Archive for the ‘Molecular’ Category

Moffitt Cancer Center researchers identify drivers of sarcoma growth and survival

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Posted 06 May 2012 — by James Street
Category Kinase, Osteosarcoma, Proteomics, Sarcoma, Tyrosine Kinase

Posted On: May 1, 2012 – 9:00pm

To better understand the signaling pathways active in sarcomas, researchers at Moffitt Cancer Center used state-of-the-art mass spectrometry-based proteomics to characterize a family of protein enzymes that act as “on” or “off” switches important in the biology of cancer. The tyrosine kinases they identified, the researchers said, could act as “drivers” for the growth and survival of sarcomas.

Sarcomas are relatively rare forms of cancer. In contrast to carcinomas, which arise from epithelial cells (in breast, colon and lung cancers, for example), sarcomas are tumors derived from bone, fat, muscle or vascular tissues.

“Sarcomas are rare, diverse malignancies that arise from connective tissues,” said study lead author Eric B. Haura, M.D., program leader for Experimental Therapeutics. “We hypothesized that we could identify important proteins that drive the growth and survival of these poorly understood sarcomas using an approach to characterize signaling proteins using mass spectrometry.”

According to Haura, whose lab focuses on signaling pathways in cancer and understanding the role of kinases, protein phosphorylation plays a significant role in a wide range of cellular processes and is commonly disrupted in diseases such as cancer. The study approach is novel by engaging proteomics, an emerging and increasingly powerful approach to study proteins in disease in a more global and unbiased manner.

In this study, the Moffitt researchers identified 1,936 unique tyrosine phosphorylated peptides corresponding to 844 unique phospho-tyrosine proteins and found 39 tyrosine kinases in sarcoma cells. Of the 99 tyrosine kinases present in the human genome, the research team identified peptides corresponding to nearly 40 percent of the tyrosine kinome.

“Tyrosine kinases play an important role in controlling the hallmarks of cancer, and they have a proven track record as druggable targets for cancer treatment. Our goal was to produce a ‘landscape’ of tyrosine phosphorylated proteins and tyrosine kinases prioritized for subsequent functional validation,” Haura said. “In our study, we identified numerous tyrosine kinases that can be important for cellular signaling in human sarcomas that could drive the natural progression of sarcoma and, therefore, could be targeted by small molecule inhibitors aimed at altering sarcoma progression.”

Questions remain, however, about which, if any, of the 40 tyrosine kinases the researchers identified in sarcoma tumor cell lines act to regulate sarcoma tumor cell growth and tumor survival.

“The answers to this question can help prioritize which potential targets to examine further, including advancement into trials of patients with advanced sarcoma,” explained Haura. “As a first step, we screened sarcoma cell lines against a number of inhibitors selected, all based on the tyrosine kinases we identified, and identified some active drugs.”

While the researchers found kinases in sarcoma cells that deserved further study, they also concluded that the sarcoma cells tested expressed multiple tyrosine kinases. That great number may limit the effectiveness of targeted agents.

“We think this approach could hold promise in profiling tumors directly from patients and can complement existing genetic data on sarcomas. Our results show this is feasible in tumor tissues, and we hope to advance this further by directly studying additional tumors from sarcoma patients.”

 

Stopping the spread of a deadly childhood bone cancer

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Posted 03 Apr 2012 — by James Street
Category Ezrin, Lung Metastases, Osteosarcoma

April 3, 2012 in Cancer

Many children with the bone cancer, osteosarcoma, die after the tumor spreads to their lungs. In a critical step toward finding a way to stop metastasis, researchers at Georgetown Lombardi Comprehensive Cancer Center say they have discovered an agent that prevents this type of cancer from spreading to the lungs in mice with the disease.

The new agent stops or inhibits “ezrin,” a protein vital to the spread of osteosarcoma, say the researchers who presented their findings today at the American Association for (AACR) Annual Meeting 2012. If proven effective in human studies, their ezrin inhibitor might potentially treat whose cancers are fueled by over-expression of this , and could be a life-saver for children with bone tumors.

“If we can prevent metastatic disease in osteosarcoma, we will significantly improve and for these patients,” says the study’s senior investigator, Aykut Üren, M.D., an associate professor of oncology, and of biochemistry and molecular & cellular biology at Georgetown Lombardi Comprehensive Center.

The molecule they discovered represents the first-in-class ezrin inhibitor, he says. “In addition to its potential clinical application, an ezrin inhibitor will be an extremely valuable tool in the laboratory as we work to better understand how ezrin works.”

