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Cancer cells send signals boosting survival and drug resistance in other cancer cells – Medical Xpress

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June 6, 2017 In this image of a human breast tumor, a cluster of malignant cells that have become resistant to chemotherapy are shown in red. Credit: NCI

Researchers at University of California San Diego School of Medicine report that cancer cells appear to communicate to other cancer cells, activating an internal mechanism that boosts resistance to common chemotherapies and promotes tumor survival.

The findings are published online in the June 6 issue of Science Signaling.

Six years ago, Maurizio Zanetti, MD, professor in the Department of Medicine at UC San Diego School of Medicine and a tumor immunologist at Moores Cancer Center at UC San Diego Health, published a paper in PNAS suggesting that cancer cells exploit an internal mechanism used by stressed mammalian cells, called the unfolded protein response (UPR), to communicate with immune cells, notably cells derived from the bone marrow, imparting them with pro-tumorigenic characteristics.

The UPR is activated in response to unfolded or misfolded proteins accumulating in the endoplasmic reticulum (ER)an organelle that carries out several metabolic functions in the cells and the site where proteins are built, folded and sent for secretion. The UPR can often decide cell death or survival.

In their new paper, Zanetti and colleagues say cancer cells appear to take the process beyond just affecting bone marrow cells, using transmissible ER stress (TERS) to activate Wnt signaling in recipient cancer cells. Wnt is a cellular signaling pathway linked to carcinogenesis in many types of cancer.

"We noticed that TERS-experienced cells survived better than their unexperienced counterparts when nutrient-starved or treated with common chemotherapies like bortezomib or paclitaxel," said Jeffrey J. Rodvold, a member of Zanetti's lab and first author of the study. "In each instance, receiving stress signals caused cells to survive better. Understanding how cellular fitness is gained within the tumor microenvironment is key to understand cooperativity among cancer cells as a way to collective resilience to nutrient starvation and therapies."

When cancer cells subject to TERS were implanted in mice, they produced faster growing tumors.

"Our data demonstrate that transmissible ER stress is a mechanism of intercellular communication," said Zanetti. "We know that tumor cells live in difficult environments, exposed to nutrient deprivation and lack of oxygen, which in principle should restrict tumor growth. Through stress transmission, tumor cells help neighboring tumor cells to cope with these adverse conditions and eventually survive and acquire growth advantages."

Importantly, he said the research may explain previous findings by other groups showing that individual tumor cells within a uniform genetic lineage can acquire functionally different behaviors in vivo. In other words, some cells acquire greater fitness and extended survivalanother way to generate intra-tumor heterogeneity, which currently represents one of the major obstacles to cancer treatment. This implies that mutations peppered throughout the cancer genome of an individual are not the only source of intra-tumor heterogeneity.

Zanetti said researchers and physicians need to consider these changing cellular dynamics in the tumor microenvironment in developing both a better understanding of cancer and more effective treatments.

Explore further: Cancer cells co-opt immune response to escape destruction

More information: Science Signaling (2017). DOI: 10.1126/scisignal.aah7177

Researchers at the University of California, San Diego School of Medicine report that tumor cells use stress signals to subvert responding immune cells, exploiting them to actually boost conditions beneficial to cancer growth.

A new study has identified a mechanism used by tumors to recruit stem cells from bone and convert them into cancer-associated fibroblasts (CAFs) that facilitate tumor progression. This work, which pinpoints the specific biochemical ...

A very high mortality rate is associated with ovarian cancer, in part due to difficulties in detecting and diagnosing the disease at early stages before tumors have spread, or metastasized, to other locations in the body.

Researchers from Oregon Health and Science University and Oregon State University have found that aspirin may slow the spread of some types of colon and pancreatic cancer cells. The paper is published in the American Journal ...

Tumor growth is dependent on interactions between cancer cells and adjacent normal tissue, or stroma. Stromal cells can stimulate the growth of tumor cells; however it is unclear if tumor cells can influence the stroma.

Researchers at University of California San Diego School of Medicine report that cancer cells appear to communicate to other cancer cells, activating an internal mechanism that boosts resistance to common chemotherapies and ...

A research study led by University of Minnesota engineers gives new insight into how cancer cells move based on their ability to sense their environment. The discovery could have a major impact on therapies to prevent the ...

The chemotherapy drug capecitabine gives patients a better quality of life and is as effective at preventing breast cancer from returning as the alternative regimen called CMF, when given following epirubicin. These are the ...

When you dine on curry and baked apples, enjoy the fact that you are eating something that could play a role starvingor even preventingcancer.

Scientists at Karolinska Institutet in Sweden report that cancer cells and normal cells use different 'gene switches' in order to regulate the expression of genes that control growth. In mice, the removal of a large regulatory ...

Doctors are reporting unprecedented success from a new cell and gene therapy for multiple myeloma, a blood cancer that's on the rise. Although it's early and the study is small35 peopleevery patient responded and all ...

