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Breast cancer research uncovers the fountain of youth

Posted: April 8, 2015 at 4:01 pm

IMAGE:These are images of Professor Rama Khokha and Dr. Hartland Jackson. view more

Credit: Courtesy of University Health Network

The Fountain of Youth has been discovered and it's not in Florida as Ponce de Leon claimed. Instead, it was found in the mammary glands of genetically modified mice.

A research team led by Professor Rama Khokha has found that when two factors that control tissue development are removed, you can avoid the impact of aging.

Think of tissue as a building that is constantly under renovation. The contractors would be "metalloproteinases," which are constantly working to demolish and reconstruct the tissue. The architects in this case, who are trying to reign in and direct the contractors, are known as "tissue inhibitors of metalloproteinases" -- or TIMPs. When the architect and the contractors don't communicate well, a building can fall down. In the case of tissue, the result can be cancer.

To understand how metalloproteinases and TIMPs interact, medical researchers breed mice that have one or more of the four different types of TIMPs removed. Khokha's team examined the different combinations and found that when TIMP1 and TIMP3 were removed, breast tissue remained youthful in aged mice. The results are presented in Nature Cell Biology.

In the normal course of aging, your tissue losses its ability to develop and repair as fast as it did when you were young. That's because stem cells, which are abundant in your youth, decline with the passing of time. The U of T team found that with the TIMP1 and TIMP3 architects missing, the pool of stem cells expanded and remained functional throughout the lifetime of these mice.

"Normally you would see these pools of stem cells, which reach their peak at six months in the mice, start to decline. As a result, the mammary glands start to degenerate, which increases the risk of breast cancer occurring," explains Khokha. "However, we found that in these particular mice, the stem cells remained consistently high when we measured them at every stage of life."

The team also found that despite large number of stem cells, there was no increased risk of cancer.

"It's generally assumed that the presence of a large number of stem cells can lead to an increased cancer risk," says Khokha. "However, we found these mice had no greater predisposition to cancer."

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Fountain of youth uncovered in mammary glands of mice, by breast cancer researchers

Posted: April 8, 2015 at 4:01 pm

The Fountain of Youth has been discovered and it's not in Florida as Ponce de Leon claimed. Instead, it was found in the mammary glands of genetically modified mice.

A research team led by Professor Rama Khokha has found that when two factors that control tissue development are removed, you can avoid the impact of aging.

Think of tissue as a building that is constantly under renovation. The contractors would be "metalloproteinases," which are constantly working to demolish and reconstruct the tissue. The architects in this case, who are trying to reign in and direct the contractors, are known as "tissue inhibitors of metalloproteinases" -- or TIMPs. When the architect and the contractors don't communicate well, a building can fall down. In the case of tissue, the result can be cancer.

To understand how metalloproteinases and TIMPs interact, medical researchers breed mice that have one or more of the four different types of TIMPs removed. Khokha's team examined the different combinations and found that when TIMP1 and TIMP3 were removed, breast tissue remained youthful in aged mice. The results are presented in Nature Cell Biology.

In the normal course of aging, your tissue losses its ability to develop and repair as fast as it did when you were young. That's because stem cells, which are abundant in your youth, decline with the passing of time. The U of T team found that with the TIMP1 and TIMP3 architects missing, the pool of stem cells expanded and remained functional throughout the lifetime of these mice.

"Normally you would see these pools of stem cells, which reach their peak at six months in the mice, start to decline. As a result, the mammary glands start to degenerate, which increases the risk of breast cancer occurring," explains Khokha. "However, we found that in these particular mice, the stem cells remained consistently high when we measured them at every stage of life."

The team also found that despite large number of stem cells, there was no increased risk of cancer.

"It's generally assumed that the presence of a large number of stem cells can lead to an increased cancer risk," says Khokha. "However, we found these mice had no greater predisposition to cancer."

The next step in this research is to understand why this is happening. Khokha is also working with her colleagues at Princess Margaret to see how altered tissue remodeling might prevent cancer development or lead to a new therapeutic treatment for patients.

Khokha is a Professor in the departments of Medical Biophysics and Laboratory Medicine and Pathobiology, as well as a Senior Scientist at the Princess Margaret Cancer Centre. Her work is supported by the Canadian Breast Cancer Foundation and the Canadian Cancer Society Research Institute.

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Reality TV show, cancer patient come to Omaha for transplant

Posted: April 8, 2015 at 4:00 pm

Tuesday, the Nebraska Medical Center will once again be in the national spotlight, featured on the reality television show 19 Kids and Counting.

