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Cancers frequently arise as a result of an acquired genomic instability and the subsequent clonal evolution of neoplastic cells with variable patterns of genetic aberrations. Thus, the presence and behaviors of distinct clonal populations in each patient's tumor may underlie multiple clinical phenotypes in cancers. We applied DNA content-based flow sorting(More)
Activating mutation of the Kras oncogene is the most frequent and perhaps the earliest genetic alteration associated with pancreatic cancer. To examine the link between mutant Kras and exocrine pancreatic cancer, we generated transgenic mice carrying an elastase-mutant Kras transgene, which targets expression to pancreatic acinar cells. Most elastase-Kras(More)
Microsatellite alterations are useful clonal markers for the early detection of cancer. An increase in microsatellite instability has been observed at certain tetranucleotide repeat markers (AAAGn) in lung, head and neck, and bladder cancer. However, the genetic mechanism underlying these elevated microsatellite alterations at selected tetranucleotide(More)
Pancreatic adenocarcinoma (PAC) is among the most lethal malignancies. While research has implicated multiple genes in disease pathogenesis, identification of therapeutic leads has been difficult and the majority of currently available therapies provide only marginal benefit. To address this issue, our goal was to genomically characterize individual PAC(More)
BACKGROUND The majority of lung carcinoma cases occur in current or former smokers. K-ras gene mutations are common in lung adenocarcinoma and have been associated with cigarette smoking, asbestos exposure, and female gender. METHODS In the current study, the authors examined the contribution of cigarette smoking to K-ras gene mutations in patients with(More)
BACKGROUND We analyzed clinical findings and results of parathyroidectomy in 42 patients treated from 1936 to 1988 at the University of California, San Francisco (UCSF) for primary hyperparathyroidism and multiple endocrine neoplasia (MEN) syndrome to document results of parathyroidectomy and reasons for failed parathyroid operations. METHODS Of the 42(More)
Insulinomas are usually solitary (greater than 90%) benign pancreatic tumors readily cured by enucleation or resection. To determine whether the 4% of insulinomas associated with multiple endocrine neoplasia type 1 (MEN-I) require a different surgical approach, we analyzed our experience in seven patients with MEN-I insulinomas treated during the past 28(More)
BACKGROUND For many years the prognosis for patients with biliary malignancies has been poor. However, recent advances in radiology and laparoscopy have improved staging, and active biliary stent management may improve outcome in these patients. In the past the goal with surgery was to excise all gross tumor. Now, the surgical goal is to achieve negative(More)
BACKGROUND Stage I (T1-2NOM0) adenocarcinoma of the pancreas is associated with a 5-year survival rate of 15-25%. Despite apparently curative resection and pathologic staging indicating localized disease, these cancers recur. The authors hypothesized that there exists microscopic regional disease that is not detected by surgical exploration or routine(More)