Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Soy-based compound may reduce tumor cell proliferation in colorectal cancer

12.04.2013
Mount Sinai researchers present targets, treatments for prostate, colon, and ovarian cancer at the American Association for Cancer Research Annual Meeting

Research on a soy-based treatment for colorectal cancer, a promising agent in ovarian cancer, and a new drug target for advanced prostate cancer was presented at the American Association for Cancer Research 2013 Annual Meeting. The meeting took place April 6-10, 2013 in Washington, DC.

Natural Product From Soy May Be Effective in Combination with Chemotherapy

The development of colorectal cancer (CRC) is largely driven by cellular signaling in the Wnt pathway, a network of proteins critical to cellular growth. Hyperactivity of the Wnt signaling pathway occurs in more than 85 percent of colon and rectal cancers. Previous research has shown that genistein, a natural supplement containing soy, modulates Wnt signaling through epigenetic mechanisms.

Led by Randall Holcombe, MD, and Sofya Pintova, MD, both from Mount Sinai, the research team treated colon cancer cell lines with genistein and found that it inhibited cell growth and blocked Wnt signaling hyperactivity. The findings are counter to some other tumor types, such as breast, for which soy, because it has estrogen-like properties, increases the risk of developing tumors. Drs. Holcombe and Pintova are launching a clinical trial later this year for patients with metastatic colorectal cancer, which utilizes genistein in combination with chemotherapy based on this research.

"Genistein is a natural product with low toxicity and few side effects and our research shows that it may be beneficial in treating colorectal cancer," said Randall Holcombe, MD, Professor of Medicine in the Division if Hematology and Oncology at the Icahn School of Medicine at Mount Sinai. "This is an exciting area of research and we look forward to studying the benefits of this compound as an adjunctive treatment in colorectal cancer in humans."

Mount Sinai Researchers Identify Promising Therapy for Treatment-Resistant Ovarian Cancer

Platinum-based therapies are the standard of care in treating ovarian cancer, however 60 percent of patients relapse requiring additional treatment. During cancer development, certain proteins that might otherwise block tumor growth are inappropriately shuttled out of the cell's nucleus, and rendered unable to attack a tumor's mutated genome. Researchers led by John A. Martignetti, MD, PhD, Associate Professor of Genetics and Genomic Sciences and Oncological Sciences at Mount Sinai, in collaboration with investigators at Karyopharm Therapeutics, inhibited a nuclear shuttle protein called exportin 1 (XPO1, also called CRM1) using a novel class of drugs called a selective inhibitor of nuclear export (SINE) that can be taken by mouth.

Ying Chen, PhD, a post-doctoral student in Dr. Martignetti's laboratory, injected tumor cells removed from ovarian cancer patients treated at Mount Sinai into mice, and then treated them with a SINE XPO1 inhibitor, KPT-330. All mice treated with KPT-330 had no visible evidence of tumor and survived six times longer than control mice.

Similarly, in another mouse model of chemotherapy-resistant ovarian cancer, KPT-330 significantly reduced the tumor burden and improved overall survival when compared against the current gold-standard platinum treatment. Moreover, mice treated with a combination of KPT-330 and platinum survived even longer. Human trials of KPT-330 are currently ongoing, and will include patients with ovarian cancer later this year.

In part, these experiments arose from a unique scientific resource established by Dr. Martignetti and Dr. Peter Dottino, MD, Associate Clinical Professor, Obstetrics, Gynecology and Reproductive Science. The Ovarian Cancer Translational Research Program preserves cancerous and normal tissues removed in the operating room from all consenting patients for genetic, genomic and therapeutic discoveries. Studies presented at AACR used patient-derived tumor tissues to create mouse tumor avatars to directly test KPT-330 provided by Karyopharm Therapeutics.
"This is truly a translational research initiative where our own Mount Sinai patients are simultaneously contributing to a potential next generation therapy for incurable ovarian cancer and gaining insight into personalized treatment of their own cancers," said Dr. Martignetti. "These results show that new oral XPO1 inhibitors may be quite promising in treating patients who do not respond to, or relapse after, treatment with platinum-based therapy. We look forward to evaluating oral KPT-330 in our patients."

These studies were in part funded through a gift from Sally and Michael Gordon, a gift from Varadi Ovarian Cancer Research Program at Mount Sinai, and a research grant from Karyopharm Therapeutics.

Researchers Identify New Drug Target for Prostate Cancer
During cancer progression, cancer cells constantly interact with and modify their surrounding tumor microenvironment through regulating the expression of a group of enzyme inhibitors called tissue inhibitors of metalloproteinases (TIMPs). Previously, William Oh, MD, Professor and Chief of the Division of Hematology/Oncology in the department of Medicine at Mount Sinai and his colleagues showed that elevated TIMP-1 levels in the blood predicted decreased survival in advanced prostate cancer patients. However, the regulation of TIMP-1 expression in prostate cancer was not fully understood and the source of TIMP-1 overproduction remains unknown.

In the current study led by Yixuan Gong, PhD, in Dr. Oh's lab, the researchers show for the first time that resistance to androgen therapy, the most common treatment for prostate cancer, was associated with TIMP-1 overproduction in both prostate cancer patients and in cell culture models. They found that two signaling pathways called MEK and NF-©§B were critical for TIMP-1 production in certain prostate cells and the production could be completely blocked by drugs that inhibit the pathways.

"Disrupting TIMP-1 signaling prevented androgen resistance providing a promising drug target for this hard-to-treat tumor type," said Dr. Gong. "We look forward to further investigating drugs that block TIMP-1 in a clinical setting."

The Tisch Cancer Institute (TCI) is a world-class translational cancer institute established in December 2007. TCI has recruited more than 30 acclaimed physicians and researchers specializing in basic research, clinical research, and population science; built outstanding programs in solid tumor oncology; enhanced existing robust programs in hematological malignancies; and advanced the study of cancer immunology and vaccine therapy. The completion of the Leon and Norma Hess Center for Science and Medicine in 2012 is enabling the recruitment of up to 20 additional cancer researchers on two full research floors, with 48,000 square feet of space dedicated to cancer research.

To learn more about TCI, visit http://www.mountsinai.org/patient-care/service-areas/cancer.

To learn more about the Hess Center, visit http://icahn.mssm.edu/about-us/hess-center.

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by US News and World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2011, US News and World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and US News and World Report and whose hospital is on the US News and World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.

For more information, visit http://www.mountsinai.org/.

Find Mount Sinai on:
Facebook: http://www.facebook.com/mountsinainyc
Twitter: @mountsinainyc
YouTube: http://www.youtube.com/mountsinainy

Mount Sinai Press Office | EurekAlert!
Further information:
http://www.mssm.edu
http://www.mountsinai.org/

More articles from Health and Medicine:

nachricht Hepatitis: liver failure attributable to compromised blood supply
19.12.2018 | Technische Universität München

nachricht Collagen nanofibrils in mammalian tissues get stronger with exercise
14.12.2018 | University of Illinois College of Engineering

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New megalibrary approach proves useful for the rapid discovery of new materials

Northwestern discovery tool is thousands of times faster than conventional screening methods

Different eras of civilization are defined by the discovery of new materials, as new materials drive new capabilities. And yet, identifying the best material...

Im Focus: Data storage using individual molecules

Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.

Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

New megalibrary approach proves useful for the rapid discovery of new materials

19.12.2018 | Materials Sciences

Artificial intelligence meets materials science

19.12.2018 | Materials Sciences

Gut microbiome regulates the intestinal immune system, researchers find

19.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>