Ezrin is present in many types of cells in the body including . It controls how the cell interacts with its environment, how the cell moves and how it survives in new locations.

In osteosarcoma, the tumor cells that produce high levels of ezrin are more aggressively invasive, Üren says. “Ezrin also helps cancer cells survive when they reach the lungs. If an osteosarcoma cell with no ezrin spreads to the , it can’t grow there. Having too much ezrin makes it easier for cancer cells to move to the lungs and, once there, it gives these cells a growth advantage.”

Osteosarcoma most commonly develops around knee and shoulder joints in children and is “relatively easy to treat the on the limbs, but when the lungs are involved, patients usually die due to pulmonary insufficiency,” he says.

If successfully developed, an ezrin inhibitor may be useful in preventing the spread of other tumors, too. Breast cancers, colon cancers, melanoma, ovarian carcinoma, brain tumors, and soft tissue sarcomas all show evidence that too much ezrin may mean poor survival outcomes for the patient, says Üren.

Üren and his research team are currently testing several novel compounds in other disease models, including rhabdomyorsarcoma (tumors of the skeletal muscles). They also are making derivatives of several compounds to further increase effectiveness. Some of these new derivatives are also presented the same annual meeting of the AACR today.

“Although we feel we have made a great discovery towards establishing a novel targeted therapy, we are far from our ultimate goal of using this in humans,” Üren says.

Other investigators on this work include Jared T. Murdoch, Sung-Hyeok Hong, Gulay Bulut, George W. Kosturko, Lauren E. Drebing, and Jeffrey A. Toretsky, all of Georgetown Lombardi. The authors also wish to thank Milton Brown and Mikell A. Paige for their contributions.

The study has been funded by a peer reviewed grant support from The Children’s Cancer Foundation of Baltimore, Md. and the Department of Defense.

Üren, Bulut, Kosturko, Toretsky, Brown and Paige are named as co- inventors on a patent application that has been filed by Georgetown University related to technology described in this abstract.

Provided by Georgetown University

Bright future ahead for antibody cancer therapy

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Posted 18 Mar 2012 — by James Street
Category CTLA-4, Immune System, ipilimumab, Melanoma, Melanoma, Monoclonal Antibody

WASHINGTON –Antibodies, once touted as the “magic bullets” of cancer care, are now fulfilling that promise and more advances are on the way, say cancer researchers at the Georgetown Lombardi Comprehensive Cancer Center

In a review article posted online March 16 in Cell, the researchers say that refinements and modifications of monoclonal antibody drugs — several of which have already revolutionized the care of breast and colon cancer –are now being tested in most tumor types.

These modifications allow antibody drugs to bind to more than one target on a cell, and to directly stimulate the body’s immune response to promote vaccine-like antitumor effects. Others have been designed to boost their killing power by carrying a payload of radiation, toxins, or other chemicals.

‘We are heading into an era where antibodies will not just be components of an effective therapeutic strategy, they will be at the core of an oncologist’s treatment plan for patients,” says the review’s lead author, Louis M. Weiner, M.D., director of Georgetown Lombardi Comprehensive Cancer Center, an internationally recognized expert in immunotherapy research.

“Advancement in antibody cancer treatment is not a minor advance or a trivial victory. This is big time stuff,” Weiner said in an interview.

His co-authors on the review are Joseph Murray and Casey W. Shuptrine, both graduate students in the Tumor Biology Training Program at Georgetown Lombardi.

A good example of the new class of antibody-based therapies is ipilimumab, a drug approved in 2011 to treat patients with metastatic melanoma, says Weiner. Ipilimumab is a fully human antibody which binds to an immune antigen (CTLA-4) on cancer cells that transmits a signal inhibiting other immune cells from destroying the tumor. Ipilimumab blocks CTLA-4, thereby inducing an active immune response.

“This agent turns off the brakes of an immune response against melanoma, liberating the body to set up long term protectiion against the cancer,” Weiner says. “About 10 percent of patients with metastatic melanoma who use it go into long-term remission, and may well be cured.”

Antigens are substances, often a cell surface receptor, which causes the immune system to produce an antibody against it, as a way to target and kill the cell. Therefore, antibody agents targeted to a receptor on a cancer cell have the unique capacity to target and kill cancer cells while activating an immune response. A monoclonal antibody (mAb) is an artificially produced antibody designed to bind to a specific cancer antigen, and currently 11 mAbs are approved for use in oncology, Most of these were approved in the last decade. The most commonly used are trastuzumab (Herceptin) to treat HER2-positive breast cancer and rituximab (Rituxan) for specific forms of lymphoma and leukemia.

