Page 472«..1020..471472473474..480490..»

Researchers share insights about the mechanisms of human embryo and create method to develop transcriptionally similar cells in tissue culture -…

Posted: May 2, 2022 at 2:18 am

Paper Title: Identification of a retinoic acid-dependent hemogenic endothelial progenitor from human pluripotent stem cells

Journal: Nature Cell Biology

Authors:Christopher Sturgeon, PhD, Associate Professor of Cell, Developmental & Regenerative Biology and Medicine, Hematology & Medical Oncology in the Black Family Stem Cell Institute at the Icahn School of Medicine at Mount Sinai, and other coauthors.

Bottom Line:Blood-forming stem cells found in bone marrow are the life-saving component used in bone marrow transplants. However, suitable donors often cannot be found in many cases. This study reveals how the human embryo develops the precursor to blood forming stem cells, which researchers say can be used in the novel method they developed to generate blood-forming stem cells from cells in tissue culture.

The studyled by researchers from Mount Sinai and the San Raffaele Telethon Institute for Gene Therapy in Milan Italyconfirms many aspects of cell development, including origins and regulation, which are known to occur within both the mouse and human embryo. In the mammalian embryo, blood-forming stem cells emerge from a specialized cell type called hemogenic endothelium. These cells develop in response to a critical signal pathway known as retinoic acid, which is essential for growth. Their analysis found that stem cell populations derived from human pluripotent stem cells were transcriptionally similar to cells in the early human embryo.

Results: For years, researchers in the field of regenerative medicine have been able to obtain hemogenic endothelium from embryonic stem cells, but these cells do not produce blood-forming stem cells. In the embryo, blood-forming stem cell development requires signaling by retinoic acid.But, current state-of-the-art methods for deriving blood progenitors from human pluripotent stem cells do so in the absence of retinoic acid. In this latest study, researchers examined the dependence on retinoic acid in early cell types derived from human pluripotent stem cells. They performed single cell RNA sequencing of stem cells in vitro to better understand patterns of mesodermal cell types during early development. The research team identified a new strategy to obtain cells that are transcriptionally similar to those hemogenic endothelial cells found in the human embryo by stimulating a very discrete original population with retinoic acid.

Why the Research Is Interesting:This new method brings researchers and scientists closer to developing blood-forming stem cells in tissue culture, but also provides a pathway to establishing specialized blood cell types for transfusions and other treatments for cancer since the new method makings it possible to obtain the same original cells in adult blood that are found in a developing embryo.

Said Mount Sinai's Dr. Christopher Sturgeon of the research:We have made a major breakthrough in our ability to direct the development of stem cells in a tissue culture dish into cells that have the same gene expression signature as the immediate progenitor of a blood-forming stem cell found in the developing embryo. With this, now we can focus our efforts at understanding how to capture embryonic blood-forming stem cells, with the goal of using them as a substitute for bone marrow.

Researchers from the Washington University School of Medicine in St. Louis, MO contributed to this study.

###

To request a full copy of the paper or to schedule an interview with the researcher, please contact the Mount Sinai Press Office at stacy.anderson@mountsinai.org or 347-346-3390.

Nature Cell Biology

28-Apr-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

See the original post here:
Researchers share insights about the mechanisms of human embryo and create method to develop transcriptionally similar cells in tissue culture -...

Posted in Stem Cell Research | Comments Off on Researchers share insights about the mechanisms of human embryo and create method to develop transcriptionally similar cells in tissue culture -…

Mini-heart chamber beats on its own just like the real thing – Futurity: Research News

Posted: May 2, 2022 at 2:18 am

Share this Article

You are free to share this article under the Attribution 4.0 International license.

A miniature replica of a heart chamber built from a combination of nanoengineered parts and human heart tissue offers a new way to study the heart.

Theres no safe way to get a close-up view of the human heart as it goes about its work: you cant just pop it out, take a look, then slot it back in.

Scientists have tried different ways to get around this fundamental problem: theyve hooked up cadaver hearts to machines to make them pump again, attached lab-grown heart tissues to springs to watch them expand and contract. Each approach has its flaws: reanimated hearts can only beat for a few hours; springs cant replicate the forces at work on the real muscle.

But getting a better understanding of this vital organ is urgent. In America, someone dies of heart disease every 36 seconds, according to the Centers for Disease Control and Prevention.

The new miniature replica of a heart chamber has no springs or external power sourceslike the real thing, it just beats by itself, driven by the live heart tissue grown from stem cells. The device could give researchers a more accurate view of how the organ works, allowing them to track how the heart grows in the embryo, study the impact of disease, and test the potential effectiveness and side effects of new treatmentsall at zero risk to patients and without leaving a lab.

The team behind the gadgetnicknamed miniPUMP, and officially known as the cardiac miniaturized Precision-enabled Unidirectional Microfluidic Pumpsays the technology could also pave the way for building lab-based versions of other organs, from lungs to kidneys.

We can study disease progression in a way that hasnt been possible before, says Alice White, a professor and chair of mechanical engineering at the Boston University College of Engineering. We chose to work on heart tissue because of its particularly complicated mechanics, but we showed that, when you take nanotechnology and marry it with tissue engineering, theres potential for replicating this for multiple organs.

The device could eventually speed up the drug development process, making it faster and cheaper, the researchers say. Instead of spending millionsand possibly decadesmoving a medicinal drug through the development pipeline only to see it fall at the final hurdle when tested in people, researchers could use the miniPUMP at the outset to better predict success or failure.

The project is part of CELL-MET, a multi-institutional National Science Foundation Engineering Research Center in Cellular Metamaterials thats led by Boston University. The centers goal is to regenerate diseased human heart tissue, building a community of scientists and industry experts to test new drugs and create artificial implantable patches for hearts damaged by heart attacks or disease.

Heart disease is the number one cause of death in the United States, touching all of us, says White. Today, there is no cure for a heart attack. The vision of CELL-MET is to change this.

Theres a lot that can go wrong with your heart. When its firing properly on all four cylinders, the hearts two top and two bottom chambers keep your blood flowing so that oxygen-rich blood circulates and feeds your body. But when disease strikes, the arteries that carry blood away from your heart can narrow or become blocked, valves can leak or malfunction, the heart muscle can thin or thicken, or electrical signals can short, causing too manyor too fewbeats. Unchecked, heart disease can lead to discomfortlike breathlessness, fatigue, swelling, and chest painand, for many, death.

The heart experiences complex forces as it pumps blood through our bodies, says Christopher Chen, professor of biomedical engineering. And while we know that heart muscle changes for the worse in response to abnormal forcesfor example, due to high blood pressure or valve diseaseit has been difficult to mimic and study these disease processes. This is why we wanted to build a miniaturized heart chamber.

At just 3 square centimeters, the miniPUMP isnt much bigger than a postage stamp. Built to act like a human heart ventricleor muscular lower chamberits custom-made components are fitted onto a thin piece of 3D-printed plastic. There are miniature acrylic valves, opening and closing to control the flow of liquidwater, in this case, rather than bloodand small tubes, funneling that fluid just like arteries and veins. And beating away in one corner, the muscle cells that make heart tissue contract, cardiomyocytes, made using stem cell technology.

Theyre generated using induced pluripotent stem cells, says Christos Michas, a postdoctoral researcher who designed and led the development of the miniPUMP as part of his PhD thesis.

To make the cardiomyocyte, researchers take a cell from an adultit could be a skin cell, blood cell, or just about any other cellreprogram it into an embryonic-like stem cell, then transform that into the heart cell.

In addition to giving the device literal heart, Michas says the cardiomyocytes also give the system enormous potential in helping pioneer personalized medicines. Researchers could place a diseased tissue in the device, for instance, then test a drug on that tissue and watch to see how its pumping ability is affected.