The show focuses on the lives of Jim Bob and Michelle Duggar and their 19 biological children. Recently, the program has also included the Dillard family, when Derick Dillard married one of the Duggar children, Jill. His mother, Cathy Dillard Byrum, has battled Non-Hodgkins Lymphoma, a fight that brought her to Nebraska Medicine last fall.

Dillard Byrum recently spoke to KETVs Brandi Petersen via Skype from her home in Arkansas.

I feel wonderful, Im back to my old self, Dillard Byrum said. She added that through her faith, she was always confident she would beat the cancer, despite a grim diagnosis. When doctors first diagnosed the cancer after a node biopsy, they determined it was stage four and had spread to Dillard Byrums spleen, liver and bone marrow.

I learned that he had not had anyone survive that at the time, said Dillard Byrum. I shall not die, but live, and declare the works of the Lord. I knew I wasnt going to die, but I didnt know how close I would come.

Dillard Byrum describes a grueling chemotherapy regimen, and a fall in her bathroom in the weeks leading up to her sons wedding, shown on 19 Kids And Counting. Doctors later told her with her weakened body from the chemo, she could have bled out in her bathroom from that fall.

About a week before the wedding, and I think you saw this on the show, they air-flighted me, thinking they were going to have to do brain surgery a week before the wedding, said Dillard Byrum. And my doctor told me later he didnt think Id survive the helicopter flight to the other hospital.

She did, and by the end of the summer tests showed the chemotherapy had been successful. Dillard Byrums next step was a stem cell transplant to try and prevent the high-risk cancer from returning. Dillard Byrums doctor told her he wanted her to go to Omaha.

I thought, why Omaha? said Dillard Byrum. I learned, especially over the course of being there, thats the go-to place for this kind of lymphoma.

Dr. Julie Vose, an oncologist and hematologist with Nebraska Medicine, became Dillard Byrums doctor.

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Tiny hair follicle holds big clues about the life and death of stem cells

Posted: April 7, 2015 at 8:52 pm

Inside the microscopic world of the mouse hair follicle, Yale Cancer Center researchers have discovered big clues about how stem cells regenerate and die. These findings, reported in the journal Nature, could lead to a better understanding of how the stem cell pool is maintained or altered in tissues throughout the body.

Stem cells are undifferentiated cells that replenish themselves and based on their tissue location can become specialized cells such as blood or skin cells. The hair follicle is an ideal site for exploring stem cell behavior because it has distinct and predictable oscillations in the number and behavior of stem cells, said the study's lead author Kailin R. Mesa, a third-year doctoral student in the lab of Valentina Greco, associate professor of genetics, cell biology and dermatology.

Using live microscopic imaging to track stem cell behavior in the skin of living mice, researchers observed that the stem cell niche, or surrounding area, played a critical role in whether stem cells grow or die.

"Prior to this, it wasn't clear whether stem cell regulation was intrinsic or extrinsic, and now we know it is external in that the niche instructs the stem cells," Mesa said. "In terms of cancer, we can next explore how we might perturb or change the niche in hopes of affecting the growth of cancer stem cells."

Also, researchers were surprised to find that the stem cells within the pool fed on other dying stem cells. This reveals a mechanism for removing dead cells, a process previously observed in mammary glands but never in the skin.

Story Source:

The above story is based on materials provided by Yale Cancer Center. Note: Materials may be edited for content and length.

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Moffitt researchers discover novel mechanism controlling lung cancer stem cell growth

Posted: April 7, 2015 at 8:52 pm

H. Lee Moffitt Cancer Center & Research Institute

TAMPA, Fla. - Lung cancer is the second most common type of cancer and the number one cause of cancer-related mortality. It is estimated that more than 158,000 people will die from lung cancer in the United States this year. Many scientists believe that targeting a type of cell called a cancer stem cell may be necessary to completely cure lung cancer. Moffitt Cancer Center researchers discovered a novel mechanism that plays an important role in the maintenance of lung cancer stem cells. This finding may lead to new potential therapeutic targets.

Cancer stem cells are a subset of cells within tumors that are believed to be responsible for the initiation of cancer. Cancer stem cells can reproduce themselves through a process called self-renewal and sustain the growth of a tumor. According to Srikumar P. Chellappan, Ph.D., chair of the Department of Tumor Biology at Moffitt, "these cells can also contribute to the metastasis of tumors as well as the reappearance of tumors after they have been eliminated from the body."

A protein called YAP1 was previously shown to contribute to the growth of lung cancer cells; however, it was unknown how YAP1 controls lung cancer growth and progression. Moffitt researchers found that YAP1 plays an important role in cancer stem cell self-renewal.

