Analysis of Cell Proliferation and Tumor Antigens of Prognostic Significance in Pancreatic Endocrine Tumors

2015 ◽  
pp. 45-59
Author(s):  
Cesare Bordi ◽  
Giuseppe Viale
Keyword(s):  
Cell Proliferation ◽  
Tumor Antigens ◽  
Prognostic Significance ◽  
Endocrine Tumors ◽  
Pancreatic Endocrine Tumors

Prognostic Significance of p27, Ki-67, and Topoisomerase IIα Expression in Clinically Nonfunctioning Pancreatic Endocrine Tumors

2000 ◽  
Vol 11 (3) ◽  
pp. 229-242 ◽  
Author(s):  
Hee Jin Chang ◽  
Kenneth P. Batts ◽  
Ricardo V. Lloyd ◽  
Thomas J. Sebo ◽  
Geoffrey B. Thompson ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Endocrine Tumors ◽  
Topoisomerase Iiα ◽  
Ki 67 ◽  
Pancreatic Endocrine Tumors

Prevalence and Prognostic Significance of Acinar Cell Differentiation in Pancreatic Endocrine Tumors

2002 ◽  
Vol 26 (7) ◽  
pp. 893-901 ◽  
Author(s):  
Rhonda K. Yantiss ◽  
Hee-Kyung Chang ◽  
Francis A. Farraye ◽  
Carolyn C. Compton ◽  
Robert D. Odze
Keyword(s):  
Cell Differentiation ◽  
Acinar Cell ◽  
Prognostic Significance ◽  
Endocrine Tumors ◽  
Pancreatic Endocrine Tumors

Targeting protein kinase C by Enzastaurin restrains proliferation and secretion in human pancreatic endocrine tumors

2011 ◽  
Vol 18 (4) ◽  
pp. 439-450 ◽  
Author(s):  
Daniela Molè ◽  
Teresa Gagliano ◽  
Erica Gentilin ◽  
Federico Tagliati ◽  
Claudio Pasquali ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase C ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Cell Viability ◽  
Cell Line ◽  
Primary Cultures ◽  
Endocrine Tumors ◽  
Kinase C ◽  
Pancreatic Endocrine Tumors

Dysregulation of the protein kinase C (PKC) signaling pathway has been implicated in tumor progression. In this study, we investigate the effects of a PKC inhibitor, Enzastaurin, in human pancreatic neuroendocrine neoplasms (PNN) primary cultures and in the human pancreatic endocrine cancer cell line, BON1. To this aim six human PNN dispersed in primary cultures and BON1 cells were treated without or with 1–10 μM Enzastaurin and/or 100 nM IGF1 in the presence or absence of serum. Cell viability and apoptosis were evaluated after 48–72 h; Chromogranin A (CgA) and/or insulin secretion was assessed after 6 h of incubation. PKC expression was investigated by immunofluorescence and western blot. We found that Enzastaurin significantly reduced human PNN primary culture cell viability, as well as CgA and insulin secretion. Moreover, in the BON1 cell line Enzastaurin inhibited cell proliferation at 5 and 10 μM by inducing caspase-mediated apoptosis, and reduced phosphorylation of glycogen synthetase kinase 3β (GSK3β) and of Akt, both downstream targets of PKC pathway and pharmacodynamic markers for Enzastaurin. In addition, Enzastaurin blocked the stimulatory effect of IGF1 on cell proliferation, and reduced CgA expression and secretion in BON1 cells. Two different PKC isoforms are expressed at different levels and have partially different subcellular localization in BON1 cells. In conclusion, Enzastaurin reduces cell proliferation by inducing apoptosis, with a mechanism likely involving GSK3β signaling, and inhibits secretory activity in PNN in vitro models, suggesting that Enzastaurin might represent a possible medical treatment of human PNN.

scholarly journals The embryonic transcription factor Hlxb9 is a menin interacting partner that controls pancreatic β-cell proliferation and the expression of insulin regulators

2013 ◽  
Vol 20 (1) ◽  
pp. 111-122 ◽  
Author(s):  
Kerong Shi ◽  
Vaishali I Parekh ◽  
Swarnava Roy ◽  
Shruti S Desai ◽  
Sunita K Agarwal
Keyword(s):  
Cell Proliferation ◽  
Cell Differentiation ◽  
Insulin Level ◽  
Cell Types ◽  
Endocrine Tumors ◽  
Β Cell ◽  
Tissue Specific ◽  
Pancreatic Endocrine Tumors ◽  
Differentiation Factors ◽  
Cell Differentiation Factor

The multiple endocrine neoplasia type 1 (MEN1) syndrome is caused by germline mutations in the MEN1 gene encoding menin, with tissue-specific tumors of the parathyroids, anterior pituitary, and enteropancreatic endocrine tissues. Also, 30–40% of sporadic pancreatic endocrine tumors show somatic MEN1 gene inactivation. Although menin is expressed in all cell types of the pancreas, mouse models with loss of menin in either pancreatic α-cells, or β-cells, or total pancreas develop β-cell-specific endocrine tumors (insulinomas). Loss of widely expressed tumor suppressor genes may produce tissue-specific tumors by reactivating one or more embryonic-specific differentiation factors. Therefore, we determined the effect of menin overexpression or knockdown on the expression of β-cell differentiation factors in a mouse β-cell line (MIN6). We show that the β-cell differentiation factor Hlxb9 is posttranscriptionally upregulated upon menin knockdown, and it interacts with menin. Hlxb9 reduces cell proliferation and causes apoptosis in the presence of menin, and it regulates genes that modulate insulin level. Thus, upon menin loss or from other causes, dysregulation of Hlxb9 predicts a possible combined mechanism for β-cell proliferation and insulin production in insulinomas. These observations help to understand how a ubiquitously expressed protein such as menin might control tissue-specific tumorigenesis. Also, our findings identify Hlxb9 as an important factor for β-cell proliferation and insulin regulation.