With this system, if I take cells from you, I can see how the drug would react in you, because these are your cells, says Michas. This system replicates better some of the function of the heart, but at the same time, gives us the flexibility of having different humans that it replicates. Its a more predictive model to see what would happen in humanswithout actually getting into humans.

That could allow scientists to assess a new heart disease drugs chances of success long before heading into clinical trials, Michas says. Many drug candidates fail because of their adverse side effects.

At the very beginning, when were still playing with cells, we can introduce these devices and have more accurate predictions of what will happen in clinical trials. It will also mean that the drugs might have fewer side effects.

One of the key parts of the miniPUMP is an acrylic scaffold that supports, and moves with, the heart tissue as it contracts. A series of superfine concentric spiralsthinner than a human hairconnected by horizontal rings, the scaffold looks like an artsy piston. Its an essential piece of the puzzle, giving structure to the heart cellswhich would just be a formless blob without itbut not exerting any active force on them.

We dont think previous methods of studying heart tissue capture the way the muscle would respond in your body, says Chen, whos also director of Boston Universitys Biological Design Center and an associate faculty member at Harvard Universitys Wyss Institute for Biologically Inspired Engineering. This gives us the first opportunity to build something that mechanically is more similar to what we think the heart is actually experiencingits a big step forward.

To print each of the tiny components, the team used a process called two-photon direct laser writinga more precise version of 3D printing. When light is beamed into a liquid resin, the areas it touches turn solid; because the light can be aimed with such accuracyfocused to a tiny spotmany of the components in the miniPUMP are measured in microns, smaller than a dust particle.

The decision to make the pump so small, rather than life-size or larger, was deliberate and is crucial to its functioning.

The structural elements are so fine that things that would ordinarily be stiff are flexible, says White. By analogy, think about optical fiber: a glass window is very stiff, but you can wrap a glass optical fiber around your finger. Acrylic can be very stiff, but at the scale involved in the miniPUMP, the acrylic scaffold is able to be compressed by the beating cardiomyocytes.

The pumps scale shows that with finer printing architectures, you might be able to create more complex organizations of cells than we thought was possible before, Chen says.

At the moment, when researchers try to create cells, he says, whether heart cells or liver cells, theyre all disorganizedto get structure, you have to cross your fingers and hope the cells create something. That means the tissue scaffolding pioneered in the miniPUMP has big potential implications beyond the heart, laying the foundation for other organs-on-a-chip, from kidneys to lungs.

An electrical and computer engineering student as an undergraduate, Michas says hed never seen cells in my life before starting this project. Now, hes preparing to start a new position with Seattle-based biotech Curi Bio, a company that combines stem cell technology, tissue biosystems, and artificial intelligence to power the development of drugs and therapeutics.

Christos is someone who understands the biology, says White, can do the cell differentiation and tissue manipulation, but also understands nanotechnology and whats required, in an engineering way, to fabricate the structure.

The next immediate goal for the miniPUMP team? To refine the technology. They also plan to test ways to manufacture the device without compromising its reliability.

There are so many research applications, says Chen. In addition to giving us access to human heart muscle for studying disease and pathology, this work paves the way to making heart patches that could ultimately be for someone who had a defect in their current heart.

The study is published in Science Advances. Additional coauthors are from Florida International University and Boston University.

Source: Andrew Thurston for Boston University

Read more:
Mini-heart chamber beats on its own just like the real thing - Futurity: Research News

Posted in Stem Cell Research | Comments Off on Mini-heart chamber beats on its own just like the real thing – Futurity: Research News

Flow Cytometry Market is Estimated Drive the Industry Growth Across World in Coming Year 2030 Queen Anne and Mangolia News – Queen Anne and Mangolia…

Posted: May 2, 2022 at 2:18 am

One of the key reasons for adoption of flow cytometry technology is its precise deliverance of results comparing to conventional methods such as ELISA. The emergence of this technology as one of the leading applications has brought various advancements in the diagnosis of diseases such as HIV and cancer as well as in research fields. With rising advancements in information technology, it finds application in drug discovery and development. Moreover, it is now used in hematopoietic stem cell research, multiparameter analysis and pharmacogenesis. Increase in research & development in life sciences has boosted flow cytometry technology market. This market has recently evidenced significant advancements such as cytometers with varying detectors and lasers, which would enable labelling of multiple antibodies and instruments capable of capturing digital images.

Flow cytometry market which is valued $3000 million in 2012, is expected to reach a value of $6530 million by 2020, experiencing a CAGR of 30.9%.

Request To Download Sample of This Strategic Report:-https://reportocean.com/industry-verticals/sample-request?report_id=26910

Market Statistics:

The file offers market sizing and forecast throughout 5 primary currencies USD, EUR GBP, JPY, and AUD. It helps corporation leaders make higher choices when foreign money change records are available with ease. In this report, the years 2020 and 2021 are regarded as historic years, 2020 as the base year, 2021 as the estimated year, and years from 2022 to 2030 are viewed as the forecast period.

The Centers for Medicare and Medicaid Services report that US healthcare expenditures grew by 4.6% to US$ 3.8 trillion in 2019, or US$ 11,582 per person, and accounted for 17.7% of GDP. Also, the federal government accounted for 29.0% of the total health expenditures, followed by households (28.4%). State and local governments accounted for 16.1% of total health care expenditures, while other private revenues accounted for 7.5%.

This study aims to define market sizes and forecast the values for different segments and countries in the coming eight years. The study aims to include qualitative and quantitative perspectives about the industry within the regions and countries covered in the report. The report also outlines the significant factors, such as driving factors and challenges, that will determine the markets future growth.

Though, increase in application has widened the scope of flow cytometry market, the cost of the instrument is impeding the growth. Moreover, advancing technologies has brought in complex instrumentation that requires highly skilled personals to operate. North America accounted for the largest share of global flow cytometry market revenue in 2012. However, Asia Pacific & RoW market is expected to have the highest growth rate of 10.6% during the analysis period and is expected to be the fastest growing market.

Get a Request Sample Report:https://reportocean.com/industry-verticals/sample-request?report_id=26910

MARKET SCOPE

Flow cytometry measures and analyzes cells of various characterizations, through a light beam that is passed through a suspension of fluid. Several properties of the cell structure and functions can be studied by labelling or non-labelling of antibodies with the help of this technique. Various factors such as protein synthesis, DNA content, RNA content, surface receptors and many more factors can be analyzed by this technology.

The scope of this report is to identify potential flow cytometry market on the basis of products, technology, application and end users

Flow cytometry as defined in this report is associated with the clinical and research fields and is used in diagnosis of certain diseases (cancer, HIV, etc.) and research (drug development and stem cell research)

The flow cytometry market in this report does not merely explain the applications of flow cytometry but also elucidates how it has replaced other conventional methods.

The report analyses the global flow cytometry market by geography, segmenting the market as North America, Europe and Asia Pacific & RoW. The emerging economies such as Asia Pacific and RoW are expected to grow due to the demand for better health care.

KEY DELIVERABLES

In the current scenario, instruments market has the highest revenue share in the total flow cytometry market. This segment is further expected to remain as the highest revenue generator during the analysis period. Increase in modularity, accessibility, imaging capabilities, availability of wavelengths and targets and size reduction are few of the significant trends in the market, assisting in adoption of these instruments by the end users. Though instruments market is at the peak in terms of revenue, reagents market is expected to experience the highest growth rate of CAGR 12%, during the analysis period. Ready to use kits is another driving factor for this market, as these reagents are easy to use and have applications in areas such as cancer diagnosis and drug discovery. These kits avoid the cost of transportation in cold storage, errors while manual pipetting of liquid reagents and the loss associated with the liquid sample degradation in high room temperature during processing, thus benefitting resource poor countries.