They reported that YAP1 is found at high levels in lung cancer stem cells and binds to a protein called OCT4. Together, YAP1 and OCT4 regulate a third protein called SOX2. This intricate regulation process allows stem cells to maintain their ability to undergo self-renewal and form blood vessel-like structures.

The team compared the levels of YAP1 and OCT4 in lung cancer and normal tissue. They discovered that YAP1 is present at higher levels and interacts with OCT4 more in primary and metastatic lung tumors than normal tissue. Additionally, lung cancer patients who have high levels of YAP1 in their tumors are more likely to have a poorer prognosis than patients with low levels of YAP1. These observations suggest that YAP1 may be a potential therapeutic target.

The researchers confirmed this hypothesis by showing that if they blocked YAP1 they could inhibit stem cells from undergoing self-renewal, forming blood vessel-like structures, and reduce lung cancer cell growth in mice.

"These results raise the possibility that inhibitors of YAP1 function or agents that can disrupt the binding of YAP1 to OCT4 could have anti-cancer effects. The identification of novel and effective inhibitors of YAP1 activity can be expected to have significant benefits as anticancer agents," explained Chellappan.

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This study was published in the March 6 edition of the journal Stem Cells, and was supported by grants from the National Institutes of Health (CA127725 and CA139612).

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Tiny hair follicle offers big clues about the life and death of stem cells

Posted: April 7, 2015 at 8:52 pm

14 hours ago by Vicky Agnew

Inside the microscopic world of the mouse hair follicle, Yale Cancer Center researchers have discovered big clues about how stem cells regenerate and die. These findings, published April 6 in the journal Nature, could lead to a better understanding of how the stem cell pool is maintained or altered in tissues throughout the body.

Stem cells are undifferentiated cells that replenish themselves and, based on their tissue location, can become specialized cells such as blood or skin cells. The hair follicle is an ideal site for exploring stem cell behavior because it has distinct and predictable oscillations in the number and behavior of stem cells, said the study's lead author, Kailin R. Mesa, a third-year doctoral student in the lab of Valentina Greco, associate professor of genetics, cell biology, and dermatology.

Using live microscopic imaging to track stem cell behavior in the skin of living mice, researchers observed that the stem cell niche, or surrounding area, plays a critical role in whether stem cells grow or die.

"Prior to this, it wasn't clear whether stem cell regulation was intrinsic or extrinsic, and now we know it is external in that the niche instructs the stem cells," Mesa said. "In terms of cancer, we can next explore how we might perturb or change the niche in hopes of affecting the growth of cancer stem cells."

Also, researchers were surprised to find that the stem cells within the pool fed on other dying stem cells. This reveals a mechanism for removing dead cells, a process previously observed in mammary glands but never in the skin.

Explore further: Limited self-renewal of stem cells in the brain

More information: Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool, Nature, DOI: 10.1038/nature14306

Journal reference: Nature

Provided by Yale University

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Dr. Owen Witte recognized with AACR G.H.A. Clowes Memorial Award

Posted: April 7, 2015 at 8:46 pm

PHILADELPHIA -- The American Association for Cancer Research (AACR) is honoring Owen N. Witte, MD, founding director of the Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research and distinguished professor of microbiology, immunology, and molecular genetics at the University of California, Los Angeles, with the 55th annual AACR G.H.A. Clowes Memorial Award at the AACR Annual Meeting 2015, to be held in Philadelphia, April 18-22.

Witte, who is also a Howard Hughes Medical Institute investigator and an elected fellow of the AACR Academy, is being recognized for his many contributions to the understanding of human leukemias, immune disorders, and epithelial cancer stem cells. Witte's work, which contributed to the development of several approved targeted therapies, has transformed the lives of patients with Philadelphia chromosome-positive leukemias and B-cell malignancies. He will present his lecture, "Finding Therapeutic Targets for Aggressive Prostate Cancer," Monday, April 20, 5:30 p.m. ET, in the Grand Ballroom of the Pennsylvania Convention Center.

The AACR and Eli Lilly and Company established the G.H.A. Clowes Memorial Award in 1961 to honor Dr. G.H.A. Clowes, a founding member of the AACR and research director at Eli Lilly. This award recognizes an individual with outstanding recent accomplishments in basic cancer research.

Witte's innovative work helped revolutionize modern cancer treatment by defining tyrosine kinases as crucial drug targets in human disease. Most notably, he pinpointed the molecular consequences of the Philadelphia (Ph) chromosome abnormality present in chronic myelogenous leukemia (CML) and related types of leukemia and defined the tyrosine kinase activity of the ABL gene product. These findings played a crucial role in the subsequent development of ABL kinase-targeted therapies, including imatinib (Gleevec), which remains the front-line treatment for Ph-positive CML.

