Biomedical subjects

A Elnemr

Publications and source records attributed to A Elnemr.

12 recordsLinked to original sources

PubMed2001

Enhanced invasiveness of pancreatic adenocarcinoma cells stably transfected with cationic trypsinogen cDNA.

Various studies have described increased expression of cationic trypsinogen in malignant tumor cells. To explore the role of secreted cationic trypsinogen in invasion by cancer cells, we introduced cationic trypsinogen cDNA into Panc-1, a pancreatic adenocarcinoma-derived cell line that lacks expression of endogeneous trypsinogen. Four independent clones (designated Panc-1-Try-7, -9, -11 and -24) stably expressing cationic trypsinogen mRNA were isolated and processed for further study. In a zymographic analysis, gelatinolytic activity for cationic trypsinogen was detectable in serum-free conditioned media obtained from all 4 transfectants but not in media from mock-transfected or parental Panc-1 cells. A Matrigel invasion assay revealed that all trypsinogen-expressing transfectants acquired significantly greater invasive ability than that shown by mock-transfected and parental Panc-1 cells. In addition, enhanced invasiveness of the transfectants was suppressed by FUT-175, a serine protease inhibitor, to the level seen in parental cells. These results provide direct evidence that cationic trypsinogen can increase the invasive ability of carcinoma cells.

Adenocarcinoma↗

PubMed2001

Human pancreatic cancer cells disable function of Fas receptors at several levels in Fas signal transduction pathway.

The aims of this study were to evaluate the functional expression of Fas receptors (Fas) in human pancreatic cancer cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2 and to search for the mechanisms of receptor-mediated inhibition of Fas signaling in these cells. Despite the expression of Fas receptors at considerable levels, exposure of these cells to agonistic Fas antibodies (500 ng/ml) induced only minimal apoptosis in 4 cell lines. The mechanisms allowing resistance to Fas-mediated apoptosis are complex. Using RT-PCR, we identified molecules which might counteract the apoptogenic signal at several levels of Fas signal transduction pathway. The most striking findings were the overexpression of Fas decoy receptors (DcR3), Fas associated phosphatase-1 (FAP-1), and FLICE-inhibitory protein (c-FLIP) in the resistant cell lines as well as in pancreatic cancer surgical specimens. In conclusion, pancreatic cancer cells express three molecules that can abrogate Fas function at different levels of Fas signaling cascade, resulting in resistance to Fas-mediated apoptosis, and this may promote the progression of this malignancy.

Adenocarcinoma↗

PubMed2001

Human pancreatic cancer cells express non-functional Fas receptors and counterattack lymphocytes by expressing Fas ligand; a potential mechanism for immune escape.

The aim of this study was to investigate the expression and functional status of Fas ligand (FasL) and its receptor (Fas) in human pancreatic cancers. Using RT-PCR and Western blotting, Fas and FasL were expressed in seven surgically resected pancreatic cancer specimens and five cell lines; Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. In the resected specimens, pancreatic cancer cells induced apoptosis in the surrounding lymphoid cells. In coculture experiments of pancreatic cancer and Jurkat T cells, 50% of Jurkat T cells underwent apoptosis after 2 days, however, almost all pancreatic cancer cells remained viable. In addition, by testing Fas function using anti-Fas antibody (CH11), all cell lines were resistant to Fas-mediated apoptosis except Capan-1 cells which showed sensitivity similar to that of Jurkat T cells. These results suggest that pancreatic cancer cells evade immune surveillance by expression of FasL and non-functioning Fas that allow them to activated T-cells. These tumor escape mechanisms may contribute to the rapid fatal course of pancreatic cancer.

Apoptosis↗

PubMed2000

Trypsinogen expression in colorectal cancers.

The purpose of this study was to evaluate the trypsinogen expression in human colorectal cancers. We observed the trypsinogen-1 mRNA expression in five of ten human colorectal cancer cell lines by reverse transcriptase-polymerase chain reaction (RT-PCR), and gelatinolytic activity in conditioned medium of cancer cells at acidic pH by gelatin zymography. Furthermore, trypsinogen protein expression was observed in 68 out of 154 (44.2%) surgical specimens of colorectal cancer immunohistochemically. However, there was no statistically significant relationship between the trypsinogen expression and the clinicopathological findings. These findings suggest that trypsinogen might be involved in cancer invasion and metastasis throughout the cancer progression.

Colorectal Neoplasms↗

PubMed2000

N-ethylmaleimide-enhanced phosphatidylserine externalization of human pancreatic cancer cells and immediate phosphatidylserine-mediated phagocytosis by macrophages.