The flow cytometry market is segmented as follows:

PRODUCT:

FC instrumentsReagentsConsumablesSoftwareServicesAccessories

TECHNOLOGY:

Cell based TechnologiesBead-based Technologies

APPLICATION

ClinicalApoptosisCell Cycle AnalysisCell sortingCell ViabilityResearch FieldsOrgan transplantationCancerImmunodeficiency DiseaseHematology Haematological Malignancies

Request full Report-https://reportocean.com/industry-verticals/sample-request?report_id=26910

END USERS

Commercial OrganizationsHospitalsAcademic InstitutesMedical SchoolsClinical Testing LabsOthers

GEOGRAPHY

North AmericaEuropeAsia PacificRoW

Table of Content:

Key Questions Answered in the Market Report

How did the COVID-19 pandemic impact the adoption of by various pharmaceutical and life sciences companies? What is the outlook for the impact market during the forecast period 2021-2030? What are the key trends influencing the impact market? How will they influence the market in short-, mid-, and long-term duration? What is the end user perception toward? How is the patent landscape for pharmaceutical quality? Which country/cluster witnessed the highest patent filing from January 2014-June 2021? What are the key factors impacting the impact market? What will be their impact in short-, mid-, and long-term duration? What are the key opportunities areas in the impact market? What is their potential in short-, mid-, and long-term duration? What are the key strategies adopted by companies in the impact market? What are the key application areas of the impact market? Which application is expected to hold the highest growth potential during the forecast period 2021-2030? What is the preferred deployment model for the impact? What is the growth potential of various deployment models present in the market? Who are the key end users of pharmaceutical quality? What is their respective share in the impact market? Which regional market is expected to hold the highest growth potential in the impact market during the forecast period 2021-2030? Which are the key players in the impact market?

Inquire or Share Your Questions If Any Before the Purchasing This Report

https://reportocean.com/industry-verticals/sample-request?report_id=26910

About Report Ocean:We are the best market research reports provider in the industry. Report Ocean believes in providing quality reports to clients to meet the top line and bottom line goals which will boost your market share in todays competitive environment. Report Ocean is a one-stop solution for individuals, organizations, and industries that are looking for innovative market research reports.

Get in Touch with Us:Report Ocean:Email:sales@reportocean.comAddress: 500 N Michigan Ave, Suite 600, Chicago, Illinois 60611 UNITED STATESTel:+1 888 212 3539 (US TOLL FREE)Website:https://www.reportocean.com

Originally posted here:
Flow Cytometry Market is Estimated Drive the Industry Growth Across World in Coming Year 2030 Queen Anne and Mangolia News - Queen Anne and Mangolia...

Posted in Stem Cell Research | Comments Off on Flow Cytometry Market is Estimated Drive the Industry Growth Across World in Coming Year 2030 Queen Anne and Mangolia News – Queen Anne and Mangolia…

A cancer no one really talks about – The Week

Posted: May 2, 2022 at 2:16 am

John Smith is a healthy 56-year-old with no family history of cancer. Other than the occasional social drinking, he followed a healthy lifestyle, with regular exercise and a balanced diet. He never smoked.

This [prostate cancer] was not something alarming to me as I had other members in the family who had it, like my paternal uncle who has been living with prostate cancer for more than 15 years without any treatment- Salil N.S. senior law officer, South Western Railway headquarters

Symptoms- Problems with urination like difficulty starting urination, slow or interrupted urinary stream, frequent urination, especially at night, difficulty emptying the bladder, painful or burning urination, blood in the urine or semen and painful ejaculation.

Screening- The two most commonly used tests to screen for prostate cancer are PSA test and the digital rectal exam. Cancer that is detected early, when it is still confined to the prostate gland, has the best chance for successful treatment.

Prostate cancer screening should be done only after discussions with ones doctors of the uncertainties, risks and potential benefits of screening- Dr James L. Gulley chief of genitourinary malignancies branch and director of medical oncology service, National Cancer Institute, US

Surgery- Novel surgical technologies such as laparoscopic and robotic surgeries to remove the prostate gland can potentially offer faster recovery and less complications.

Lately, he started getting up at night to urinate. He did not make much of it. But when he started noticing blood in the urine, he consulted a urologist. Following the prostate examination, which showed a hard nodule, the urologist ordered a blood prostate specific antigen test (PSA) test. The blood test revealed that his PSA level was very high. After an ultrasound, the urologist recommended a prostate biopsy.

A week later, Smith and his wife were sitting in the urologists office listening to alien terms like Gleason score, radical prostatectomy, radiation and hormonal blockade. The only word Smith heard and registered was prostate cancer.

Prostate cancer is a disease in which malignant cells develop in the prostate gland. The prostate is a small walnut-shaped gland that is a part of the male reproductive system. It produces some of the fluid that is a part of the semen that transports sperm during ejaculation. It is located just below the bladder and in front of the rectum. Testosterone, the male hormone, acts like a food for prostate cancer, explains Dr Jatin Bhatia, consultant-radiation oncology, Jupiter Hospital, Pune. Testosterone gets converted into various chemical forms, and the form that acts as a feeder for prostate cancer increases. Meanwhile, the other forms decrease.

Prostate cancer is the second most common cancer in men worldwide and the fourth most common cancer overall, after breast, lung and colorectal cancers. According to the World Health Organization, there were about 1.41 million newly diagnosed cases of prostate cancer in 2020.

Prostate cancer is less prevalent in Asia. It is more common in North America, northwestern Europe, Australia and on the Caribbean islands. While more intensive prostate cancer screening in many of the developed countries could probably be the reason, lifestyle factors such as diet and exercise could also play a role. For instance, while Asian Americans have a lower risk of prostate cancer compared to white Americans, their risk is greater compared to men of similar ethnic backgrounds living in Asia.

In India, one in every 10,000 men is diagnosed with prostate cancer, says Dr Ramakrishna Vangara, consultant-radiation oncologist, Manipal Hospitals, Vijayawada. According to data from national cancer registries, prostate is the second leading site of cancer among men in cities like Delhi, Kolkata and Pune and the third leading site of cancer in cities like Bengaluru and Mumbai. With the increase in life expectancy, the incidence of prostate cancer has gone up phenomenally, says Dr P.P. Singh, senior consultant and head of department of urology, PSRI Hospital, New Delhi.

Despite the increase in numbers, prostate cancer remains one of the least talked about cancers, at least in India. Hence, there remains a great deal of misinformation about the disease and sometimes the symptoms are attributed to something else, says Dr Ramesh Kinha, vice president and head of lab operations at Medall Healthcare in Chennai.

The exact aetiology of prostate cancer is unclear. Prostate cancer is caused when the DNA of a normal prostate cell starts to change. These gene changes can cause the cells to grow out of control and form tumours. Certain well-established risk factors for prostate cancer include advancing age, family history and certain genetic mutations.

As we know, any cancer is from chronic inflammation. Inflammation could be caused by prostatitis. It could be even related to viral infections, says Dr B.S. Ajaikumar, chairman and CEO, HCG Group of Hospitals, Bengaluru. Over a period of time, these can cause prostate cancer. It can also be ethnic-based. It is also an ageing process.

All men are at risk for prostate cancer, and the risk increases with age. About one in eight men will be diagnosed with prostate cancer during their lifetime in the US. Prostate cancer is rare in men younger than 40. About 60 per cent of cases are diagnosed in men 65 or older. The average age of men at the time of diagnosis is 66.

Prostate cancer can run in families. Having a first-degree relative (father, brother) with prostate cancer more than doubles a mans risk of developing this cancer. The risk is also higher if several family members have had a diagnosis. That is one reason why Salil N.S., 52, a senior law officer at South Western Railway headquarters in Hubli, was not shocked when he was diagnosed. This was not something alarming to me as I had other members in the family who had it, like my paternal uncle who has been living with prostate cancer for more than 15 years without any treatment, he says. The only difference was that he was diagnosed after the age of 65, whereas my diagnosis was before I turned 51.