In addition to his research involving ABL, Witte also co-discovered Bruton agammaglobulinemia tyrosine kinase (BTK). This particular kinase is essential for B-cell maturation and when mutated, results in the onset of the immunodeficiency disease, X-linked agammagloblulinemia. Recent studies involving this protein have resulted in the U.S. Food and Drug Administration approval of ibrutinib (Imbruvica), a selective BTK inhibitor, for the treatment of chronic lymphocytic leukemia mantle cell lymphoma, and Waldenstrm macroglobulinemia.

More recently, Witte's work has focused on defining the epithelial stem cell populations that contribute to prostate cancer. He is currently using mass spectrometry approaches to identify kinases that could be potential therapeutic targets for human prostate cancer.

"Much progress has been made in the area of personalized cancer medicine due to the dedication of scientists and physicians around the world, many of whom I've had the pleasure of working with through the AACR's innovative initiatives," said Witte. "But much more work is needed as we seek to understand cancer, which is not a single disease but rather many diseases that develop differently. I thank the AACR for their leadership in this effort and am honored to receive the Clowes Memorial Award."

An active AACR member, Witte has served on the AACR board of directors and several grant review committees. He is a past recipient of the AACR-Richard and Hinda Rosenthal Award and a co-leader of the Stand Up to Cancer Dream Team: Targeting Adaptive Pathways in Metastatic Treatment-Resistant Prostate Cancer. Additionally, he is also serving an appointed term on the President's Cancer Panel.

Witte has been recognized throughout his career with numerous honors. He has received the Nakahara Memorial Lecture Prize, the Cotlove Lectureship from the Academy of Clinical Laboratory Physicians and Scientists, the de Villiers International Achievement Award from the Leukemia and Lymphoma Society, the Warren Alpert Prize, and is elected member of the Institute of Medicine, National Academy of Sciences, and fellow of the American Academy of Arts and Sciences and the American Academy of Microbiology.

Witte received his medical degree from Stanford University School of Medicine in California, and was a postdoctoral fellow at the Center for Cancer Research at the Massachusetts Institute of Technology in Cambridge. He joined the UCLA faculty in 1980.

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Dr. Raj at Beverly Hills Orthopedic Institute Now Offering Stem Cell Therapy to Heal Chronic Tendonitis

Posted: April 7, 2015 at 8:46 pm

Beverly Hills, California (PRWEB) April 07, 2015

Dr. Raj, the top Orthopedic Surgeon in Beverly Hills and Los Angeles, is now offering stem cell therapy to heal chronic tendonitis. The treatment works exceptionally well for those suffering from tendonitis of the rotator cuff, achilles, elbow and knee. For more information and scheduling, call (310) 247-0466.

As a pioneer in regenerative medicine, Dr. Raj has been helping patients with degenerative arthritis achieve relief and avoid joint replacements for years with stem cell procedures. By adding the procedures for tendonitis, Dr. Raj is now helping patients avoid potentially risky surgeries and get back to being more active for soft tissue related pain.

"Surgery for tendonitis is often not 100% successful for patients, and the rehabilitation period may take six months," states Dr. Raj. "With the stem cell therapy, pain relief is quick and athletes get back to sports faster!"

Regenerative medicine for tennis elbow has been shown in research studies to be effective at relief and helping avoid surgery. A 2013 study out of South Florida showed that 28 out of 30 patients with chronic tennis elbow avoided surgery and got back to being very active.

For several years in a row, Dr. Raj has been named the top orthopedic doctor in Los Angeles and Beverly Hills. He is an ABC News Medical Correspondent as well as a WebMD Medical Expert.

Hundreds of patients have benefited from stem cell procedures with Dr. Raj at Beverly Hills Orthopedic Institute. They come from all over Southern California, along with throughout the country. Call (310) 247-0466 for scheduling stem cell therapy with an orthopedic surgeon Beverly Hills trusts and respects.

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Regen BioPharma expands Its differentiation therapy of cancer stem cells platform

Posted: April 7, 2015 at 8:46 pm

(MENAFN - ProactiveInvestors) () a biotechnology company announced the expansion of its cancer stem cell intellectual property portfolio to include targeting of the gene NR2F2 (also known as COUP-TFII) a closely related family member to the cancer stem cell gene NR2F6 with the filing of two patent applications.

Patent application #14588374 is for treatment of myelodysplastic syndrome (MDS) by inhibition of NR2F2 and patent application # 14588373 is for methods and compositions for treatment of cancer by inhibition of NR2F2 the San Diego California-based company said in a statement today.

