Researchers Identify “Missing Link” Underlying DNA Repair & Platinum Drug Resistance

Researchers have discovered an enzyme crucial to a type of DNA repair that also causes resistance to a class of cancer drugs most commonly used against ovarian cancer.

Scientists from The University of Texas MD Anderson Cancer Center and the Life Sciences Institute of Zhejiang University in China report the discovery of the enzyme and its role in repairing DNA damage called “cross-linking” in the Science Express advance online publication of Science.

Junjie Chen, Ph.D., Professor and Chair, Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center

“This pathway that repairs cross-linking damage is a common factor in a variety of cancers, including breast cancer and especially in ovarian cancer. If the pathway is active, it undoes the therapeutic effect of cisplatin and similar therapies,” said co-corresponding author Junjie Chen, Ph.D., professor and chair of MD Anderson’s Department of Experimental Radiation Oncology.

The platinum-based chemotherapies such as cisplatin, carboplatin and oxaliplatin work by causing DNA cross-linking in cancer cells, which blocks their ability to divide and leads to cell death. Cross-linking occurs when one of the two strands of DNA in a cell branches out and links to the other strand.

Cisplatin and similar drugs are often initially effective against ovarian cancer, Chen said, but over time the disease becomes resistant and progresses.

Scientists have known that the protein complex known as FANCIFANCD2 responds to DNA damage and repairs cross-linking, but the details of how the complex works have been unknown. “The breakthrough in this research is that we finally found an enzyme involved in the repair process,” Chen said.

The enzyme, which they named FAN1, appears to be a nuclease, which is capable of slicing through strands of DNA.

In a series of experiments, Chen and colleagues demonstrated how the protein complex summons FAN1, connects with the enzyme and moves it to the site of DNA cross-linking. They also showed that FAN1 cleaves branched DNA but leaves the normal, separate double-stranded DNA alone. Mutant versions of FAN1 were unable to slice branched DNA.

Like a lock and key

The researchers also demonstrated that FAN1 cannot get at DNA damage without being taken there by the FANCI-FANCD2 protein complex, which detects and moves to the damaged site. The complex recruits the FAN1 enzyme by acquiring a single ubiquitin molecule. FAN1 connects with the complex by binding to the ubiquitin site.

“It’s like a lock and key system, once they fit, FAN1 is recruited,” Chen said.

Analyzing the activity of this repair pathway could guide treatment for cancer patients, Chen said, with the platinum-based therapies used when the cross-linking repair mechanism is less active.

Scientists had shown previously that DNA repair was much less efficient when FANCI and FANCD2 lack the single ubiquitin. DNA response and damage-repair proteins can be recruited to damage sites by the proteins’ ubiquitin-binding domains. The team first identified a protein that had both a ubiquitin-binding domain and a known nuclease domain. When they treated cells with mitomycin C, which promotes DNA cross-linking, that protein, then known as KIAA1018, gathered at damage sites. This led them to the functional experiments that established its role in DNA repair.

They renamed the protein FAN1, short for Fanconi anemia-associated nuclease 1. The FANCI-FANCD2 complex is ubiquitinated by an Fanconi anemia (FA) core complex containing eight FA proteins. These genes and proteins were discovered during research of FA, a rare disease caused by mutations in 13 fanc genes that is characterized by congenital malformations, bone marrow failure, cancer and hypersensitivity to DNA cross-linking agents.

Chen said the FANCI-FANCD2 pathway also is associated with the BRCA1 and BRCA2 pathways, which are involved in homologous recombination repair. Scientists know that homologous recombination repair is also required for the repair of DNA cross-links, but the exact details remain to be resolved, Chen said. Mutations to BRCA1 and BRCA2 are known to raise a woman’s risk for ovarian and breast cancers and are found in about 5-10 percent of women with either disease.

Co-authors with Chen are co-first author Gargi Ghosal, Ph.D., and Jingsong Yuan, Ph.D., also of Experimental Radiation Oncology at MD Anderson; and co-corresponding author Jun Huang, Ph.D., co-first author Ting Liu, Ph.D., of the Life Sciences Institute of Zhejiang University in Hangzhou, China.

This research was funded by a grant from the U.S. National Institutes of Health and the Startup Fund at Zhejiang University.

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“Smile, Open Your Eyes, Love and Go On.”

Today marks the 2nd anniversary of Libby’s death from ovarian cancer at the age of 26. Although the family healing process continues, we celebrate Libby’s life formally on this day to honor her memory, and remind ourselves that life is precious and should not be taken for granted.

