Stem Cell Clinic

An Oncologist Asks When Its Time to Say Enough – The New York Times

Raza documents the failure of chemotherapy to help the great majority of patients with metastatic disease, and the immense cost and suffering involved. She castigates pharmaceutical companies (as have many others) for concentrating on drugs that often fail and at best achieve, on average, a few extra months of life. She quotes research that in the United States, over 14 years, 42.4 percent of the 9.5 million cancer cases had lost all of their life savings within two-plus years.

Raza also accuses research scientists and her fellow oncologists of unshakable hubris, convinced as we are that we possess the power to untangle the intricacies of as complex a disease as cancer. She dismisses much current research with the comment that it is pure arrogance to think the problem can be solved by a few molecular biologists; research, she says, should be based on studying humans, not mice. She goes on to say: Our lives are at stake. Our future is at stake.

Cancer is overwhelmingly a disease of old age, even though ads for cancer charities invariably show pictures of children and young women. It is worth noting that most of the patients whose stories Raza recounts are relatively young as well. She writes, An effective treatment for cancer can only be developed essentially after we understand how life works, how we age, since aging and cancer are two sides of the same coin. Fine words, but the reader can be forgiven for feeling that they smack of the same hubris afflicting those molecular biologists, toiling away in the lab with their mouse models.

So what is the answer? Raza suggests the first cancer cell that gives rise to a tumor is like a grain of sand that precipitates the collapse of a sand pile. Research, she says, should concentrate on finding these early changes, before an actual tumor develops. There is research going on along these lines, but Raza argues that its funding is insufficient compared with the resources being poured into new drug development.

A quantum leap is required, and this will involve genomics, transcriptomics, proteomics, metabolomics; indeed, panomics. It will also involve smart bras and special toilets real-life technologies in various stages of development, she assures us. I am in no position to know whether these technologies represent a paradigm shift in the treatment of cancer, or whether they are akin to the magical thinking that geoengineering will save us from the unfolding apocalypse of climate change, or to the gullibility that gave rise to the Theranos scandal.

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An Oncologist Asks When Its Time to Say Enough - The New York Times

CRISPR Therapeutics and KSQ Therapeutics Announce License Agreement to Advance Companies’ Respective Cell Therapy Programs in Oncology – SynBioBeta

CRISPR Therapeutics to receive non-exclusive access to certain KSQ IP for its allogeneic CAR-T programs

KSQ Therapeutics to receive non-exclusive access to certain CRISPR IP for its autologous cell therapies, including its existing eTILTM cell franchise

ZUG, Switzerland & CAMBRIDGE, Mass.(BUSINESS WIRE)CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, and KSQ Therapeutics, a biotechnology company using CRISPR technology to enable the companys powerful drug discovery engine to achieve higher probabilities of success in drug development, today announced a license agreement whereby CRISPR Therapeutics will gain access to KSQ intellectual property (IP) for editing certain novel gene targets in its allogeneic oncology cell therapy programs, and KSQ will gain access to CRISPR Therapeutics IP for editing novel gene targets identified by KSQ as part of its current and future eTILTM (engineered tumor infiltrating lymphocyte) cell programs. The financial terms of the agreement are not being disclosed.

We are thrilled to gain access to CRISPR Therapeutics foundational IP estate through this agreement, said David Meeker, M.D., Chief Executive Officer at KSQ Therapeutics. Our eTILTM programs involve editing gene targets in human TILs that were discovered at KSQ by applying our proprietary CRISPRomics approach to immune cells in multiple in vivo models. This agreement clears an important path for us to be able to bring these programs through development and commercialization, leveraging CRISPR Therapeutics proprietary editing technology.

The gene targets within the scope of the license agreement were identified using KSQs proprietary CRISPRomics drug discovery engine, which allows genome-scale, in vivo validated, unbiased drug discovery. These specific targets were uncovered in screens to identify genetic edits that could enhance the functionality and quality of adoptive cell therapies in oncology.

KSQ has built an industry-leading platform to screen for novel gene targets using its technology, and has identified a group of targets that could help unlock the full potential of adoptive cell therapy in oncology, said Samarth Kulkarni, Ph.D., Chief Executive Officer at CRISPR Therapeutics. As a result of this license agreement, CRISPR Therapeutics will have the opportunity to bring these novel targets into our leading allogeneic CAR-T development platform to further strengthen our future programs in this important therapeutic area.

