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December 2, 2016

Study Examines High Rate of Rare Mesothelioma Among Young Women in Eastern China

HONOLULU – A research team led by Michele Carbone, director of Thoracic Oncology at the University of Hawai'i Cancer Center in collaboration with scientists at New York University, and Zhejiang Cancer Hospital in Hanghzou, China, discovered an unusually high rate of a rare form of mesothelioma among young women in Eastern China.

Mesotheliomas are malignant cancers usually caused by exposure to asbestos. Most occur in the chest cavity of older men who have worked in the asbestos industry. However, UH Cancer Center researchers found a rare form of mesothelioma infrequently linked to asbestos exposure in young women in Eastern China.

"This localized epidemic of peritoneal mesothelioma in Eastern China is unique. The finding gives us the opportunity to study these women, identify the causes, and develop preventive strategies in China and throughout the world. We want to save many women from this deadly disease," said Michele Carbone.

The new study published in JAMA Oncology examined tumors diagnosed as mesothelioma from 2002 through 2015 at two Chinese hospitals – one in Hangzhou, China, where there is no asbestos industry and one in Yuyao, China, located in the Chinese textile industrial area, where most patients are exposed to asbestos.

Researchers found the male-to-female ratio of mesothelioma was 1 to 4 compared to 4 to 1 in the U.S, and the pleural (chest cavity mesothelioma)-to-peritoneal ratio was 1 to 3 compared to 5 to 1 in the US. Also, only 1 of 14 peritoneal malignant mesothelioma cases in Hangzhou was associated with asbestos.

"In recent years we have seen an increase around the world of peritoneal mesothelioma in young women not exposed to asbestos, and the cause is still unknown," said Carbone.

"These new findings allow UH Cancer Center researchers to study the causes and develop critical preventive strategies," said Randall Holcombe, UH Cancer Center director. "The collaborative study highlights the importance of the Center's location in Hawai'i, making us the cancer research bridge between Asia and the United States."

Publication
Publication: http://jamanetwork.com/journals/jamaoncology/fullarticle/2588462
DOI: 10.1001/jamaoncol.2016.5487

The University of Hawai'i Cancer Center through its various activities, cancer trial patients and their guests, and other visitors adds more than $54 million to the O'ahu economy. This is equivalent to supporting 776 jobs. It is one of only 69 research institutions designated by the National Cancer Institute. Affiliated with the University of Hawai'i at Manoa, the center is dedicated to eliminating cancer through research, education, and improved patient care. Learn more at www.uhcancercenter.org. Like us on Facebook at www.facebook.com/UHCancerCenter. Follow us on Twitter @UHCancerCenter.

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News Highlights

November 9, 2016

UH CANCER CENTER RESEARCHERS DISCOVER GENES THAT CONTRIBUTE TO GROWTH OF A RARE AND AGGRESSIVE CANCER

HONOLULU – An international research team led by Dr. Michele Carbone at the University of Hawai'i Cancer Center discovered novel genes that contribute to the growth of malignant mesothelioma, a rare and aggressive cancer caused by asbestos that forms in the linings of the lungs, abdomen, or heart.

"As we discover key mechanisms responsible for the growth of this cancer, we are finding more targeted ways to prevent mesothelioma. This helps reduce the number of future patients, and increase the development of more effective therapies," said Dr. Michele Carbone, UH Cancer Center's director of Thoracic Oncology.

The findings published in "Proceedings of the National Academy of Sciences" highlight the discovery that gene mutations and deletions are frequent in mesothelioma and occur through a variety of DNA alterations. Dr. Carbone and collaborators also found that studies using modern DNA sequencing technologies such as Next Generation Sequencing (NGS) under-estimated the frequency of genetic alterations in mesothelioma.

"An integrated research approach combining NGS with other genetic techniques can reveal additional genetic alterations in cancer biopsies, thereby allowing us to design more precise and effective personalized therapies," said Dr. Haining Yang, co-senior author of the study.

This research is the result of a 2-year collaboration with UH Cancer Center researchers, Drs. Yoshie Yoshikawa and Mitsuru Emi at Hyogo College of Medicine in Japan, and Dr. Harvey I. Pass at New York University.

"These discoveries are an indication of the high quality science at the Center, and Dr. Carbone and Dr. Yang as international leaders in mesothelioma research," said Dr. Randall Holcombe, UH Cancer Center director. "This research collaboration with Japanese and New York institutions demonstrates the importance of the UH Cancer Center as a key player in connecting researchers on the mainland and in Asia in the global fight against cancer."

Publication
http://owl.li/ECsi3061Grr

The University of Hawai'i Cancer Center through its various activities, cancer trial patients and their guests, and other visitors adds more than $54 million to the O'ahu economy. This is equivalent to supporting 776 jobs. It is one of only 69 research institutions designated by the National Cancer Institute. Affiliated with the University of Hawai'i at Manoa, the center is dedicated to eliminating cancer through research, education, and improved patient care. Learn more at www.uhcancercenter.org. Like us on Facebook at www.facebook.com/UHCancerCenter. Follow us on Twitter @UHCancerCenter.

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News Highlights

November 14, 2016

UH CANCER CENTER RESEARCHER FINDS NEW DRIVER OF AN AGGRESSIVE FORM OF BRAIN CANCER

HONOLULU – University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age. The discovery can help researchers create novel targeted therapies potentially reducing deaths from this devastating cancer.