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Cancer cells send signals boosting survival and drug resistance in other cancer cells - Medical Xpress

‘Immunoswitch’ particles may be key to more-effective cancer immunotherapy – Phys.Org

By Uncategorized

June 7, 2017 T cells (red) and tumor cells (green) incubated with control particles (left) or immunoswitch particles (right). T cells that have latched on to tumor cells are indicated by green arrows. Credit: Alyssa Kosmides, Johns Hopkins Medicine

Scientists at Johns Hopkins have created a nanoparticle that carries two different antibodies capable of simultaneously switching off cancer cells' defensive properties while switching on a robust anticancer immune response in mice. Experiments with the tiny, double-duty "immunoswitch" found it able to dramatically slow the growth of mouse melanoma and colon cancer and even eradicate tumors in test animals, the researchers report.

The findings, described online June 7 in ACS Nano, could lead to ways to boost the effectiveness and promise of immunotherapies in people with cancer, the investigators say.

"Immunotherapies have significant potential and yet room for improvement," says Jonathan P. Schneck, M.D., Ph.D., professor of pathology in the Johns Hopkins University School of Medicine's Institute for Cell Engineering and a member of the Johns Hopkins Kimmel Cancer Center. "The improvement here was to make, for the first time, a nanoparticle that can interact simultaneously with multiple types of cells in the complex tumor microenvironment, dramatically increasing its effectiveness."

Schneck and study co-leader Alyssa K. Kosmides, a graduate student in his laboratory, explain that several cancer treatments designed to stimulate a patient's immune system to fight the disease have been approved by the U.S. Food and Drug Administration, including three known as checkpoint inhibitors. Those drugs help overcome cancer cells' ability to evade a person's immune system by using antibodies to shut down proteins on tumor cell surfaces that hide them from immune cells.

However, they point out, checkpoint inhibitors work only in a relatively limited number of patients and against a small number of cancers so far. Follow-up studies show that overall response rates against melanoma, bladder cancer, Hodgkin's lymphoma and non-small cell lung cancer is around 30 percent, and complete response rates, resulting in eradication of a patient's tumors, are as low as 5 percent.

But combining multiple forms of immunotherapy in doses high enough to be effective can cause severe, even life-threatening, side effects.

For their study, the Johns Hopkins researchers combined two different immunotherapy strategies on manmade nanoparticles about 1,000 times smaller in diameter than a human hair, similar to drug-delivery platforms already in use in some cancer therapies, including chemotherapies such as Doxil, Abraxane and Myocet.

Nanoparticles have clear advantages over free drug, Kosmides explains, such as their "enhanced permeability and retention effect," which causes nanosized particles to be taken up more readily by tumor cells than by healthy cells. Additionally, each particle can hold dozens of antibodies at once, which dramatically raises the local concentration of antibodies. This makes them more effective and reduces the chances of side effects, she says.

"Nanoparticles provide more bang for your buck," Schneck says.

Using paramagnetic iron particles about 100 nanometers in diameter, the researchers placed two different kinds of antibodies on them: one blocks a protein called programmed death ligand 1 (PD-L1), which cancer cells use to cloak themselves from immune cells; another that stimulates T cells, a type of immune cell that fights cancer. By combining these two functions, Schneck explains, the goal was to effectively switch off a tumor's immune-inhibiting ability while simultaneously switching on the immune system's capacity to attack.

In mice injected with mouse melanoma cells, which grew into tumors over the course of several days, only mice who subsequently received the "immunoswitch" particles had significantly delayed tumor growth and longer survival compared to those who received the control treatments or no treatment.

Specifically, the immunoswitch-treated mice had tumors nearly 75 percent smaller than animals that received no treatment, whereas soluble antibody only reduced tumor growth by approximately 25 percent. Half of immunoswitch-treated mice were still alive after 30 days, whereas all untreated mice died by day 22.

"The double-duty immunoswitch particles were clearly more effective than a mixture of nanoparticles that each targeted just one protein and acted in a synergistic fashion, but we don't yet know why," says Schneck. "It may be that the immunoswitch particles' success comes from bringing T cells and their targeted tumor cells into close proximity."

The researchers say they found even more dramatic results in a mouse model of colon cancer. In those experiments, about half the mice had a complete regression of tumors and about 70% could be considered long-term survivors, living more than 55 days.

Looking for the mechanism behind the immunoswitch particles' positive effects, further experiments showed that the particles appear to bring cancer cells and the immune cells that fight them together more easily, providing a synergy that's not possible even with the same two antibodies on separate particles. The immunoswitch particles also were retained in tumor cells significantly longer than soluble antibodies, offering more time for them to work, Schneck and Kosmides say.

The researchers add that they plan to work on improving the immunoswitch particles by searching for more effective combinations of antibodies to include on the platform. Because the particles are magnetic, they also plan to test whether results can be improved by using magnets to guide the particles and keep them at the tumor site.

Explore further: Researchers develop new tumor-shrinking nanoparticle to fight cancer, prevent recurrence

More information: "Dual Targeting Nanoparticle Stimulates the Immune System to Inhibit Tumor Growth", ACS Nano, pubs.acs.org/doi/abs/10.1021/acsnano.6b08152

A Mayo Clinic research team has developed a new type of cancer-fighting nanoparticle aimed at shrinking breast cancer tumors, while also preventing recurrence of the disease. In the study, published today in Nature Nanotechnology, ...

