The Sol Goldman Pancreatic Cancer Research Center

What's New 2002

Over 1 Million Dollars Donated!
December 26, 2002

We are pleased to announce that to date over 1 million dollars has been donated to pancreatic cancer research at Johns Hopkins by the users of this Web site! This is a truly remarkable achievement and it has had a significant impact on the war against pancreatic cancer. Since 1995 over 4700 donors have contributed! Some have given as little as $5 and others over $250,000. Almost all were given to honor a friend or loved one who either is battling pancreatic cancer or who lost the battle against this disease.

As you can see, these donations have added up and the 1 million dollars raised has allowed us to hire three talented scientists and provide equipment and space necessary for their research. Michael Goggins M.D. is a gastroenterologist and he has established a laboratory dedicated to developing an early detection test for pancreatic cancer. Just as there is a PSA test for prostate cancer, so too do we need a blood test for early pancreatic cancer. Gloria Su, Ph.D. trained in Scott Kern's laboratory and has started her own lab dedicated to developing a mouse model of pancreatic cancer that directly mirrors human disease. This mouse model will greatly facilitate the testing of new treatments and screening tests for pancreatic cancer. Finally Christine Iacobuzio-Donahue M.D., Ph.D. has just joined our faculty and her laboratory will be dedicated to identifying new targets for the treatment of pancreatic cancer. She will do this by applying cutting-edge gene chip technology to a series of well-characterized pancreatic cancers resected here at Johns Hopkins. These three exciting new laboratories exist because of the support of the users of this Web site and, importantly, all three of these scientists have obtained additional grant support for their pancreatic cancer research from private foundations and from the federal government. Thus, your donations have not only allowed new talented young scientists to join the battle against pancreatic cancer, but your donations have also given us a foundation on which to obtain additional support for pancreatic cancer research from other agencies.

We congratulate all of you for your generous support. It is sincerely appreciated and it has made a wonderful difference!

Information on giving.



December 2002 Issue of NFPTR News Available On-line
December 12, 2002

Enrollment in The National Familial Pancreas Tumor Registry (NFPTR) continues to grow. Over 1,000 families now participate in this research registry. A number of you have asked for periodic updates on the research being conducted through the NFPTR. For those of you interested in our studies of why pancreatic cancer runs in some families, the December 2002 issue of NFPTR News is now available on-line. The url for the pdf version of NFPTR News is: 2002 Newsletter.

If you have a strong family history of pancreatic cancer (at least two family members with pancreatic cancer), but have not enrolled in the NFPTR, please consider participating in our research. If you would like to join our research please contact the coordinator of the NFPTR Kieran Brune (410-955-3502 or kbrune@jhmi.edu).

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Critical Early Step in the Development of Pancreatic Cancer Identified
November 5, 2002

In the November 2002 issue of the American Journal of Pathology Dr. Tjarda van Heek and colleagues from Johns Hopkins report that the ends of chromosomes (called "telomeres") are dramatically shortened in the lesions that are the precursors to invasive pancreatic cancer (called "PanINs"). Telomeres normally function to keep the ends of chromosomes from "sticking together". When telomeres are too short, chromosome ends stick together and can be damaged when a cell tries to divide. This chromosome damage, in turn, may promote the development of an invasive pancreatic cancer.

The study by van Heek and colleagues suggests that telomere shortening may be a critical early event in the development of a pancreatic cancer and the findings open a whole new area of pancreatic cancer research- the role of telomeres and the mechanisms of telomere shortening in pancreatic cancer.

Reference:
Telomere Shortening Is Nearly Universal in Pancreatic Intraepithelial Neoplasia N. Tjarda van Heek, Alan K. Meeker, Scott E. Kern, Charles J. Yeo, Keith D. Lillemoe,| John L. Cameron, G. Johan A. Offerhaus, Jessica L. Hicks, Robb E. Wilentz, Michael G. Goggins, Angelo M. De Marzo, Ralph H. Hruban and Anirban Maitra American Journal of Pathology. 2002;161:1541-1547

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Another Monastra Foundation Fundraiser to Benefit Hopkins Pancreas Cancer Research
November 2, 2002

Joseph C. Monastra passed away on April 4, 2002 only four short weeks after being diagnosed with Pancreatic Cancer. Joseph dedicated his life and career to his family, friends and to the United States Defense Industry. In honor of Joseph's memory, his family has established the "Joseph C. Monastra Fund for Pancreatic Cancer Research" at Johns Hopkins. The Monastra Foundation held its second fundraiser, "The First Annual Ride to Make a Difference for Pancreatic Cancer", a Motocycle Ride, in Atlanta, Georgia on November 2, 2002. To learn more about this remarkable family and their fundraising efforts, click here.

