.I.V., by refusing to permit the countrys health service to treat AIDS with antiretroviral drugs. Mbeki and his health minister, Manto Tshabalala-Msimang, insisted that antiviral medicine was the product of a plot by Western pharmaceutical companies to kill Africans. The Harvard study concluded that the drugs were withheld largely because of Mbekis well-known refusal to initially accept that AIDS is caused by a virus, H.I.V.

No single national leader would have been able to prevent the coronavirus pandemic. But Trumps denialism and hostility toward public-health officials has greatly increased Americas share of suffering and death. On Fox & Friends, on Wednesday, he said that the virus is spreading in a relatively small portion of the country, and that children are virtually immune; both statements are false. And, as he has done many times before, he declared at a briefing that the pandemic would just go away.

Trump has had one consistent response to the pandemic: he attacks leading experts when they attempt to tell the truth. Last week, when Deborah Birx, the cordinator of the White House coronavirus task force, characterized the epidemic as extraordinarily widespread, Trump tweeted that she was pathetic. Earlier this year, when Anthony Fauci, the nations leading infectious-disease expert, was asked at a briefing to discuss his view on hydroxychloroquine, Trump prevented him from answering. The Presidents refusal either to lead or to recognize the leadership of others has made it impossible to develop a national plan to combat this virus.

Without such a plan, the nation has been subjected to a giant game of viral roulette. With no coherent system of rapid tests, contact tracing is all but useless. Since we have neither a vaccine nor any general therapy, tests and tracing offer the only near-term hope of controlling the pandemic. States have largely been left to fend for themselves. Last week, seven governors, Republicans and Democrats, formed their own testing coalition.

On Wednesday, Fauci was asked if the United States had the worlds worst COVID-19 outbreak. It is quantitatively, if you look at it, he said. I mean, the numbers dont lie. Trump is asked similar questions nearly every day. And, although the numbers may not lie, the President does. As he put it in a recent tweet, You will never hear this on the Fake News concerning the China Virus, but by comparison to most other countries, who are suffering greatly, we are doing very well. No amount of statistical massaging could make that statement true.

This war on reality has deeply wounded Americas public-health system. In March, under relentless pressure from Trump and his trade adviser, Peter Navarro (who has no medical training), the Food and Drug Administration issued an emergency-use authorization (E.U.A.) for hydroxychloroquine. That allowed doctors to administer the drug to patients who were severely ill, but it was not an approval of the drug for general use. As Janet Woodcock, who runs the F.D.A.s Center for Drug Evaluation and Research, put it in an interview with Stat, We simply said its possible from the in vitro data this may have a beneficial effect and the benefits may outweigh the risks. Few people understood that distinction, and, goaded on by the President, few listened to those who urged caution.

Trump announced on national television that hydroxychloroquine could be a game changer. It wasnt. Former F.D.A. officials were astonished by the rushed action. I understand the desire to find hope, but we need more evidence than is currently available before we encourage widespread use, Margaret A. Hamburg said at the time. She served as the F.D.A. commissioner for six years under Barack Obama.

In June, when the drugs ineffectiveness had become apparent, the F.D.A. revoked the E.U.A. It was a remarkable retreat. While it is reassuring that the agency finally made a decision based on data, the drug should not have been released for this use in the first place. But, when politics takes precedence, facts no longer matter. Rick A. Bright, one of the nations experts on pandemic preparedness and the chief of BARDA (the Biomedical Advanced Research and Development Authority), had objected to the use of the drug and tried to stop it. He was fired. As the Times reported on Monday, Stephen Hahn, the current F.D.A. commissioner, is not allowed to speak to the press unless Michael Caputo, an assistant secretary of the Department of Health and Human Services, or another official, is also on the line. Caputo has long been associated with Trump, once serving as his driver.

We have recently witnessed an even more pernicious example of an American scientific colossus bowing to Trumps ignorance. In May, the Centers for Disease Control and Prevention issued stringent guidelines to determine when and if schools should reopen this fall. Trump has insisted, against all scientific advice, that all schools should open. He tweeted, I disagree with the @CDCgov on their very tough & expensive guidelines for opening schools. While they want them open, they are asking schools to do very impractical things. I will be meeting with them!!!

Robert Redfield, the director of the C.D.C., immediately issued an update to the guidelines, announcing that it is critically important for our public health to open schools this fall. The reversal was stunning; past C.D.C. directors were not immune to politics, and they understood that a President might overrule them. But there has always been an understanding at the agency that all public-health decisions made there would have to be governed by data.

No agency or scientist is infallible. Early in the pandemic, the C.D.C. failed to introduce accurate test kits; many of the kits it distributed were contaminated and useless. The agency used highly sensitive tests based on PCR technology, which is a kind of molecular copying machine that makes millions (or billions) of copies of a DNA sample. That makes it much easier for clinicians to detect any specific sequence of DNA, including those in the coronavirus. The technology has been used routinely for more than three decades, but it is sensitive to small errors, and there were several in the C.D.C. kits. The misstep delayed accurate data collection throughout the United States at one of the most critical moments in the pandemic.

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Trumps Unprecedented Attacks on Our Public-Health System - The New Yorker