The Sol Goldman Pancreatic Cancer Research Center

What's New 2009

PANCAN's Purple Stride Maryland 2009
October, 2009

On Sunday October 11,2009, Team Hopkins comprised of Diane Echavarria, Coordinator of the National Familial Pancreas Tumor Registry, Brian Kirby and Alexis Kirby, Research Specialist in Dr. James Eshleman's lab, ran the 5K fun run in Oregon Ridge Park in support of PANCAN's Purple Stride Maryland-2009. The team helped raise money and awareness for pancreatic cancer by collecting donations in support of their run in addition to making winning bids on items in Purple Stride's Silent Auction.

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PanCan Visit
September, 2009

Close to 60 members of the Baltimore and Washington D.C. branches of Pancreatic Cancer Action Network (PanCAN) visited the pancreatic cancer research labs at Johns Hopkins on Saturday September 12th. The event was organized by Mary Zapor and Marsha Garil (Co-Coordinators of PanCAN’s National Capital Area Affiliate). The day started bright and early with a meet and greet breakfast which was followed by welcoming remarks by Mary Zapor, Marsha Garil, and an introduction by Dr. Ralph Hruban. From there the PanCAN visitors split into ten small groups for multiple informal sessions with the Hopkins' doctors and scientists. One of the visitors from PanCAn described the day saying' "They sat down with us, looked us in the eye and explained what they were doing on OUR level." At the end of the day Mary Zapor summarized the experience with "these docs rock!"

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The Team at Johns Hopkins Discovers Genetic Marker of Prognosis
September, 2009

Scientists at Johns Hopkins combed through all 21,000 known human genes to identify the genetic changes (mutations) in pancreatic cancer that are associated with prognosis. Using data from the pancreatic cancer genome initiative conducted at Johns Hopkins, the investigators were able to show that cancers which harbor mutations in the DPC4 (also known as SMAD4) gene have a worse prognosis after surgical resection than do cancers with normal (intact or "wild-type") DPC4. These results suggest that genetic changes may be useful markers for patient prognosis. The results of this study appeared in the July 15th, 2009 issue of Clinical Cancer Research.

PubMED Web site, PMID: 19584151


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Scientist at Johns Hopkins Team with Scientists in Cambridge to Identify Cause of Drug Resistance in Pancreatic Cancer
May, 2009

In the May 14th on-line issue of Science magazine scientists from the Cambridge Research Institute in the United Kingdom, together with scientists from the Sol Goldman Pancreatic Cancer Research Center, report that poor blood flow may explain some of the insensitivity of pancreatic cancer to treatment. Kenneth Olive and colleagues found that there are very few blood vessels in most human pancreatic cancers, and as a result, the cancers are poorly perfused and little chemotherapy enters the tumors. The team then tested the drug IPI-926 in a mouse model of pancreatic cancer. This drug depletes some of the stroma (scar tissue) within pancreatic cancers by inhibiting the Hedgehog cellular signaling pathway. The scientists found that combined treatment of pancreatic cancers in mice with the drug IPI-926 and with gemcitabine produced an increase in the blood flow to tumors, an increase in drug deliver to the tumors, and stabilization of disease. This study is exciting because it suggests that inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer. Finding the cause of a problem is an important step in overcoming the hurdle.

Click here to listen to the interview of Dr. Tuveson.


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Work at Johns Hopkins for Early Detection of Cancer
May, 2009

Victor Velculescu, M.D., Ph.D. Victor Velculescu, M.D., Ph.D. Watch the video
Romanian-born Victor Velculescu has won the 2009 Outstanding Achievement Award in Cancer Research from the American Association of Cancer Research (AACR). The award recognizes young investigators for their contributions to the field. He will receive his prize and give a lecture at the AACR annual meeting on April 22 in Denver.

Velculescu (pronounced Vel-ku-les-ku) pinpointed the PIK3CA gene as one of the most frequently mutated genes ever identified in human cancer. He also developed a method to rapidly identify disease-related genes and measure gene expression called SAGE (Serial Analysis of Gene Expression), and, with his colleagues, developed the first draft genome sequence of the four human cancer types: breast, colorectal, pancreatic and an aggressive form of brain cancer called glioblastoma multiforme.


Bert Vogelstein, M.D. Watch the video
Bert Vogelstein, M.D. whose published studies of cancer genetics are the most highly cited works in the field, will receive this year’s American Society of Clinical Oncology "Science of Oncology" Award at the group’s annual meeting in Orland, Fla., on June 1, 2009.