The purpose of this study was to examine whether N-ethylmaleimide (NEM) can enhance phosphatidylserine (PS) externalization on the outer surface of cancer cells, and PS-externalized cancer cells can be phagocytosed immediately by macrophages. NEM could externalize PS of cancer cells in concentration- and time-dependent manners. When treated with 5 mM NEM for 1 h, 80% of the carcinoma cells externalized their PS. In phagocytosis assay, these cells were engulfed immediately by macrophages before undergoing apoptosis. These results suggest that NEM can immediately externalize PS of cancer cells, leading to their recognition and phagocytosis by macrophages before undergoing apoptosis morphologically.

Animals↗

PubMed2000

PPARgamma ligand (thiazolidinedione) induces growth arrest and differentiation markers of human pancreatic cancer cells.

The aim of this study was to examine whether a specific PPARgamma ligand can inhibit the growth of human pancreatic cancer cells through induction of terminal differentiation. PPARgamma was expressed in five human pancreatic cancer cell lines: Capan-1, AsPC-1, BxPC-3, PANC-1, and MIA PaCa-2. Treatment of these cells with a specific PPARgamma ligand, thiazolidinedione (TZD), resulted in inhibition of both cellular and clonogenic growth, and G1 cell cycle arrest. Finally, thiazolidinedione treatment resulted in induction of p21WAF-1 and increased expression of differentiation markers. These results suggest that thiazolidinedione treatment inhibits growth and induces cellular differentiation in pancreatic cancer cells and thereby reduces their development in favor of differentiated and stable cell phenotype.

Adenocarcinoma↗

PubMed2000

[An effective case of hepatic arterial infusion chemotherapy based on biochemical modulation for hepatic recurrence of non-functioning islet cell carcinoma of the pancreas].

A 55-year-old man had a metastasis in segment 3 of the liver 5 months after surgery for non-functioning islet cell carcinoma of the pancreas. The metastatic lesion increased in size in a short period, and other liver micro-metastases that could not be detected by imaging may exist, so hepatic arterial infusion chemotherapy was scheduled for 3 months. The patient underwent hepatic arterial infusion chemotherapy of 5-fluorouracil (250 mg/day/body for 5 days/week) and adriamycin (10 mg/day/body for 2 days/week) and cisplatin (10 mg/day/body for 5 days/week) and he was put on Leucovorin 30 mg/day as a biochemical modulator of 5-FU and tamoxifen 40 mg/day as a biochemical modulator of ADM. A total 6,000 mg of 5-FU, 100 mg of ADM and 240 mg of CDDP had been administered, until hepatic arterial infusion chemotherapy was discontinued because of complicated gastric ulcer. Three months later, the size of the metastatic liver tumor was reduced remarkably and no other metastasis was detected on CT scan, so he underwent partial hepatectomy of the metastatic lesion. No recurrence was found and he has survived in good physical condition during the follow-up period of 5 months after the second operation.

Administration, Oral↗

PubMed1999

Analysis of paraaortic lymph node involvement in pancreatic carcinoma: a significant indication for surgery?

BACKGROUND: Lymph node status is a key prognostic factor for pancreatic carcinoma. The paraaortic lymph nodes are the highest level of lymph nodes that can be resected safely in the abdomen for pancreatic and other gastrointestinal tumors. The pattern of paraaortic lymph node involvement and its relation with other lymph node groups were analyzed and the significance of this information relative to surgical therapy examined. METHODS: Between 1974-1996, 99 patients with invasive ductal carcinoma of the pancreas underwent pancreatectomy at the study institution. The pattern of lymph node involvement, particularly paraaortic, was evaluated by careful pathologic review of extended lymphadenectomy specimens. RESULTS. Fifty-eight of 76 patients (76%) with carcinoma in the pancreatic head (Ph) and 19 of 23 patients (83%) with carcinoma of the pancreatic body and tail (Pbt) had lymph node involvement. Fourteen patients with Ph disease (18%) and 4 with Pbt disease (17%) had paraaortic lymph node involvement. Tumor size did not correlate with paraaortic lymph node involvement. A correlation was found between Group 13 (posterior pancreaticoduodenal lymph nodes), Group 14 (lymph nodes surrounding the superior mesenteric artery), and the paraaortic lymph nodes for Ph disease. All paraaortic lymph node metastases were located in the 16M region (the region between the celiac trunk and the inferior mesenteric artery). For patients with Pbt disease, the distribution of paraaortic lymph node metastases was the same as for those with Ph disease. Only 33% of cases of paraaortic lymph node metastases were suspected preoperatively or perioperatively. The longest survival for a patient with paraaortic lymph node metastases was 36 months and 17 months, respectively, for patients with Ph and Pbt disease. CONCLUSIONS: The paraaortic lymph nodes are frequent sites of metastasis from pancreatic carcinoma, and are difficult to evaluate preoperatively or perioperatively. This situation mandates paraaortic lymph node dissection, at least in the 16M region.