Several inherited gene mutations can also raise prostate cancer risk. Inherited mutations of the BRCA1 or BRCA2 genes, which are linked to an increased risk of breast and ovarian cancers, can also increase prostate cancer risk in men. Salil had a genetic profiling done, which indicated some mutations that could be the cause for his disease. Men with Lynch syndrome also have an increased risk for prostate cancer. Other contributing factors may include obesity, diet, hormones, smoking and alcohol consumption.

In general, prostate cancer grows very slowly and often does not cause any symptoms in its early stages. Symptoms of prostate cancer include problems with urination like difficulty starting urination, slow or interrupted urinary stream, frequent urination, especially at night, difficulty emptying the bladder, painful or burning urination, blood in the urine or semen and painful ejaculation. Symptoms of a more advanced prostate cancer that has spread outside of the prostate gland may include pain in the hips, back, pelvis, chest or other areas if the cancer has spread to bones, swelling or weakness or numbness in the legs or feet, weight loss, fatigue and loss of bladder or bowel control.

Prostate cancer often does not have any warning signs or symptoms. That is why screening and early detection are important. Cancer that is detected early, when it is still confined to the prostate gland, has the best chance for successful treatment.

The two most commonly used tests to screen for prostate cancer are PSA test and the digital rectal exam (DRE). Prostate-specific antigen test is a blood test that measures PSA levels in a persons blood. The possibility for a cancer diagnosis increases as the PSA level goes up. Prostate cancer is commonly detected by elevated levels of prostate-specific antigen (PSA >4 ng/mL), says Dr Kirti Chadha, chief scientific officer and consultant onco-pathologist at Metropolis Healthcare, Mumbai. Men with a PSA level between 4 and 10 have about a 25 per cent chance of having prostate cancer. The chances of having prostate cancer are over 50 per cent if the PSA level is more than 10. But PSA levels alone cannot determine a cancer diagnosis. The PSA level could also be elevated due to other conditions that affect the prostate.

While screening can identify cancer early, the benefits may not always outweigh the risks. Both the PSA and DRE tests can yield false negative (a person may actually have cancer) and false positive test results (a person may not actually have cancer) and can often lead to unnecessary tests, like a biopsy of the prostate, as well as cause anxiety and confusion.

Screening can also lead to over-diagnosis and treatment. Since prostate cancer grows very slowly, some men with prostate cancer would never have had symptoms from their cancer nor would they die from it. Treatment of cancer that would never have caused a problem can lead to unnecessary complications from treatment like surgery and radiation, such as urinary incontinence, bowel problems and erectile dysfunction that can ruin a persons quality of life, with no added benefit.

The US National Cancer Institute does not have screening recommendations for prostate cancer. Prostate cancer screening should be done only after discussions with ones doctors of the uncertainties, risks and potential benefits of screening, says Dr James L. Gulley, chief of genitourinary malignancies branch and director of medical oncology service, National Cancer Institute, US.

If the PSA and DRE tests are abnormal, a prostate biopsy is often recommended. Prostate cancer is assigned a grade if the biopsy results show cancerous cells. The higher the grade the greater risk that the cancer is more likely to be aggressive and spread quickly.

A Gleason score is the most common scale used to determine the grade of prostate cancer cells. The score ranges from 2 to 10. A Gleason score of 6 or less indicates a low-grade prostate cancer; a score of 7 indicates an intermediate-grade cancer; and scores from 8 to 10 indicate high-grade cancer.

Once prostate cancer is diagnosed, other tests such as bone scan, ultrasound, CT scan, MRI or PET scans are done to determine if the cancer cells have spread to other parts of the body. This will help determine the stage of the cancer. Stage I means the cancer is confined to the prostate, while stage IV indicates the cancer may have spread to other areas of the body.

Treatment options depend on several factors, including the patients age, Gleason score, stage of the cancer, how aggressive the cancer is, whether it is confined to the prostate or has spread to other parts of the body, overall health of the person, as well as the potential benefits vs side effects of the treatment.

We experience an unprecedented era of rapid new developments in the field of prostate cancer therapeutics, including radiopharmaceuticals/'theranostics' (using one radioactive drug to diagnose and another to deliver therapy), targeted therapies for selected patients (eg, PARP inhibitors) and novel immunotherapy strategies, says Dr Petros Grivas, professor and clinical director, genitourinary cancers program, Fred Hutchinson Cancer Research Center, Seattle. The advent of novel imaging, for eg Prostate Specific Membrane Antigen (PSMA) Imaging or fluciclovine/axumin PET, represents another great opportunity for more accurate prostate cancer staging. However, the clinical utility, impact and practical implications on decision making need to be better defined in clinical trials.

Early stage, low-grade prostate cancer, especially in older men, may need minimal or even no treatment. Doctors may recommend active surveillance or watchful waiting. Active surveillance involves closely monitoring the prostate cancer by performing PSA tests and prostate biopsies regularly and opting for treatment if the cancer grows or causes symptoms. In watchful waiting, fewer tests are done. The patient is treated only if he has any symptoms. This is usually recommended for older patients with low-grade tumour.

But prostate cancer in younger patients and cancer that is aggressive need multidisciplinary treatments. A radical prostatectomy involves removing the prostate gland as well as some surrounding tissue and a few lymph nodes, an option for cancer that is confined to the prostate. Jitendra Yadav, 58, from Mumbai did a PSA test as part of his executive health check-up. Thanks to that, his cancer was detected early. Also, the cancer was localised to prostate with no spread elsewhere in the body, recalls Dr Shrikanth Atluri, uro-oncologist and robotic surgeon, Sir H.N. Reliance Foundation Hospital, Mumbai. He was treated with robotic radical prostatectomy where the entire prostate was removed by surgery. Yadav has been disease free for seven years.

Novel surgical technologies such as laparoscopic and robotic surgeries to remove the prostate gland can potentially offer faster recovery and less complications. According to Dr Ashwin Tamhankar, consultant, uro-oncology and robotic surgery, Apollo Hospitals Navi Mumbai, surgeons prefer robotic surgery because it gives the advantage of better precision, control, 3D vision, negligible blood loss, quick recovery and early discharge.

Another treatment option is radiation therapy, which uses high energy rays to kill the cancer. There are various types of radiation therapy approaches like external beam radiation therapy, wherein a patient lies on a table, and a machine moves around the body, directing radiation at the cancer cells; brachytherapy (internal radiation therapy) involving small radioactive seeds or pellets that are surgically placed into or next to the tumour to destroy the cancer cells; and proton beam radiation therapya type of high-energy, external radiation therapy that uses streams of protons to kill tumour cells. There have been rapid advances in radiation therapy, like the CyberKnife device, which results in less damage to surrounding tissues when compared to conventional radiotherapy.

Apart from chemotherapy and immunotherapy, there are other therapies like cryotherapy, which uses extremely cold temperature to freeze and kill cancer cells, and hormone therapy that uses medications or surgery to reduce the levels of male hormones, called androgens, that fuel the growth of cancer cells in the body. There is also targeted drug therapy that uses drugs to target specific proteins that control the growth of the cancer cells. Bisphosphonate therapy has drugs, such as clodronate or zoledronate, that reduce bone disease when cancer has spread to the bones and reduce the risk of fractures. High-intensity focused ultrasound uses high-energy ultrasonic beams to kill cancer cells. And, photodynamic therapy uses a drug and a certain type of laser light to kill cancer cells.

Since Salils cancer had spread to the lymph nodes, he had a combination of therapies at HCG Bengaluru. His PSA levels were brought under control with hormone therapy. Initially, surgery was being planned, he says. However, the decision was left to an interdisciplinary medical board. As the disease had responded well to hormonal treatment, the medical board advised to go for radiotherapy through CyberKnife. His treatment lasted six weeks. There is no significant weakness or other problems related to this radiation therapy, says Salil. It is a painless outpatient process. I was at the hospital alone during the treatment; no bystanders were needed. The PSMA PET scan was repeated after the treatment. The results were heartening. However, Salil is still on hormonal therapy. The treatment, particularly the hormonal therapy, has adverse effects on sexual life. Apart from that, life goes on as normal, says Salil.

