The Sol Goldman Pancreatic Cancer Research Center

What's New 2005

Pancreatic Cancer in Individuals of Ashkenazi Jewish Ancestry
December 2005

One of the first steps to effective screening for early pancreatic cancer is the identification of individuals with an increased risk of developing the disease. For years it has been known that individuals of Ashkenazi Jewish descent have an increased risk of developing pancreatic cancer, but the basis for this increased risk is only now being elucidated. Inherited mutations (DNA changes) in the first and second breast cancer genes, called BRCA1 and BRCA2, explain some of this increased risk. In order to provide more details about this increased risk we have added a new section to this web site . This new section is entitled "Pancreatic Cancer in Individuals of Ashkenazi Jewish Ancestry". We hope you find this information educational and useful.



Early Results Using Therapeutic Pancreatic Cancer Vaccine Show Promise
November 2005

Researchers in the Sol Goldman Pancreatic Cancer Research Center in the Johns Hopkins Kimmel Cancer Center are encouraged by early results of a treatment vaccine for pancreatic cancer. At about two years into a study of 60 patients, the researchers report that 88 percent survived one year and 76 percent are alive after two years.

"Even though our results are preliminary, the survival rates are an improvement over most published results of pancreatic cancer treatment studies," says Daniel Laheru, assistant professor at the Johns Hopkins Kimmel Cancer Center. Laheru is expected to present his findings in a press briefing at a joint meeting of the American Association for Cancer Research/National Cancer Institute/European Organization for Research and Treatment of Cancer in Philadelphia on November 15.

Until recently, most studies have shown pancreatic cancer survival rates at about 63 percent one year after diagnosis and 42 percent at two years. The long-term outlook is more grim - only 15 to 20 percent of patients with local disease are alive at five years. "Since there is no universal standard for treating pancreatic cancer, it is difficult to make direct comparisons between all the studies, " says Laheru.

In the current study, his team combined an immune-boosting vaccine with surgery and conventional postoperative chemotherapy and radiation. The vaccine, originally developed at Johns Hopkins, uses irradiated pancreatic cancer cells incapable of growing, but genetically altered to secrete a molecule called GM-CSF. The molecule acts as a lure to attract immune system cells to the site of the tumor vaccine where they encounter antigens on the surface of the irradiated cells. Then, these newly armed immune cells patrol the rest of the patient's body to destroy remaining circulating pancreatic cancer cells with the same antigen profile.

Patients get one vaccine injection eight to ten weeks after surgery, then four booster shots after chemotherapy and radiation. Laheru and his team completed enrolling patients in the study this past January. The average follow-up time is 32 months.

"It is important that we continue to follow these patients to know how the treatment will work in the long-term," says Elizabeth Jaffee, M.D., the Dana and Albert "Cubby" Broccoli Professor in Oncology and Pathology. "We're hopeful that these early results will hold true."

Jaffee and Laheru hope to begin multi-institutional studies in about a year. They are working with Hopkins pathologists from the Sol Goldman Pancreatic Cancer Research Center to analyze proteins from pancreatic cancer cells that may help them refine the vaccine's targets.

This research was funded by the National Cancer Institute and in part by Cell Genesys, Inc. (see below information on the licensing agreement between the Johns Hopkins University and Cell Genesys, Inc.) and presented at the Proceedings, AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, November 2005. (Abstract #2229, A Safety and Efficacy Trial of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected with the GM-CSF Gene in Combination with Adjuvant Chemoradiotherapy for the Treatment of Adenocarcinoma of the Pancreas).

Questions and Answers

Is the Hopkins pancreatic cancer vaccine available now?
No, the vaccine is not commercially available. The current Phase II clinical trial of 60 patients at Johns Hopkins is closed to accrual. No additional patients can be enrolled in this study. When this study concludes, in about a year, more results will be made known. The current study is one step in the process of evaluating new therapies. Johns Hopkins researchers are working as fast as they can to develop new therapies, but it may take more than a year before the next phase of clinical studies begins at Johns Hopkins and other universities. There are no other universities currently participating in this vaccine study.