About KSQ Therapeutics

KSQ Therapeutics is using CRISPR technology to enable the companys powerful drug discovery engine to achieve higher probabilities of success in drug development. The company is advancing a pipeline of tumor- and immune-focused drug candidates for the treatment of cancer, across multiple drug modalities including targeted therapies, adoptive cell therapies and immuno-therapies. KSQs proprietary CRISPRomics drug discovery engine enables genome-scale, in vivo validated, unbiased drug discovery across broad therapeutic areas. KSQ was founded by thought leaders in the field of functional genomics and pioneers of CRISPR screening technologies, and the company is located in Cambridge, Massachusetts. For more information, please visit the companys website at http://www.ksqtx.com.

About CRISPR Therapeutics

CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with leading companies including Bayer AG, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR Therapeutics Forward-Looking Statement

This press release may contain a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding CRISPR Therapeutics expectations about any or all of the following: (i) the intellectual property coverage and positions of CRISPR Therapeutics, its licensors and third parties and (ii) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. Without limiting the foregoing, the words believes, anticipates, plans, expects and similar expressions are intended to identify forward-looking statements. You are cautioned that forward-looking statements are inherently uncertain. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: the outcomes for each CRISPR Therapeutics planned clinical trials and studies may not be favorable; that one or more of CRISPR Therapeutics internal or external product candidate programs will not proceed as planned for technical, scientific or commercial reasons; that future competitive or other market factors may adversely affect the commercial potential for CRISPR Therapeutics product candidates; uncertainties inherent in the initiation and completion of preclinical studies for CRISPR Therapeutics product candidates; availability and timing of results from preclinical studies; whether results from a preclinical trial will be predictive of future results of the future trials; uncertainties about regulatory approvals to conduct trials or to market products; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology and intellectual property belonging to third parties; and those risks and uncertainties described under the heading Risk Factors in CRISPR Therapeutics most recent annual report on Form 10-K, and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SECs website at http://www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

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CRISPR Therapeutics and KSQ Therapeutics Announce License Agreement to Advance Companies' Respective Cell Therapy Programs in Oncology - SynBioBeta

Accomplishments of Dr. Steven Rosenberg in Cancer Immunotherapy Inspire Young Researchers in Japan & XIV Fujio Cup Quiz on Stem Cells Is Won by…

TOKYO Utilizing the capability of ones own immune system to tackle cancer, an out-of-the box idea was the brain child of Dr. Steven Rosenberg almost three decades ago. His initiative which paved way for a new chapter in oncology, inspired many young scientists and clinicians in the NCRM NICHE 2019 held in Tokyo, Japan, as his acceptance speech in the Edogawa NICHE Prize ceremony was videocast.

NCRM NICHE, an active knowledge gaining academic event since 2006 in which young scholars from all over the world compete for the Fujio Cup Quiz (FCQ) in regenerative medicine is evolving to be an open innovation platform according to Dr. Shojiro Katoh, Chairperson of Edogawa Evolutionary Lab of Science (www.eels.tokyo), a co-host. He added that the FCQ motivated his team research on 16 different themes in Regenerative Medicine in various clinical specialties, among which two have completed clinical pilot studies with successful outcome viz., corneal endothelial regeneration and urethral stricture repair.

The XIV edition of FCQ contest that witnessed teams from Malaysia, Indonesia and India in the finals, was won by Reshma Romanas and Aayurshi Agrahari of Kasturba Medical College, India. Alumni of the FCQ are now eligible to nominate the awardees for Edogawa NICHE Prize which was established in 2018 to honour scientists or clinicians who develop novel solutions in healthcare, based on inter-disciplinary interactions. Dr. Steven A. Rosenberg, Chief of surgery, National Cancer Institute, NIH, USA is the recipient of the award in 2019. The award portrays such accomplished role models to the FCQ Elites according to the organizers who have instituted Joyce & James Till Travel Grant with a generous grant by Prof James Till, that supports travel of yesteryears FCQ Elites, who are now accomplished researchers in their own rights to meet and inspire the FCQ Elites of today, thus bringing together science and generations across nations.

