Faculty Bibliography

Screening and early detection of pancreatic cancer has the potential to substantially impact outcomes in this deadly disease. Over the last ten years several cohort studies have been conducted and report on the yield of screening in high risk populations. With better understanding of the cellular compartments and the genetic and epigenetic changes that occur, biomarkers have also emerged as promising means of early detection. In this paper we summarize the results of the latest screening cohort and highlight a novel proteomic approach that may be used in future biomarker studies.

Pancreatic cancer presents at an advanced stage in majority of the patients, hence resulting in a very dismal prognosis. Novel and effective methods to detect and screen pancreatic cancer and its precursors are warranted. The U.S. Multi-Society Task Force recommends against routine screening for pancreatic cancer in asymptomatic adults using abdominal palpation, ultrasonography, or serologic markers. Moreover, the screening for persons with hereditary predisposition to develop pancreatic cancer has not been validated. Herein, the authors summarize the data presented at the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in detecting early stage pancreatic cancer (Abstracts #187 and #193).

Carcinoma-associated fibroblasts (CAFs) that express α-smooth muscle actin (αSMA) contribute to cancer progression, but their precise origin and role are unclear. Using mouse models of inflammation-induced gastric cancer, we show that at least 20% of CAFs originate from bone marrow (BM) and derive from mesenchymal stem cells (MSCs). αSMA+ myofibroblasts (MFs) are niche cells normally present in BM and increase markedly during cancer progression. MSC-derived CAFs that are recruited to the dysplastic stomach express IL-6, Wnt5α and BMP4, show DNA hypomethylation, and promote tumor growth. Moreover, CAFs are generated from MSCs and are recruited to the tumor in a TGF-β- and SDF-1α-dependent manner. Therefore, carcinogenesis involves expansion and relocation of BM-niche cells to the tumor to create a niche to sustain cancer progression.

INTRODUCTION/BACKGROUND:Intussusception (IS) is rare in adults. However, the more frequent use of cross-sectional imaging has resulted in an increase in its detection. Because of the reported association with celiac disease, we determined the prevalence of IS among a cohort with celiac disease. METHODS:An anonymized prospectively maintained celiac disease database and radiological database were reviewed. RESULTS:Of a total of 880 patients, 14 (age 47 ± 17.5 years; 50% female) had IS that was detected by CT in 10, capsule endoscopy in three, and barium studies in two. The reason for evaluation was abdominal pain in 78% (11/14), whereas in the remainder (3/14) were incidental. IS was the initial manifestation of celiac disease in 57% (8/14). Two patients were found to have lead-point intussusceptions and both had small-bowel adenocarcinoma, and 10/14 had severe villous atrophy (subtotal or total). Among those with established celiac disease, IS was detected early, within 3 years of diagnosis. Follow-up was available for 11 patients, 9 of who adhered strictly to a gluten-free diet, and six had no recurrence. Among all the patients diagnosed with IS on radiologic studies at our institution, 45 were considered to have idiopathic IS. Only two of these patients had evaluation for celiac disease. CONCLUSION/CONCLUSIONS:IS occurs in celiac disease. It may be the initial presentation and is associated with abdominal pain. Adenocarcinoma needs to be excluded. The majority of patients do not have recurrent symptoms after adherence to a gluten-free diet. Celiac disease should be considered more frequently when IS is encountered.

It is increasingly recognized that the non-neoplastic stromal compartment in most solid cancers plays an active role in tumor proliferation, invasion and metastasis. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types in the tumor stroma, and these cells are pro-tumorigenic. Evidence that CAFs are epigenetically and possibly also genetically distinct from normal fibroblasts is beginning to define these cells as potential targets of anti-cancer therapy. Here, we review the cell-of-origin and molecular biology of CAFs, arguing that such knowledge provides a rational basis for designing therapeutic strategies to coordinately and synergistically target both the stromal and malignant epithelial component of human cancers.

Chronic inflammation often precedes or accompanies a substantial number of cancers. Indeed, anti-inflammatory therapies have shown efficacy in cancer prevention and treatment. The exact mechanisms that turn a wound healing process into a cancer precursor are topics of intense research. A pathogenic link has been identified between inflammatory mediators, inflammation related gene polymorphisms and carcinogenesis. Animal models of cancer have been instrumental in demonstrating the diversity of mechanisms through which every tumor compartment and tumor stage may be affected by the underlying inflammatory process. In this review, we focus on the interaction between chronic inflammation, tumor stem cells and the tumor microenvironment. We summarize the proposed mechanisms that lead to the recruitment of bone marrow derived cells and explore the genetic and epigenetic alterations that may occur in inflammation associated cancers.