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Aspirin Use May Reduce Risk of Pancreatic Cancer
August 8, 2002

In the August 7, 2002 issue of the Journal of the National Cancer Institute (volume 94, pages 1168-1171) K.E. Anderson and colleagues from the University of Minnesota report that aspirin might be chemopreventive for pancreatic cancer. They followed over 28,000 post-menopausal women in Iowa from 1992 and 1999. Eighty of these women developed pancreatic cancer. When the investigators looked at self-reported aspirin use among all 28,000 women, they found a trend of decreasing risk of pancreatic cancer with increasing frequency of aspirin use per week. While these data suggest that aspirin use may reduce one's risk of developing pancreatic cancer, you are advised to consult with your personal physician before beginning any treatment course.

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Grass-Roots Fundraiser to Benefit Pancreas Cancer Research at Hopkins
August 2002

The Third Annual Michael Rolfe Research Foundation Gala to benefit pancreatic cancer research at Johns Hopkins will be held on Sunday August 25, 2002 at RAVINIA FESTIVAL, in HIGHLAND PARK Illinois. Cocktails & gathering time will start at 4:30pm, followed by a Gala Dinner in the tent at 5:00 pm and a live concert at 7:00 pm. The concert "Happy Birthday, Doc!" will feature Doc Severinsen and the Ravinia Festival Orchestra with Erich Kunzel Conducting. Limited tickets available.

For more information please contact: Michael Rolfe Research Foundation, P.O. Box 1762, Highland Park, IL 60035 847-432-4926. More details

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Johns Hopkins Hospital Rated #1 Again
July 15, 2002

#1 Hospital Badge

THE JOHNS HOPKINS HOSPITAL TOPS U.S.NEWS & WORLD REPORT'S "HONOR ROLL" FOR THE 12th YEAR IN A ROW

For the 12th consecutive year, Johns Hopkins comes in at the very top of the list in the U.S. News & World Report's annual ranking of American hospitals. Hopkins was also rated as exceptional in 16 of 17 specialties, including cancer. Ratings are based on reputation (ranking by randomly selected physicians), mortality rates, and hospital factors such as discharges, ratio of nurses to beds, technology services, hospice/palliative care services, and whether or not the hospital is an NCI Cancer Center.

The methodology section of the report refers to a journal article featured in our What's New section a few months ago [What's New April 22, 2002] regarding the role of patient volume in hospital excellence. Specifically, the report points out that patients undergoing pancreatic cancer surgeries do better in hospitals with large volumes.

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Pancreatic Cancer Fundraiser to Honor Football Player's Father
June 30, 2002

The Jeffrey M. Zgonina Foundation will hold its first annual fundraiser on June 30, 2002. The fundraiser will be held at the Stonegate Banquet and Conference Center in Hoffman Estates, Illinois. Jeffrey Zgonina is a football player on the St. Louis Rams and this fundraiser will honor his father, Kaz Zgonina, who died from pancreatic cancer in September 2000. The fundraiser will begin at 4:00 p.m. with cocktails, hors d'oeuvres and a silent auction, followed by dinner, entertainment and a live auction. Auction items include football memorabilia collected by Jeffrey Zgonina. The proceeds from this event will benefit the Pancreatic Research Program at Johns Hopkins University. In particular, the monies raised at the Jeffrey Zgonina Foundation Fundraiser will help a young physician-scientist at Johns Hopkins, Dr. Christine Iacobuzio-Donahue, start a brand new pancreatic cancer research lab at Johns Hopkins.

Click here to learn more about this wonderful event.