NCRM NICHE is supported by a consortium with EELS as knowledge partners and JBM Inc., as industry partners based in Tokyo which has set up a hybrid cell culture cum biomaterials lab for taking forward the cell therapy and tissue engineering innovations to bed side, with future plans to propagate them globally through networking with like-minded academic and industry partners.

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Accomplishments of Dr. Steven Rosenberg in Cancer Immunotherapy Inspire Young Researchers in Japan & XIV Fujio Cup Quiz on Stem Cells Is Won by...

Tucson Tech: Ventana Medical Systems founder tells the rest of the story in new book – Arizona Daily Star

If youve been in Tucson long, you may have heard the story of how Ventana Medical Systems was founded here more than 30 years ago by a University of Arizona pathologist who invented an automated instrument to deliver fast diagnostics for cancer.

And you may have also heard what seemed to be the end of the story: How Ventana grew into a multi-billion-dollar public company and was acquired by Swiss drug giant Roche for $3.4 billion in 2008.

Now, company founder and UA professor emeritus Dr. Thomas Grogan has penned the rest of the story.

Grogans new book, Chasing the Invisible: A Doctors Quest to Abolish the Last Unseen Cancer Cell is a remarkable story, a loving memoir with elements of a spy thriller, a medical whodunit and a compelling business story.

It also has an intriguing cast of characters, including Grogans own mother, former Libyan strongman Moammar Gadhafi, an Inuit woman, intrepid scientists and Wall Street money men.

Grogan, 74, who retired from the UA about nine years ago and stepped down in 2017 from active duty at what is now Roche Tissue Diagnostics, said he may have learned as much about himself as he did about book publishing during the writing process.

Its been a great experience. The amazing part of writing a memoir is you relive what happened, Grogan said. And my story is one part personal, one part diagnostic medicine, one part technology, one part entrepreneurship and one part big pharma and Roche.

But getting the book published wasnt easy, said Grogan, who noted that his work was rejected by a dozen traditional publishers.

He finally reached a deal with Virginia-based Koehler Books to print the book under a co-publishing deal.

The initial critique from Koehlers editor was decidedly mixed.

The editor said, Okay, its interesting, its well-written but its a lousy memoir because you dont talk about yourself, Grogan said.

At one point in his draft, the editor demanded Grogan explain a passage noting that he had grown up living in dangerous places in dangerous times.

Finally I admitted to him, if I tell that part of the story I have to say something I was raised in the family to never talk about that my father was a CIA officer in the Middle East and Africa, Grogan said.

With his mothers blessing, Grogan detailed his familys life on the Mediterranean island of Cyprus in the early 1950s, when Cypriots rebelled against the last vestiges of British rule as Greece and Turkey began fighting for control.

Grogan recounted how his mother fearlessly drove the family car through an angry mob of Cypriots to deliver him and his brother to a Christmas pageant rehearsal at church.

Theres this whole episode where were attacked by a mob, and my mom says, Get down! And hits the accelerator, he said.

Grogans book starts with a scene about five years ago, when his 90-year-old mother asks him for advice after doctors discovered a cancerous tumor in her skull they believed may have been a recurrence of earlier breast cancer and suggested she consider hospice care.

She decided to get further tests and instead of metastatic breast cancer, the tumor was identified as a large B-cell lymphoma.

Well, I dont see giving up yet, she says. After all, they havent done a biopsy and we dont know the nature of the beast yet.

After testing with Ventana instruments and treatment with a Roche drug, Grogans mother recovered and remains disease-free today, Grogan said.

Grogan relates his inspiring meeting with a Libyan doctor who treated Gadhafis sister and later won funding for Ventana instruments from late dictator.

He also tells the story of how during a fishing trip to Alaska he met a native Inuit woman with cancer.

Grogan helped her understand the importance of testing to get the right treatment, and after her successful treatment, the need to keep the invisible disease from recurring using the analogy of how mosquitoes return every summer.

The book also describes Ventanas diagnostic technology in detail, but in terms most laymen can understand.

Grogans story of how he started Ventana seems to parallel his own life, overcoming obstacles, fighting the unseen, never giving up.

He relates how, after filing for a business license to start Ventana in 1985, a UA lawyer told him he could already be a felon because state law prohibited state employees from forming private businesses while on the state payroll.