Vogelstein was selected for his role in discovering the specific genes and mutations responsible for colorectal cancer and for establishing a genetic model that explains how most solid tumors form and progress. In addition to discovering these genes, Vogelstein and his team have developed blood tests which are now used to identify patients with inherited mutations in the genes linked to colorectal cancer. They are currently working on the development of non-invasive methods to detect individuals who have early, curable colorectal tumors and to design therapies based on the new understanding of the molecular basis of cancer.

In the past year, Vogelstein and colleagues mapped the complete genetic blueprints for pancreatic and brain cancer, two of the most deadly tumor types. And they completed the first genome maps for breast cancer and colorectal cancer in 2007.

The above content was originally posted here. Media Contact: Amy Mone, 410-955-1287


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Scientists at Johns Hopkins Receive a Large Grant to Follow-up on the
Goldman Pancreatic Cancer Genome Project
May, 2009

Investigators in the Sol Goldman Pancreatic Cancer Research Center, the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and the McKusick-Nathans Institute of Genetic Medicine have been awarded an $8 million dollar P01 Program Project Grant (PPG) from the National Cancer Institute. This program, entitled "Functional Annotation of the Pancreatic Cancer Genome", will seek to functionally characterize novel oncogenes and tumor suppressor genes identified through next generation sequencing of human pancreatic cancer genomic DNA, using cell-, zebrafish- and mouse-based model systems. The program is directed by Dr. Steven Leach, and includes individual projects directed by Dr. Leach, Dr. Scott Kern, Dr. Anirban Maitra and Dr. Joshua Mendell. The grant also supports both a Zebrafish Core, directed by Dr. Michael Parsons, and a Phenotyping Core, directed by Dr. David Huso. The effort builds on the Pancreatic Cancer Genome Sequence project spearheaded by Dr. Ralph Hruban, Dr. Bert Vogelstein and Dr. Victor Velculescu, and is ultimately made possible by the high volumes of pancreatic cancer patients cared for by specialists in the Departments of Surgery, Oncology, and Radiation Oncology.


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DNA Changes Caused By Smoking
April, 2009

smoking

Scientists at the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins report in the April 15th issue of Cancer Research (Cancer Research volume 69, pages 3681-3688, 2009) that up to 25% of the genetic mutations found in pancreatic cancers from cigarette smokers are caused by cigarette smoking.

Smoking cigarettes is known to double the risk of pancreatic cancer, and cigarette smoking is believed to account for 20% to 25% of pancreatic cancers. The recent sequencing of the pancreatic cancer genome provided the team at Johns Hopkins a unique opportunity to discover the DNA changes (mutations) caused by cigarette smoking. The scientists compared the DNA mutations in pancreatic cancers obtained from individuals who smoked cigarettes to the DNA mutations in pancreatic cancers obtained from individuals who never smoked cigarettes. They found more DNA mutations in the pancreatic cancers obtained from smokers (average 53.1 mutations per tumor) than in the pancreatic cancers obtained from never smokers (average 38.5 mutations per tumor). The types and patterns of these mutations provide insight into the mechanisms by which cigarette smoking causes pancreatic cancer.


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Team at Johns Hopkins to Partner with team from Australia to Sequence 500 Pancreatic Cancers
April, 2009

The Australian Governement has committed $27.5 million (Australian dollars) to sequence completely 500 pancreatic cancers as part of the International Cancer Genome Consortium. The work will be led by Sean Grimmond of the University of Queensland, one of Australia’s leading genome sequencing experts, and by Professor Andrew Biankin, who heads a pancreatic cancer research group at Sydney’s Garvan Institute. The team from the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins, including Drs. Anirban Maitra and Ralph Hruban, will collaborate with the Australians, providing critical biosamples needed for the project.

This project builds on the recent sequencing of the pancreatic cancer genome by the Hopkins team, and it is a wonderful demonstration of international collaboration in the war against pancreatic cancer. To learn more, click here.