Is the vaccine available through a compassionate use program?
It is our understanding that the manufacturer of the vaccine, Cell Genesys, Inc. does not have a compassionate use program; however, you may want to check their web site for more information.

When will the next study begin? Can I put my name on a list?
It may be more than a year before the next study begins; therefore, we are unable to keep a list of individuals interested in the vaccine.

Are there other new therapies that might be helpful to me?
Research on a wide variety of pancreatic cancer treatment strategies is ongoing nationwide. Information on Johns Hopkins clinical trials, search our online list. Information about clinical trials at other cancer centers is available through the National Cancer Institute at www.cancer.gov and 1-800-4-CANCER.

How do I make an appointment with a Johns Hopkins expert?
If you would like to schedule an appointment with a Johns Hopkins pancreatic cancer specialist to learn of other treatment recommendations, please call:

Surgery: 410-955-5800
Medical Oncology: 410-955-8964
(Chemotherapy and other options)

Please note: due to the high level of interest in pancreatic cancer vaccine research at Johns Hopkins, our experts cannot answer individual phone calls or emails.

My cancer is widely metastatic. Will the vaccine be able to help me?
Our investigators do not have clear answers on whether the vaccine will be helpful to patients w ith metastatic disease, so they will be opening a study at Johns Hopkins in the next few months using the vaccine with a targeted therapy called erbitux for patients with metastatic pancreas cancer. The clinical trials section of our web site will have study information when the trial opens.

Under a licensing agreement between the Johns Hopkins University and Cell Genesys, Inc., the University is entitled to a share of royalty received by the University on sales of technology used in the study described in this news release. This arrangement is being managed by the University in accordance with its conflict of interest policies.

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New Leadership in Pancreatic Cancer Surgery at Johns Hopkins
August 2005

Dr. Charles Yeo has accepted the position of Chairman of the Department of Surgery at Thomas Jefferson University in Philadelphia, PA. While we are pleased for Dr. Yeo's promotion, we will miss him here at Hopkins.

With Dr. Yeo's departure, we are proud to announce that Dr. Kurtis Campbell has been chosen to provide continued leadership to the surgical efforts against pancreatic cancer at The Johns Hopkins Hospital. Dr. Campbell is an Associate Professor of Surgery and active attending surgeon at The Johns Hopkins Medical Institutions. He graduated from The Johns Hopkins University School of Medicine in 1986. After completing his surgical residency at Johns Hopkins, he spent an advanced year of training in pancreatic and biliary tract surgery. Thereafter, he was recruited to the Hopkins surgical faculty and has been an important part of the efforts against pancreatic cancer since that time.

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Microarray Sequencing of Mitochondrial Genome Uncovers New Clues for Cancer Detection
July 2005

* Reprinted with permission from July Issue of the Affymetrix Microarry Bulletin

Scientists led by Dr. Anirban Maitra, assistant professor of pathology, genetic medicine and oncology at Johns Hopkins Medical Center are using a new microarray-based method to rapidly sequence the genome of human mitochondria to find mutations linked to cancers, including prostate and pancreatic cancer. The microarray, called the MitoChip, sequences more than 12,000 bases of the mitochondrial genome, and takes less than a third the time of conventional sequencing methodologies.

“Right now we're using the MitoChip to look at a larger number of pancreatic tumor and juice samples to see if we are able to detect tumor-specific mutationsin pancreatic juice samples,” said Maitra. “While we developed the MitoChip to study cancer biomarkers, it certainly has uses in non-cancer applications as well, everything from evolutionary studies to metabolic diseases to aging.”

Maitra recently spoke with Amanda Baumann, a pre-doctoral fellow in Duke University's department of Pharmacology and Cancer Biology regarding the new challenges facing mitochondrial research now that the genome sequence can be readily accessed. The two discussed:

To read the whole article, please click here.