Today marks the 2nd anniversary of Libby’s death from ovarian cancer at the age of 26. Although the family healing process continues, we celebrate Libby’s life formally on this day to honor her memory, and remind ourselves that life is precious and should not be taken for granted.  This day also reminds us that there is a considerable amount of work yet to be done in raising ovarian cancer awareness and finding a reliable screening test, and ultimately a cure, for this unforgiving disease.

As reported by the American Cancer Society earlier this month, the estimated number of newly diagnosed ovarian cancer cases and related deaths in the U.S. during 2010 will be 21,880 and 13,850, respectively.  Simply stated, a U.S. woman will die every 38 minutes from ovarian cancer in 2010. Cancer Research U.K. also reported this month that the 10-year ovarian cancer survival rate nearly doubled since the 1970s. Unfortunately, this much heralded statistical “doubling” represents an increase of the long-term ovarian cancer survival rate from 18% to only 35%. Ovarian cancer still remains the most lethal gynecologic cancer in women. I know that if Libby were alive today, she would say, “we must do better.”

Although the vast majority of visitors to this website never knew Libby, it is because of her that Libby’s H*O*P*E*™ was created and shared with the general public. What began as a family website used to exchange ovarian cancer and cancer-related information within the family during Libby’s illness, has rapidly become a global information resource for ovarian cancer survivors and their families after her death. It is my greatest hope that Libby would be proud of the following accomplishments achieved over the past two years, which are dedicated to her memory:

  • Created Libby’s H*O*P*E*™ mission statement to be carried out by a future nonprofit, tax-exempt organization.
  • Generated approximately 145,000 website visitors, from 60 countries around the world.
  • Generated 5% to 10% of daily website visitors from major U.S. and international cancer centers and elite academic institutions actively engaged in cancer research.
  • Established a website library containing over 500 videos relating to ovarian cancer and cancer-related topics.
  • Responded to approximately 700 ovarian cancer survivor (and family) general informational inquiries, which were answered within 96 hours of website posting or email receipt.
  • Created Vox Populi website article features which provide the general public with a better understanding of how ovarian cancer impacts the daily life of a woman diagnosed with the disease and her family. These stories have been well-received by our readers as a source of inspiration and hope.
  • Highlighted in the Eyes on Advocacy section of the 2010 University of Washington Tumor Vaccine Group (UWTVG) quarterly (Winter) newsletter entitled, TVG Focus. The UWTVG is headed by Mary L. (Nora) Disis, M.D., a Professor of Medicine and Adjunct Professor of Pathology and Obstetrics & Gynecology at the University of Washington, and a Member of the Fred Hutchinson Cancer Research Center. Dr. Disis is a world-renowned cancer immunologist.
  • Established a new working relationship with Women’s Oncology Research & Dialogue (WORD), a non-profit, tax-exempt organization dedicated to raising gynecological cancer awareness.  To promote this new relationship, WORD recently shot a video of Paul Cacciatore, the Libby’s H*O*P*E* founder.  In the video, Paul addresses the genesis of the website, the Libby’s H*O*P*E* mission statement, and why it is important for all women to educate themselves about the early warning signs of ovarian cancer.  WORD will be launching a new website before the end of 2010, and it is anticipated that this video will appear on both the WORD and Libby’s H*O*P*E* websites at that time.

“Remember Me”

Based upon instructions from Her Majesty Queen Elizabeth II (“Her Majesty”), a poem entitled, She Is Gone, was recited at the Queen Mother’s funeral, which was held in Westminster Abbey on April 9, 2002. The poem recitation sparked a glut of media interest because of its simple, upbeat nature – and mystery author, who was credited in the service program as “Anon” [i.e., Anonymous].  Apparently, Her Majesty found the poem while leafing through old memorial service books and she chose it to be read at her mother’s funeral, where it struck a chord with millions of mourners.

After the conclusion of the Queen Mother’s funeral, the BBC, The Times, and other U.K. media outlets took great effort to identify the author, with attributions going to, among others, Immanuel Kant and Joyce Grenfell. Eventually, it was discovered that the true author was Mr. David Harkins, who wrote the poem in 1981 while working at a bakery.  Mr. Harkins, who now works as an artist selling paintings over the Internet, said he “couldn’t believe his eyes” when he saw his poetry published in several newspapers after the funeral.