Novel treatments and technologies are changing the landscape of prostate cancer management. PARP inhibitors, such as Olaparib and rucaparib, are found to be highly effective in patients with genetic mutations such as BRCA1 and 2.

PSMA PET scans are one of the most exciting recent developments in prostate cancer, says Dr Rahul Tendulkar, clinical director and residency program director for the department of radiation oncology, Cleveland Clinic, US. By detecting early recurrences while they are small in size and number, we can offer patients treatment with stereotactic body radiation therapy and hopefully eradicate their visible disease.

Ramlal Sahu, 85, from Nagpur was suffering from frequent urination, difficulty in passing urine, back pain and pain in his left leg because of which he was unable to walk. He was admitted in a critical condition to HCG NCHRI Cancer Centre, Nagpur, and was diagnosed with prostate cancer. Sahu had multiple comorbidities such as diabetes and hypertension and he also suffered from cardiac-related issues, which prevented him from being a candidate for chemotherapy.

We started him on targeted therapy and tested for genetic mutations and he tested positive, says Dr Nikhil Pande, medical oncologist, HCG NCHRI Cancer Centre, Nagpur. He is now on second-line treatment with Olaparib, a form of targeted therapy and is doing well.

Chadha is thankful for scientific advances. The glands location on the neck of the urethra by the bladder means that whole-gland treatments like radical prostatectomy or radiation therapy often leave men with incontinence and erectile dysfunction, she says. However, developments in MRI are enabling more targeted treatments to the prostate without damaging surrounding structures.

Researchers are now testing the use of artificial intelligence to recognise suspicious areas in a prostate MRI that should be biopsied, says Chadha. AI tools also help pathologists who arent prostate cancer experts to accurately assess prostate cancer grade, she says.

Can prostate cancer be prevented? There is no absolute way to prevent prostate cancer. Risk factors such as age, genetics and family history cannot be modified. While several drugs and supplements are being studied, there isnt enough evidence to make conclusive recommendations on prostate cancer prevention.

Maintaining a healthy weight, staying physically active, eating a balanced diet and avoiding smoking are all factors that could improve your overall health and lower your risk of prostate cancer.

Some studies have suggested that high consumption of dairy products may increase the risk of prostate cancer. Limiting dairy products and calcium intake could be beneficial.

A couple of studies have suggested that men with a higher frequency of ejaculation may have a lower risk.

Since prostate cancer tends to grow slowly, most men diagnosed with prostate cancer will live a long, normal life and do not die from it. The 10-year survival rate is about 98 per cent. Many of the elderly men detected with prostate cancer die with prostate cancer rather than because of it, says Bhatia.

There are hundreds of clinical trials in different phases related to prostate cancer treatment that are in progress around the world. These trials will help the medical community better understand how to diagnose, treat and prevent prostate cancer and improve patient outcomes.

While significant strides have been made in treating localised and advanced prostate cancer, understanding the disparities in prostate cancer outcomes by age, stage, race and ethnicity is crucial to decreasing global incidence of prostate cancer, especially in developing countries says Dr Shilpa Gupta, director of genitourinary oncology program, Cleveland Clinic.

Some names have been changed.

More:
A cancer no one really talks about - The Week

Posted in HCG Diet | Comments Off on A cancer no one really talks about – The Week

Are we treating long COVID wrong? Immune-boosting treatment takes new approach – Medical News Today

Posted: May 2, 2022 at 2:15 am

A monoclonal antibody treatment called leronlimab could reduce long COVID symptoms in some patients, according to a recent pilot study published in the journal Clinical Infectious Disease.

The studys results suggest that leronlimab can alleviate long COVID symptoms by boosting the immune system in individuals who previously had a suppressed immune system.

Scientists have considered persistent inflammation as one of the causes underlying long COVID. In contrast, the studys findings suggest that the downregulation of the immune system could be responsible for long COVID in some individuals.

A majority of individuals with COVID-19 recover fully within the initial 3-4 weeks after contracting the illness. However, around 10-30% of individuals experience lingering symptoms weeks and months after the acute phase of the illness. These symptoms have been collectively described as long COVID or post-acute COVID-19 syndrome.

Since the symptoms of long COVID vary from person to person, the mechanisms underlying long COVID are not well understood. This has also hindered the development of treatments targeting the factors responsible for causing long COVID.

Severe illness during the acute phase of a SARS-CoV-2 infection is characterized by excessive inflammation and a dysregulated immune response. Scientists have hypothesized that these atypical immune responses during the acute infection phase could lead to persistent inflammation. This chronic inflammation could be potentially responsible for long COVID symptoms.

Indeed, studies have reported that individuals with long COVID show elevated levels of inflammatory cytokines, which are a class of proteins involved in mediating the bodys immune response.

Thus, scientists have been turning to treatments that normalize the immune system to help alleviate symptoms of long COVID. One such candidate is the monoclonal antibody leronlimab which blocks the cytokine receptor CCR5.

The CCR5 receptor is expressed by immune cells and is involved in mediating an immune response against an infection. Previous studies have shown that leronlimab can reduce the levels of inflammatory cytokines in individuals hospitalized with severe COVID-19.

Hence, the studys authors decided to assess the ability of leronlimab in reducing long COVID symptoms.

The present study involved 55 individuals with long COVID who received a weekly injection of either leronlimab or saline placebo over an 8-week period.

To evaluate the effectiveness of leronlimab, the researchers tracked changes in 24 symptoms commonly associated with long COVID over the duration of the study.

They found that a higher percentage of individuals in the leronlimab-treated group showed improvements in several long COVID symptoms than in the placebo group.

However, not all individuals receiving leronlimab showed an improvement in their symptoms.

The researchers then examined the impact of leronlimab on CCR5 expression in long COVID.

Individuals treated with leronlimab showed an increase in the percentage of immune cells expressing CCR5 after 8 weeks. The control group did not show an increase in their CCR5 expression.

In addition, the researchers found differences in CCR5 expression among individuals within the leronlimab-treated group. Individuals who responded to leronlimab showed lower levels of CCR5 expression at the beginning of the study than those who did not respond to the treatment.

Significantly, only individuals in the leronlimab-treated group who responded to the treatment showed an increase in CCR5 expression during the 8-week period. Such an increase in CCR5 expression was absent in non-responders.

The studys co-author, Dr. Otto Yang, a professor of medicine at the University of California in Los Angeles, explains:

Patients who improved were those who started with low CCR5 on their T cells, suggesting their immune system was less active than normal, and levels of CCR5 actually increased in people who improved.

Dr. Yang indicates that this could change approaches to long COVID treatments.

This leads to the new hypothesis that long COVID in some persons is related to the immune system being suppressed and not hyperactive and that while blocking its activity, the antibody can stabilize CCR5 expression on the cell surface leading to upregulation of other immune receptors or functions, he says.

The researchers also found that treatment with leronlimab increased the number of specific immune cell populations, such as T cells. This further suggests that blocking CCR5 with leronlimab boosted the immune system in some individuals with long COVID.

Dr. Rajeev Mehlotra, a research associate at Case Western Reserve University, who was not involved in the study, told Medical News Today that the findings add another perspective to efforts to understand long COVID.

As the studies targeting CCR5 for COVID-19 treatment are performed, and such treatments start becoming increasingly available, this study adds another view to the mechanism associated with leronlimab treatment, Dr. Mehlotra said.

Considering this unexpected mechanism together with existing knowledge may lead to a more comprehensive understanding of the pathogenesis and treatment outcomes in COVID-19 patients, he added.