That law was changed to accommodate Ventana and has led to the formation of countless faculty startups.

Grogan details how he was rejected by 35 investor groups before finding investors to bankroll Ventanas development, how the company went public and at one point losses had piled up to nearly $50 million, and how convincing the famed Cleveland Clinic to adopt the companys instruments helped the company break into the market.

He details how Roches advances were initially viewed with skepticism but what began as a hostile takeover put the company on a path to global acceptance as a standard of cancer diagnostics.

Despite his editors best efforts to get Grogan to talk about himself, he spends much of the book praising the efforts of colleagues, including his UA pathology department head, the late Dr. Jack Layton, for encouraging his work; key investor John Patience for his unwavering support; and his UA lab team and fellow pathologists for their hands-on work to develop and perfect the game-changing diagnostics.

Grogan does acknowledge he has one talent.

I had my own talents, but my success had to do with the ability to create alliances, Grogan, said, describing how he lured top talent with the promise of transforming medicine.

The reason to read this is, theres something to learn about global medicine, something to learn about how it is that this hidden world is really something thats actionable, he said.

Because its like the story I tell about the Inuit woman theres a strength you gain when you know what youre dealing with.

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Contact senior reporter David Wichner at dwichner@tucson.com or 573-4181. On Twitter: @dwichner.

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Tucson Tech: Ventana Medical Systems founder tells the rest of the story in new book - Arizona Daily Star

The Medicine Cabinet Of The Future: If You Can Imagine A Drug, This Company Can Make It – Forbes

Codexis CEO John Nicols has made his company a protein engineering powerhouse, and in doing so has become an important resource for the biopharma industry. If you can imagine a drug, chances are his company can help make it.

I have previously written how big pharma has been slow to innovate and adopt the latest synthetic biology tools, which could vastly speed the creation of new treatments and vaccines.

Im changing my mind.

Last week, on the heels of SynBioBeta 2019, Codexis held its annual Protein Engineering Forum in Palo Alto, California. The forum brought together leading scientists and engineers to share the latest in protein engineering, which is being revolutionized by the tools of synthetic biology. The forum aimed to see where science is taking proteins, and what proteins can offer the world.

Codexis CEO John Nicols opened the two-day forum by remarking on the extraordinary success protein engineering has had in bringing real-world applications to market faster and more often, and the hope that the meeting would represent another milestone in the progress of proteins.

It certainly seemed to be. Here are a few examples of how biopharma is making the jump to lightspeed:

Accelerating evolution to make drugs with biology: I recently wrote about Nobel Laureate Frances Arnolds pioneering principles for nudging nature to do what she does best: evolve. Merck has taken this to heart by using her directed evolution methods to go from chemistry-based to biology-based production of its diabetes drug, Januvia. The result: an efficient, economical, and environmentally friendly process for manufacturing a range of drugs.

Unleashing computers: To respond to a wider range of more complex diseases, companies like Amgen are making their R&D pipeline more flexible and higher volume. To do this, they are integrating the latest in computation and experimental methods. This promises to speed the development of protein therapeutics, which can replace abnormal or deficient proteins in diseases like arthritis, cardiovascular disease, and blood disorders.

Cascade reactions: The ability to engineer extremely effective enzymes the proteins that catalyze chemical transformations allows biologists to put many steps in a single pot, going from starting materials to finished product in one go. This makes the process more sustainable and more efficient; to paraphrase one participant, If its sustainable, its also cheaper. Researchers at biopharma giant GSK reported that most of their projects are going in this direction. GSKs commitment to the environment is reflected in giving projects an environmental score and cascade reactions are a green dream.

The DNA to build it all: Using the power of silicon to write the DNA needed for just about any biopharma application, CEO Emily Leproust described how her company helped researchers develop a rapid response tool to make antibodies to fight global viral threats like Zika and Ebola. The company also spun out Twist Biopharma with an emphasis on creating new antibody drugs for difficult-to-target diseases.

The protein revolution isnt limited to biopharma, either. Here are a few other areas highlighted at the forum where protein design is having big impacts:

Cannabinoids: Ive previously written about the benefits of brewing cannabinoids as you would beer, such as producing rare cannabinoids not easily purified from plants. Companies like Invizyne are going one step further by taking biology pathways out of cells and into cell-free systems. Invizyne is just one player in a field of heavy-hitters pursuing cannabinoids, including Amyris, Ginkgo Bioworks, and Intrexon.

