Induction of matrix metalloprotease-1 gene expression by retinoic acid in the human pancreatic tumour cell line Dan-G.
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We have investigated the effects of retinoic acid (RA) on matrix metalloprotease-1 (MMP-1) gene expression in the human pancreatic tumour cell line Dan-G. 13-cis RA results in a time- and dose-dependent increase of MMP-1 protein concentration. These stimulatory effects were paralleled by a time- and dose-dependent increase of MMP-1 mRNA steady-state concentrations. Nuclear run-on analysis revealed that the increase of MMP-1 mRNA was partially due to an increase of MMP-1 gene transcription. In addition, 13-cis RA treatment results in an increase of MMP-1 mRNA stability. These data demonstrate that RA stimulates MMP-1 gene expression in human pancreatic carcinoma cells by transcriptional and post-transcriptional mechanisms. (+info)
Bcl-2 expression related to altered p53 protein and its impact on the progression of human pancreatic carcinoma.
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p53 and Bcl-2 are two important factors related to apoptosis and tumorigenesis. In this study, a series of 52 cases of pancreatic carcinoma (PC) were investigated using an immunohistochemical assay to determine whether altered expression of Bcl-2 and p53 has an impact on the progression of this malignancy. Cytoplasmic immunoreactivity for Bcl-2 and nuclear staining of p53 was found in 12 (23.1%) and 32 (63.5%) cases of PC respectively. Furthermore, an inverse correlation between the expression of p53 and Bcl-2 existed in this series (P < 0.01). In a subgroup, the proportion of tumours showing that p53-positive and Bcl-2-negative staining was increased with increasing histological grade and clinical stage (P < 0.05), and moreover, the survival period of those patients whose tumour had this staining was shorter than those with other staining patterns of combined p53 and Bcl-2 (P < 0.05). Therefore, it is concluded that simultaneously aberrant expression of Bcl-2 and p53 may confer PC with more malignant clinicopathological characteristics. (+info)
Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers.
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Peutz-Jeghers syndrome (PJS) is an autosomal-dominant disorder characterized by hamartomatous polyps in the gastrointestinal tract and by pigmented macules of the lips, buccal mucosa, and digits. Less appreciated is the fact that PJS also predisposes patients to an increased risk of gastrointestinal cancer, and pancreatic cancer has been reported in many PJS patients. It was recently shown that germline mutations of the STK11/LKB1 gene are responsible for PJS. We investigated the role of STK11/LKB1 in the development of pancreatic and biliary cancer in patients with and without the PJS. In a PJS patient having a germline splice site mutation in the STK11/LKB1 gene, sequencing analysis of an intestinal polyp and pancreatic cancer from this patient revealed loss of the wild-type allele of the STK11/LKB1 gene in the cancer. Inactivation of STK11/LKB1, by homozygous deletions or somatic sequence mutations coupled with loss of heterozygosity, was also demonstrated in 4-6% of 127 sporadic pancreatic and biliary adenocarcinomas. Our results demonstrate that germline and somatic genetic alterations of the STK11/LKB1 gene may play a causal role in carcinogenesis and that the same gene contributes to the development of both sporadic and familial forms of cancer. (+info)
Mucin Hypersecreting Intraductal Papillary Neoplasm of the pancreas.
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Mucin Hypersecreting Intraductal Papillary Neoplasm is a rare neoplasm that arises from ductal epithelial cells. This entity is distinct from the more commonly known Mucinous Cystadenoma or Mucinous Cystadenocarcinoma. Despite this distinction, it has been erroneously categorized with these more common cystic neoplasms. Characteristic clinical presentation, radiographic, and endoscopic findings help distinguish this neoplasm from the cystadenomas and cystadenocarcinomas. Histopathologic identification is not crucial to the preoperative diagnosis. This neoplasm is considered to represent a premalignant condition and, therefore, surgical resection is warranted. Prognosis, following resection, is felt to be curative for the majority of patients. We present two cases of Mucin Hypersecreting Intraductal Papillary Neoplasm and discuss their diagnosis and surgical therapy. (+info)
Influence of recombinant retroviral vector expressing antisense TGF alpha on malignant phenotype of human pancreatic carcinoma cell line.
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OBJECTIVE: To observe the effects of antisense TGF alpha on the growth of human pancreatic carcinoma cell line cells. METHODS: A recombinant retroviral vector expressing antisense TGF alpha was constructed, and transfected the ecotropic packaging cell line psi-2 with lipofectin. After the amphotropic packaging cell line PA317 was transfected with the virus supernatant of psi-2, the replication-defective, amphotropic retroviral supernatant was used to infect human pancreatic carcinoma cell line PC-7. Following puromycin selection, puromycin-resistant colonies were pooled and expanded to a cell line PC-7/AS-TGF alpha. RESULTS: The retroviral integration in the genomes of psi-2, PA317 and transformant PC-7 cells was confirmed by Southern blot hybridization. Northern blot hybridization showed a down regulation of endogenous TGF alpha in PC-7/AS-TGF alpha cell line. The high levels of growth inhibition and reduction of 3H-TdR incorporation in PC-7/AS-TGF alpha were evident. Also, the soft agar colony-formation and tumorigenicity in nude mice were significantly suppressed by antisense TGF alpha. CONCLUSION: The antisense TGF alpha expressing vector can block the target gene expression, suppress the cell growth and partially reverse the malignant phenotype of pancreatic carcinoma cells. (+info)
Cellular composition and anatomic distribution in nonfunctioning pancreatic endocrine tumors: immunohistochemical study of 30 cases.
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OBJECTIVE: To investigate the cytological pattern and distribution in nonfunctioning pancreatic endocrine tumors. METHODS: Using labeled streptavidin-biotin (LSAB), immunohistochemical staining for insulin, glucagon, somatostatin, pancreatic polypeptide and gastrin was performed on 30 nonfunctioning pancreatic endocrine tumors from 30 patients. The cellular composition and anatomic distribution in these tumors were analyzed. RESULTS: Of 30 tumor tissues, 22 (73.3%) were found to contain cells immunoreactive to 1-4 kinds of peptide hormones; 17 (56.7%) showed positive staining for more than one peptide and up to 4 peptides; and 8 (26.7%) showed negative immunoreaction to all antiserum applied. No tumor was found to contain immunoreactive gastrin. Among 17 multihormonal tumors, 4 contained 2 kinds of peptide hormones, 8 had 3 kinds, and 5 harbored 4 kinds of peptide hormones. In addition, the difference in the number and type of positive endocrine cells between the tumors arising from the head of the pancreas and those arising from the body and tail of the pancreas were statistically significant (P < 0.05). CONCLUSIONS: Immunohistochemically, the high positive rate to peptide hormones suggests that the nonfunctioning pancreatic endocrine tumors are actually not nonfunctioning; they are asymptomatic pancreatic endocrine tumors. Moreover, an uneven distribution of positive endocrine cells in the nonfunctioning pancreas endocrine tumors within the pancreas was identified. (+info)
Photodynamic modulation of cellular function.
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Photodynamic action with a large number of photosensitisers has important practical implications such as photodynamic cancer therapy. But the cellular and molecular mechanisms involved have been rather poorly understood. In this paper, photodynamic modulation of cell signal transduction and the resultant changes in cellular function are reviewed, with a particular emphasis on smooth muscle and the pancreas. (+info)
Comparison of survival between malignant neuroendocrine tumours of midgut and pancreatic origin.
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The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognosis in neuroendocrine tumours of pancreatic rather than midgut origin. This infers that these tumour types must be separated when treatments are evaluated. (+info)