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EPFL scientists have improved the efficacy of cancer immunotherapy by blocking two proteins that regulate the growth of tumor blood vessels.

In several types of cancer, elevated expression of the chemokine receptor CCR4 in tumors is associated with poor patient outcomes. Communication through CCR4 may be one mechanism that cancer cells use to create a pro-tumor ...

MIT researchers have devised a way to make tumor cells more susceptible to certain types of cancer treatment by coating the cells with nanoparticles before delivering drugs.

Scientists at Johns Hopkins have created a nanoparticle that carries two different antibodies capable of simultaneously switching off cancer cells' defensive properties while switching on a robust anticancer immune response ...

Recent research from the University of Nebraska-Lincoln may help future engineers of digital components get two (or more) for the space of one.

Scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory have developed a new way to track dynamic molecular features in soft materials, including the high-frequency molecular vibrations that transmit ...

Before new nanoparticles or other nanomedicines can be injected into the human body, a whole series of tests must be conducted in the laboratory, then in living cells, and in the end on humans. But often the results obtained ...

An engineer with the Erik Jonsson School of Engineering and Computer Science at The University of Texas at Dallas has designed a novel computing system made solely from carbon that might one day replace the silicon transistors ...

(Phys.org)A team of researchers with the National Center for Nanoscience and Technology in China has developed what it is calling a skin-like triboelectric nanogenerator (STENG). In their paper published in the journal ...

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'Immunoswitch' particles may be key to more-effective cancer immunotherapy - Phys.Org

Celgene updates on two T cell therapy collaborations – The Pharma Letter (registration)

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As the annual meeting of the American Society of Clinical Oncology enters its final day, US biotech major

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Celgene updates on two T cell therapy collaborations - The Pharma Letter (registration)

A first: All respond to CAR-T therapy in a blood cancer study – STAT

By Uncategorized

C

HICAGO Doctors are reporting unprecedented success from a new cell and gene therapy for multiple myeloma, a blood cancer thats on the rise. Although its early and the study is small 35 people every patient responded and all but two were in some level of remission within two months.

In a second study of nearly two dozen patients, everyone above a certain dose responded.

Experts at an American Society of Clinical Oncology conference in Chicago, where the results were announced Monday, say its a first for multiple myeloma and rare for any cancer treatment to have such success.

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Chemotherapy helps 10 to 30 percent of patients; immune system drugs, 35 to 40 percent at best, and some gene-targeting drugs, 70 to 80 percent, but you dont get to 100, said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society.

These are impressive results, but time will tell if they last, he said.

Meet the biotech company trying to shake up how the FDA thinks about cancer drugs

Multiple myeloma affects plasma cells, which make antibodies to fight infection. More than 30,000 cases occur each year in the United States, and more than 115,000 worldwide. Its the second fastest growing cancer for men and the third for women, rising 2 to 3 percent per year, according to the National Cancer Institute. About 60,000 to 70,000 Americans have it now.

Nine new drugs have been approved for it since 2000 but theyre not cures; only about half of U.S. patients live five years after diagnosis.

With cell therapy, I cant say we may get a cure, but at least we bring hope of that possibility, said Dr. Frank Fan. He is chief scientific officer of Nanjing Legend Biotech, a Chinese company that tested the treatment with doctors at Xian Jiaotong University.

The treatment, called CAR-T therapy, involves filtering a patients blood to remove immune system soldiers called T cells. These are altered in a lab to contain a gene that targets cancer and then given back to the patient intravenously.

Doctors call it a living drug a one-time treatment to permanently alter cells that multiply in the body into an army to fight cancer. Its shown promise against some leukemias and lymphomas, but this is a new type being tried for multiple myeloma, in patients whose cancer worsened despite many other treatments.

In the Chinese study, 19 of 35 patients are long enough past treatment to judge whether they are in complete remission, and 14 are. The other five had at least a partial remission, with their cancer greatly diminished. Some are more than a year past treatment with no sign of disease.

Most patients had a group of side effects common with this treatment, including fever, low blood pressure, and trouble breathing. Only two cases were severe and all were treatable and temporary, doctors said.

The second study was done in the U.S. by Bluebird Bio and Celgene, using a cell treatment developed by the National Cancer Institute. It tested four different dose levels of cells in a total of 21 patients. Eighteen are long enough from treatment to judge effectiveness, and all 15 who got an adequate amount of cells had a response. Four have reached full remission so far, and some are more than a year past treatment.

The results are very remarkable, not just for how many responded but how well, said Dr. Kenneth Anderson of Dana-Farber Cancer Institute in Boston.

We need to be looking for how long these cells persist and keep the cancer under control, he said.

Dr. Carl June, a University of Pennsylvania researcher who received the conferences top science award for his early work on CAR-T therapy, said its very rare to see everyone respond to a treatment. His lab also had this happen all 22 children testing a new version of CAR-T for leukemia responded, his colleagues reported at the conference.

U.S. could save $825 million a year with a small change in immunotherapy dosing, study says

The first patients we treated in 2010 havent relapsed, June said.