Bioplastics: Theres a buzz about bioplastics. Protein engineers are evolving enzymes to break down plastic in the environment. Conversely, they can and have created bioplastics from biological sources, ones that are more biodegradable than their petrochemical cousins.

Biofuels: In the earliest days of synthetic biology, pioneers like Jay Keasling went after biofuels. As a commodity chemical, this was a very challenging first target: its a commodity chemical that must be produced on a tremendous scale, and compete economically with the petrochemical industry. (Thats why much of the industry retreated to higher-value chemicals from the top of the barrel.) Fast-forward to 2019: James Liao, Keasling, and other researchers have tools to radically change the way we ferment ethanol and other fossil fuel replacements, hinting at the new golden age of biofuels to come.

What does this mean for manufacturing?

The science and technology we use to make proteins are going to transform manufacturing, but how? Will manufacturing continue to require central manufacturing facilities with their high capital equipment costs? Or are markets going to benefit from faster, cheaper, and better ways of making chemicals and materials?

We think about this all the time, said one participant. We see a day when, instead of large, expensive manufacturing facilities, you will have your entire biomanufacturing platform on a skid. Add glucose and your enzyme cocktail, and it will produce your final product, maybe even in pill form. You could pick it up, put it on a plane, send it anywhere in the world that its needed.

Where do big data and AI fit in?

Industry has invested billions in R&D to bring products to the market. In doing so, it has accumulated enormous amounts of data. Much of that data is about failed attempts, such as drug candidates that fail in the late stages of clinical testing. Companies tend to share info about successes, but not about failures. So all that data remains locked in company databases, waiting for the day we can learn from it with computer algorithms and other sources of big data.

How can we encourage companies to share with the rest of the world? Can the government play a role in providing sharing incentives? If companies could find good ways to share that information, with the right incentives for everyone involved, it would open up a huge range of new possibilities for the industry. Maybe advanced encryption techniques could allow companies to share some data and conceal others.

What does it all mean for you and me?

Some of us are already benefiting from advances in protein science, such as the diabetes medicine Januvia I mentioned above, where the same product is now made with reduced pollution and waste. But for others, the revolution in protein engineering is shortening the time it takes to take a drug from bench to bedside.

At the Codexis forum, there was a confidence on the part of the biopharma participants that synthetic biology tools and technologies will soon be able to make just about any drug or vaccine you can think of. As one participant put it, When were asked, Do you have an enzyme that can make that?, the answer isnt yes or no. The answer is yes or not yet.

In the future, we can expect entirely new products. For example, an engineered probiotic is now available to prevent hangovers.

Perhaps the most important area is the one we can all relate to the most: human disease. Gjalt Huisman, Senior VP of Strategic Development at Codexis, has spent most of his career in biotherapeutics, and he shared an experience he had at a conference on phenylketonuria a rare but potentially devastating disease.

I was speaking at a conference with patients and their family members in the audience, as well as scientists, Huisman said. After our session, this older man came up to me and said, simply, My granddaughter has PKU, and we count on you. It was a revelation to me, and a reminder of the big job we have ahead of us in the real world.

With a little courage and the right tools, biopharma is poised to make me a believer.

Acknowledgment: Thank you to Kevin Costa for additional research and reporting in this post.

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The Medicine Cabinet Of The Future: If You Can Imagine A Drug, This Company Can Make It - Forbes

Past, Present and Future: How Non-Clear Cell Kidney Cancer Has Evolved – Curetoday.com

Those with non-clear cell kidney cancer have much to look forward to as oncologists understanding of the disease is evolving.

BY Kristie L. Kahl

At A Vision of Hope: A Kidney Cancer Educational Symposium, which was hosted by the Judy Nicholson Kidney Cancer Symposium and Penn Medicine Abramson Cancer Center, Narayan discussed the past, present and future of the treatment of non-clear cell kidney cancer.

Non-clear cell kidney cancer accounts for 15% to 20% of kidney cancers and consists of papillary type 1 and 2, chromophobe and unclassified disease, as well as several additional less common subtypes. However, with all of these types, oncologists understanding of treatment for non-clear cell kidney cancer has evolved over the last several years, Narayan explained.