Advanced antibody engineering techniques are being used to create more effective treatments, Weiner says. One group, known as bispecific antibodies (bsAbs) can bind to two different tumor antigens, or to a tumor antigen and another target in the tumor microenvironment, such as an immune system killer cell. Other mAbs are being designed as “conjugates” to carry a toxic payload, which can be a radionuclide, other drugs, toxins, or enzymes. Researchers are also now increasing the capacity of antibodies to be absorbed by cancer cells so that they can bind to antigens inside the cell – not just on the outside of the cell surface.

“The field of cancer antibodies is definitely maturing. There are scores of new cancer antibody agents now being tested in virtually every kind of solid cancer, and oncologists, researchers and pharmaceutical companies are excited about their promise,” Weiner says. “To me this is like watching a child grow up and do well — very well — in young adulthood.”

###

The work was supported by funding from the National Cancer Institute. Weiner serves as an expert consultant on cancer immunotherapy to several pharmaceutical companies, none of whose products are mentioned in this article.

About Georgetown Lombardi Comprehensive Cancer Center

Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 40 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington, DC, area. For more information, go to http://lombardi.georgetown.edu.

About Georgetown University Medical Center

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC’s mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis — or “care of the whole person.” The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical Translation and Science Award from the National Institutes of Health. In fiscal year 2010-11, GUMC accounted for 85 percent of the university’s sponsored research funding.

How cancer cells start new tumor sites

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Posted 14 Mar 2012 — by James Street
Category CXCL12, metastases
Posted On: March 14, 2012 – 4:30pm

MAYWOOD, Il. — A Loyola University Chicago Stritch School of Medicine study has revealed details of the complex molecular process involving a protein that enables cancer cells to establish tumors in distant parts of the body.

The finding could lead the way to new drugs to prevent breast cancer and other cancers from spreading to new sites.

The study by Adriano Marchese, PhD and colleagues is published in the March 16 issue of the Journal of Biological Chemistry, and is now available online.

The study involves a molecule on the surface of cells called CXCR4. There is an abnormal abundance of this molecule in 23 types of cancer, including cancers of the breast, lung, pancreas and thyroid.

What usually kills patients is the spread of cancer from the primary site to other sites. A tumor cell breaks away from the primary site and circulates through the body. A molecule called CXCL12 acts like a beacon to CXCR4, signaling the cancer cell to land and start a new tumor.

The goal of the study was to better understand this complex signaling pathway. (A signaling pathway involves a group of molecules that work together in a cell. After the first molecule in the pathway receives a signal, it activates another molecule, and the process is repeated until the last molecule is activated.)

“We understand the final outcome of this signaling pathway,” Marchese said. “What we are trying to do now is understand the molecular details.”

In the study, Marchese and colleagues used a line of human cancer cells called HeLa. (The cell line is the subject of the bestselling book “The Immortal Life of Henrietta Lacks”.)

Using HeLa cancer cells, the researchers identified a molecule that is a critical link in the signaling pathway. Researchers hope to target this molecule, thereby disabling the signaling pathway and preventing the cancer cell from setting up shop in a new site, Marchese said.

The next step will be to develop a drug that blocks the target molecule. Researchers then would test the drug on an animal model. If the drug worked in animals, it later could be tested in a clinical trial of cancer patients, Marchese said.

“We are laying the groundwork for the development of new drugs to stop cancer from spreading,” Marchese said.

Marchese is an associate professor in the Department of Molecular Pharmacology and Therapeutics of Loyola University Chicago Stritch School of Medicine. His co-authors are Rohit Malik, PhD (first author), Unice J.K. Soh, PhD, and JoAnn Trejo, PhD.

 

Taking a Leap in Cancer Diagnostics: Clarient Enters New Era in Molecular Tumor Testing, Drug Discovery Research

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Posted 13 Mar 2012 — by James Street
Category ALK, Biomarkers, BRAF, Diagnostic, EGFR, genetic research, Kras, Molecular, PI3K
Anita T. Shaffer
Published Online: Friday, March 9th, 2012

When Kenneth J. Bloom, MD, began his career in pathology more than 25 years ago, the field of genomic and molecular diagnostics in cancer therapeutics was virtually nonexistent. Today, the sector is exploding and Bloom is at the forefront of efforts to develop new oncologic tools and bring them to clinical practice.

Bloom is the chief medical officer of Clarient, Inc, a once-fledgling company that GE Healthcare acquired in December 2010 for $425 million.