Dr. Michael Sabel of the University of Michigan called the treatment revolutionary.

This is really the epitome of personalized medicine, extending immune therapy to more types of patients, he said.

Legend Biotech plans to continue the study in up to 100 people in China and plans a study in the U.S. early next year. The treatment is expected to cost $200,000 to $300,000, and whos going to pay for that is a big issue, Fan said.

The manufacturing process is very expensive and you cant scale up. Its individualized. You cannot make a batch as is done with a drug, he said.

Nick Leschly, Bluebirds chief executive, said the next phase of his companys study will test what seems the ideal dose in 20 more people.

Marilynn Marchione

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A first: All respond to CAR-T therapy in a blood cancer study - STAT

Doctors Targets Stem Cell Therapy Launch – Bahamas Tribune

By Stem Cell Treatment

ByNEIL HARTNELL

Tribune Business Editor

nhartnell@tribunemedia.net

DOCTORS Hospital plans to launch stem cell therapy and enter the primary healthcare market during its current financial year, after profits for the year to end-January 2017 increased five-fold.

The BISX-listed healthcare provider said it planned to launch both initiatives at its Bahamas Medical Centre facility on Blake Road, having received the necessary approvals for one stem cell programme and another in its final stages.

Doctors Hospitals 2017 annual report did not identify the types of stem cell treatment involved, but said: It is envisioned that stem cell therapy will occur at the facility [Bahamas Medical Centre] in fiscal 2018, with one programme already receiving the necessary approvals and the second programme in its final stages of assessment and approval......

We anticipate that in fiscal 2018 we will launch one of our primary care centres at this location, supported by increased specialist services to best serve the neighbouring communities.

Joe Krukowski, Doctors Hospitals chairman, told shareholders via the annual report that the launch of primary care services will be a vital component in the continuum of care we provide.

We will seek to provide our customers with multiple entry points for this level of care, he added.

Doctors Hospitals stem cell initiatives, in particular, represent a potential boost to the Bahamas national effort to make greater inroads into the medical tourism market while also exploiting legislation passed by the former Christie administration.

The healthcare providers move into primary care will effectively create a fully-integrated model, combining with its core business in secondary and tertiary care provision to potentially make Doctors Hospital almost a one-stop shop for all medical needs.

The expansion comes after Doctors Hospital saw total comprehensive income for the year to end-January 2017 grow by 409 per cent or more than five-fold, from $702,790 to $3.578 million year-over-year.

The growth was driven entirely by the companys main Collins Avenue facility, where profits more than doubled, increasing by 157.4 per cent to $4.778 million compared to $1.856 million the year before. The Bahamas Medical Centres net loss increased slightly compared to the prior year, rising from $1.153 million to $1.2 million.

An improved top-line drove Doctors Hospitals improved profitability, with patient services revenue up $3.65 million or 7.4 per cent at $52.713 million.

Patient days increased by 6 per cent from the previous year, the annual report said of the main Collins Avenue hospital. Increases in the Intensive and Intermediary Care Units accounted for 37per centof the change, and the balance in medical surgical and maternity.

Total admissions to the facility were 4,114 in fiscal 2017 compared to 4,063 in fiscal 2016. The continued flat admission numbers and increased patient days are indicative of the trend toward a rising severity of illness. The average daily census increased to 33 patients per day from 31.2 in the previous year.

Doctors Hospitals total expenses grew by $818,452 or 1.7 per cent year-over-year, with salaries and benefits rising by $1.176 million or 5.6 per cent to $23.209 million. Due to the top-line growth, these fell as a percentage of patient net revenue from 44.3 per cent to 43.5 per cent.

At Bahamas Medical Centre, revenues rose by $28,015 or 1.9 per cent to $1.462 million. This slightly outpaced the increase in expenses, which jumped by 1.5 per cent or $43,479 to $2.819 million as a result of rising medical supplies costs.

Doctors Hospital is budgeting $7 million for capital spending projects in its financial year to end-January 2018, a sum more than double the prior years $3.1 million, as it bids to upgrade facilities and replace equipment.

Bad debt expense, as a percentage of patient service revenues, decreased to 2.6per centfor the year ended January 31, 2017, compared to 3.4per centthe previous year, Doctors Hospital said.This represented a decrease of $316,808, or 18.8per cent. This decrease is a result of a write-off of third-party receivables.

The number of days revenue in accounts receivable at year-end (AR Days) for fiscal 2017 stand at 51 compared with fiscal 2016 at 43 days, and net receivables as a percentage of net patient revenue increased to 14.1per centfrom 11.8per cent. These increases area result of high activity in the months of December and January, and payments not received until after year-end.

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Doctors Targets Stem Cell Therapy Launch - Bahamas Tribune

Column: Stem Cell Therapy A medical revolution – Current in Carmel

By Stem Cell Treatment

Commentary by Dmitry M. Arbuck, MD, President and Medical Director, Indiana Polyclinic

We are at a truly revolutionary time in health and medicine. The introduction of stem cell technology represents innovation on the same level as the development of antibiotics or the invention of modern imaging (MRIs, etc.). Stem cells are already changing the way medicine is delivered, increasing lifespans and saving countless lives.