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Reaction of the Normal Pancreas to an Adjacent Pancreatic Cancer Provides Clues about Tissue Invasion and Detection
July 2005

Two papers from the Hopkins group help define the genes that are expressed (made) in the tissues adjacent to pancreatic cancer. In the first paper by Ricci and colleagues, the technique of in situ hybridization was used to determine the genes that are turned on in the body's response (called a stromal reaction) to an infiltrating cancer (analogous to the body trying to heal a wound). Importantly, Dr. Ricci found that the genes that are made in this stromal response to an invasive pancreatic cancer are related to how aggressively the tumor invades the surrounding pancreas, and not to the underlying biology of the tumor. Understanding how pancreatic cancers invade the normal pancreas and spread to other organs is a critical step to understanding how to interfere with this process. In the second paper by Fukushima and colleagues, gene expression profiling was used to better understand the gene expression patterns of pancreatic tissue adjacent to infiltrating pancreatic cancers as compared to pancreatic tissue adjacent to chronic pancreatitis. Dr. Fukushima found 20 different genes were overexpressed in pancreatic tissue adjacent to an invasive cancer compared to normal pancreatic tissue adjacent to chronic pancreatitis. These results demonstrate that some of the molecular alterations in normal pancreatic tissues that occur in response to adjacent infiltrating pancreatic ductal adenocarcinoma can provide a rich source of markers for detecting pancreatic cancer.

References:
Ricci F, Kern SE, Hruban RH, Iacobuzio-Donahue CA. Stromal Responses to Carcinomas of the Pancreas: Juxtatumoral Gene Expression Conforms to the Infiltrating Pattern and Not the Biologic Subtype. Cancer Biol Ther. 2005 Mar 23;4(3)

Fukushima N, Koopmann J, Sato N, Prasad N, Carvalho R, Leach SD, Hruban RH, Goggins M. Gene expression alterations in the non-neoplastic parenchyma adjacent to infiltrating pancreatic ductal adenocarcinoma. Mod Pathol. 2005 Jun;18(6):779-87

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Gastrointestinal Cancer Rapid Medical Donation Program for Pancreatic Cancer
July 2005

In February 2003, Dr. Christine Iacobuzio-Donahue and colleagues at Johns Hopkins initiated a new program for patients with advanced stage pancreatic cancer, called the Gastrointestinal Cancer Rapid Medical Donation Program, or GICRMDP. Through this program, patients with pancreatic cancers that have spread outside the pancreas to other organs can consent to have a research autopsy. Through the hard work and team effort approach at Johns Hopkins, this program has grown to the largest of its kind in the country with patients from more than 13 different states participating as of June 2005. The tissues collected through this program are now providing an invaluable resource for ongoing research of the causes and treatment of pancreatic cancer at Johns Hopkins. Initial findings related to the tissues collected through this program have been published recently in the journal Cancer Biology and Therapy. In this paper, Dr. Iacobuzio-Donahue showed that deletions of key genes are present at a higher rate in advanced stage pancreatic cancers than previously recognized and provides the first clues to why pancreatic cancers may spread to other organs.

Reference:
E.E. Embuscado, D. Laheru, F. Ricci, K.J. Yun, S. Witzel, A. Seigel, K. Flickinger, M. Hidalgo, G.S. Bova, C. A. Iacobuzio-Donahue. Immortalizing the Complexity of Cancer Metastasis: Genetic Features of Lethal Metastatic Pancreatic Cancer Obtained from Rapid Autopsy. Cancer Biol. Ther. 2005 May 12;4(5)

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Shaarey Zedek Kindergarten
July 2005

We recently received the following moving letter and donation from a very talented Kindergarten class.

Dr. Hruban,M

As our Kindergarten year ends once again this year. I am happy to say that my students created a wonderful Britto canvas and auctioned it off at our "Gallery Opening Night." This year, our 10 boys (yes we had all boys this year) raised $190 for Pancreatic Cancer Research in memory of my Mom, Rebecca Nathanson. This is our 6th year doing this activity. Please find a cure for Pancreatic Cancer quickly. I hate to think of all of the people suffering with this horrible disease like my Mom did.

