The Sol Goldman Pancreatic Cancer Research Center

Advances and Discoveries Made at Johns Hopkins

Genes isolated from Tumor Vessels:
Dr. St. Croix in Bert Vogelstein and Kern Kinzler's laboratory identified 46 genes which appear to be specifically elevated (or "turned on") in tumor-associated blood vessels.

Why is this important?
The identification of these genes is exciting because they are potential targets for drugs aimed at shrinking tumors by starving them of their blood supply.

Science 289:1121-2,2000

Thousands of Chemical Compounds Tested
Drs. Gloria Su and Taylor Sohn in Scott Kern's laboratory tested over 16,000 chemical compounds looking for compounds that can "turn on" on a specific function that is often "broken "in pancreatic cancer (DPC4 signaling pathway). They identified half a dozen promising compounds, one of which turned out to be a novel and specific inhibitor of a protein called HDAC (histone deacetylase).

Why is this important?
This finding represents a new method to develop drugs to treat pancreatic cancer - "fixing" the cancer cells by screening for compounds that turn on specific functions lost in the cancer.

Gene Inactivation in Precursors to Invasive Pancreatic Cancer
Drs. Michael Goggins and Robb Wilentz studied the genetic changes in the very earliest lesions that give rise to invasive pancreatic cancer. They found that the BRCA2 and DPC4 genes are inactivated in some of these early lesions (called "Pancreatic Intraepithelial Neoplasia").

Why is this important?
These studies provide an important first step in the development of novel screening tests to detect early, and therefore potentially curable, pancreatic cancers.

Am J Pathol 156:1641-1651,2000
Cancer Research 60:2002-2006,2000


DNA Methylation in Pancreatic Cancer
Dr. T. Ueki in Michael Goggins' laboratory discovered that a number of genes are selectively "hypermethylated" in pancreatic cancer. Methylation refers to the addition of an extra carbon atom to DNA and it is a common mechanism by which cancer preventing genes (tumor-suppressor genes) are inactivated in cancers.

Why is this important?
These findings provide a novel target for the development of a new screening test for pancreatic cancer.

Cancer Research 60:1835-1839,2000.


Quality of Life After a Whipple
Drs. Taylor Sohn and Charles Yeo studied patients' self-reported quality of life after Whipple surgery (pancreaticoduodenectomy). Over 192 patients were studied and over 30 quality of life measurements assayed. Remarkably, quality of life scores for patients who underwent a Whipple at Johns Hopkins were comparable to those patients who had their gallbladder removed for stones.

Why is this important?
These data demonstrate that surviving Whipple patients as a group have near normal quality of life scores. This corrects the misimpression that Whipple patients have severely impaired quality of life, and cannot return towards normal activities.

Journal of Gastrointestinal Surgery 4:355-365,2000


New Immunohistochemical Stain for the DPC4 Gene Product
In 1996, Dr. Scott Kern and colleagues at Hopkins discovered a new gene which appeared to be selectively inactivated (deleted) in the development of cancer of the pancreas. Dr. Kern and his colleagues named this gene "DPC4" for Deleted in Pancreas Cancer locus 4 (see Science 1996, vol. 271:350-353). The discovery of this gene was exciting because DPC4 is inactivated in a large number of cancers of the pancreas, and because its inactivation appears to be relatively specific for cancer of the pancreas. That is, DPC4 appears to be only rarely inactivated in other tumor types (see Cancer Research 1996, vol 56:2527-2530).

Robb Wilentz and colleagues from Johns Hopkins developed a new immunohistochemical stain for DPC4. This new stain can detect DPC4 in tissue sections (such as biopsies), and the staining pattern directly mirrors the DPC4 gene status.

Why is this important?
Because of its simplicity and availability, the immunohistochemical staining technique Dr. Wilentz developed for DPC4 has a number of direct clinical applications. For example, staining for DPC4 may help to distinguish benign chronic pancreatitis (which should express DPC4) from cancer of the pancreas (half of which will not express DPC4). Thus, DPC4 staining will add a valuable tool to the interpretation of needle biopsies of the pancreas. In addition, the immunohistochemical assay reported by Wilentz and colleagues for DPC4 may lead to answers in the investigative area. For instance, the immunohistochemical study of early lesions in the pancreas may help determine the stage at which DPC4 inactivation contributes to neoplastic progression and thereby help in the development of new screening tests for early pancreatic cancer.

American Journal of Pathology 156:37-43,2000