Quite shocked by all of the media attention, David Harkins sent the original manuscript of the poem to Prince Charles (of Wales), and St. James’s Palace replied thanking Mr. Harkins for explaining its origin. As it turned out, the poem was originally written by David Harkins in homage to an unrequited love. Mr. Harkins recalled: “I was 23 when I first met Anne Lloyd, my inspiration for the poem I called Remember Me.”  The reply received by David Harkins from the Prince of Wales’s office stated: “I have no doubt that it [Remember Me] will be reproduced on many occasions over the years to come. The Prince of Wales has asked me to send you his very best wishes.”

I chose to include Remember Me as part of our tribute to Libby for two reasons.  First, the poem is instructive as to how Libby would want all of us to continue on with our lives, energized by our loving memories of her.  Second, Libby would no doubt find great joy and humor in the fact that a talented baker from a small U.K. town became famous worldwide for his literary prowess rather than his pastries. The full text of Remember Me is provided below.

Remember Me

You can shed tears that she is gone

Or you can smile because she has lived

You can close your eyes and pray that she will come back

Or you can open your eyes and see all that she has left

Your heart can be empty because you can’t see her

Or you can be full of the love that you shared

You can turn your back on tomorrow and live yesterday

Or you can be happy for tomorrow because of yesterday

You can remember her and only that she is gone

Or you can cherish her memory and let it live on

You can cry and close your mind, be empty and turn your back

Or you can do what she would want: smile, open your eyes, love and go on.

— written by David Harkins, Silloth, Cumbria, U.K. (1981)

Did You Ever Hear An Angel Sing?

The inspirational story of Rhema Marvanne provides further proof that it is possible to “smile, open your eyes, love and go on,” after the death of a family member from ovarian cancer. It is difficult to believe that the life lesson highlighted by this touching story is provided to us through the example of a 7-year old child, albeit it a very talented one.

Rhema Marvanne was born on September 15, 2002.  Rhema lives with her father Teton Voraritskul, and a family pet dog named, “Mojo.” According to her father, Rhema began singing at the same time she began talking.

Rhema’s mother, Wendi Marvanne Voraritskul, loved Rhema with all of her heart. Wendi was diagnosed with ovarian cancer when Rhema was just 3 years old. Succumbing to the disease three years later, Wendi Marvanne died at the age of 36 on November 8, 2008.  According to Teton Voraritskul, most of Rhema’s memories with her mom were pleasant ones, but revolved around surgery, multiple chemotherapy treatments, sickness and struggle. Wendi was a strong believer in God and never complained about or questioned God during her illness. Teton explains that Wendi always encouraged those around her, even in the midst of her cancer battle. During Wendi’s final months, Rhema and Teton took care of her. Rhema spent almost every hour with her mother. When asked what her greatest accomplishment was prior to her death, Wendi simply replied, “Rhema.” A YouTube video featuring Wendi and her original songs is provided below. You can learn more about Wendi Marvanne’s life and music at www.jchouseofmercy.org.

It was less than a year ago that Rhema recorded her first song, Amazing Grace, and quickly became an Internet singing sensation. She obtains great inspiration from her mother, Wendi.  It is Rhema’s greatest hope to make her mother proud, both as a singer and as a “servant of God,” which is why she also performs for church congregations, non-profit organizations, charities, hospitals and special events.

Already a supremely talented singer, recording artist, and actor, Rhema counts the following among her recent accomplishments:

  • Acted in 1st featured film entitled Machine Gun Preacher, a Lionsgate production set to release in Fall 2011. The movie Machine Gun Preacher is based upon the true story of Sam Childers (portrayed by well-known actor Gerard Butler), a drug-dealing biker who finds religion and dedicates his life to helping Sudanese children escape the Lord’s Resistance Army (LRA) in Africa. Childers founded the Angels of East Africa, a children’s village located in southern Sudan, for the children he saves from the LRA.

During her free time Rhema enjoys playing with her friends and dolls, and loves to watch movies. The best description of Rhema is provided by her father:

…The best way to describe Rhema is that she has a beautiful heart and soul. She is sweet, kind, caring and most importantly pure in heart. Most people who have dealt with or are currently dealing with cancer, disease, challenges, etc…..see hope and inspiration in Rhema. The little girl who should have been scared or harmed by seeing her mother suffer and gone, is strong and perfect. I see Rhema as a cancer survivor. She gives me hope for goodness in mankind. God gave her a beautiful heart and the voice of an angel. Most people that hear her sing can not deny that God does speak through a child. Her voice touches people’s hearts.