Previous studies have shown that individuals who are genetically predisposed to express lower levels of CCR5 are at an increased risk of severe COVID-19. Similar genetic differences that influence CCR5 expression could influence whether individuals with long COVID respond to leronlimab treatment.

Dr. Saurabh Mehandru, a professor of gastroenterology at the Icahn School of Medicine at Mount Sinai, told MNT that the studys findings could help reveal some of the yet-unknown mechanisms behind long COVID.

It is encouraging to note that there are interesting cellular and receptor expression differences between treatment responders and non-responders. This could suggest an underlying biological mechanism that could be further explored in pre-clinical or clinical studies on patients with long COVID, he said.

Original post:
Are we treating long COVID wrong? Immune-boosting treatment takes new approach - Medical News Today

Posted in Cell Medicine | Comments Off on Are we treating long COVID wrong? Immune-boosting treatment takes new approach – Medical News Today

Kelonia Therapeutics Launches with $50 Million Series A Financing to Pioneer Precision Targeted Genetic Medicines – Yahoo Finance

Posted: May 2, 2022 at 2:15 am

In Vivo Gene Delivery Platform Will Dramatically Expand the Benefit and Reach of Genetic Medicines

Founded and Led by Leading Experts in Immunology, Oncology, and Cell and Gene Therapy

Strategic Collaborations with Leading Industry Partners Enable and Accelerate Platform Capabilities

BOSTON, April 28, 2022--(BUSINESS WIRE)--Kelonia Therapeutics, a biotech company revolutionizing in vivo gene delivery, launched today with a $50 million Series A financing to usher in a new era of genetic medicines for a wide range of diseases. Kelonias platform overcomes the central challenge that has prevented the full realization of gene therapy for patients. Despite life-changing responses, existing gene therapies are highly complex, costly, and limited by complicated treatment paradigms, tractable therapeutic applications, and dose-limiting toxicities. By enabling precisely targeted, highly efficient, manufacturable "off-the-shelf" in vivo gene delivery, Kelonias technology has the potential to dramatically expand the impact and reach of genetic medicines to every patient in need.

Kelonia is backed by a strong syndicate of investors with a track record of successfully launching and building disruptive biotech companies. Alta Partners, Horizons Ventures, Venrock and other investors participated in the Series A round. The company will use the funding to redefine whats possible for genetic medicines starting with an "off-the-shelf" chimeric antigen receptor (CAR) to treat hematologic cancer that may enable the unrivalled clinical benefit of CAR T without the typical toxicities and with the ease of access of conventional medicines. Additionally, the company will advance other programs for oncology and non-oncology indications, and further expand its gene delivery platform and capabilities.

"The cell and gene therapy field has been searching for solutions to durable in vivo genetic modifications regardless of whether applying gene editing, RNA expression or viral-mediated gene integration," said Kevin Friedman, Ph.D., President and Chief Scientific Officer of Kelonia. "At Kelonia, we believe we have found an in vivo gene delivery solution that is safe, effective, and manufacturable for broad therapeutic application. With our Series A funding and key strategic collaborations, we will advance our lead product candidate toward clinical studies and further optimize our technology to explore treating diseases never thought possible with genetic medicines."

Story continues

Based on discoveries made in the lab of Massachusetts Institute of Technologys Michael Birnbaum, Ph.D., and leveraging pioneering research from leading scientists at the French National Centre for Scientific Research (CNRS), Kelonias in vivo gene delivery technology enables a few potent lentiviral vector-like particles armed with an adjustable targeting system to precisely, efficiently, and safely deliver payloads exactly where needed to treat a broad range of diseases. The companys early applications combine oncology-targeted therapeutics, such as CAR and T cell receptor molecules, with Kelonias precision in vivo targeting technology. When used in concert, this combination enables potent and precise tumor targeting with limited "off-tumor" toxicity, which would otherwise be a concern. Administered directly in vivo as an "off-the-shelf" medicine, Kelonias transformational therapies in development for solid and hematologic tumors have the potential to democratize patient access to genetic medicines. Beyond oncology, the company will advance its technology to unlock delivery to previously hard-to-reach tissues, such as neurological, muscular or renal, to deliver different types of genetic cargo with the goal of radically transforming the treatment of diseases in these areas.

"It turns out, a relatively simple and elegant idea to de-target and redirect lentivirus-like particles based on recently published research from my lab can potentially provide a solution to in vivo gene delivery," said Dr. Birnbaum, Ph.D., Co-Founder of Kelonia. "Im incredibly excited about the potential of Kelonias platform and team to vastly expand the utility of gene therapies to treat oncology, autoimmune disease, rare monogenic or other diseases currently intractable to gene therapies."

"Kelonia is combining the two crucial elements required to develop truly novel medicines: breakthrough biology and an exceptional team," said Bryan Roberts, Partner at Venrock. "Michael Birnbaums industrially robust platform affords a targeting specificity log orders better than anything else out there and the team has a stellar track record for translating groundbreaking scientific gene therapy discoveries into viable products that are transformative for patients."

Strategic Collaborations

In addition to the completion of its Series A, Kelonia has established strategic collaborations with Adimab and ElevateBio. With both collaborations already successfully underway, each of these outstanding partners brings differentiating capabilities that enable and accelerate the companys vision to bring breakthrough genetic medicines to patients.

Adimab is the leading provider of therapeutic antibody discovery and engineering technologies. Kelonia will leverage Adimabs expertise and proprietary technologies, across a range of applications, to access tissue-specific antibodies that enable unlocking precise in vivo gene delivery to different tissues as well as antibodies that can be leveraged within the therapeutic genetic cargo.

ElevateBio is a technology-driven company focused on powering transformative cell and gene therapies with multiple next-generation technology platforms and a fully integrated R&D and manufacturing facility. Through an expanding partnership, Kelonia will utilize ElevateBios lentiviral vector platform, process and analytical development expertise, and cGMP manufacturing capabilities to develop and advance novel manufacturing processes for Kelonia and manufacture of Kelonias products.

Leadership and Founding Team

Kelonia brings together industry leaders in cell and gene therapy responsible for the discovery and development of multiple clinical and commercial products including ABECMA, the first FDA-approved anti-BCMA CAR T cell therapy product for relapsed or refractory multiple myeloma. The companys leadership team includes Kevin Friedman, Ph.D., President and Chief Scientific Officer, Thomas Galbo, Ph.D., Chief Business Officer, and Molly Perkins, Ph.D., Vice President of Research.

Kelonias scientific founders include Michael Birnbaum, Ph.D., Associate Professor of Biological Engineering, Massachusetts Institute of Technology, and Michael Fischbach, Ph.D., Associate Professor of Bioengineering and of Medicine, Stanford University, both world-leading experts in the fields of microbiology, immunology, oncology, and cell and gene engineering.

The companys board of directors comprises Michael Birnbaum, Michael Fischbach, Kevin Friedman, Bryan Roberts and Bob More, Managing Director at Alta.

About Kelonia TherapeuticsKelonia is pioneering a new wave of genetic medicines using its next generation gene delivery platform. The companys simple and elegant cutting-edge in vivo gene delivery technology uses a few potent lentiviral vector-like particles to precisely and efficiently deliver in vivo genetic cargo to the desired target tissue, and only that tissue, every time. With an initial focus on developing transformational therapies for solid tumors and hematologic cancers, Kelonia is building a pipeline of genetic medicines for a wide range of diseases, with the bold goal of bringing genetic medicines to every patient in need. Learn more about Kelonia at http://www.keloniatx.com and follow us on LinkedIn and Twitter.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220428005083/en/

Contacts

Michele RozenScient PRmrozen@scientpr.com

The rest is here:
Kelonia Therapeutics Launches with $50 Million Series A Financing to Pioneer Precision Targeted Genetic Medicines - Yahoo Finance

Posted in Cell Medicine | Comments Off on Kelonia Therapeutics Launches with $50 Million Series A Financing to Pioneer Precision Targeted Genetic Medicines – Yahoo Finance

Tufts Researchers Discover New Function Performed by Nearly Half of Brain Cells – Tufts Now

Posted: May 2, 2022 at 2:15 am

To make the discovery, the team used brand new technology to devise a technique that enables them to see and study the electrical properties of brain cell interactions, which could not be observed previously.

