Identifying Molecular Markers for the Early Detection of Pancreatic Neoplasia

Goggins, Michael

doi:10.1053/j.seminoncol.2007.05.003

Cited by 86 publications

(86 citation statements)

References 112 publications

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“…By using array-based technology and reverse transcription (RT)-PCR, the global miRNA expression profiles as well as the level of individual miRNA species have been analyzed in various human cancers, and aberrant miRNA expression was found in all tumor types studied to date, including hematological malignancies, 6 lymphoma, 7 melanoma, 8 glioblastoma, 9,10 as well as epithelial cancers from lung, 11,12 breast, 13,14 colon, 15,16 liver, 17,18 thyroid, [19][20][21][22] pancreas [23][24][25][26] etc. When compared to their normal-tissue counterparts, both overexpression and underexpression of miRNA has been observed, with decreased expression appearing to be more common in some studies, 8,27 leading to the hypothesis that oncogenes might be target genes for these miRNAs.…”

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confidence: 99%

MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma

et al. 2008

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MicroRNA (miRNA) microarray analysis has consistently found altered expression of miRNAs in thyroid tumors, suggesting their roles in thyroid carcinogenesis. To explore whether this differential expression can be used as a diagnostic tool in surgical pathology and fine-needle aspirate (FNA) specimens, the expression of selected miRNA was evaluated by quantitative RT-PCR, using total RNA from 84 formalin-fixed paraffin-embedded tissues and 40 ex vivo aspirate specimens. miRNA from all paraffin-embedded tissues and all but one FNA sample were found to be analyzable, with paraffin sections yielding better miRNA quality. Preliminary analysis of 6 miRNAs in 10 papillary thyroid carcinoma and 10 follicular adenoma identified significant overexpression of miR-146b, -221, and -222 in papillary thyroid carcinoma (Po0.02), but not miR-146a, -155, or -187 (P40.08). The expression of these first three miRNAs was examined in a series of 5 normal thyroid, 11 hyperplastic nodules, 24 follicular adenoma, 27 classical papillary thyroid carcinoma, 5 follicular variant papillary thyroid carcinoma, 2 follicular carcinoma, and 10 encapsulated follicular lesions with partial nuclear features of papillary carcinoma. Results showed miR-146b to be most consistently overexpressed in both classical papillary carcinoma and follicular variants, whereas all other groups showed lower expression at a similar level (Po0.001 for pair-wise comparisons between papillary carcinoma and all other groups). Follicular lesions with partial features of papillary carcinoma all showed low miR-146b levels similar to other non-papillary carcinoma groups, suggesting that they are biologically distinctive from papillary carcinoma. miR-221 and miR-222 also showed higher expression in papillary carcinoma, but with substantial overlaps with the other groups. When applied to 40 FNA samples of various lesions, only miR-146b and miR-222 persisted as distinguishing markers for papillary carcinoma. We concluded that miRNAs, particularly miR-146b, might potentially be adjunct markers for diagnosing papillary thyroid carcinoma in both FNA and surgical pathology specimens.

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confidence: 99%

MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma

et al. 2008

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“…Pancreatic ductal adenocarcinoma is the most common pancreatic neoplasm and evolves from a progressive cascade of cellular, morphological and architectural changes from normal ductal epithelium. The late diagnosis, rapid disease progression and resistance to conventional therapy are the major contributing factors for high mortality of pancreatic cancer patients (39). On this basis identifying novel ways of treating and preventing pancreatic cancer is important.…”

Section: Discussionmentioning

confidence: 99%

“…Approximately 33,000 new cases of pancreatic cancer occur annually in the United States with approximately the same number of deaths (38,39). Pancreatic ductal adenocarcinoma is the most common pancreatic neoplasm and evolves from a progressive cascade of cellular, morphological and architectural changes from normal ductal epithelium.…”

Section: Discussionmentioning

confidence: 99%

Anti-proliferative and proapoptotic effects of benzyl isothiocyanate on human pancreatic cancer cells is linked to death receptor activation and RasGAP/Rac1 down-modulation

Basu

Haldar²

2009

Int J Oncol

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Abstract. Benzyl isothiocyanate can exert anti-tumor effect by arrest of cell cycle progression and induction of apoptosis in human pancreatic cancer cells. Among them, the dissection of the molecular mechanism of induction of apoptosis is important because the knowledge may be exploited for both cancer prevention and treatment. Our studies reported here indicate that BITC-mediated apoptosis involves the disappearance of intact 21-kDa Bid protein, cytochrome c release and predominant procaspase-3 cleavage. Using adenocarcinoma and metastatic pancreatic cancer cells, we investigated whether this dietary isothiocyanate induces apoptosis by converging two major pathways: the death receptor-mediated extrinsic and the mitochondrial intrinsic pathway. Indeed, cell surface receptor analysis by flow cytometry demonstrates the upregulation of DR4, a member of death receptor family in BITC exposed pancreatic cancer cells. Since BITC is able to trigger death receptor signaling, we were interested in examining the effects of BITC and death receptor ligand TRAIL together on pancreatic cancer cell death. Interestingly, BITC augments TRAIL-induced apoptosis in both metastatic and adenocarcinoma cells. Moreover, we report for the first time that the sensitivity of metastatic pancreatic cancer cells to this isothiocyanate might be due to down-modulation of the proangiogenic molecule small GTPase Rac1 and caspase-3 substrate RasGAP, a regulator of Rho GTPase family.

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“…17 Serum CA19-9 has been the most studied, and has at best a limited role in diagnosis; 17 however, reliable markers that are superior to or enhance the diagnostic accuracy of CA19-9 are yet to be defined. Efforts to better characterize the molecular pathology of precursor lesions of PC, including pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms may better define candidates for early detection strategies.…”

Section: Diagnosismentioning

confidence: 99%