Clarient provides more than 350 diagnostic tests to assess and characterize tumors, including tests for BRAF, KRAS, and EGFR gene mutations, as well as the recently launched Clarient InsightDx Mammostrat test for breast cancer recurrence. The company also offers PATHSITE, an Internet-based service where physicians can view and manage digital images, patient case histories, and test results.

In December, Clarient announced a partnership with ACORN Research, LLC, a network of community oncology practices and hospitals, through which tumor-specific biomarker data for each new patient will be collected and analyzed under standardized protocols. The data will be used to personalize treatment for individual patients, as well as to build a databank of information about particular tumor types that can be used in clinical trials and other research.

Such developments are likely to mean a big jump forward not only for the Aliso Viejo, California-based company, but also for patients, according to Bloom.

“This is the perfect storm,” Bloom said in an interview. “All of the things that are necessary are coming together as one. We can really start bringing the highest level of care to every patient anywhere within the United States, and then eventually anywhere in the world. It is incredibly exciting.”

“It’s something that five years ago nobody could have contemplated,” he added. “If you were sick in rural Georgia, you would have to go to Atlanta. But those days are changing. You’re going to be able to get access to the same level of care no matter where you are.”

Bloom said GE ownership will boost Clarient’s ability to expand internationally, while the ACORN partnership will enable the company to compare outcomes with clinical trial results and conduct drug discovery research.

“To me, when we talk about personalized healthcare, it means giving healthcare locally,” he added. “It means you don’t pick up and travel 200 miles to some other institution where your family and friends can’t visit you and you undergo therapy in isolation. If that care could be given locally with your family and friends around you, that would be hugely advantageous. I think that’s what we’ve really been striving for all along, and it’s achievable.”

“

To me, when we talk about personalized healthcare, it means giving healthcare locally. It means you don’t pick up and travel 200 miles to some other institution where your family and friends can’t visit you and you undergo therapy in isolation. ”
–Kenneth J. Bloom, MD

Growing With Community Oncologists in Mind

The trends now shaping the cancer diagnostics field in some ways mirror the trajectories of both Bloom’s career and Clarient’s corporate evolution.

Now, as a result of the sequencing of the human genome and advances such as polymerase chain reaction and microarray technology, the options in genomic and molecular testing in cancer diagnostics are expanding dramatically.

“When I went through medical school, molecular pathology didn’t exist,” Bloom said. “So I got zero molecular pathology in medical school, zero molecular pathology in residency. It’s really only the last 10 or 15 years of my practice that molecular pathology has come to the forefront.”

Bloom, who became a member of the College of American Pathologists in 1987, held a number of positions related to oncology at Rush-Presbyterian- St. Luke’s Medical Center, now Rush University Medical Center, in Chicago, Illinois, for more than 20 years before joining US Labs as senior medical director in 2002.

Within a few years, the Irvine, California, cancer diagnostics company was purchased by industry giant LabCorp. Bloom, who moved on to Clarient in August 2004, said he shared Clarient’s philosophy of partnering with local pathologists rather than supplanting them with a centralized lab.

Clarient itself has grown from a small company launched in the early 1990s to develop medical imaging technologies into a 400-employee business focused on diagnostics.

General Electric Company, which operates GE Healthcare, said in its 2010 annual report that Clarient was a “leading player” in a rapidly growing market, and that its purchase of the company would accelerate GE’s presence in the field. The demand for cancer diagnostics is expected to grow from $15 billion in 2010 to $47 billion by 2015, GE said.

Although the acquisition is an example of the consolidation in the industry, Bloom believes Clarient maintains a business model that preserves both local pathologists, and helps the community oncologists and hematologists with whom they work.

“We really had a passion of bringing cancer testing directly to local pathologists and hence local oncologists,” Bloom said. “The idea was that we would never compete with the local pathologists. The things that a local pathologist knew how to do, and do well, they should do.

“But all of the advanced things that they should be doing but didn’t have access to, either because they didn’t have the space, the resources, the training, or the technicians, we would not only provide that test to them, but we also would engage them in the process, and we would educate them along the way,” he said. “And that’s been an incredibly successful model.”

The GE Healthcare acquisition gives Clarient the resources to expand its model worldwide and to pursue original research, Bloom said. “Now we can lead the charge and develop the next generation of tests that will lead the way to personalized healthcare,” he said.

The Clarient InsightDx Mammostrat

The Clarient InsightDx Mammostrat

Emphasizing Role of Pathologists Amid Change

As the options in cancer diagnostics grow in number and complexity, Bloom believes oncologists will be bombarded with choices they might not be equipped to evaluate. That is why he feels pathologists are vital members of the treatment team.