Where, instead of viewing this as a single uniform entity, we began to appreciate that this actually represents a spectrum of different diseases, all with distinctive molecular and genetic clinical courses and variable responses to treatment, he said.

In the past, most initial trials evaluated agents only for clear cell kidney cancer which comprises 80% of patients with little consensus on how to treat non-clear cell disease.

Two trials evaluated systemic treatments for non-clear cell kidney cancer the ESPN and ASPEN trials, both comparing Sutent (sunitinib) with Afinitor (everolimus). Although both drugs appeared effective in patients with clear cell kidney cancer, outcomes were merely modest for those with non-clear cell disease.

Moving forward to present day, oncologists began to think about the disease differently. We've begun to change our thinking in terms of how we think about non-clear cell kidney cancer. Instead of acting as lumpers, we begin to think (of the disease) more as splitters and recognize that this is truly a heterogeneous disease, Narayan said.

With this, oncologists began to think about their improved understanding of the molecular underpinnings of each subtype of the disease, and defined characteristics based on chromosomal alteration, tumor metabolism and more, he added.

As part of the Cancer Genome Atlas, a collaborative project to create comprehensive maps of the key genomic changes in different cancer types, oncologists were able to define pathways among each subtype.

There are areas of overlap with clear cell kidney cancer, but also some very important and unique differences with each of the subtypes of non-clear cell, Narayan explained. So as we start to think about how to use this information to improve the treatments for patients with non-clear cell disease, were really starting to have a change in the treatment paradigm. Instead of simply extrapolating treatments from clear cell kidney cancer, and testing them in non-clear cell patients, it would be ideal to have biology-driven clinical trials that assess specific treatments for specific subtypes.

He added that there are challenges with this ideology, however, because it is difficult to accrue patients in a trial for uncommon kidney cancers, but the benefit of having uniform biology to test the rationale for new treatment strategies could help.

Currently, researchers have evaluated Sutent, Cabometyx (cabozatinib), savolitinib (an experimental drug) and Xalkori (crizotinib) in patients with papillary renal cell carcinoma types 1 and 2. More recently, however, Sutent and Cabometyx have become the only two horses in the race, Narayan said.

In the future, he is hopeful that oncologists understanding of overlap and the differences seen with conventional clear cell kidney cancer will continue to evolve.

In thinking about the treatment of non-clear cell kidney cancer, especially as we move to the future, it's clear that our understanding of this disease is evolving, Narayan concluded. Our clinical trials will hopefully evaluate treatment strategies to target unique biology.

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Past, Present and Future: How Non-Clear Cell Kidney Cancer Has Evolved - Curetoday.com

Study focuses on repair and reversal of damage caused by Huntington’s disease – UCLA Newsroom

UCLA research identifies a potential strategy that may lead to treatment for the disorder

UCLA

The image shows astrocytes (in purple) with mutant huntingtin protein inclusions (green). Some of these were located within astrocytes as shown in the expanded image on the right.

A new study examining the role that star-shaped brain cells called astrocytes play in Huntingtons disease has identified a potential strategy that may halt the disease and repair some of the damage it causes.

Astrocytes interact with and support neurons, or nerve cells, and other brain cells. Although astrocytes outnumber neurons, little is known about how they interact with synapses, the junctions between neurons that enable them to communicate and convey messages to each other.

The study, led by UCLA researchers and published in the journal Science Translational Medicine, found that Huntingtons disease damages astrocytes at the early stages of the disease, which contributes to the neuropsychiatric symptoms that develop as the disease progresses.

Huntingtons is caused by a mutation in the huntingtin gene. People with Huntingtons experience depression, irritability and other neurological and behavioral problems. They may also have difficulty processing information and controlling their bodys movements.

Its likely that we will not understand brain diseases without also understanding what happens to the cells that actually form the brain, including astrocytes, said Baljit Khakh, the studys lead investigator and a professor of physiology and neurobiology at the David Geffen School of Medicine at UCLA.

Khakh led a team that previouslypioneereda method that enables scientists to look inside thebrainsof mice to observe astrocytes influence over nerve-cell communication in real time. The scientists are able to see how interactions between synapses and astrocytes change over time, and as a result of neurological diseases.