scholarly journals VHL inactivation is an important pathway for the development of malignant sporadic pancreatic endocrine tumors

2009 ◽  
Vol 16 (4) ◽  
pp. 1219-1227 ◽  
Author(s):  
A M Schmitt ◽  
S Schmid ◽  
T Rudolph ◽  
M Anlauf ◽  
C Prinz ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Adverse Outcome ◽  
Hypoxia Inducible Factor ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Small Subset ◽  
Endocrine Tumors ◽  
Glucose Transporter 1 ◽  
Glut 1 ◽  
Pancreatic Endocrine Tumors

A small subset of familial pancreatic endocrine tumors (PET) arises in patients with von Hippel–Lindau syndrome and these tumors may have an adverse outcome compared to other familial PET. Sporadic PET rarely harbors somatic VHL mutations, but the chromosomal location of the VHL gene is frequently deleted in sporadic PET. A subset of sporadic PET shows active hypoxia signals on mRNA and protein level. To identify the frequency of functionally relevant VHL inactivation in sporadic PET and to examine a possible prognostic significance we correlated epigenetic and genetic VHL alterations with hypoxia signals. VHL mutations were absent in all 37 PETs examined. In 2 out of 35 informative PET (6%) methylation of the VHL promoter region was detected and VHL deletion by fluorescence in situ hybridization was found in 14 out of 79 PET (18%). Hypoxia inducible factor 1α (HIF1-α), carbonic anhydrase 9 (CA-9), and glucose transporter 1 (GLUT-1) protein was expressed in 19, 27, and 30% of the 152 PETs examined. Protein expression of the HIF1-α downstream target CA-9 correlated significantly with the expression of CA-9 RNA (P<0.001), VHL RNA (P<0.05), and VHL deletion (P<0.001) as well as with HIF1-α (P<0.005) and GLUT-1 immunohistochemistry (P<0.001). These PET with VHL alterations and signs of hypoxia signalling were characterized by a significantly shortened disease-free survival. We conclude that VHL gene impairment by promoter methylation and VHL deletion in nearly 25% of PET leads to the activation of the HIF-pathway. Our data suggest that VHL inactivation and consecutive hypoxia signals may be a mechanism for the development of sporadic PET with an adverse outcome.

scholarly journals Study of LBHD1 Expression with Invasion and Migration of Bladder Cancer

2019 ◽  
Vol 14 (1) ◽  
pp. 440-447
Author(s):  
Chunhui Dong ◽  
Yihui Liu ◽  
Guiping Yu ◽  
Xu Li ◽  
Ling Chen
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Tumor Antigens ◽  
Urinary Bladder Cancer ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
Bladder Cancer Cells

AbstractLBHD1 (C11ORF48) is one of the ten potential tumor antigens identified by immunoscreening the urinary bladder cancer cDNA library in our previous study. We suspect that its expression is associated with human bladder cancer. However, the exact correlation remains unclear. To address the potential functional relationship between LBHD1 and bladder cancer, we examined the LBHD1 expression at the mRNA and protein level in 5 different bladder cancer cell lines: J82, T24, 253J, 5637, and BLZ-211. LBHD1 high and low expressing cells were used to investigate the migration, invasion, and proliferation of bladder cancer cells following transfection of LBHD1 with siRNA and plasmids, respectively. Our experiment showed that the degree of gene expression was positively related to the migration and invasion of the cancer cells while it had little effect on cell proliferation. Knocking down LBHD1 expression with LBHD1 siRNA significantly attenuated cell migration and invasion in cultured bladder cancer cells, and overexpressing LBHD1 with LBHD1 cDNA plasmids exacerbated cell migration and invasion. Nevertheless, a difference in cell proliferation after transfection of LBHD1 siRNA and LBHD1 cDNA plasmids was not found. Our findings suggest that LBHD1 might play a role in cell migration and invasion.

Nonfunctioning pancreatic endocrine tumors: a multicenter clinical study

2003 ◽  
Vol 98 (11) ◽  
pp. 2435-2439 ◽  
Author(s):  
Lucio Gullo ◽  
Marina Migliori ◽  
Massimo Falconi ◽  
Paolo Pederzoli ◽  
Rossella Bettini ◽  
...  
Keyword(s):  
Clinical Study ◽  
Endocrine Tumors ◽  
Pancreatic Endocrine Tumors ◽  
Multicenter Clinical Study

scholarly journals Pancreatic endocrine tumors

2011 ◽  
Vol 24 (S2) ◽  
pp. S66-S77 ◽  
Author(s):  
Sylvia L Asa
Keyword(s):  
Endocrine Tumors ◽  
Pancreatic Endocrine Tumors

Pancreatic Endocrine Tumors

2007 ◽  
Vol 36 (2) ◽  
pp. 431-439 ◽  
Author(s):  
Niraj Jani ◽  
A. James Moser ◽  
Asif Khalid
Keyword(s):  
Endocrine Tumors ◽  
Pancreatic Endocrine Tumors

scholarly journals Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1Cin pancreatic endocrine tumors

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Giorgio Malpeli ◽  
Eliana Amato ◽  
Mario Dandrea ◽  
Caterina Fumagalli ◽  
Valentina Debattisti ◽  
...  
Keyword(s):  
Endocrine Tumors ◽  
Down Regulation ◽  
Pancreatic Endocrine Tumors
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