Whenever we remember Libby, or any woman who lost her battle to ovarian cancer, we should follow Rhema’s example and heed the call to action set forth in the last line of the poem Remember Me, ” … smile, open your eyes, love and go on.”

Libby, we will always love you and keep your memory alive in our hearts and minds.

How Can You Help?

To support Libby’s H*O*P*E*™, you can make a donation ($10 minimum) through our Facebook Cause page.  All donations made to the Libby’s H*O*P*E*™ Facebook cause are designated for the benefit of the Ovarian Cancer Research Fund (OCRF). OCRF is one of the largest U.S. private, non-profit organizations dedicated to finding an early detection test, and ultimately a cure, for ovarian cancer.

If you are not a Facebook member, you can still make a donation through the Libby’s H*O*P*E*™ Facebook donation page (no membership or registration required).

If you are unable to donate, you can nevertheless support OCRF without any out-of-pocket cost by clicking on our “SocialVibe” widget that appears on the website homepage right sidebar, or by using our designated SocialVibe website. For each reader that clicks on the SocialVibe widget (or goes to our designated SocialVibe website), and watches the video presented and/or answers the question(s) listed, our current SocialVibe sponsor will donate money to OCRF on your behalf for ovarian cancer research. It’s fast & it’s free!

Special Thanks:

We would like to extend special thanks to Teton Voraritskul for allowing us to feature Rhema’s story and music videos, as well as the video of Wendi’s life.  To learn more about Rhema Marvanne and her music, go to www.RhemaMarvanne.com. Rhema’s songs are sold on iTunes®, Amazon.com, and RhemaMarvanne.com.

Sources:

  • Jemal A., Siegel R., Xu J. et. al. Cancer Statistics, 2010.  CA Cancer J Clin. 2010 Jul 7. [Epub ahead of print] [PMID: 20610543].
  • Remember Me, written by David Harkins, Silloth, Cumbria, U.K., PoeticExpressions.co.uk.

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*“Vox Populi,” a Latin phrase that means “voice of the people,” is a term often used in broadcast journalism to describe an interview of the “man on the street.”

In the spirit of Vox Populi, Libby’s H*O*P*E*™ searches online for original writings and visual media created by ovarian cancer survivors, survivors’ family members, cancer advocates, journalists, and health care professionals, which address one or more aspects of ovarian cancer within the context of daily life. The written and visual media features that we discover run the gamut; sometimes poignant, sometimes educational, sometimes touching, sometimes comedic, but always honest. The Vox Populi feature may take the form of an essay, editorial, poem, letter, story, song or video picture montage.

It is our hope that the Vox Populi feature will allow our readers to obtain, in some small way, a better understanding of how ovarian cancer impacts the life of a woman diagnosed with the disease and her family. We invite all readers to submit, or bring to our attention, original writings and visual media suitable for publication as Vox Populi features.

Yale Identifies KRAS Gene Variant in Ovarian Cancer Patients With “Non-BRCA” Family History of Breast/Ovarian Cancer

A team of Yale researchers have identified a genetic marker that can help predict the risk of developing ovarian cancer, a hard to detect and often deadly form of cancer.

A team of Yale researchers have identified a genetic marker that can help predict the risk of developing ovarian cancer, a hard to detect and often deadly form of cancer.

Reporting online in the July 20 edition of the journal Cancer Research, the team showed that a variant of the KRAS oncogene [KRAS variant allele at rs61764370] was present in 25 percent of all ovarian cancer patients. In addition, this variant was found in 61 percent of ovarian cancer patients with a family history of breast and ovarian cancer, suggesting that this marker may be a new marker of ovarian cancer risk for these families, said the researchers.

Joanne B. Weidhaas, M.D., Associate Professor of Therapeutic Radiology & Researcher, Yale Cancer Center

Frank Slack, Ph.D., Professor of Molecular, Cellular & Developmental Biology, Yale University

“For many women out there with a strong family history of ovarian cancer who previously have had no identified genetic cause for their family’s disease; this might be it for them,” said Joanne B. Weidhaas, M.D., associate professor of therapeutic radiology, researcher for the Yale Cancer Center and co-senior author of the study. “Our findings support that the KRAS-variant is an new genetic marker of ovarian cancer risk.”