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Dr. Iacobuzio-Donahue wins Ramzi Cotran Prize for Her Pancreatic Cancer Research
March, 2009

Dr. Michael Gimbrone and Dr. Christine Iazobuzio-Donahue
Dr. Michael Gimbrone and Dr. Christine Iazobuzio-Donahue

Congratulations Dr. Christine Iacobuzio-Donahue, winner of the 2009 Ramzi Cotran Young Investigator Award. This award was presented to Dr. Iacobuzio-Donahue at the 98th Meeting of the United States and Canadian Academy of Pathology in Boston, MA. The award recognizes a body of work by a scientist under the age of 45 which has contributed significantly to the diagnosis and understanding of human disease. Dr. Iacobuzio-Donahue was awarded this prestigious award specifically for her pancreatic cancer research, including her discoveries into why some pancreatic cancers metastasize (spread). To learn more about Dr. Iacobuzio-Donahue’s award and her discoveries, click here.


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Hopkins Scientists Discover a New Familial Pancreatic Cancer Gene
March, 2009

Scientists at the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins are the first to discover a disease-causing gene by sequencing all 21,000 known human genes from a single individual, a patient with familial pancreatic cancer. The team, led by Dr. Alison Klein, Ph.D., compared the changes observed in the patient’s DNA to those found in healthy individuals and identified a single mistake in a gene, called PALB2, that was responsible for this patient's familial pancreatic cancer. Their findings, which have implications for all genetic diseases, not just pancreatic cancer, are reported in the March 5 edition of Science Express.

Both the patient sequenced and his sister developed pancreatic cancer, suggesting an inherited predisposition. It would have been impossible to identify the gene responsible for such a predisposition with conventional techniques, which generally require very large families. So the investigators sequenced all the genes (close to 21,000!), hoping that they'd find the responsible alteration. "Gene sequencing has always had the potential to help us learn if a person is susceptible to certain diseases," says Alison Klein, Ph.D., director of the National Familial Pancreas Cancer Tumor Registry at Johns Hopkins. "By finding the genetic error responsible for this patient’s familial pancreatic cancer, our team has provided an excellent example of the power of this approach."

This study was based on the Goldman Center's recently completed pancreatic cancer genome sequencing project. Specifically, the team reviewed all of the DNA sequences from the individual whose brother also had pancreatic cancer. With the help of high-powered computer software, the team scanned all known protein-coding genes -- approximately 21,000 of them – to find variations in this individual. "Most of the variations were normal ones coding for such things as eye or hair color, but the search was designed to track down particular mutations that caused certain proteins to be shortened, a process that commonly occurs in cancers," says James Eshleman, M.D., Ph.D., Associate Professor of Pathology and Oncology. This search led to a variant in one gene, called PALB2, that resulted from a substitution of a DNA base cytosine with a different one, thymidine.

The research team then looked for PALB2 gene alterations in 96 other individuals with pancreatic cancer, each of whom at least one additional relative with pancreatic cancer. They found that three of these 96 individuals had errors in the PALB2 gene that resulted in similar shortening of the protein product. Interestingly, the PALB2 protein binds to the BRCA2 protein, the product of another breast and pancreatic cancer susceptibility gene. Learn more about PALB2, BRCA2 and other causes of familial pancreatic cancer.

The investigators believe that their approach could be used to identify inherited alterations that predispose to many other types of cancers as well as other diseases with genetic components. Sequencing of all the genes in a cancer and in person's genome has the potential to discover the inherited genes that predispose to the cancer, as well as the acquired genetic changes that allow that cancer to blossom. If funding can be found, the team would like to try this approach on other cancer types. They would like to sequence a series of well-characterized islet cell tumors of the pancreas.

In addition to Klein, Eshleman, Goggins and Vogelstein, investigators who conducted the research included Siân Jones, Ralph Hruban, Mihoko Kamiyama, Michael Borges, Xiaosong Zhang, D. Williams Parsons, Jimmy Cheng-Ho Lin, Emily Palmisano, Keiran Brune, Elizabeth Jaffee, Christine Iacobuzio-Donahue, Anirban Maitra, Giovanni Parmigiani, Scott Kern, Victor Velculescu, and Kenneth Kinzler of the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins.


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Dr. Akhilesh Pandey featured as one of the breakthrough technology leaders of Baltimore
January, 2009

Akhilesh Pandey

Congratulations to Johns Hopkins pancreatic cancer research team member Dr. Akhilesh Pandey for being featured as one of the breakthrough technology leaders of Baltimore - it is part of the cover story for January's Urbanite magazine.

Dr. Pandey is a leader in the field of proteomics and his team is dedicated to developing am early detection test for pancreatic cancer.

Congratulations Akhilesh!


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