“Probably the biggest question for oncologists is, ‘How do I deal with all these new tests that are coming on the market?’” he said.

“To me, it’s not obvious that just because there’s a new test, that everybody should instantly understand how that test works and how to apply it,” Bloom said. “There’s going to have to be experts that understand how to do that.”

In Bloom’s view, local pathologists should supply that expertise by working with oncologists and with labs such as Clarient that offer advanced testing.

“The pathologist can be your biggest tool, because they are charged with understanding all of the tests, monitoring the performance of those tests, and discovering why laboratory A might be better than laboratory B for a more consistent and a more robust test result,” Bloom said.

“That would be the single biggest thing that I would tell oncologists to do,” he noted. “You need to become partners with a local pathologist, even if your local pathology lab doesn’t perform the test.”

Top Tests Available at Clarient

Combining innovative diagnostic technologies with world-class pathology expertise, Clarient’s state-of-the-art laboratories provide advanced oncology testing and diagnostic services to assess and characterize cancer. Using a wide range of methodologies, including flow cytometry, IHC, ISH, FISH, cytogenic karotyping, immunofluorescence, microarray, and molecular testing, these are the 7 leading tests Clarient performs:

Mammostrat Breast Recurrence Assay

Methodology: Immunohistochemistry
Highlights:

  • Mammostrat is a novel test for estimating the risk for recurrence in hormonereceptor positive, early-stage breast cancer.
  • Mammostrat stratifies breast cancer patients into low risk (patients have a 7.6% chance of distant recurrence over a 10-year period); moderate risk (patients have a 16.3% chance of distant recurrence over a 10-year period), and high risk (patients have a 20.9% chance of distant recurrence over a 10-year period).

ALK Rearrangement

Methodology: FISH
Highlights:

  • ALK mutations have been identified in 3% to 7% of patients with non-small cell lung cancer (NSCLC).
  • The presence of ALK gene rearrangements may help treating physicians select more effective therapies for patients with NSCLC.
  • ALK gene rearrangements define a distinct molecular subset of NSCLC that is mutually exclusive from EGFR and KRAS mutations.
  • The FISH test results should be used in conjunction with other clinical information.

BRAF

Methodology: Real-time polymerase chain reaction
Highlights:

  • BRAF mutations account for approximately 12% to 15% of colorectal cancer cases.
  • BRAF mutations are biomarkers of nonresponse to anti-EGFR therapies.
  • BRAF mutations are highly predictive of nonresponse to therapy with cetuximab or panitumumab in combination with chemotherapy and as monotherapy.

BRAF V600 Mutation

Methodology: Real-time polymerase chain reaction
Highlights:

  • Approximately 60% of melanomas harbor activating mutations in BRAF V600E as identified by the cobas 4800 test.
  • The cobas 4800 test is the first FDA-approved diagnostic test to help identify patients with the BRAF V600E mutation.
  • Patients with BRAF V600 mutation-positive melanoma as detected by the cobas 4800 test showed dramatic results with vemurafenib.

EGFR Mutation Analysis

Methodology: Molecular polymerase chain reaction
Highlights:

  • EGFR mutations can be seen in approximately 10% to 15% of patients.
  • The development of selective tyrosine kinase inhibitors is an important area of drug discovery for the treatment of a variety of solid tumors such as breast, ovarian, and colorectal cancers, NSCLC, and carcinoma of the head and neck.
  • Patients with EGFR mutations respond more favorably to EGFR tyrosine kinase inhibitors than non-mutation carriers.

KRAS Mutation Analysis

Methodology: Real-time polymerase chain reaction
Highlights:

  • KRAS mutations can be detected in approximately 30% to 40% of patients with colon cancer.
  • Patients with wild-type KRAS have shown much greater benefit to anti-EGFR therapies.
  • Identification of mutations along the KRAS gene suggests that anti-EGFR therapies will not be efficacious in most patients.

PI3K

Methodology: Molecular polymerase chain reaction
Highlights:

  • The PI3K pathway plays an important role in many cancers, including colorectal, breast, and lung cancers.
  • The presence of activating mutations in the PIK3CA gene, which encodes PI3K, can occur in 20% to 30% of cases.
Source: Clarient Inc’s website www.clarient.com.