Joe Ramos
Joe Ramos

"New treatment options for brain cancer patients are desperately needed," said Joe W. Ramos, PhD, UH Cancer Center deputy director and lead researcher on the study. "Treatment options include chemotherapy in combination with radiation, but they only prolong a patient's life by a few months."

Glioblastoma remains a lethal cancer with only a 14-month average survival rate after initial diagnosis.

The study published in "Oncotarget" reveals that a protein called RSK2 is increased in many patients with glioblastoma. The protein pushes glioblastoma cells into surrounding healthy brain tissue. The invasion of these cells throughout the brain makes it difficult to remove the tumor by surgery, which contributes to high recurrence and poor survival rates in patients. The invading glioblastoma cells are less sensitive to current standard therapies. The research team found that inhibiting RSK2 stops invasion of the tumor cells and enhances the effectiveness of standard chemotherapy in tumor cells obtained from patients.

Santosh Kesari
Santosh Kesari

"This study paves the way for development of new brain cancer therapies focused on RSK2 inhibitors for brain invasion," said co-author Dr. Santosh Kesari, chair of Department of Translational Neurosciences and Neurotherapeutics of the John Wayne Cancer Institute and Pacific Neuroscience Institute at Providence Saint John's Health Center.

"The next steps include identifying better compounds to target the RSK2 protein. We are hoping to discover a powerful new drug to treat this aggressive brain cancer," said Dr. Ramos.

The findings resulted from several years of collaboration among the labs of Drs. Ramos and Michelle Matter at the UH Cancer Center, Kesari at the John Wayne Cancer Institute, and Dirk Geerts of Erasmus University Medical Center in the Netherlands.

"The new discovery can potentially lead to a new class of drugs to treat not only brain cancers, but other invasive cancers as well. With about 60 new cases of brain cancer diagnosed every year in Hawai'i, and about 40 deaths, an effective treatment can help many patients in our state," said Dr. Randall Holcombe, UH Cancer Center director.

Publication
https://goo.gl/UZK4UK
DOI: 10.18632/oncotarget.13084

The University of Hawai'i Cancer Center through its various activities, cancer trial patients and their guests, and other visitors adds more than $54 million to the O'ahu economy. This is equivalent to supporting 776 jobs. It is one of only 69 research institutions designated by the National Cancer Institute. Affiliated with the University of Hawai'i at Manoa, the center is dedicated to eliminating cancer through research, education, and improved patient care. Learn more at www.uhcancercenter.org. Like us on Facebook at www.facebook.com/UHCancerCenter. Follow us on Twitter @UHCancerCenter.

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News Highlights

November 1, 2016

New Cancer Treatment Strategy Discovered for Acute Myeloid Leukemia

HONOLULU – University of Hawai'i Cancer Center researchers discovered a novel therapeutic target and treatment strategy for acute myeloid leukemia (AML), a cancer of the blood and bone marrow that normally requires prompt and aggressive treatment.

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Wei Jia

"New therapeutic targets and drugs are urgently needed to improve AML patient outcomes," said Wei Jia, PhD, researcher in the UH Cancer Center's Cancer Epidemiology Program. Jia continued, "We found an increased use of fructose in AML patients. This unique metabolic feature predicts poor treatment outcomes in patients. Our study provides strong evidence that blocking fructose utilization using a small molecule drug shows dramatic therapeutic benefit for AML treatment."

The conventional regimen for AML treatment is limited. Only about 25 to 30 percent of patients survive for 5 years or more after they are diagnosed.

"This discovery can have a profound impact on cancer treatment outcomes, not just for AML patients, but possibly for many other patients with different types of cancers," said Dr. Randall Holcombe, UH Cancer Center director. "Metabolomics is a unique program at the Center, for which Dr. Jia is an international leader."

The findings published in Cancer Cell highlight the unique ability of AML cells to switch their energy supply from glucose to fructose, when glucose is in short supply. Fructose is the second most abundant blood sugar in the body and is used as a glucose alternative by AML cells in order for the cells to retain energy. After the switch, cancer cells begin to multiply faster.

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The study found a treatment potential by stopping the glucose transporter (GLUT 5). This method restricts the AML energy supplies and effectively stops cancer growth. By targeting the GLUT 5, researchers can effectively slow the growth of the cancer cells leading to a new promising treatment for AML patients.

"Our normal cells hardly rely on fructose for growth. This makes the fructose transport in cancer cells an attractive drug target. We are in the process of developing a GLUT5 inhibitor, thus cutting the cancer cells' energy source and eventually killing them. The new GLUT5 inhibitor can potentially be used alone, or in addition to the current chemotherapy drugs to enhance anti-cancer effects," said Jia.

Leukemia in Hawai'i (Hawai'i Tumor Registry)
Leukemia is one of the top ten most common cancers among women in Hawai'i and the top ten causes of cancer deaths in both men and women.

From 2004 to 2013, the incidence of leukemia significantly increased in Hawai'i men and women.

Cancer Cell publication
http://www.cell.com/cancer-cell/fulltext/S1535-6108(16)30441-X

The University of Hawai'i Cancer Center through its various activities, cancer trial patients and their guests, and other visitors adds more than $54 million to the O'ahu economy. This is equivalent to supporting 776 jobs. It is one of only 69 research institutions designated by the National Cancer Institute. Affiliated with the University of Hawai'i at Manoa, the center is dedicated to eliminating cancer through research, education, and improved patient care. Learn more at www.uhcancercenter.org. Like us on Facebook at www.facebook.com/UHCancerCenter. Follow us on Twitter @UHCancerCenter.

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