For the recent study, researchers observed the progression of Huntingtons disease in samples from the brains of deceased humans, and in living mice that carry the gene mutation. They found that by suppressing the mutation in astrocytes, they were able to stop the disease progression in mice and repair some of the damage that can be seen when examining the cells closely.

We believe that if we are able to stop the progression of the disease in astrocytes and neurons, then we may be able to restore activity in the brain to what it was before the disease developed, Khakh said.

Study author Blanca Diaz-Castro, a former UCLA postdoctoral scholar, said that while its well-known that the mutation causes the cell death in neurons, this is the first study to identify how the mutation affects astrocytes.

We believe the findings will lead to further studies on astrocytes in brain diseases, she said.

The study also established a database that can now be used for future studies of astrocytes in many neurodegenerative diseases. Khakh said the findings add to a growing body of evidence that suggests impaired astrocytes play a role in many neurological diseases, such as Huntingtons, ALS, multiple sclerosis and Alzheimers.

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Study focuses on repair and reversal of damage caused by Huntington's disease - UCLA Newsroom

Quantum dots that light up TVs could be used for brain research – The Conversation US

While many people love colorful photos of landscapes, flowers or rainbows, some biomedical researchers treasure vivid images on a much smaller scale as tiny as one-thousandth the width of a human hair.

To study the micro world and help advance medical knowledge and treatments, these scientists use fluorescent nano-sized particles.

Quantum dots are one type of nanoparticle, more commonly known for their use in TV screens. Theyre super tiny crystals that can transport electrons. When UV light hits these semiconducting particles, they can emit light of various colors.

That fluorescence allows scientists to use them to study hidden or otherwise cryptic parts of cells, organs and other structures.

Im part of a group of nanotechnology and neuroscience researchers at the University of Washington investigating how quantum dots behave in the brain.

Common brain diseases are estimated to cost the U.S. nearly US$800 billion annually. These diseases including Alzheimers disease and neurodevelopmental disorders are hard to diagnose or treat.

Nanoscale tools, such as quantum dots, that can capture the nuance in complicated cell activities hold promise as brain-imaging tools or drug delivery carriers for the brain. But because there are many reasons to be concerned about their use in medicine, mainly related to health and safety, its important to figure out more about how they work in biological systems.

Researchers first discovered quantum dots in the 1980s. These tiny particles are different from other crystals in that they can produce different colors depending on their size. They are so small that that they are sometimes called zero-dimensional or artificial atoms.

The most commonly known use of quantum dots nowadays may be TV screens. Samsung launched their QLED TVs in 2015, and a few other companies followed not long after. But scientists have been eyeing quantum dots for almost a decade. Because of their unique optical properties they can produce thousands of bright, sharp fluorescent colors scientists started using them as optical sensors or imaging probes, particularly in medical research.

Scientists have long used various dyes to tag cells, organs and other tissues to view the inner workings of the body, whether that be for diagnosis or for fundamental research.

The most common dyes have some significant problems. For one, their color often cannot survive very long in cells or tissues. They may fade in a matter of seconds or minutes. For some types of research, such as tracking cell behaviors or delivering drugs in the body, these organic dyes simply do not last long enough.

Quantum dots would solve those problems. They are very bright and fade very slowly. Their color can still stand out after a month. Moreover, they are too small to physically affect the movement of cells or molecules.

Those properties make quantum dots popular in medical research. Nowadays quantum dots are mainly used for high resolution 3D imaging of cells or molecules, or real-time tracking probes inside or outside of animal bodies that can last for an extended period.

But their use is still restricted to animal research, because scientists are concerned about their use in human beings. Quantum dots commonly contain cadmium, a heavy metal that is highly poisonous and carcinogenic. They may leak the toxic metal or form an unstable aggregate, causing cell death and inflammation. Some organs may tolerate a small amount of this, but the brain cannot withstand such injury.

My colleagues and I believe an important first step toward wider use of quantum dots in medicine is understanding how they behave in biological environments. That could help scientists design quantum dots suitable for medical research and diagnostics: When theyre injected into the body, they need to stay small particles, be not very toxic and able to target specific types of cells.

We looked at the stability, toxicity and cellular interactions of quantum dots in the developing brains of rats. We wrapped the tiny quantum dots in different chemical coats. Scientists believe these coats, with their various chemical properties, control the way quantum dots interact with the biological environment that surrounds them. Then we evaluated how quantum dots performed in three commonly used brain-related models: cell cultures, rat brain slices and individual live rats.