Best wishes,

Shelly Mettzer
Shaarey Zedek Kindergarten
West Bloomfield, Michigan
Kindergarten Painting Shaarey Zedek Kindergarten

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Precursor Lesions of Pancreatic Cancer Catching the Horse before It has Fled the barn
July 2005

Three recent articles by Johns Hopkins scientists have expanded our knowledge of the precursor lesions which are thought to develop into invasive pancreatic cancers. Understanding the biology of these precursor lesions is of critical importance if we are to detect, and potentially treat, pancreatic cancer before it spreads. In the first article, Anirban Maitra and collegues comprehensively reviewed the various subtypes of precursor lesions that are known to progress to invasive pancreatic cancer. While Pancreatic Intraepithelial Neoplasia or "PanIN" is the prototype precursor lesion associated with the "usual" cancers (ductal adenocarcinomas), other larger precursor subtypes such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are being increasingly recognized with better imaging and screening techniques. The pancreatic cancers that arise in the context of these latter precursor lesions, particularly IPMNs, can have a different biology and outcome than the usual PanIN-associated invasive cancers. Therefore, it is important that pathologists who examine surgically removed pancreata are familiar with the histology of the various non-invasive precursors to invasive pancreatic cancers.

The second and third articles identify potential therapeutic targets in PanINs, the most common precursor lesion of pancreatic cancer. Inactivation of function of a critical gene that controls the cell cycle – p16 (CDKN2A) – is extremely frequent in invasive pancreatic cancers. In about a third of these cases, loss of p16 function occurs via deletion of both p16 gene copies (called "homozygous deletion" in genetic terminology) and is large enough to include a neighboring gene known as MTAP in the deletions. Complete loss of MTAP function can be exploited for therapy using drugs that selectively affects MTAP-negative pancreatic cancer cells without damage to normal tissues. Now, Dr. Hustinx and collegues have shown that even subsets of non-invasive precursor lesions (PanINs) harbor deletions of both copies of the MTAP gene. This is the first demonstration of a homozygous deletion in a PanIN lesion, and the authors have described a simple assay that will enable determining MTAP gene status in limited tissue materials, such as biopsy specimens. Why is this important? Compounds that selectively target MTAP-negative pancreatic cancers are already in clinical trials; if successful, one can envision extrapolating these trials to treat the precursors to invasive cancer before a cancer develops. The challenge will be in identifying patients with non-invasive, MTAP-negative precursor lesions who might potentially benefit from this therapy. With advances in molecular imaging and biopsy techniques, scientists are hopeful that this strategy will be actualized in the future.

In the third article, Dr. Prasad and colleagues performed the first large scale gene expression profiling of PanIN lesions using "gene chips". Johns Hopkins scientists were one of the first to comprehensively determine the gene expression profile of invasive pancreatic cancer, and the group at Hopkins has now extended this knowledge to precursor lesions as well. In order to isolate these tiny ductal lesions from surrounding normal tissues, the scientists used a technique called "laser capture microdissection". They found 49 genes that were expressed differentially compared to normal ductal epithelium. Of note, they found many of the overexpressed genes in PanINs are normally turned on by activation of the sonic hedgehog pathway during development, thereby confirming that abnormal activation of this pathway plays a role in both early and advanced pancreatic cancers. Hopkins scientists had previously demonstrated that the sonic hedgehog pathway is a powerful therapeutic target in invasive pancreatic cancers, and this current work provides rationale for investigating this line of therapy in the prevention of pancreatic cancers as well.