Arbuck

Scientists and researchers have been studying the benefits of stem cells for more than 30 years. They have found that these special cells provide great benefits all over the body, from muscles and joints to chronic diseases, to growing new teeth. You may have read about athletes treated with stem cells to speed healing after an injury or about burn victims who use stem cell therapy to minimize scarring.

Stem cells used to be associated with embryos, but this is no longer the case. Today, live cells for treatment are either adult stem cells or umbilical cord blood stem cells. Adult stem cells are most likely extracted from tissue, like bone marrow or fat, which can be a painful and invasive process. Additionally, as we age, so do our stem cells, which become less potent and productive over time. Like every other tissue in our bodies, they are exposed to the toxins, radiation and other pollutants in the environment. Umbilical cord blood stem cells are collected from the donated cord blood and placenta of healthy newborns. The cells are then screened for disease and genetic problems. These umbilical stem cells are vibrant, vital and healthy.

When umbilical cord stem cells are infused, they carry a whole host of immune stabilizing factors throughout the body and work to repair the immune system. This is likely why stem cells are so helpful in the treatment of autoimmune diseases such as rheumatoid arthritis, Crohns disease, dermatitis and myasthenia gravis. Other things that may be successfully treated with this therapy include MS, lupus, graft vs. host disease and other immune conditions.

The future is today. For more, visit StemCellsIndy.com.

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Column: Stem Cell Therapy A medical revolution - Current in Carmel

Stem cell researcher takes on the brain’s fight against age-related … – USC News

By Stell Cell Research

What happens to the stem cells in our brains as we age? Albina Ibrayeva, a PhD student in the USC Stem Cell laboratory of Michael Bonaguidi, addresses this question as she tries to understand how the brain naturally fights against aging and suggests promising therapeutic avenues for treating age-related neurodegeneration, disease and disorders.

I love science. As an undergraduate student back in Kazakhstan, I constantly sought ways to put my knowledge into practice. During my sophomore year, I interned at the National Center for Biotechnology in Astana. This experience enabled me to work with some of the brightest minds dedicated to scientific research in my country and showed me the meaningfulness of a career in biomedical research. Since then, I knew that I wanted to be a scientist.

I won a scholarship and was accepted to graduate school at USC, first to study biomedical engineering as a masters student, then the biology of aging as a PhD student. In 2015, I joined Michael Bonaguidis lab. So here I am, excited and really passionate about contributing to a not-so-distant future where research and medicine advance all humans well-being.

USC is one of the worlds top research universities, especially for someone who is studying neuroscience, stem cells and aging. The synergy among the LAC-USC Medical Center, the Alzheimers Disease Research Center, the Geriatric Studies Center, the Alzheimers Therapeutic Research Institute, the Laboratory of NeuroImaging, the Zilkha Neurogenetic Institute and USCs stem cell research center provides one of the best avenues to do great research and advance clinical and basic science.

Not only I am blessed to work at USC, but also I like the fact that we are surrounded by the best universities, such as Caltech and the University of California campuses in L.A., San Diego, San Francisco and Santa Barbara with whom we collaborate. California is known to be the most progressive place on Earth in science, technology and innovation. That is why I think I am in the right place, where I too can contribute to science and research on aging and its effects.

After graduating from the USC PhD program, I would like to work as a professor and researcher at a U.S. university. It is one of my dreams to be able to share my knowledge and being a professor would allow me to do so, while continuing my research to benefit U.S. health care and the science of aging.

Research, of course, is and will remain a big part of my life. Science is there to help people who are suffering from different diseases and disorders. In particular, stem cell research has a great potential for its therapeutic application across fields. Science can be really challenging. However, at the same time it is really exciting, and I am a firm believer that science is changing and will change the world, if given a chance.

In high school, I was a professional volleyball player. But then I realized that I dont want to pursue a career in sports, but science.

Sometimes it is hard to stay active, especially when all day long you are analyzing your data, conducting experiments and running simulations on your computer. But whenever I have free time, I try to spend it being as active as possible. I try to hike at least once a week. The Santa Monica Mountains are the best place to hike, with their breathtaking views of the Pacific Ocean, native California grasslands, famous Malibu beaches, and even some historical and cultural sites of Native American life. This is what makes me happy outside of science.

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Stem cell researcher takes on the brain's fight against age-related ... - USC News

Baldness: How close are we to a cure? – Medical News Today

By Stem Cell Medical Center

Baldness is an accepted part of the aging process for some, and a source of distress for others. Hair loss affects millions of men and women, yet despite decades of research, a cure is still not available. Just how close are we to finding a magic bullet for baldness? Medical News Today take a look at the evidence.

Androgenetic alopecia - which is more commonly known as male pattern baldness and female pattern baldness - is the most common type of hair loss, affecting around 30 million women and 50 million men across the United States.

In men, hair loss begins above both temples and recedes over time to form an "M" shape. Hair also tends to thin at the crown and may progress to partial or complete baldness. In women, the hairline does not recede and rarely results in total baldness, but the hair does usually become thinner all over the head.

