October 20, 2014
Angiogenin sheds light on bladder cancer biology and provides diagnostic valueby Chantal Jackson
HONOLULU, HI - University of Hawai'i Cancer Center's (UHCC) director of the Clinical and Translational Research program, Dr. Charles Rosser, has received the Center's October 2014 award for "Publication of the Month." The paper is: Miyake M, Goodison S, Lawton A, Gomes-Giacola, Rosser CJ, Angiogenin promotes tumoral growth and angiogenesis by regulating matrix metallopeptidase-2 expression via the ERK1/2 pathway, Oncogene, 2014, February 24, doi: 10.1038/onc.2014.2.
In this paper, Dr. Rosser and his team provide evidence for angiogenin (ANG) as a therapeutic target in bladder cancer. Specifically, these researchers have shown the importance in the ERK1/2 pathway in ANG's ability to promote both tumor growth and angiogenesis, essential in the spread of cancer.
One major area of focus at UHCC is to develop a clinically useful non-invasive method of diagnosing bladder cancer. Through this work, researchers have uncovered 10 biomarkers (combination of genes and proteins) that are abnormal in bladder cancer. ANG is one of these biomarkers. However, prior to the work leading to the paper cited above, the role of ANG in bladder cancer was not clear.
In this study, researchers checked and manipulated ANG levels in cells, both in the petri dish as well as in animals. From this, they determined that higher ANG levels promotes increased cancer cell growth. In particular, when ANG increases, it promotes an increase in matrix metallopeptidase-2 (MMP2). MMP2 breaks down the extracellular matrix which enables cell mobility, thus allowing cancer to spread. MMP2 also increases angiogenesis, essential for both tumor growth and metastasis.
The authors determined that the ERK1/2 pathway plays an integral role in tumor-growth progression and the spread of cancer. Dr. Charles Rosser explains, "This is a project that began in the clinic with the goal of finding a non-invasive way to test for bladder cancer. That is, whether voided urine could be tested to determine the likelihood that a person has bladder cancer. From this test, only persons with a higher likelihood of having bladder cancer would need to undergo invasive testing, such as cystoscopy and biopsy. We demonstrated that ANG is one of a panel of biomarkers capable of diagnosing bladder cancer. Next, we set out to leverage this new knowledge to better understand ANG's role in tumor growth and its possibility to serve as a new therapeutic target."
Through this work on the biology of ANG, these researchers have demonstrated that its presence in cells leads to a growth advantage, capable of further enhancing the tumor's environment to sustain and promote the growth of human cancers. The ultimate goal in this type of research is to identify ANG as a suitable therapeutic target, leading to new weapons in our fight against cancers.
October 6, 2014
Dr. Peiwen Fei awarded RO1 grant from the National Cancer Institute
HONOLULU, HI - The University of Hawaii Cancer Center is happy to announce that on June 12, 2014, Dr. Peiwen Fei was the recipient of the RO1 grant in the amount of $1,577,000.00 from the National Cancer Institute (NCI) for her project âMolecular Insights into the Fanconi Anemia Tumor Suppressor Signaling Pathway.â The project began on July 1, 2014. Dr. Fei earned her medical degree (M.D.) from the Xu Zhou Medical College in Xu Zhou, China and her PhD in Pathology and Cell Biology from Thomas Jefferson University in Philadelphia, PA. She completed her fellowship programs in the Howard Hughes Medical Institute (HHMI), University of Pennsylvania and National Institute on Aging (NIA), National Institutes of Health (NIH) for Cancer Biology and Cancer Genetics respectively. Currently she is an associate professor in the cancer biology program at University of Hawaii Cancer Center. Her grant funded project focuses on a rare genetic human disease called Fanconi Anemia (FA). Due to the high incidence of cancer in those with this condition, it is suggested that the FA signaling pathway is a tumor suppressor pathway. However, it is not clear how this pathway operates in human tumorigenesis. The objective of Dr. Feiâs study is to employ FA as a genetic model system to discern the following: FA signaling pathway, how FA proteins mediate tumor suppression, and to examine the possibility of targeting this pathway as a therapeutic approach in cancer treatment. These studies have the potential to improve our current understanding of the pathogenesis of human cancer. These studies could offer insights into anti-cancer actions of tumor suppressors. They could also lead to the development of additional methods for the prevention, diagnosis, and treatment of human cancers.
October 20, 2014
New genetic risk factor identified in a large trans-ethnic genome-wide association studyBy Chantal Jackson
HONOLULU, HI - In a large collaborative effort, University of Hawai'i Cancer Center's Dr. LoÃ¯c Le Marchand has highlighted a new association between colorectal cancer risk and a common genetic variant. Dr. Le Marchand is a professor in the Cancer Epidemiology Program at University of Hawai'i Cancer Center, as well as a clinical professor in Public Health at John A. Burns School of Medicine, University of Hawai'i at Manoa. His research focuses upon the interaction between genetic and lifestyle factors which contribute to increased cancer risk among ethnic/racial populations in Hawai'i and California. With a specific focus on colorectal, lung and breast cancer, the aim of his research is to better understand the causes of cancer and develop new means of prevention.
Colorectal cancer (CRC) is the second leading cause of cancer deaths and the third most common cancer in the United States. Although it has been established that genetics play an essential role in CRC susceptibility, genome-wide association studies (GWASs) have primarily been conducted within European-descent populations; furthermore, these studies have only identified 30 common risk variants, which is significantly fewer than for prostate or breast cancer.
Le Marchand notes, "We have seen varying risks of developing colorectal cancer associated with ethnicity. In particular, an increased risk of colorectal cancer has been observed among Japanese individuals who migrated to Hawai'i and their descendants; furthermore, in Japan since 1950, there has also been a notable increased risk in colorectal cancer development". Due to this, Le Marchand has conducted decade-long studies to explain this susceptibility associated with the incorporation of a Westernized lifestyle.
To better understand the genetic basis of non-familial colorectal cancer (CRC), Le Marchand and his team performed genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry, and in 1,894 cases and 4,703 controls of African ancestry. They observed an association between CRC risk and a common variant in the VTI1A gene in both populations. They, then, reproduced their findings in a large collaborative study of European descent populations.
This finding demonstrates the usefulness of multiethnic studies in identifying new genetic risk factors. "The next step is to demonstrate that genetic risk variants, considered together, are sufficiently predictive of risk to help in determining who should be screened by colonoscopy", says Dr. Le Marchand. The use of these genetic markers, along with more typical risk factor information, may facilitate in more efficient screening. The study: "Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A," was published on August 8, 2014 in Nature Communications.
September 23, 2014
Lana Garmire, PhD, recently awarded $1.8 million for two 5-year NIH Grants
Lana Garmire, PhD, at the University of Hawaii Cancer Center (UHCC) has recently been awarded two 5-year NIH grants. One is a K01 career award for new investigators to conduct research in Big Data Science. The amount of the award is for $934,000 for the study of single cancer cell heterogeneity using the integrated bioinformatics approach. Dr. Garmire is the Project Leader of one of the four projects in a program project grant called the COBRE P20. The principal investigator (PI) of the COBRE is Dr. Steve Ward at the UH John A, Burns School of Medicine. For her project, Dr. Garmire was awarded $875,000 to investigate the effect of maternal obesity on offspring cancer risk through analyzing the methylome and transcriptome of the cord blood stem cells. Dr. Garmire is a tenure-track Assistant Researcher (equivalent to Assistant Professor) who received her PhD in computational biology from UC Berkeley. She joined the UHCC in December 2012, and in less than 2 years has won multiple grants from several funding agencies.