REVIEW ARTICLE Kasmintan Schrader, et al; ONCOLOGY Vol. 26 No. 5
In this article, we use a case-based approach to focus on the hereditary aspects of the most common GI cancers, including pancreatic, gastric, and colon cancer.
REVIEW ARTICLE Lyen C. Huang, George A. Poultsides, Jeffrey A. Norton; ONCOLOGY Vol. 25 No. 9
This article reviews the surgical management of gastrointestinal neuroendocrine tumors, including the preoperative control of hormonal symptoms, extent of resection required, postoperative outcomes, and differing management strategies.
REVIEW ARTICLE Manisha Palta, Christopher Willett, Brian Czito; ONCOLOGY Vol. 25 No. 8
Older trials evaluating outcomes of CRT, CT, and surgery alone in patients with resected pancreatic cancer are fraught with flaws. Despite this, adjuvant CT alone has evolved and remains the standard of care in the adjuvant treatment of resectable pancreatic cancer throughout much of Europe.
REVIEW ARTICLE Talia Golan, Milind Javle; ONCOLOGY Vol. 25 No. 6
Recently, randomized phase II trials combining IGF-1R with epidermal grown factor receptor (EGFR) inhibition in colorectal cancer have been completed. Preclinical studies have indicated that several biomarkers may have potential predictive value.
In this case report, we discuss the presentation, workup, and therapeutic management of a 40-year-old man who presented with borderline resectable, periampullary pancreatic cancer and underwent a margin-negative resection following neoadjuvant chemoradiotherapy.
• Novel Approaches to ‘Borderline Resectable’ Pancreatic Tumors
Pancreatic ductal adenocarcinoma (PDAC) is one of the most frequently diagnosed cancers and the fourth leading cause of cancer-related death in the United States, suggesting that there is an urgent need to design novel strategies for achieving better treatment outcome of patients diagnosed with PDAC. Our previous study has shown that activation of Notch and NF-B play a critical role in the development of PDAC in the compound K-Ras(G12D) and Ink4a/Arf deficient transgenic mice. However, the exact molecular mechanism by which mutated K-Ras and Ink4a/Arf deficiency contribute to progression of PDAC remains largely elusive. In the present study, we used multiple methods, such as real-time RT-PCR, Western blotting assay, and immunohistochemistry to gain further mechanistic insight. We found that the deletion of Ink4a/Arf in K-Ras(G12D) expressing mice led to high expression of PDGF-D signaling pathway in the tumor and tumor-derived cell line (RInk-1 cells). Furthermore, PDGF-D knock-down
Pancreaticcancer is the fourth most common cause of cancer death worldwide with large geographical variation, which implies the contribution of diet and lifestyle in its etiology. We examined the association of meat and fish consumption with risk of pancreaticcancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 477,202 EPIC participants from 10 European countries recruited between 1992 and 2000 were included in our analysis. Until 2008, 865 nonendocrine pancreaticcancer cases have been observed. Calibrated relative risks (RRs) and 95% confidence intervals (CIs) were computed using multivariable-adjusted Cox hazard regression models. The consumption of red meat (RR per 50 g increase per day = 1.03, 95% CI = 0.93-1.14) and processed meat (RR per 50 g increase per day = 0.93, 95% CI = 0.71-1.23) were not associated with an increased pancreaticcancer risk. Poultry consumption tended to be associated with an increased pancreaticcancer risk (RR
Pancreaticcancer is almost always fatal, in part because of its delayed diagnosis, poor prognosis, rapid progression and chemoresistance. Oncogenic proteins are stabilized by the Hsp90, making it a potential therapeutic target. We investigated the oxidative stress-mediated dysfunction of Hsp90 and the hindrance of its chaperonic activity by a carbazole alkaloid, mahanine, as a strategic therapeutic in pancreaticcancer. Mahanine exhibited antiproliferative activity against several pancreaticcancer cell lines through apoptosis. It induced early accumulation of reactive oxygen species (ROS) leading to thiol oxidation, aggregation and dysfunction of Hsp90 in MIAPaCa-2. N-acetyl-L-cysteine prevented mahanine-induced ROS accumulation, aggregation of Hsp90, degradation of client proteins and cell death. Mahanine disrupted Hsp90-Cdc37 complex in MIAPaCa-2 as a consequence of ROS generation. Client proteins were restored by MG132, suggesting a possible role of ubiquitinylated protein
Inhibition of centromere-associated protein-E (CENP-E) has demonstrated preclinical anti-tumor activity in a number of tumor types including neuroblastoma. A potent small molecule inhibitor of the kinesin motor activity of CENP-E has recently been developed (GSK923295). To identify an effective drug combination strategy for GSK923295 in neuroblastoma, we performed a screen of siRNAs targeting a prioritized set of genes that function in therapeutically tractable signaling pathways. We found that siRNAs targeted to extracellular signal-related kinase 1 (ERK1) significantly sensitized neuroblastoma cells to GSK923295-induced growth inhibition (p = 0.01). Inhibition of ERK1 activity using pharmacologic inhibitors of mitogen-activated ERK kinase (MEK1/2) showed significant synergistic growth inhibitory activity when combined with GSK923295 in neuroblastoma, lung, pancreatic and colon carcinoma cell lines. Synergistic growth inhibitory activity of combined MEK/ERK and CENP-E inhibition was
Progress during the past 3 decades in the treatment of advanced neuroendocrine tumors (NET) has been slow, despite a substantial increase in the incidence of NET at all primary sites and stages of disease. In the United States, the annual incidence of pancreatic NET (pNET) was estimated as 0.32 per 100,000 people in 2004. Until recently, there were few available therapies for the treatment of patients with advanced pNET. Nonetheless, substantial strides have been made within the past several years. In 2011, 2 new systemic therapies (everolimus and sunitinib) were approved by the US Food and Drug Administration (FDA) for the treatment of patients with advanced pNET, based on recently published results from 2 phase III studies. Additions to the pNET treatment arsenal significantly expanded options for clinicians who treat these patients. However, important differences between the key clinical studies existed, preventing optimal direct comparison of the study results. Therefore, the
CancerNetwork discusses the diagnosis and treatment of metastatic pancreatic cancer with Dr. Diane Simeone, who is involved in both pancreatic cancer clinical trials as well as research to better characterize important pancreatic cancer pathways and identify biomarkers for the disease.