A new approach to managing intraductal papillary mucinous pancreatic neoplasms

Ghaneh, Paula; Neoptolemos, John P.

doi:10.1136/gut.2006.113068

Cited by 141 publications

(16 citation statements)

References 33 publications

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“…Periampullary cancers carry a poor prognosis due to their insensitivity to most conventional therapies [23,24]. Currently, surgical resection offers the only potential chance for a cure in these patients.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of mitochondrial membrane complexes (MMCs) I, III, IV and V in malignant and benign periampullary epithelium: a potential target for drug therapy of periampullary cancer?

et al. 2010

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BackgroundMitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis.MethodsThis was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied.ResultsMMCs I, III, IV and V were highly expressed (p < 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p < 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours.ConclusionsDifferential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical expression of mitochondrial membrane complexes (MMCs) I, III, IV and V in malignant and benign periampullary epithelium: a potential target for drug therapy of periampullary cancer?

et al. 2010

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“…Pancreatic cancer is an aggressive and deadly disease, with an average median survival of less than a year (1). Several genetic pathways have been identified as being active in the progression of this tumor, including signaling through MET (MET tyrosine kinase receptor protein).…”

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confidence: 99%

PAX6 Is Expressed in Pancreatic Cancer and Actively Participates in Cancer Progression through Activation of the MET Tyrosine Kinase Receptor Gene

Mascarenhas

Young

Littlejohn

et al. 2009

Journal of Biological Chemistry

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Tumors of the exocrine pancreas have a poor prognosis. Several proteins are overexpressed in this cancer type, including the MET tyrosine kinase receptor and the transcription factor PAX6. In this report, we find that PAX6(5a), an alternately spliced variant form of PAX6, is expressed in pancreatic carcinoma cell lines at higher levels than the canonical PAX6 protein. Both protein forms of PAX6 bind directly to an enhancer element in the MET promoter and activate the expression of the MET gene. In addition, inhibition of PAX6 transcripts leads to a decline in cell growth and survival, differentiation, and a concurrent reduction of MET protein expression. These data support a model for a neoplastic pathway, where expression of a transcription factor from development activates the MET receptor, a protein that has been directly linked to protumorigenic processes of resisting apoptosis, tumor growth, invasion, and metastasis.Pancreatic cancer is an aggressive and deadly disease, with an average median survival of less than a year (1). Several genetic pathways have been identified as being active in the progression of this tumor, including signaling through MET (MET tyrosine kinase receptor protein). The MET gene encodes a tyrosine kinase receptor for the ligand hepatocyte growth factor/scatter factor. The MET gene produces a partially glycosylated 170-kDa precursor protein. This precursor is glycosylated further and cleaved into a 50-kDa ␣ chain and a 140-kDa ␤ chain to create a mature receptor (2). The MET receptor is essential for normal development and plays a role in cell migration, growth, survival, differentiation, angiogenesis, and tube formation/ branching morphogenesis (reviewed in Ref.3). MET has also been implicated in cancer progression and is directly involved in metastasis, resistance to apoptosis, and tumor growth.MET is expressed in the developing pancreatic bud of the embryo and marks candidate stem/progenitor cells in the embryonic and adult pancreas (4 -6). MET expression is expressed at very low levels in normal adult differentiated pancreatic cells (7). MET is overexpressed in pancreatic cancer cells and has been linked to the aggressiveness of this tumor in terms of growth, invasion, and metastasis (7-10).Although mutations in the MET locus have been identified, overexpression of MET occurs mainly due to aberrant transcriptional regulation (3). The MET gene is regulated by several transcription factors that can either activate or repress expression. Activators include HIF1 (hypoxia-induced factor 1) in response to oxygen deficiency (11), ETS1 (12), Sp1 (13), AP1 (14), Smads downstream of transforming growth factor-␤ signaling (13), and the p53 protein (15) The transcription factor PAX3 can also activate MET expression during the embryonic development of muscle cells (23). PAX3 belongs to the PAX gene family, and most of what is known about these related proteins is their role during development. Only recently has the expression of PAX proteins in adult stem cells and in disease been discovered...

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“…Pancreatic cancer (PC) is one of the most fatal malignant tumors among human; although infrequent, it takes up 3 % of all reported cases of cancer and it is the fourth most common cause of cancer-related deaths in the USA and the eighth worldwide [1–3]. What was worse, the prognosis of PC is very poor; the 5-year survival rate is less than 5 % even with the surgical and chemotherapy intervention.…”

Section: Introductionmentioning

confidence: 99%

Association of OGG1 Ser326Cys polymorphism and pancreatic cancer susceptibility: evidence from a meta-analysis

Yan

et al. 2013

Tumor Biol.

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The 8-oxoguanine DNA glycosylase (OGG1) gene has been considered to be associated with cancer susceptibility. The OGG1 Ser326Cys polymorphism has been reported to be associated with pancreatic cancer (PC), but the published studies have yielded inconsistent results. For better understanding of the effect of OGG1 Ser326Cys polymorphism on PC susceptibility, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database before May 2013. The association between the OGG1 Ser326Cys polymorphism and PC risk was conducted by odds ratios (ORs) and 95 % confidence intervals (CIs). A total of five case–control studies with 1,690 cases and 3,650 controls were eventually collected. Overall, we found that OGG1 Ser326Cys polymorphism was not associated with PC susceptibility (Cys/Cys vs. Ser/Ser: OR = 0.95, 95 % CI = 0.80–1.14; Cys/Cys vs. Ser/Ser + Ser/Cys: OR = 0.95, 95 % CI = 0.78–1.14; Cys/Cys + Ser/Cys vs. Ser/Ser (OR = 1.00, 95 % CI = 0.89–1.12)). In the subgroup analysis based on ethnicity, source of control, sample size, and genotyping method, no significant association was found in any genetic models. This meta-analysis suggests that the OGG1 Ser326Cys polymorphism may not associated with PC susceptibility. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results.

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A new approach to managing intraductal papillary mucinous pancreatic neoplasms

Cited by 141 publications

References 33 publications

Immunohistochemical expression of mitochondrial membrane complexes (MMCs) I, III, IV and V in malignant and benign periampullary epithelium: a potential target for drug therapy of periampullary cancer?

Immunohistochemical expression of mitochondrial membrane complexes (MMCs) I, III, IV and V in malignant and benign periampullary epithelium: a potential target for drug therapy of periampullary cancer?

PAX6 Is Expressed in Pancreatic Cancer and Actively Participates in Cancer Progression through Activation of the MET Tyrosine Kinase Receptor Gene

Association of OGG1 Ser326Cys polymorphism and pancreatic cancer susceptibility: evidence from a meta-analysis

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