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Patients Undergoing Whipple Surgery Can Significantly Reduce Their Risk of Operative Death by Selecting a High-Volume Center
April 22, 2002

In the April 11, 2002 issue of the New England Journal of Medicine Dr. Birkmeyer and colleagues from Department of Veterans Affairs, Vermont, report their analysis of surgical mortality in the United States (N Engl J Med 2002 Apr 11;346(15):1128-37). Using information from the national Medicare claims database and the Nationwide Inpatient Sample they examined the relationship between hospital volume (total number of procedures performed per year) and mortality (death in hospital or within 30 days) for a variety of surgical procedures. The mortality rate for Whipple procedures (pancreaticoduodenectomy) at low-volume centers (16.3%) was much greater than the mortality rate at high-volume centers (3.8%). From their analyses the authors conclude that patients "can significantly reduce their risk of operative death by selecting a high-volume hospital." High-volume centers were defined in this study as centers that perform more than 16 whipples per year. Last year close to 240 whipples were performed at Johns Hopkins.

Reference:
Birkmeyer JD, Siewers AE, Finlayson EV, Stukel TA, Lucas FL, Batista I, Welch HG, Wennberg DE. Hospital volume and surgical mortality in the United States. N Engl J Med 2002 Apr 11;346(15):1128-37.

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New Markers of Pancreatic Cancer Discovered Using Global Gene Expression Technology
April 10, 2002

In the April issue of the American Journal of Pathology (Am J Pathol 2002 Apr;160(4):1239-49) Dr. Iacobuzio-Donahue and colleagues from Johns Hopkins report the discovery of 69 genes that are made at higher levels in pancreatic cancers than in normal tissues. Dr. Iacobuzio-Donahue used recently "Gene Chips" to compare the genes expressed (made) in a large series of pancreatic cancers to the genes expressed (made) in normal tissues. When she did this she identified 97 genes that were highly overexpressed (made at very high levels in cancers compared to the normal samples). 28 of these genes had been reported before, leaving a remarkable 69 new genes selectively overexpressed in pancreatic cancer. These 69 new genes have immediate potential as novel therapeutic targets and tumor markers of pancreatic cancer. The group at Hopkins is now systematically evaluating each these 69 new genes.

Reference:
Am J Pathol 2002 Apr;160(4):1239-49

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Rob Larsen Bike Ride to Support Pancreatic Cancer Research at Hopkins
March 26, 2002

Rob Larsen will ride his bicycle 100 miles on June 15, 2002 in the hope that it will inspire donors to make a contribution toward pancreatic cancer research at Johns Hopkins University. Rob is making this ride in honor of his mother, Suzanne Larsen, who died from the disease in 1999. Rob is calling this fund raiser "The Ride For Mom 1" because he hopes to make it the first of many annual rides dedicated to raising money for pancreatic cancer research at Hopkins. To learn more about this remarkable man and his effort to both honor his mother and fight the disease that took her life, please click here.

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Hopkins Researchers Discover New Marker for Survival
March 25, 2002

In the December issue of Clinical Cancer Research, Dr. Tascilar and colleagues report the discovery of an important marker of survival among a large number of patients who undergo surgical resection of their pancreatic cancer at Johns Hopkins Hospital. Working in the laboratory of Dr. Goggins, Dr. Tascilar found that patients whose pancreatic cancers still had a normal SMAD4 (DPC4) gene and protein lived significantly longer than those patients whose pancreatic cancers had already lost SMAD4 at the time of surgery. These findings highlight the important role of SMAD4 in preventing cancer growth and highlight the need for treatments that can function like SMAD4 in cancers that have lost the function of this gene. The presence or absence of normal SMAD4 in a cancer can be determined by routine immunohistochemistry and its measurement can provide prognostic information for patients.

Reference:
Tascilar M, Skinner HG, Rosty C, Sohn T, Wilentz RE, Offerhaus GJ, Adsay V, Abrams RA, Cameron JL, Kern SE, Yeo CJ, Hruban RH, Goggins M. The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res 7:4115-21, 2001.