With these new tools, we've essentially uncovered completely novel aspects of the biology," says Armbruster, research assistant professor of neuroscience at the School of Medicine. As better tools come alongfor example, new fluorescent sensors are being developed constantlywe'll get a better understanding of things we didn't even think about before.

The new technology images electrical activity with light, Dulla explains. Neurons are very electrically active, and the new technology allows us to see that astrocytes are electrically active, as well.

Dulla describes astrocytes as making sure everything is copacetic in the brain, and if something goes wrong, if theres an injury or viral infection, they detect it, try to respond, and then try to protect the brain from insult. What we want to do next is determine how astrocytes change when these insults happen.

Neuron-to-neuron communication occurs through the release of packets of chemicals called neurotransmitters. Scientists knew that astrocytes control neurotransmitters, helping to make sure that neurons stay healthy and active. But the new study reveals that neurons also release potassium ions, which change the electrical activity of the astrocyte and how it controls the neurotransmitters.

So the neuron is controlling what the astrocyte is doing, and they are communicating back and forth. Neurons and astrocytes talk with each other in a way that has not been known about before, he says.

The discovery of astrocyte-neuron crosstalk raises numerous questions as to how the interactions work in brain pathology and in the development of learning and memory. It makes us rethink everything astrocytes do, and how the fact that astrocytes are electrically active may be influencing a wide range of neurological diseases, he says.

For example, in Alzheimers disease, astrocytes dont control neurotransmitters, even though that is their fundamental job, Dulla explains. Similar problems occur with traumatic brain injury and epilepsy. For years scientists have thought perhaps the problem is caused by a protein being absent, or a mutation that causes a protein not to work.

Build-up of extracellular potassium in the brain, has been hypothesized to contribute to epilepsy and migraine pathologies, says Armbruster. This new study gives us a better understanding of how astrocytes clear this buildup and help maintain a balance of excitation.

The researchers are now screening existing drugs to see if they can manipulate the neuron-astrocyte interactions. By doing so, can we one day help people learn faster or better? Can we repair a brain injury when it occurs? Dulla asks.

The new technology used to make this discovery not only opens up new ways to think about astrocyte activity, it also provides new approaches for imaging activity through the brain. Before now, there was no way to image potassium activity in the brain, for example, or study how potassium is involved in sleep, metabolism, or injury and infection in the brain.

We are giving these tools to other labs so they can use the same assays and techniques to study the questions they are interested in, he says. Scientists are getting the tools to study headache, breathing, developmental disorders, and a wide range of different neurological diseases.

View original post here:
Tufts Researchers Discover New Function Performed by Nearly Half of Brain Cells - Tufts Now

Posted in Cell Medicine | Comments Off on Tufts Researchers Discover New Function Performed by Nearly Half of Brain Cells – Tufts Now

Evolving Treatment Landscape of Acute Lymphocytic Leukemia – Targeted Oncology

Posted: May 2, 2022 at 2:15 am

Hagop M. Kantarjian, MD, discusses how the treatment landscape of acute lymphocytic leukemia compares to what it used to be.

Hagop M. Kantarjian, MD, professor, department of Leukemia, division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses how the treatment landscape of acute lymphocytic leukemia (ALL) compares to what it used to be.

The ongoing paradigm shift in the treatment of ALL can be credited to the introduction of the BCR-ABL tyrosine kinase inhibitors as well as new antibodies targeting CD19, CD20 and CD22. Agents like ponatinib (Iclusig), blinatumomab (Blincyto), inotuzumab ozogamicin (Besponsa) have also yielded positive results in regard to survival and rates of remission within this patient population.

Kantarjian hopes that by combining these agents with one another or with chemotherapy will better the cure rate of patients with Philadelphia chromosome-positive ALL and pre B-cell ALL.

Transcription:

0:08 | In acute lymphocytic leukemia, I think there's now a paradigm shift in the cytopathic approaches. This is because we started introducing targeted therapies like the BCR-ABL tyrosine kinase inhibitors in Philadelphia-positive acute lymphocytic leukemia, as well as introducing the antibodies targeting CD19 and CD22.

0:32 | In Philadelphia-positive acute lymphocytic leukemia, using the third generation TKIs like ponatinib in combination with blinatumomab, which is a CD19 bispecific T-cell engager, we found that we can induce almost all patients in remission. The estimated 2 year survival is over 90%, and we are not needing to send the patients to transplant. We have shifted from a combination of intensive chemotherapy with first and second generation TKIs and relying on allogeneic transplantation to a strategy that has no chemotherapy, no need for transplant, and a very high cure potential.

1:17 | In pre B-cell acute lymphocytic leukemia, we introduced both blinatumomab and inotuzumab into the frontline therapy with less chemotherapy. We again found that almost all patients achieved a complete remission, and at 3 to 4 years, their estimated survival is over 80%, which is the first time that we've seen such survivor rates at MD Anderson. I'm hoping that 5 years from now, there's going to be a therapeutic revolution in ALL instead of giving 3 years of intensive chemotherapy in adults and older patients. I hope for a cure rate of 40- 50% so we will be able to give the newer regimens and double the cure rate to levels which are similar to childhood ALL.

Go here to see the original:
Evolving Treatment Landscape of Acute Lymphocytic Leukemia - Targeted Oncology

Posted in Cell Medicine | Comments Off on Evolving Treatment Landscape of Acute Lymphocytic Leukemia – Targeted Oncology

New Research: Tumor Cells Can Manipulate the Body’s Natural Antibody Response to Triple Negative Breast Cancer – ChristianaCare News

Posted: May 2, 2022 at 2:15 am

April 27, 2022

In breakthrough research at ChristianaCares Helen F. Graham Cancer Center & Research Institute, scientists have discovered that a protein secreted by tumor cells can switch off the bodys natural defenses against triple negative breast cancer (TNBC).

The study, led by Jennifer Sims-Mourtada, Ph.D., lead research scientist at the Cawley Center for Translational Cancer Research (CTCR), at the Graham Cancer Center, is reported in The Journal of Translational Medicine which is available online.

What we found is that TNBC tumor cells can effectively shut down the bodys defense systems against the tumor by secreting a type of protein called IL-10, Dr. Sims-Mourtada said.

The presence of this immune system protein forces the antibodies that would normally be created to attack the tumor to become non-reactive and not do what they are supposed to do.

The study was initiated in partnership with The Wistar Institute of Philadelphia, Pennsylvania, in collaboration with the late Raj Shyam Somasundaram, Ph.D., a cell biologist at the Melanoma Research Center.

Dr. Sims-Mourtada and her team have brought us tantalizingly close to understanding what drives the aggressive nature of triple negative breast cancer, a treatment-starved disease that disproportionately affects Delaware women, said Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute.

Their work underscores our belief that scientific collaborations such as this one between our Cawley CTCR clinicians and Wistar scientists can smooth the way for new findings to become effective therapies, especially for hard-to-treat and aggressive forms of cancer like TNBC.

Understanding the mechanism behind TNBC

Delaware ranks highest in the nation for incidence of triple negative breast cancer. TNBC is an aggressive form that affects Black women at twice the rate of white women with poorer outcomes. Patients have higher rates of early recurrence than other breast cancer subtypes, particularly in the first five years after diagnosis. Currently there is no targeted therapy for TNBC.