Male pattern baldness is hereditary and may be linked to male sex hormones. Male hair loss can start as early as during adolescence. It affects two thirds of men by age 35, and around 85 percent of men by the age of 50.

The causes of female pattern baldness are unclear. However, hair loss happens most frequently in women after menopause, which indicates that the condition may be associated with decreasing female hormones.

With androgenetic alopecia affecting so many people, a permanent cure would not only lessen anxiety for a significant percentage of the population, but it would also prove financially advantageous to the pharmaceutical company responsible for the discovery.

Hair is made up of the hair follicle (a pocket in the skin that anchors each hair) and the shaft (the visible fiber above the scalp). In the hair bulb, located at the base of the follicle, cells divide and grow to produce the hair shaft, which is made from a protein called keratin. Papilla that surround the bulb contain tiny blood vessels that nourish the hair follicles and deliver hormones to regulate the growth and structure of the hair.

Hair follicles, much like all cells, have cycles. A natural part of the cycle involves shedding around 50 to 100 hairs per day.

Each follicle produces hair for 2 to 6 years and then takes a break for several months. While the hair follicle is in its rest phase, the hair falls out. There are around 100,000 follicles on the scalp, but because each follicle rests at a different time and others produce hairs, hair loss is usually unnoticeable. More noticeable hair loss occurs when there is a disruption to the growth and shedding cycle, or if the hair follicle is obliterated and replaced with scar tissue.

Scientists now understand that pattern baldness occurs through a phenomenon known as miniaturization. Some hair follicles appear to be genetically oversensitive to the actions of dihydrotestosterone (DHT), which is a hormone that is converted from testosterone with the help of an enzyme held in the follicle's oil glands.

DHT binds to receptors in the hair follicles and shrinks them, making them progressively smaller. Over time, the follicles produce thinner hairs, and they grow for a shorter time than normal. Eventually, the follicle no longer produces hair, leaving the area bald.

Currently, there are few available treatment options to halt or reverse miniaturization. Most hair loss treatments only manage hair loss, rather than being a permanent solution.

The only two drugs approved by the U.S. Food and Drug Administration (FDA) to treat hair loss are minoxidil (Rogaine) and finasteride (Propecia).

Minoxidil's use for pattern baldness was discovered by accident. Minoxidil was widely used to treat high blood pressure, but researchers found that one of drug's side effects was hair growth in unexpected areas.

Minoxidil lotion is applied to the scalp and may work by increasing blood flow, and therefore nourishment, to the hair follicles. The American Hair Loss Association say that most experts agree that Minoxidil is "a relatively marginally effective drug in the fight against hair loss."

The treatment has zero effect on the hormonal process of hair loss, and its benefits are temporary. Hair loss continues if usage is discontinued.

Finasteride's side effects of hair growth were stumbled upon during the development of a drug to treat enlarged prostate glands.

Finasteride inhibits type II 5-alpha-reductase, which is the enzyme responsible for converting testosterone into the more potent androgen DHT. DHT levels are reported to be reduced by 60 percent when the drug is taken, which prevents the susceptible follicles from being affected by the hormone and returning their normal size.

This treatment does not work in women, and its effect only remains for as long as it is taken.

Dutasteride (Avodart) is used to treat prostatic enlargement. While the FDA has not approved the drug to treat hair loss, physicians sometimes prescribe dutasteride off-label for male pattern baldness.

Dutasteride works similarly to finasteride, but it may be more effective. Like finasteride, dutasteride inhibits the activity of type II 5-alpha reductase. However, dutasteride additionally inhibits type I of the enzyme. Blocking both types of the enzyme lowers DHT even more and reduces the risk of damage to hair follicles.

This drug faces the same limitations as finasteride, meaning that it only works if taken daily and might become less effective over time.

These therapies may slow down or prevent further hair loss, and they could stimulate regrowth from follicles that have been dormant but still viable. However, they can do little for follicles that have already become inactive. Using them at an earlier stage of hair loss will see more favorable results.

Hair transplantation involves harvesting follicles from the back of the head that are DHT resistant and transplanting them to bald areas. A surgeon will remove minuscule plugs of skin that contain a few hairs and implant the plugs where the follicles are inactive. Around 15 percent of hairs emerge from the follicle as a single hair, and 15 percent grow in groups of four or five hairs.

At the end of the procedure, the person will still have the same amount of hair - it will just be distributed more evenly around the scalp. Treating hair loss through surgical procedure can be painful and expensive. There is also a risk of scarring and infection.

Low-level laser therapy (LLLT) is a form of light and heat treatment. LLLT has been shown to stimulate hair growth in both men and women. Researchers hypothesize that the main mechanisms involved in the process is the stimulation of epidermal stem cells in the follicle and shifting the follicle back into the growth phase of the cycle.

Existing medicines for treating hair loss have limited effectiveness and require ongoing use for the benefits of the treatment to continue.

Researchers continue to strive for the holy grail of hair loss cures by trying to gain a better understanding of how the hair growth cycle is controlled. Rather than treating the symptoms of hair loss, scientists aim to target the cause, which, in turn, may yield fewer side effects. Recently, there have been numerous discoveries in the hair loss arena that may lead to new promising treatments.