References:
1. Maitra A, Fukushima N, Takaori K, Hruban RH.
Precursors to invasive pancreatic cancer.
Adv Anat Pathol. 2005 Mar;12(2):81-91. PMID: 15731576

2. Hustinx SR, Leoni LM, Yeo CJ, Brown PN, Goggins M, Kern SE, Hruban RH, Maitra A.
Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion.
Mod Pathol. 2005 Jul;18(7):959-63. PMID: 15832197

3. Prasad NB, Biankin AV, Fukushima N, Maitra A, Dhara S, Elkahloun AG, Hruban RH, Goggins M, Leach SD.
Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells.
Cancer Res. 2005 Mar 1;65(5):1619-26. PMID: 15753353

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Johns Hopkins Is Number One Again!!!
July 2005

#1 Hospital Badge

THE JOHNS HOPKINS HOSPITAL TOPS U.S.NEWS & WORLD REPORT'S "HONOR ROLL" FOR THE 15th YEAR IN A ROW

For the 15th consecutive year, U.S. News & World Report's annual ranking of American hospitals has placed The Johns Hopkins Hospital at the top of the list.

The magazine's recognition is, as always, a tribute to the Hospital, its dedicated nurses and staff, the School of Medicine's faculty physicians and the community physicians whose contributions are significant.

As we endeavor to rebuild, renew, enrich and expand our services and facilities, and to assure our continued commitment to safety and excellence, such independent evaluations as these rankings are of growing value to patients, the public, referring physicians and insurers.

This year's annual guide ranked American medical centers in 17 specialties to identify hospitals that excel in a variety of difficult areas of care by conducting research, pioneering advanced treatments and bringing the best technology and expertise to bear. Just 176 hospitals scored high enough this year to rank in even a single area out of all 6007 U.S. medical centers, and only 16 accumulated enough points to make it to the Honor Roll reserved for medical centers that ranked at or near the top in at least six specialties. Hopkins placed #3 in Cancer, #1 in Gynecology, # 3 in Digestive Disorders. For a complete list of all rankings, go to www.usnews.com or www.hopkinsmedicine.org.

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Joseph C. Monastra Foundation
July 2005

The Joseph C. Monastra Foundation will hold two fundraisers this summer to benefit pancreatic cancer research at Johns Hopkins. On Saturday July 16, 2005, the foundation will hold the "1st Annual JCM Motorcycle Ride" in Valley View, Ohio. The ride begins and ends at the Quaker Steak and Lube on Canal Road. For more information on this fundraiser contact Grace Saunders at: 330-656-0770.

The Joseph C. Monastra Foundation will hold a second fundraiser- the 4th Annual 5K Run/1 Mile Walk, on Saturday August 6, 2005. This event will be held in Hudson, Ohio. For more information contact 216-623-9933, or BMLodge@aldelphia.net.

The proceeds from both events will benefit pancreatic cancer research at Johns Hopkins.
Check out our fundraising page.

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Animation
June 2005

In an effort to keep the users of this website up to date on some exciting new developments in the pancreatic cancer research labs here at Hopkins, we have added a new animation to our research prensentation page of this web site. This animation on nanotechnology describes some of the exciting new nanotechnology research in Anirban Maitra’s pancreatic cancer research lab. The animation was developed by Leslie Leonard, M.A., as a part of her Masters thesis for the Art as Applied to Medicine program here at Johns Hopkins. The animation requires Macromedia Flash Player. We thank Leslie for her beautiful art work, and we hope you find this new addition to our web site educational.

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New Book on Pancreatic Cancer
April 2005

pcbook

Dr. Ralph Hruban, Director of the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins, is one of the editors of a new book on pancreatic cancer. The book "Pancreatic Cancer" has just been published by Jones and Bartlett (http://medicine.jbpub.com/catalog/0763721786/). "Pancreatic Cancer" is co-edited by Drs. VonHoff and Evans, and includes chapters written by many of the experts at Johns Hopkins. All aspects of the disease are covered, from embryology, through genetics and treatment. It is hoped that this new book will form the basis for better patient care and that it will spark new research in this field. The book is written for scientists and physicians and may be too technical for the lay public.