Patent application #14588374 covers methods compositions and treatment protocols for the treatment of MDS. This patent application also covers induction of differentiation or stimulation of apoptosis as a result of NR2F2 inhibition to reduce the state of MDS and/or in other embodiments to inhibit or revert progression to leukemic states Regen said.

Patent application #14588373 covers utilizing of gene silencing technologies pertaining to suppression of the nuclear receptor NR2F2 for use as cancer stem cell inhibitors as well as cancer stem cell pathway inhibitors and methods of using such compounds to treat cancer.

These new patent applications add to the company's existing portfolio of intellectual property covering therapeutics that can be used as differentiation therapy a new form of cancer treatment that works by instructing cancer stem cells to mature in to normal cells that have a limited lifespan.

This intellectual property will compliment other intellectual property in the gene silencing of cancer stem cells therapeutics platform including in-house and acquired IP from the University of Toronto for the cancer stem cell gene NR2F6 (also known as EAR-2) and the company's CTCFL technology also known as BORIS).

We are working on establishing an area of expertise in gene silencing of cancer stem cell target genes that builds upon a licensing agreement with Benitec Biopharma for use in conjunction with their shRNA gene silencing platform chief executive officer David Koos said in the statement.

This allows us to take advantage of synergisms by establishing strengths and programs that we can use to comprehensively target the important genes in the cancer stem cell space. This will lead to economies of scale in therapy development.

The cancer stem cell is the most important and sought after cellular target of cancer therapy. Not every cancer cell within a tumour is able to divide. Cancer stem cells are the cells within the tumour that can divide an infinite number of times and are the cells within the tumour that allow a tumour to maintain its cancerous ability therefore it is important to target those cells specifically.

"Patent protection is also essential for thoroughly protecting the Company's space in this field chief scientific officer Thomas Ichim said in the statement.

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Can cancer vaccines prolong survival?

Posted: April 7, 2015 at 6:59 pm

IMAGE:Cancer Biotherapy and Radiopharmaceuticals, published 10 times per online with open access options and in print, is under the editorial leadership of Co-Editors-in-Chief Donald J. Buchsbaum, PhD, Department of Radiation... view more

Credit: Mary Ann Liebert, Inc., publishers

New Rochelle, NY, April 6, 2015--Therapeutic anti-cancer vaccines developed to treat metastatic disease such as advanced prostate cancer or melanoma rarely have a noticeable effect on the tumor but have been associated with a statistically significant increase in patient survival. Robert O. Dillman, MD, NeoStem, Inc., asserts that "overall survival" rather than "progression-free survival" should be the gold standard for evaluating the efficacy of cancer vaccines in clinical trials, in a provocative new article published in Cancer Biotherapy and Radiopharmaceuticals, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Cancer Biotherapy and Radiopharmaceuticals website until May 6, 2015.

In the article "Cancer Vaccines: Can They Improve Survival?" Dr. Dillman differentiates between the two key endpoints typically used to assess therapeutic cancer vaccines in clinical studies. As cancer vaccines are designed to stimulate an immune response to cancer cells and induce long-term memory recognition of a tumor, they may improve overall survival even if they do not appear to slow the progression of disease. Although measuring overall survival compared to progression-free survival would usually require longer clinical trials, overall survival may be the only relevant efficacy endpoint, the author concludes.

"This is a timely article considering the number of vaccine and antibody immunotherapy trials ongoing or planned," says Co-Editor-in-Chief Donald J. Buchsbaum, PhD, Department of Radiation Oncology, Division of Radiation Biology, University of Alabama at Birmingham. "The conclusion that overall survival is the best clinical endpoint for efficacy in therapeutic vaccine and antibody immunotherapy trials in patients with metastatic cancer is based on an analysis of four completed trials."

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About the Journal

Cancer Biotherapy and Radiopharmaceuticals , published 10 times per online with open access options and in print, is under the editorial leadership of Co-Editors-in-Chief Donald J. Buchsbaum, PhD, Department of Radiation Oncology, Division of Radiation Biology, University of Alabama at Birmingham, and Robert K. Oldham, MD, CAMC-Teay's Valley Cancer Center. Cancer Biotherapy and Radiopharmaceuticals, celebrating 30 years in 2015, is the only journal with a specific focus on cancer biotherapy, including monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapy. The Journal includes extensive reporting on advancements in radioimmunotherapy and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments. Tables of content and a sample issue may be viewed on the Cancer Biotherapy and Radiopharmaceuticals website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Journal of Interferon & Cytokine Research, Human Gene Therapy, and Stem Cells and Development. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN) (http://www.genengnews.com), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

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