Weidhaas and co-senior author Frank Slack, also of Yale, first searched for the KRAS-variant among ovarian cancer patients and found that one in four had the gene variant, compared to 6 percent of the general population. To confirm that the KRAS-variant was a genetic marker of ovarian cancer risk, they studied women with ovarian cancer who also had evidence of a hereditary breast and ovarian cancer syndrome. All these women had strong family history of cancer, but only half in their study had known genetic markers of ovarian cancer risk, namely BRCA1 or BRCA2 mutations.

Six out of 10 women without other known genetic markers of ovarian cancer risk had the KRAS-variant. Unlike women with BRCA mutations who develop ovarian cancer at a younger age, women with the KRAS-variant tend to develop cancer after menopause. Because ovarian cancer is difficult to diagnose and thus usually found at advanced stages, finding new markers of increased ovarian cancer risk is critical, note the researchers.

Genetic tests for the KRAS-variant [PreOvar™] are currently being offered to ovarian cancer patients and to women with a family history of ovarian cancer by MiraDx, a New Haven-based biotechnology company that has licensed the Yale discoveries.

The study was funded by the National Institutes of Health. Weidhaas and Slack have a financial interest in MiraDX.

Other Yale authors of the paper include: Elena Ratner, Lingeng Lu, Marta Boeke, Rachel Barnett, Sunitha Nallur, Lena J. Chin, Cory Pelletier, Rachel Blitzblau, Renata Tassi, Trupti Paranjape, Herbert Yu, Harvey Risch, Thomas Rutherford, Peter Schwartz, Alessandro Santin, Ellen Matloff, Daniel Zelterman.

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Challenges Of “Enriched Environment” Significantly Curb Cancer Growth In Mice

Living in an environment rich with physical, mental and social stimulation – a setting that causes mild stress – appears by itself to curb cancer growth in mice, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

Matthew During, M.D., Ph.D., Professor, Neuroscience, Neurological Surgery & Molecular Virology, Immunology & Medical Genetics, College of Medicine, Ohio State Univ. Medical Center

Living in an environment rich with physical, mental and social stimulation – a setting that causes mild stress – appears by itself to curb cancer growth in mice, according to a new study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

The animal study, published as the lead cover story of the July 9 issue of the journal Cell, also shows how this effect happens and that it might have therapeutic use.

The researchers discovered that an enriched environment activates a nervous-system pathway used by the brain to talk to fat tissue. That pathway, called the hypothalamicsympathoneuraladipocyte (HSA) axis tells fat cells to stop releasing a hormone called leptin into the bloodstream. Leptin normally helps restrain appetite, but this study discovered that it also accelerates cancer growth.

The enriched environment had the same cancer-curbing influence in models of melanoma and colon cancer.

“People tend to think that cancer survivors should avoid stress, but our data suggests that this is not completely true,” says study leader Dr. Matthew J. During, professor of neuroscience, of neurological surgery and of molecular virology, immunology and medical genetics.

“The anti-cancer effect we observed in this study was not due simply to increased activity by the animals, but rather it was induced by social and physical challenges that cause mild stress, as measured by the release of hormones from the adrenal.

“But the most dramatic hormonal change we observed was the drop in leptin from fat after enhanced housing conditions activated the HSA pathway. That pathway is also present in humans, where it is likely to be activated by a more complex and challenging life,” he adds.

The enriched environment created for this study housed 20 mice in large containers equipped with toys, hiding places and running wheels, along with unlimited food and water. Control mice were housed in groups of five in smaller, standard laboratory containers with no toys but with unlimited food and water.

The researchers injected human melanoma cells under the skin in both sets of animals. After three weeks of enriched housing, mice had tumors that were about half the size of those in control mice. After six weeks of enrichment, the tumors dropped to approximately one-fifth the size of those in control animals, and almost 20 percent of enriched-group animals had no visible tumors. In contrast, all of the control animals had visible tumors.

Investigating this effect further, During and his colleagues looked for changes in several metabolic hormones in the blood. Notably, the hormone leptin showed a dramatic drop in the enriched group.

A series of experiments demonstrated that leptin and the nervous system pathway really did influence tumor growth.

Looking closely at the region of the brain called the hypothalamus, the researchers found that a gene called BDNF, which plays an important role in controlling food intake and energy balance, was much more active in the enriched group.

Transplanting extra copies of this gene into the hypothalamus of mice in standard housing mimicked the effects of the enriched environment and reduced the size of the tumors in these animals by 75 percent. Such an intervention is also possible clinically and could potentially be developed into a human therapeutic. Blocking the gene, on the other hand, cancelled this effect and caused even enriched animals to develop large tumors.