One of our missions within the Cawley CTCR is to understand the mechanisms behind TNBC and find a treatment for it, Dr. Sims-Mourtada said. Our study sheds new light on what is prompting the bodys immune response to the cancer cells and offers clues to potential new therapeutic targets.

Normally it is the job of the B cells to regulate the immune response against foreign invaders like cancer. Among other jobs, they control inflammation at the site of an attack by releasing proteins, including IL-10, to signal the defender cells to stand down.

Previously it was thought that the immune cells were the ones to express IL-10 to regulate themselves, Dr. Sims-Mourtada said. But our study shows that the tumor cells also release this protein, which means they are driving how the immune system behaves.

Within the tumor microenvironment, IgG4 is one of four antibody subclasses expressed and secreted by B cells. Whereas another type of antibody would urge the immune system to press on with the attack, activation of IgG4 signals the job is done.

TNBC and activation of IgG4

Our findings support that TNBC may create a tumor environment that supports activation of IgG4, and messaging from IL10 is triggering the switch, Dr. Sims-Mourtada said.

As previously reported with other cancers, such as melanoma, this study confirms that the presence of IgG4-positive B cells within the tumor associates with advanced disease increased recurrence and poor overall breast cancer survival. It is also possible that IL-10 expression by tumor cells may also be a cause of poor outcomes in TNBC, and this may be independent of IgG4+ B cells.

At this point, we dont know what causes tumor cells to start secreting IL-10, but we know that B cell-tumor cell interactions are involved, Dr. Sims-Mourtada said.

We still have to look at what is really going on in the B cell population to determine which subtypes of B cells are affected by this tumor crosstalk and why some forms of TNBC express IL-10 (the ones with poor outcomes) and others do not.

We think that the presence or absence of other immune cells in the microenvironment may affect how B cells interact with tumor cells to drive IL-10 expression, she said.

Resources for the study, including blood and tissue samples from consenting patients, were obtained through the Graham Cancer Centers Tissue Procurement program. Interestingly, in a small subset of samples, the researchers found that IL-10 expression was significantly higher in Black patients than non-Hispanic white patients. These findings need to be confirmed in a larger more diverse population with different TNBC subtypes.

Understanding tumor-infiltrating B cells

Our growing understanding of the contribution of IgG4+ cells to the immune microenvironment of TNBC and what drives IL-10 expression may reveal ways in which tumor-infiltrating B cells can contribute to tumor growth and provide new targets to increase the immune response to TNBC, Dr. Sims-Mourtada said.

As partners for more than a decade, Graham Cancer Center research clinicians and Wistar scientists collaborate across disciplines to translate cancer research into more effective therapies for patients everywhere. In addition to providing high-quality, viable tissue samples for Wistar research studies, Graham Cancer Center clinicians actively participate in concept development, sharing their unique understanding of the everyday patient experience.

Original post:
New Research: Tumor Cells Can Manipulate the Body's Natural Antibody Response to Triple Negative Breast Cancer - ChristianaCare News

Posted in Cell Medicine | Comments Off on New Research: Tumor Cells Can Manipulate the Body’s Natural Antibody Response to Triple Negative Breast Cancer – ChristianaCare News

WVU researcher develops data-driven approach to help reduce drug costs and treat diseases – West Virginia University

Posted: May 2, 2022 at 2:15 am

MORGANTOWN, W.Va. -- A new data-driven mechanistic approach that predicts cell types within tissue will help to reduce drug costs and treat diseases that were difficult to develop drugs for, according to a West Virginia University scientist.

David Klinke, professor in the Department of Chemical and Biomedical Engineering, developed and tested a mechanistic approach to predict the number and function of different cell types within a particular tissue and how they change when a malignant (cancerous) cell acquires the ability to secrete a protein.

Ultimately, we want to develop drugs that broaden the clinical benefit of immunotherapies, said Klinke, whos also an adjunct assistant professor in the WVU School of Medicine and member of the Cancer Institute.

Mechanistic models have been created by hand by experts, but there are gaps in researchers understanding of biology because 90% of research publications focus on only 20% of genes in humans.

Research from this study, published in Nature Communications, sifts through large datasets to predict how secretion of one gene product by a malignant cell influences other cell types within a tissue directly from the data. This provides a complement to the hand-created models that play important roles in drug development.

Under normal conditions, ones immune system defends against infectious disease, Klinke said. However, most cancers arise through an evolutionary process of mutation and selection. Every cell has the blueprint in its DNA to make every gene product. In that process of mutation and selection, re-expression of some of these gene products may provide malignant cells with the ability to suppress immune response.

Human tissues are made up of specialized cell types that are organized to maintain function in a changing environment. Ultimately, the functional orientation of cell types within a tissue interact to create a heterocellular network -- a network of many different cell types that interact to collectively achieve a goal. A heterocellular network is important to create and maintain tissue equilibrium.

While researchers know that tissue equilibrium is disrupted during oncogenesis, or the development of a tumor, there is no clear understanding of how genetic alterations influence the heterocellular network within human tissues.

Klinke said one of the barriers for broadening clinical benefit is that malignant cells create environments that suppress host immunity.

This new data-driven approach allows researchers to predict how a gene product secreted by a malignant cell changes the prevalence and functional orientation of other cell types within a human tissue.

Klinke said that studying how one event causes another is challenging to do in systems where it's difficult for researchers to see what is happening like within an intact human tissue.

To test their predictions, using digital cytometry and Bayesian network inference, Klinke and his team examined immunocompetent mouse models of cancer. With this approach, Klinke was able to predict how a protein secreted by malignant cells alters the heterocellular network in the context of melanoma and breast cancer.

Digital cytometry, which is the measurement of the number and characteristics of cells, and Bayesian network (a probabilistic graphical model) inference were used because there are datasets available with these models that contain sequenced homogenized (similar) tumor tissue.

We can change the expression of a gene and then see whether the prevalence and functional orientation of different cell types in the tumor changes similarly as predicted by the Bayesian network model.

Klinke said the conventional approach to predict the functional orientation of cell types is to change the expression of a secreted protein and then quantify different cell types using different experimental approaches.

For this study, Klinke used mechanistic modeling to represent the mechanisms that support the biology and predict scenarios using simulation instead of actually testing the scenario in humans.

These models are highly complicated but let me use a simple analogy, Klinke said. Say that we want to hit a target using an artillery shell and we have only one shot. Given our understanding of the laws of physics, we know that we need to know a few things about the projectile and all the forces acting on the projectile. Given this information, we can simulate with a computer that if we fire the projectile in a certain direction or angle, it will land in a certain location.

Similarly, we know a lot about the underlying biology associated with a drug, but there are also some things that we dont know, and we cant test everything in humans. Given common conversations in the media about the high price of drugs, testing new drugs in humans is expensive and the vast majority of new drugs tested dont work.

Klinke said that one of the ways that mechanistic modeling and simulation can help is by providing a way to bring all the different pieces of understanding together in the same context.

If there are key aspects missing, we run simulations to see if targeting some aspect of the biology with a drug makes sense. Mechanistic modeling and simulation have had an impact on a number of other industries, and this is now being applied to drug development.

Klinke hopes that this research can be used in other contexts like cancers or immunologic diseases.

Ultimately, we all care that when we get sick, there are treatments that can improve our health and not bankrupt us in the process. Like many other industries, the pharma industry is turning increasingly to mechanistic modeling and simulation to better prioritize potential targets and reduce the time to clinic. Collectively, this will help reduce drug costs and help treat diseases that were difficult to develop drugs for.

Citation: Data-driven learning how oncogenic gene expression locally alters heterocellular networks

See the rest here:
WVU researcher develops data-driven approach to help reduce drug costs and treat diseases - West Virginia University

Posted in Cell Medicine | Comments Off on WVU researcher develops data-driven approach to help reduce drug costs and treat diseases – West Virginia University

Page 472«..1020..471472473474..480490..»