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Hopkins Researchers Discover Genes Silenced in Pancreatic Cancer Development
March 25, 2002

In the December issue of Cancer Research, Dr. Ueki and colleagues report the discovery of a number of genes that become silenced during pancreatic cancer development by DNA methylation. Methylation refers to the addition of an extra carbon atom to DNA, and methylation of a gene can switch off its function. Methylation, like mutation, frequently occurs in cancer and is a common way in which cancer-preventing (tumor suppressor) genes are inactivated in cancers. Working in Dr. Goggins' lab and using a technique known as RDA (representational difference analysis), Dr Ueki compared methylation patterns in normal pancreas with those in pancreatic cancers, and found that the gene ppENK (also called "enkephalin") is silenced by methylation in ~90% of pancreatic cancers. Enkephalin suppresses the growth of pancreas cancer cells and switching off enkephalin by methylation increases cancer growth. Importantly, since it is possible to detect abnormal methylation of DNA, it is hoped that diagnostic tests can be developed to detect methylated encephalin in pancreatic juice, thereby permitting the early detection of pancreatic cancer. Finally, the authors of this study are much indebted to PANCAN (the PANcreatic Cancer Action Network) and to the friends and family of Michael Rolfe who provided generous donations to make this research possible.

Reference:
Ueki T, Toyota M, Skinner H, Walter KM, Yeo CJ, Issa JP, Hruban RH, Goggins M. Identification and characterization of differentially methylated CpG islands in pancreatic carcinoma. Cancer Res 61:8540-6, 2001.

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Advance Made in Hunt for Familial Pancreas Cancer Gene
March 4, 2002

In this month's issue of the American Journal of Human Genetics (abstract) Drs. Teresa Brentnall (Fred Hutchinson Cancer Research Center), David Whitcomb (University of Pittsburgh School of Medicine) and colleagues, report that they have narrowed done the search for the gene responsible for the aggregation of pancreatic cancer in a family (called "Family= X"). Using a technique called "linkage analysis" Drs. Brentnall and Whitcomb were able to show that the gene in this family most likely resides on chromosome 4 at a chromosome location called "4q32-34". Their finding is exciting because, if the gene can be found and if the gene in this family is the same as the gene responsible for the aggregation of pancreatic cancer in other families, then it will help us understand why pancreatic cancer runs in some families and, importantly, it will help us predict who is at increased risk for developing pancreatic cancer and who is not. If you are from a family in which more than one family member has been diagnosed with pancreatic cancer and you would like to help scientists at Johns Hopkins with their research you may wish to consider participating in the National Familial Pancreas Tumor Registry (NFPTR) at Johns Hopkins. Please contact Kieran Brune, Coordinator, at 410-955-3502 or kbrune@jhmi.edu. Your participation in this research may help us discover the "familial pancreas cancer gene".

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New Marker of Pancreatic Adenocarcinoma Discovered by Serial Analysis of Gene Expression (SAGE)
January 25, 2002

In the December issue of Clinical Cancer Research, Dr. Argani and colleagues from Johns Hopkins describe the discovery of a new marker of pancreatic adenocarcinoma. Dr. Argani and colleagues used the same technique developed at Johns Hopkins, serial analysis of gene expression (SAGE), as was used to discover another new marker of pancreatic cancer, prostate stem cell antigen (PSCA) (See What's New, June 7, 2001). Again, they used an online database of SAGE data on a variety of tissues and cancers (http://www.ncbi.nlm.nih.gov/SAGE ) to identify genes that are turned on in pancreatic cancer. The gene identified, mesothelin, has been shown to be expressed in cancers of the lung, cervix, and ovary, but had not been analyzed in pancreatic cancer. Interestingly, it appears that this protein was actually initially described in a pancreas cancer cell line seven years previously, but this information had been ignored until the current study. Using techniques to study RNA expression (reverse transcriptase PCR and in situ hybridization) and protein expression (immunohistochemistry), Dr. Argani and colleagues found mesothelin to be overexpressed in over 90% of pancreatic adenocarcinomas with minimal to no expression in normal tissues.

These findings are exciting for several reasons. First, they confirm the ability of SAGE to identify new tumor markers. Second, mesothelin, because it is selectively overexpressed in pancreatic cancers, may be useful as a new marker for pancreatic cancer. Third, mesothelin has been extensively studied and is a potential target for immune treatment of ovarian cancer. The demonstration of mesothelin overexpression in pancreatic cancer suggests that a similar approach could be used. Since pancreatic cancer cells overexpress mesothelin, immunotherapy against mesothelin could be helpful to treat pancreatic cancer.