“This is the first time anyone has shown that putting a single gene into the brain could have a dramatic impact on cancer,” During says.

Next, they studied a strain of mice that was unable to make leptin and so lacked the hormone altogether. When they infused these animals with leptin, they developed melanoma tumors that were 40 percent larger than those in similar animals infused with a saline solution.

An enriched environment also produced a similar cancer-controlling effect in two colon-cancer models. In one of these, tumors develop spontaneously in the intestine; in the other, visible tumors develop after cancer cells are injected under the skin.

Using the second model, researchers discovered that the anti-cancer effect occurred when animals were placed in the enriched environment six days after visible tumors were well established.

“This finding suggests that such an enriched environment might have therapeutic importance,” During says.

During notes that increased physical activity – running in a wheel – alone did not produce the anti-cancer effect or activate the HSA axis. Increased activity did reduce levels of the stress hormone corticosterone in control animals, whereas levels of this hormone rose in animals in enriched housing, an outcome likely due to the challenges and social conflicts associated with larger and more complex group housing.

“Overall, our study suggests that an environmental or genetic activation of this nervous system pathway leads to a marked drop in serum leptin levels, and that this inhibits tumor growth.”

Funding from the National Institute for Neurological Disorders and Stroke supported this research.

Other researchers involved in this study were first and co-corresponding author Lei Cao, as well as Xianglan Liu, En-Ju D Lin, Chuansong Wang, Eugene Choi and Veronique Riban with The Ohio State University; and Benjamin Lin with Weill Medical College of Cornell University.

About the Ohio State University Comprehensive Cancer Center

The Ohio State University Comprehensive Cancer Center- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (http://cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top 20 cancer hospitals in the nation, The James is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.

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2010-2011 U.S. News & World Report “Best Hospitals” List

This week, U.S. News & World Report issued its 2010-2011 rankings of the best U.S. hospitals for adults. The University of Texas, M.D. Anderson Cancer Center is rated #1 in cancer treatment, and Johns Hopkins is rated #1 in gynecology and #1 overall based upon all medical specialties.

If you would like more information regarding the 2010-2011 U.S. News & World Report best U.S. hospital rankings, click here. To better understand how U.S. News & World Report ranked the hospitals in each specialty, read Best Hospitals 2010-11: The Methodology, written by U.S. News & World Report’s Avery Comarow.  If you would like to review the current U.S. News & World Report America’s Best Children’s Hospitals list, click here.

Top 10 U.S. Hospitals: Cancer

Top 10 U.S. Hospitals: Gynecology

Top 10 U.S. Hospitals (highest scores in at least six medical specialties)
1. Univ. of Texas M.D. Anderson Cancer Center, Houston, Texas Johns Hopkins Hospital, Baltimore, Maryland Johns Hopkins Hospital, Baltimore, Maryland
2. Memorial Sloan-Kettering Cancer Center, New York, New York Mayo Clinic, Rochester, Minnesota Mayo Clinic, Rochester, Minnesota
3. Mayo Clinic, Rochester, Minnesota Brigham and Women’s Hospital,Boston, Massachusetts Massachusetts General Hospital, Boston, Massachusetts
4. Johns Hopkins Hospital, Baltimore, Maryland Cleveland Clinic, Cleveland, OH Cleveland Clinic, Cleveland, Ohio
5. University of Washington Medical Center, Seattle, Washington Massachusetts General Hospital, Boston, Massachusetts Ronald Reagan UCLA Medical Center, Los Angeles
6. Dana-Farber Cancer Institute, Boston, Massachusetts Magee-Womens Hospital of Univ. of Pittsburgh Medical Center, Pittsburgh, Pennsylvania New York-Presbyterian Univ. Hospital of Columbia & Cornell, New York, New York
7. Massachusetts General Hospital, Boston, Massachusetts Duke University Medical Center, Durham, North Carolina Univ. of California, San Francisco (UCSF) Medical Center
8. Univ. of California, San Francisco (UCSF) Medical Center Univ. of California, San Francisco (UCSF) Medical Center Barnes-Jewish Hospital/Washington University, St. Louis
9. Cleveland Clinic, Cleveland, Ohio New York-Presbyterian Univ. Hospital of Columbia & Cornell, New York, New York Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
10. Ronald Reagan UCLA Medical Center, Los Angeles Memorial Sloan-Kettering Cancer Center, New York, New York Duke University Medical Center, Durham, North Carolina