Researchers from University of Texas (UT) Southwestern Medical Center in Dallas have identified a protein called KROX20, which switches on cells in the skin and tells them to become hair. Furthermore, these hair precursor cells then go on to produce a protein called stem cell factor (SCF), which plays a critical role in hair pigmentation.

When the SCF gene was deleted in the hair precursor cells in mice, they grew gray hair that turned white with age. Moreover, when the KROX20-producing cells were removed, the hair ceased growing, and the mice became bald.

"With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems," said Dr. Lu Le, associate professor of dermatology at UT Southwestern.

Future work by the team will focus on finding out whether KROX20 and the SCF gene stop functioning properly and lead to male pattern baldness.

A study led by the University Edinburgh in the United Kingdom discovered 287 genetic regions involved in male pattern baldness. Many of the genes that the researchers identified were linked with hair structure and development.

"We identified hundreds of new genetic signals," said Saskia Hagenaars, a Ph.D. student from the University of Edinburgh's Centre for Cognitive Ageing and Cognitive Epidemiology. "It was interesting to find that many of the genetics signals for male pattern baldness came from the X chromosome, which men inherit from their mothers."

Not only could the team's findings help to predict a man's likelihood of experiencing severe hair loss, but they could also provide new targets for drug developments to treat baldness.

University of California-San Francisco (UCSF) researchers reported that defects in a type of immune cell called Tregs - which are usually associated with controlling inflammation - might be responsible for a different kind of hair loss: alopecia areata. They say that Tregs may also play a role in male pattern baldness.

In a mouse model, Michael Rosenblum, Ph.D., an assistant professor of dermatology at UCSF, and colleagues found that Tregs trigger stem cells in the skin, which promote healthy hair. Without partnering up with Tregs, the stem cells are unable to regenerate hair follicles, and this leads to hair loss.

"It's as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work," explained Prof. Rosenblum. "Now the stem cells rely on the Tregs completely to know when it's time to start regenerating."

Hair growth can be restored by inhibiting the Janus kinase (JAK) family of enzymes that are located in hair follicles, according to investigators from Columbia University Medical Center (CUMC) in New York City, NY.

Tests with mouse and human hair follicles showed that applying JAK inhibitors directly to the skin promoted "rapid and robust hair growth." Two JAK inhibitors that are approved by the FDA include ruxolitinib (for the treatment of blood diseases), and tofacitini (for the treatment of rheumatoid arthritis).

In a small clinical trial, Angela M. Christiano, Ph.D. - the Richard and Mildred Rhodebeck Professor of Dermatology and professor of genetics and development at CUMC - reported that treating moderate to severe alopecia areata with ruxolitinib triggered an average hair regrowth of 92 percent.

Prof. Christiano and team plan to expand their studies to include testing JAK inhibitors in other conditions and pattern baldness. "We expect JAK inhibitors to have widespread utility across many forms of hair loss based on their mechanism of action in both the hair follicle and immune cells," she added.

Researchers from the Sanford-Burnham Medical Research Institute in San Diego, CA, developed a technique to generate new hair using pluripotent stem cells. This method would provide an unlimited source of cells without being limited to transplanting follicles from one part of the head to another.

Alexey Terskikh, Ph.D., associate professor in the Development, Aging, and Regeneration Program at Sanford-Burnham, and collaborators coaxed human pluripotent stem cells to become dermal papilla cells.

"We developed a protocol to drive human pluripotent stem cells to differentiate into dermal papilla cells and confirmed their ability to induce hair growth when transplanted into mice," said Prof. Terskikh. The next step in their research is "to transplant human dermal papilla cells derived from human pluripotent stem cells back into human subjects."

Although giant strides to cure baldness are being made in laboratories globally, research is ongoing and the wait for a permanent solution continues.

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Baldness: How close are we to a cure? - Medical News Today

United Veterinary Center Norwalk Offers Stem Cell Therapy to Treat Pets Without Invasive Therapy – Digital Journal

By Stem Cell Medical Center

Norwalk, CT - United Veterinary Center Norwalk humbly announces that their veterinary clinic now offers stem cell therapy to treat pets without any invasive therapy. This Norwalk veterinarian is the first among any other veterinary clinic to offer such a groundbreaking procedure. With its release, pet lovers and owners who have pets with serious medical conditions can now avail of this procedure at their clinic. The research for the stem cell therapy was backed by the Kansas State University independent of MediVet Biologics based on the work of Dr. David A. Upchurch and Dr. Mark L. Weiss.

In a statement by Dr. Gil Stanzione, a CT veterinarian and one of their senior vets, he stated that Our team of medical experts is equipped with up to date advances in veterinary research and technology. Hereat the Center, our experienced Norwalk vet understands the value of your pet to your family." By adopting the stem cell therapy, the clinic stands firm to their word to provide their clients with the newest and latest procedures available. He also added that We are devoted to giving your pets the excellent healthcare and medical services they truly deserve. With the latest technology and state-of-the-art veterinary equipment available in our medical center in Norwalk, Connecticut, your beloved pets are safe in our hands.