Breakthrough Cancer Research Presented at Naturopathic Oncology Conference

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Posted 11 Mar 2012 — by James Street
Category Galectin, Honokiol, Modified Citrus Pectin (MCP)

press release

March 6, 2012, 5:13 a.m. EST

CAREFREE, Ariz., Mar 6, 2012 (GlobeNewswire via COMTEX) — Isaac Eliaz, M.D., M.S., L.Ac., distinguished medical doctor and researcher, presents Galectin-3 as a breakthrough biomarker for numerous life-threatening diseases. He also shared new research on the critical role of Modified Citrus Pectin (MCP) as the foremost Galectin-3 blocker. Dr. Eliaz’s latest presentation was given to hundreds of integrative oncologists during the Oncology Association of Naturopathic Physician’s 2012 Convention (OncANP).

OncANP is one of the largest naturopathic organizations with members who specialize in the treatment of cancer. A major focus of the association’s mission is to provide advanced training in the practice of naturopathic oncology for its membership and by doing so to improve the quality of care and patient outcome.

“It’s truly rewarding to share cutting edge research with the medical community, demonstrating Modified Citrus Pectin’s ability to promote health and prevent disease,” says Dr. Eliaz. Modified Citrus Pectin offers remarkable health benefits, which includes binding and blocking excess Galectin-3 molecules throughout the body.

Role of Galectin-3 Molecules

Galectin-3 is produced naturally by our bodies, but new research proves that elevated levels can lead to serious health conditions like heart disease, fibrosis and metastatic cancer. By binding to and blocking excess Galectin-3 molecules, Modified Citrus Pectin prevents Galectin-3 from wreaking havoc on our bodies. A new blood test that measures circulating levels of Galectin-3 as a risk factor in progressive heart failure is now approved by the FDA and covered by most health insurance. This test can also help to determine risks of damage in other organs, including the liver, lungs, brain, kidneys, and others, as well as the progression of cancer.

Versatile Health Benefits of MCP

Recent studies also demonstrate that Modified Citrus Pectin enhances immune function, and reduces galectin-3 expression and disease severity in kidney injury. MCP is also proven to remove lead, mercury, arsenic and cadmium, without reducing essential minerals. “When the toxic burden is high, I recommend a gentle, yet highly effective heavy metal detoxification program using Modified Citrus Pectin,” says Dr. Eliaz.

In addition, groundbreaking new research proves Modified Citrus Pectin (MCP) works synergistically to inhibit aggressive cancer cell behavior, when combined with two of Dr. Eliaz’s advanced poly-botanical formulas: one for breast health and one for prostate health. This study was presented at the last Experimental Biology meeting and is presently in press for publication.

“The findings are extremely promising! Researchers have shown that MCP, in combination with either the breast or prostate formula, significantly further inhibits the metastatic processes of adhesion and migration of breast and prostate cancer cells, in a dose dependant manner,” says Dr. Eliaz.

Honokiol For Cancer, Antioxidant and Anxiety Support

Research presented during Dr. Eliaz’s lecture shows Honokiol has multiple health benefits ranging from anti-cancer and anti-oxidant, to a calming effect. Honokiol is extracted from the bark of the Magnolia tree and is safe to use with conventional cancer therapies. It also works synergistically with Modified Citrus Pectin for increased anti-cancer support.

The new discoveries give Modified Citrus Pectin greater potential in the prevention and treatment of many serious health conditions for which there are currently limited or no treatments available. For more information on Modified Citrus Pectin and the Poly-Botanical Formulas, contact (707) 583-8622 or e-mail info@betterhealthpublishing.com.

About Better Health Publishing

Better Health Publishing (BHP) focuses on the publication of key works promoting health and wellness. BHP believes that education and accessible information are the core components of a healthy and sustainable society.

For Media Questions/Interviews with Dr. Isaac Eliaz, Contact:

Amy Pellegrini Communications Specialist Better Health Publishing amy@dreliaz.org (707) 583-8622

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Better Health Publishing

This information was brought to you by Cision http://www.cisionwire.com http://www.cisionwire.com/better-health-publishing/r/breakthrough-cancer-research-presented-at-naturopathic-oncology-conference ,c9227939

Metabolic profiles essential for personalizing cancer therapy

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Posted 18 Feb 2012 — by James Street
Category metablome, Molecular, Proteomics

February 7, 2012

One way to tackle a tumor is to take aim at the metabolic reactions that fuel their growth. But a report in the February Cell Metabolism shows that one metabolism-targeted cancer therapy will not fit all. That means that metabolic profiling will be essential for defining each cancer and choosing the best treatment accordingly, the researchers say

The evidence comes from studies in mice showing that tumors’ metabolic profiles vary based on the genes underlying a particular cancer and on the tissue of origin.