ESMO Clinical Practice Guidelines Regarding BRCA Gene Mutations, Ovarian Cancer & Supportive Cancer Care

The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology, and promoting a multidisciplinary approach to cancer treatment and care. …  The ESMO Clinical Practice Guidelines include coverage of  (i) BRCA gene mutations in breast and ovarian cancer, (ii) gynecologic tumors, and (iii) supportive cancer care …

The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology, and promoting a multidisciplinary approach to cancer treatment and care.  Since its founding in 1975 as a non-profit organization, ESMO’s mission is to support oncology professionals in providing people with cancer the most effective treatments available at the highest quality of care.

Formerly known as the ESMO Clinical Recommendations, the ESMO Clinical Practice Guidelines (CPG) are intended to provide users with a set of requirements for the highest standard of care for cancer patients. The ESMO CPG represent vital, evidence-based information including the incidence of the malignancy, diagnostic criteria, staging of disease and risk assessment, treatment plans and follow-up.

A growing number of the new guidelines were developed using large, multidisciplinary writing groups, ensuring optimal input from the oncology profession and better geographic representation.

For example, two revised guidelines address the prevention of chemotherapy- and radiotherapy–induced nausea and vomiting, developed as a result of the 3rd Perugia Consensus Conference organized by the Multinational Association of Supportive Care in Cancer (MASCC) and ESMO.

The new guidelines published this month and available online represent the first stage of a process that will include recommendations for more than 55 different clinical situations, covering almost all tumor types as well as various other topics including the therapeutic use of growth factors.

The ESMO Clinical Practice Guidelines include coverage of  (i) BRCA gene mutations in breast and ovarian cancer, (ii) gynecologic tumors, and (iii) supportive cancer care, as provided below.

Breast Cancer

Gynecologic Tumors

Supportive Care

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UCL Scientists Discover How To Switch On Critical Ovarian Cancer “Protector” Gene & Arrest Tumor Growth

A new University College London study reveals that a gene [EPB41L3] which normally protects against ovarian cancer is switched off in 66% of ovarian cancer cases and switching it back on arrests tumor growth.

A new University College London study reveals that a gene which normally protects against ovarian cancer is switched off in 66% of ovarian cancer cases and switching it back on arrests tumor growth.

The researchers found that the “protector gene,” known as EPB41L3, is inactivated in 65 per cent of ovarian cancers and reactivating the gene halted tumor growth and triggered large numbers of ovarian cancer cells to commit suicide.

The research, co-funded by Cancer Research UK and the gynecological cancer research charity The Eve Appeal, raises the prospect for developing therapies that mimic or restore the function of the gene to kill ovarian cancer cells in a targeted way.

UCL’s Dr. Simon Gayther, who led the study, said:

“Previous studies have found similar ‘protector genes’ but ours is the first to uncover EPB41L3 as a gene specific to ovarian cancer. We also discovered that the gene is completely lost in about two-thirds of the ovarian tumours we looked at. When we switched it back on in these tumours, it had a positive effect in killing cancer cells. This is a very exciting result because it means therapies that mimic or reactivate this gene could be a way to kill many ovarian cancers.”

The scientists, based at UCL’s Institute of Women’s Health, used a cutting-edge approach which involves transferring whole chromosomes into ovarian cancer cells. They found that introducing an additional copy of chromosome 18 boosted the activity of 14 key genes, triggering large numbers of the cancer cells to die.

The scientists examined more than 800 ovarian tumors and found that one of the 14 genes – EPB41L3 – was inactivated in around 66% of malignant ovarian tumors, compared to 24% of benign tumors and 0% of normal ovarian cells.

Reactivating the gene had the same deadly effect on the cancer cells, suggesting that it was the trigger that was causing the cells to self-destruct.

Jane Lyons, CEO of The Eve Appeal, said:

“This research is an exciting step forward – a gene has been identified that can help halt the growth and spread of ovarian cancers. The challenge now is for the researchers and clinicians to find a way to use this new information to increase survival from the disease.”

Dr. Lesley Walker, director of cancer information at Cancer Research UK, said:

“We know that there is a class of genes that protect us from developing cancer. This is an exciting new one specific to ovarian cancer. Advanced ovarian cancer is very difficult to cure, which makes this type of research even more important.”

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