We found that different chemical coats give quantum dots different behaviors. Quantum dots with a polymer coat of polyethylene glycol (PEG) were the most promising. They are more stable and less toxic in the rat brain, and at a certain dose dont kill cells. It turns out that PEG-coated quantum dots activate a biological pathway that ramps up the production of a molecule that detoxifies metal. Its a protective mechanism embedded in the cells that happens to ward off injury by quantum dots.

Quantum dots are also eaten by microglia, the brains inner immune cells. These cells regulate inflammation in the brain and are involved in multiple brain disorders. Quantum dots are then transported to the microglias lysosomes, the cells garbage cans, for degradation.

But we also discovered that the behaviors of quantum dots vary slightly between cell cultures, brain slices and living animals. The simplified models may demonstrate how a part of the brain responds, but they are not a substitute for the entire organ.

For example, cell cultures contain brain cells but lack the connected cellular networks that tissues have. Brain slices have more structure than cell cultures, but they also lack the full organs blood-brain barrier its Great Wall that prevents foreign objects from entering.

Our results offer a warning: Nanomedicine research in the brain makes no sense without carefully considering the organs complexity.

That said, we think our findings can help researchers design quantum dots that are more suitable for use in living brains. For example, our research shows that PEG-coated quantum dots remain stable and relatively nontoxic in living brain tissue while having great imaging performance. We imagine they could be used to track real-time movements of viruses or cells in the brain.

In the future, along with MRI or CT scans, quantum dots may become vital imaging tools. They might also be used as traceable carriers that deliver drugs to specific cells. Ultimately, though, for quantum dots to realize their biomedical potential beyond research, scientists must address health and safety concerns.

Although theres a long way to go, my colleagues and I hope the future for quantum dots may be as bright and colorful as the artificial atoms themselves.

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Prognostic Significance Of Platelet-To-Lymphocyte Ratio (PLR) And Mean | CMAR – Dove Medical Press

Xia-Bo Shen,1,2,* Yong Wang,2,* Ben-Jie Shan,2 Lin Lin,2 Li Hao,2 Yu Liu,1,2 Wei Wang,2 Yue-Yin Pan1,2

1Department of Medical Oncology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Peoples Republic of China; 2Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Yue-Yin PanDepartment of Medical Oncology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Peoples Republic of ChinaEmail yueyinpan1965@163.comWei WangDepartment of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Peoples Republic of ChinaEmail docweiwang@fsyy.ustc.edu.cn

Background: Small cell lung cancer (SCLC) is a special type of lung cancer and it is responsive to chemotherapy. Blood parameters have been proved to be associated with survival for many types of malignancies. This study aimed to investigate the prognostic significance of platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) for SCLC patients with etoposide-based first-line treatment.Methods: We retrospectively identified 138 patients diagnosed as SCLC who underwent etoposide-based first-line chemotherapy. The patients baseline clinical characteristics and blood parameters were collected. KaplanMeier analysis and Cox regression methods were used to determine the factors associated with progression-free survival (PFS).Results: The optimal cut-off value of diagnosis was depended on the ROC curve, the cut-off value of pretreatment PLR was 190 (sensitivity 39.0%, specificity 88.5%), and the cut-off value of pretreatment MPV was 10.0 (sensitivity 60.7%, specificity 61%). KaplanMeier analysis showed patients with high PLR levels in baseline had worse PFS than those with low PLR levels (P <0.001). Multivariate analysis revealed pretreatment MPV was an independent prognostic factor for PFS (HR: 0.815, 95% CI: 0.7110.933, P =0.003). Further research suggested continuous high PLR indicated a poor therapy outcome (P =0.002).Conclusion: Pretreatment MPV can be an independent predictor for first-line treatment outcome and a continuously high level of PLR suggested inferior PFS in etoposide-treated SCLC patients.

Keywords: small cell lung cancer, SCLC, first-line chemotherapy, mean platelet volume, MPV, platelet-to-lymphocyte ratio, PLR, prediction

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Prognostic Significance Of Platelet-To-Lymphocyte Ratio (PLR) And Mean | CMAR - Dove Medical Press