“Cancer research is dominated now by genomics and the hope that genetic fingerprints will allow us to guide therapy,” said J. Michael Bishop of the University of California, San Francisco. “The issue is whether that is sufficient. We argue that it isn’t because are complex and hard to predict. You may need to have the metabolome as well as the genome.”

Just as a cancer genome refers to the complete set of genes, the metabolome refers to the complete set of metabolites in a given tumor.

The altered metabolism of tumors has been considered a target for anticancer therapy. For instance, tumors and cancer cell lines consume more glucose than normal cells do, a phenomenon known as the Warburg effect. There has often been the impression that such changes in metabolism are characteristic of cancers in general, but cancer is a genetically heterogeneous disease. The team led by Bishop and Mariia Yuneva wondered how metabolism might vary with the underlying of cancer.

They found in mice that liver cancers driven by different cancer-causing genes (Myc versus Met) show differences in the metabolism of two major nutrients: glucose and glutamine. What’s more, the metabolism of Myc-induced is different from Myc-induced .

“Our work shows that different tumors can have very different metabolisms,” Yuneva said. “You can’t generalize.”

Bishop and Yuneva say their findings also highlight glutamine metabolism as a potential new target for therapy in some tumors, noting that the focus has been primarily on glucose metabolism. Interestingly, the data shows that a version of a glutaminase enzyme normally found in kidney cells turns up in cancerous liver cells. That means there might be a way to attack the metabolism of the cancer without damaging normal liver tissue.

“We shouldn’t lose sight of the rather immediate therapeutic potential,” Bishop said.

The researchers will continue to inventory metabolic variation in mouse models. Ultimately, they say it will be important to catalogue the metabolic variation in the much more complex, human setting.

Provided by Cell Press (news : web)

Curcumin May Support Body’s Ability to Slow Prostate Tumor Growth

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Posted 18 Feb 2012 — by James Street
Category Androgren Deprivation, CPB, CURCUMIN, p300, Prostate Cancer

ProHealth.com
February 11, 2012
Source: Thomas Jefferson University news release, Feb 10, 2012

Curcumin, an active component of the Indian curry spice turmeric, may help the body slow tumor growth in prostate cancer patients whose cancers become resistant to androgen deprivation therapy (ADT), a study by researchers at Thomas Jefferson University suggests.

The situation in these patients is that, over time, prostate cancer cells can start to become resistant to hormonal therapies designed to block the release and/or uptake of androgen (testosterone), which is an important male hormone in the development and progression of prostate cancer: Two known nuclear receptor activators, p300 and CPB (or CREB1-binding protein), have been shown to work against androgen deprivation therapy, and with their help, sophisticated tumor cells sometimes bypass the therapy (become ADT resistant).

But the TJU team, led by cancer biologist Karen Knudsen, PhD, have observed in a pre-clinical (animal) study that supplementation with curcumin may support suppression of p300 and CPB.

As described in their report, published in the February issue of Cancer Research, they began by studying prostate cancer cells subjected to hormone deprivation – both without curcumin and with curcumin in doses that were “physiologically attainable.” (Previous studies, which found similar results, had involved doses that were not realistic.)

They found that the curcumin supported greater ADT results, and reduced cell numbers compared with ADT alone. Moreover, the curcumin was found to be a potent inhibitor of both cell cycle and survival in prostate cancer cells.

Next, the researchers investigated curcumin supplementation in a study involving mice that were castrated to mimic ADT. They were randomized into two cohorts: curcumin and control. Tumor growth and mass were significantly reduced in the mice supplemented with curcumin, the researchers report.

These data demonstrate for the first time that curcumin helps the body to both hamper the transition of ADT-sensitive disease to castration-resistance, and block the growth of established castrate-resistant prostate tumors, the researchers say. And “It also has implications beyond prostate cancer, since p300 and CBP are important in other malignancies, like breast cancer.”

Note: This information has not been evaluated by the FDA. It is general information and is not meant to prevent, diagnose, treat or cure any illness, condition or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

Pitt Team Finds Protein That Keeps Balance Between Tumor Cell Growth and Suppression

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Posted 31 Jan 2012 — by James Street
Category KLF4, Molecular

PITTSBURGH – Using an approach that combines molecular biology, genetics, cell biology and physiology, and pathology, researchers at the University of Pittsburgh Cancer Institute (UPCI) and the University of Pittsburgh School of Medicine have identified a protein that governs a key molecule involved in orchestrating the balance between tumor growth and tumor suppression.

The findings, published today in Molecular Cell, reveal a regulatory pathway that could provide new targets for future cancer treatment.