 

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New Technology Developed for the Early Detection of Pancreatic Cancer
April 2005

There are no early warning signs of pancreatic cancer and there are no early detection tests. As a result, most patients are not diagnosed until after the cancer has spread. Just as there is a PSA test for prostate cancer, so too do we urgently need an early detection test for pancreatic cancer. Dr. James Eshleman at Hopkins has recently developed a new technology that can detect rare DNA mutations (alterations in the DNA sequence) even when these mutations are admixed with much larger numbers of normal DNA sequences (Nat Methods. 2004 Oct 21;1(2):141-147 ). The technology, called "LigAmp" detected the most common mutation found in pancreatic cancer (KRAS2 gene mutations) even when a single mutant KRAS2 gene was admixed with 1,000 normal genes. Dr. Eshleman and colleagues have further shown that LigAmp can be used to detect DNA mutations shed from pancreatic cancers in pancreatic juice samples.

To learn more about this exciting advance see www.jhu.edu/~gazette/2004/08nov04/08typos.html

Reference:
Shi C, Eshleman SH, Jones D, Fukushima N, Hua L, Parker AR, Yeo CJ, Hruban RH, Goggins MG, Eshleman JR. LigAmp for sensitive detection of single-nucleotide differences. Nat Methods. 2004 Oct 21;1(2):141-147

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New Potential Target for Therapy
March 2005

Dr. Anirban Maitra and colleagues at Johns Hopkins have identified a genetic change in pancreatic cancers that has potential therapeutic implications. MTAP is a gene on chromosome 9 and novel chemotherapeutic strategies exploiting the selective loss of MTAP function in cancers have been proposed. The MTAP gene is adjacent to the p16 gene and MTAP and p16 are frequently deleted from the DNA of pancreatic cancers. Dr. Maitra has found these deletions of the MTAP and p16 genes in 30% of pancreatic cancers, suggesting that selected patients with pancreatic cancer may benefit from therapies targeting this loss. Studies are now underway in animal models to test this potential new treatment approach.

To learn more about this exciting finding visit www.landesbioscience.com/journals/cbt/abstract.php?id=1380

Reference:
Hustinx SR, Hruban RH, Leoni LM, Iacobuzio-Donahue C, Cameron JL, Yeo CJ, Brown PN, Argani P, Asfaq R, Fukushima N, Goggins M, Kern SE, Maitra A. Homozygous Deletion of the MTAP Gene In Invasive Adenocarcinoma of the Pancreas and in Periampullary Cancer: A Potential New Target for Therapy. Cancer Biol Ther. 2005 Jan 15;4(1): 83-86.

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Goldman Family Trust To Fund New Pancreatic Cancer Research Center at Hopkins
March 2005

Cancer specialists at Johns Hopkins today announced the start of a collaborative research initiative focused on developing novel means of earlier diagnosis and treatment of pancreatic cancer, which kills nearly 31,000 Americans each year and has one of the lowest survival rates for any type of cancer. With $10 million in funding from the Sol Goldman Charitable Trust, a New York-based philanthropy with historic ties to Baltimore, the new initiative will support a team of more than 12 faculty and young researchers.

Click here for the Sol Goldman Center for Pancreatic Cancer Research Website
Read more of the official press release

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Do You Have Pancreatic, Stomach? or Colon Cancer?
February 2005

Researchers at Johns Hopkins are seeking individuals who have the above cancers and may be experiencing weight loss.

Purpose: To evaluate the benefits of fish oil supplementation to maintain weight in individuals with pancreatic, stomach, and colon cancer.

To qualify for the study, you must:

Qualified participants will receive study medication, physical exams, laboratory tests, and evaluation of functional status. Parking vouchers will be provided.

For more information, please call the Clinical Trials Unit at 410-502-0033 or email amunson1@jhmi.edu

Visit our website at http://www.hopkinsmedicine.org/Research/ora/Clinical_research/

Principal Investigator: Adrian S. Dobs, MD

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