Finally, the authors of this study are much indebted to the friends and family of Michael Rolfe. This work was supported in large part by generous donations from the family and friends of Michael Rolfe, demonstrating again the power of private giving to advance cancer research.

Reference:
Clin Cancer Res. 2001 Dec;7(12):3862-8

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New Study Highlights the Importance of the Body's Reaction to Pancreatic Cancer
January 16, 2002

In this month's issue of the American Journal of Pathology, Dr. Iacobuzio-Donahue and colleagues from Johns Hopkins report an extensive study of the body's reaction to pancreatic cancer (American Journal of Pathology 2002, Vol. 160, pages 91-99; http://ajp.amjpa thol.org/cgi/content/full/160/1/91). Dr. Iacobuzio-Donahue and colleagues in the laboratory of Dr. Scott Kern used the recently developed technique of "serial analysis of gene expression" (SAGE) to identify nearly a hundred genes that are overexpressed (made at high levels or "turned on") in pancreatic carcinoma. Dr. Iacobuzio-Donahue didn't stop there. She selected twelve of these genes and asked, exactly where, in what cells, are these genes turned on in resected pancreatic cancer? In so doing, she was able to develop a remarkable picture of the "architecture" of gene expression in pancreatic cancer. Eight of the genes she identified were made within the small blood vessels and scar tissue (an exuberant response of connective tissues of the patient, termed the "desmoplastic" response) that become intermixed with the cancer. It is an intriguing fact about pancreatic cancer that this scarring response makes up most of the volume, or space, occupied by the tumor - the ability to understand it better would be of considerable help in understanding how these cancers grow and destroy neighboring areas. The invasive cancer cells, themselves, specifically made four additional genes. This set the stage for an unanticipated and eye-opening finding: the patterns of gene expression that Dr. Icaobuzio-Donahue identified in these cancers suggested an important communication between the cancer cells and the adjacent scar tissue and blood vessels. In one example, a gene called connective tissue growth factor was expressed by the cancer cells and may explain why the scar tissue (also called connective tissue) is so prominent in pancreatic cancer.

Importantly, not only does Dr. Iacobuzio-Donahue provide insight into the basic nature of the body's reaction to a pancreatic cancer, but it also suggests a number of new targets for the development of future therapeutics to treat this disease.

Reference:
Iacobuzio-Donahue CA, Ryu B, Hruban RH, Kern SE. Exploring the host desmoplastic response to pancreatic carcinoma : gene expression of stromal and neoplastic cells at the site of primary invasion. Am J Pathol. 2002 Jan;160(1):91-9. abstract | full text

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Precursor to Invasive Colloid Cancers of the Pancreas Identified
January 15, 2002

There are several variants of ductal adenocarcinoma of the pancreas. One of those variants is called colloid or mucinous carcinoma. This entity is defined by adenocarcinomas comprised largely of malignant cells floating free within pools of mucin. While this type of adenocarcinoma has already been well studied in organs like breast, colon, and prostate, it has not been well studied in the pancreas, duodenum, or ampulla of Vater. In the most recent issue of the American Journal of Surgical Pathology, Wilentz, et al. try to fix this problem by analyzing a set of 39 colloid carcinomas that arise in the pancreas, duodenum, and ampulla of Vater. They find that the overwhelming majority of these carcinomas (38 of 39, 97%) arise from a low-grade precursor, either an intraductal papillary mucinous neoplasm (in the pancreas) or a tubulovillous adenoma (duodenum or ampulla). In addition, they find that the colloid differentiation is not as important a prognostic factor for patients with pancreatic cancer as are other factors (for example, tumor location, tumor stage or margin status after resection). Nevertheless, because colloid carcinomas almost always arise within a low-grade component, the findings in this paper are significant. If the low-grade component is discovered before cancer develops, a patient will have a much better chance of survival. We at Johns Hopkins are now working on ways to detect these low-grade components at early stages.

Reference:

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