Kruppel-like factor 4 (KLF4) is one of four molecules known to play an important role in transforming the body’s mature cells back into stem cells, said senior author Yong Wan, Ph.D., associate professor, Department of Cell Biology, Pitt School of Medicine and UPCI. His team began studying KLF4 to better understand its biology.

“This molecule has been shown in other studies to encourage tumor growth in some cases, such as breast cancer, but to suppress it in others, such as gastrointestinal cancer,” he said. “We wanted to learn how that was possible.”

From a cultured cancer-cell line, the researchers began purifying proteins and examining their interactions using sophisticated combinatorial techniques. They found that a protein made by the von Hippel-Lindau gene (pVHL) binds to KLF4 and triggers a biochemical pathway that leads to KLF4’sdegradation.

Dr. Wan noted that KLF4 determines cell fate by activating or inhibiting a network of genes involved in cellular functions as diverse as cell cycle regulation and metabolism, stem cell renewal and cell death.  In some cells, it leads to production of proteins that suppress cell proliferation. That means pVHL performs a balancing act: if it is high, the lifespan of KLF4 shortens; if it is low, KLF4 lasts longer, with a consequent impact on the number of cells.

“In colon cancer cells, pVHL levels are high and KLF4 is low, which suggest promotion of tumor cell growth,” he said. “But our other research shows that in breast cancer, KLF4 is high. The abnormal proteins produced by cancer cells could be influencing this pathway, so we are working to better understand these processes.”

Learning more about the role of pVHL, KLF4 and other proteins that interact with them could also lead to new cancer drugs, the researchers said.

Co-authors of the paper include Armin M. Gamper, Ph.D., Xinxian Qiao and Liyong Zhang, Ph.D., of the Department of Cell Biology, Pitt School of Medicine, and UPCI; Jennifer Kim of Carnegie Mellon University; and Michelle C. DeSimone and W. Kimryn Rathmell, M. D., Ph.D., of the University of North Carolina. The research was funded by National Institutes of Health grants CA154695 and CA115943 and the American Cancer Society.

 

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Scientists illuminate cancer cells’ survival strategy

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Posted 31 Jan 2012 — by James Street
Category CDCP1, metastases, Molecular

January 26, 2012

A team led by scientists at The Scripps Research Institute has discovered key elements of a strategy commonly used by tumor cells to survive when they spread to distant organs. The finding could lead to drugs that could inhibit this metastasis in patients with tumors.

A cell that breaks away from the primary and finds itself in the alien environment of the or a new organ, normally is destroyed by a process known as apoptosis. But that express high levels of a certain surface are protected from apoptosis, greatly enhancing their ability to colonize distant organs. How this protein blocks apoptosis and promotes has been a mystery—until now.

“What we found in this study is that it’s not the increased expression of the protein per se that protects a tumor cell, but, rather, the cleavage of this protein by proteolytic enzymes,” said Scripps Research Professor James P. Quigley. “This cleavage triggers a signaling cascade in the tumor cell that blocks apoptosis.” Quigley is the principal investigator for the study, which was recently published online before print by the journal Oncogene.

“We think that a reasonable strategy for inhibiting metastasis would be to try to prevent the cleavage of this using antibodies or small-molecule drugs that bind to the cleavage site of the protein,” said Elena I. Deryugina, a staff scientist in Quigley’s laboratory and corresponding author of the manuscript.

A Protein Linked to Poor Outcomes

The cell-surface protein at the center of this research is known as CUB Domain Containing Protein 1 (CDCP1). In 2003, a postdoctoral fellow in Quigley’s laboratory, John D. Hooper, discovered and co-named CDCP1 as a “Subtractive Immunization Metastasis Antigen,” also finding that it is highly expressed on the surfaces of metastasis-prone human tumor cells.

Quigley’s laboratory and others soon found additional evidence that CDCP1 plays a major role in enabling metastasis. Clinical studies reported CDCP1 on multiple tumor types and linked its presence to worse outcomes for patients. Deryugina and Quigley reported in 2009 that CDCP1, when expressed in tumor-like cells, strongly promotes their ability to colonize new tissues and that unique monoclonal antibodies to CDCP1, generated in Quigley’s lab, significantly block CDCP1-induced tumor colonization. Hooper, who now leads a laboratory at the Mater Medical Research Institute in Brisbane, Australia, reported in a cell culture study in 2010 that most of the CDCP1 protein on the cell membrane could be cleaved by serine proteases. This cleavage event seems to lead to the biochemical activation of the internal fragment of CDCP1 by a process called tyrosine phosphorylation, in this case involving the cancer-linked protein Src.

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