The stem cell therapy this Norwalk veterinarian offers is called the ActiStem. The procedure involves an incorporation of a concentration of regenerative stem cells and other repair cells to the damaged portion of the pets body. With the procedure now available at their disposal, the fear of losing a precious member of the family will slowly decrease knowing that there is a veterinary clinic available to treat their pets. Pet owners can rest assured that the procedure their pet will undergo will have no adverse side effects and without the need of intensive therapy.

United Veterinary Center is a veterinary clinic that offers a variety of services and treatments for family pets. The services they offer include administration of vaccinations, wellness programs for pets to keep them healthy, dental care, as well as surgeries and microchip installations. The facilities and services that this Norwalk, CT vet offers are specially designed to take care of your pets. Their clinic can handle medical conditions that may require hospitalization or intensive care for their clients beloved pet.

To avail of their stem cell therapy, United Veterinary Center Norwalk is located at 48 Westport Avenue #2 Norwalk, CT 06851. To know more about the services and the procedures this Norwalk CT veterinarian offers, please visit their website at http://unitedveterinarycenter.com/, or call them at (203) 349-6895.

They can also be contacted via email at info@unitedveterinarycenter.com

Media Contact Company Name: United Veterinary Center Norwalk Contact Person: Dr. Gil Stanzione Email: info@unitedveterinarycenter.com Phone: (203) 349-6895 Address:48 Westport Avenue #2 City: Norwalk State: Connecticut Country: United States Website: http://unitedveterinarycenter.com/

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United Veterinary Center Norwalk Offers Stem Cell Therapy to Treat Pets Without Invasive Therapy - Digital Journal

2017 Innovation Authority Budget Approved for Kadimastem: NIS 12 M for ALS Project – PR Newswire (press release)

By Stem Cell Medical Center

The Company plans to begin its first trial on ALS patients towards the end of 2017, under the supervision of the Israeli Ministry of Health, following completion of the necessary preparations under the outline coordinated with the FDA. The trial will be conducted in the Department of Neurology of the Hadassah Ein-Kerem Medical Center in Ein Kerem, a world-leading center in the field of ALS. The clinical trial will enable the company to prove its innovative treatment in ALS patients.

Yossi Ben-Yossef, the company's CEO, noted: "With the final preparations for the company's clinical trial in ALS patients, we are very pleased with the significant support by the Innovation Authority for the company. The budget which was approved will help us meet our goals and move forward with the initiation of the clinical trial. The budget that was approved for the ALS program for 2017 is the largest budget the company has received for the program to date, indicating confidence in Kadimastem and in the program for the treatment of ALS."

Professor Michel Revel, the company's Chief Scientist, noted that the strong support from the Innovation Authority is a confirmation of the scientific quality of the treatment for ALS that the company is developing.

About Kadimastem

Kadimastem is a biotechnology company, operating in the field of regenerative medicine - a groundbreaking field in which the malfunctioning of organs which leads to diseases is repaired by external cells, tissues or organs. The company specializes in the development of human stem cell-based medical solutions for the treatment of diabetes and neurodegenerative diseases, such as ALS and Multiple Sclerosis. The company was founded in August 2009 by Professor Michel Revel and Yossi Ben Yossef, and is traded on the Tel Aviv Stock Exchange (TASE: KDST). Kadimastem employs 35 people, of which 11 are PhDs, and its 1,700m2offices and labs are located in the Ness Ziona Science Park.

Kadimastem was founded based on patent protected technology that was developed at the Weizmann Institute of Science, in Prof. Michel Revel's laboratory. Prof. Revel, who serves as the company's Chief Scientist and director, developed Merck KGaA's blockbuster drug, Rebif for the treatment of MS (sales of around $2.4 billion sales in 2014).

Based on the company's unique platform, Kadimastem is developing two types of medical applications: A. Regenerative medicine, which repairs and replaces organs and tissue by using functioning cells differentiated from stem cells. The company focuses on transplanting healthy brain cells to support the survivability of nerve cells as cell therapy for ALS, and transplanting insulin-secreting pancreatic cells for the treatment of insulin-dependent diabetes; B. Drug screening platforms, which use functional human cells and tissues to discover new medicinal drugs. The company has two collaboration agreements with leading global pharmaceutical companies.

The company is headed by Yossi Ben-Yossef, an entrepreneur with extensive experience in life sciences companies. The company's chairman is Dr. Eli Opper, formerly the Chief Scientist of the Israeli Ministry of Industry, Labor and Trade, and its investors include Altshuler Shaham Investment House, foreign investors (Julien Ruggieri and Avi Meizler), and the company's founders.

Kadimastem has an extensive scientific advisory board, featuring prominent scientists and pioneers: in the embryonic stem cells field, Professor Benjamin Reubinoff and Professor Joseph Itskovich, in the neurodegenerative disease field, Professor Tamir Ben-Hur, and in the diabetes field, Professor Shimon Efrat and Professor Eddy Karnieli.

Contact: Kadimastem Yehuda Feinberg +972-73-7971600 y.feinberg@kadimastem.com

SOURCE Kadimastem

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2017 Innovation Authority Budget Approved for Kadimastem: NIS 12 M for ALS Project - PR Newswire (press release)

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