Adult↗

PubMed1999

Expression of nerve growth factor in hepatolithiasis.

AIMS/BACKGROUND: Nerve growth factor (NGF) has recently been shown to influence the survival and function of non-neuronal inflammatory cells, possibly through its activity as a colony-stimulating factor. It may also play an important role in acute inflammation and tissue repair. However, no prior report has focused on NGF in chronic inflammatory diseases of the gastrointestinal and biliary tracts. The aim of this study was to examine the expression of NGF in hepatolithiasis. METHODS: Twenty-six liver specimens resected from 22 patients with intrahepatic calcium bilirubinate stones and from 4 patients with intrahepatic cholesterol stones were examined immunohistochemically. RESULTS: The 22 patients with calcium bilirubinate stones demonstrated NGF immunoreactivity associated with surrounding inflammatory cells that was localized to the epithelia of proliferative peribiliary glands in the ductal wall. However, neither the surface lining of the bile duct nor hepatocytes expressed detectable NGF immunoreactivity. In the cholesterol stones cases in contrast, peribiliary glandular elements and inflammatory cell infiltration were less extensive than those observed in cases of calcium bilirubinate stones, and NGF immunoreactivity was not noted. CONCLUSIONS: These observations suggest that proliferative peribiliary glands express NGF protein in chronic proliferative cholangitis. This is characteristic of intrahepatic calcium bilirubinate stones.

Adult↗

PubMed1999

Activated lansoprazole inhibits cancer cell adhesion to extracellular matrix components.

Integrins play an important role in tumor dissemination. The purpose of this study was to examine whether a SH-reactive reagent inhibits the adhesion of the human pancreatic cancer cell line AsPC-1 to extracellular matrix components. Activated lansoprazole (AG-2000) was used as the SH-reactive reagent because this compound is known to react with SH groups but does not permeate the cell membrane. The effect of AG-2000 on the adhesion of AsPC-1 cells to matrix was examined, using both an in vitro adhesion assay and an in vivo nude mouse xenograft model of peritoneal implantation. In the in vitro adhesion assay, a 60-min exposure of AsPC-1 cells to AG-2000 resulted in a dose-dependent inhibition of AsPC-1 cell adhesion to laminin, fibronectin and type IV collagen, although AG-2000 did not affect the viability of AsPC-1 cells by MTT assay. In the in vivo assessment of AsPC-1 cell implantation, the AsPC-1 cells were initially preincubated with AG-2000 for 60 min to ensure adequate exposure of the AsPC-1 cells to AG-2000 before intraperitoneal injection. AG-2000 significantly inhibited the peritoneal implantation of the AsPC-1 cells in nude mice. These findings suggest that a short exposure of cancer cells to AG-2000 can inhibit cancer cell adhesion to extracellular matrix components.

Animals↗

PubMed1998

Trypsinogen expression and early detection for peritoneal dissemination in gastric cancer.

BACKGROUND AND OBJECTIVES: The most reliable method for the diagnosis of peritoneal dissemination of gastric cancer at the present time is cytological examination of ascitic fluid, which is unavailable to patients without ascites or may be inadequate for those with ascites containing few cancer cells. It has been reported recently that human gastric cancer immunoreacted with a monoclonal antibody against pancreatic trypsinogen. We therefore examined the expression of trypsinogen as a new marker for the early diagnosis of peritoneal dissemination of gastric cancer. METHODS: Pancreatic trypsinogen protein was immunohistochemically stained with a three-step indirect immunoperoxidase method and cationic trypsinogen (trypsinogen-1) mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in gastric cancer. Twenty-nine of 30 primary tumors (97%) and all 12 tumors (100%) of the peritoneal seedings immunohistochemically reacted with trypsinogen. Preliminary study for early diagnosis of peritoneal dissemination was carried out for eight more recent patients who showed positive immunoreactivity to trypsinogen protein and expressed trypsinogen- mRNA in the primary tumor. The expression of trypsinogen-1 mRNA was detected by using peritoneal lavage fluid preoperatively collected in these patients. RESULTS: All three patients in whom peritoneal dissemination was diagnosed at the time of their operation(s) expressed trypsinogen-1 mRNA. One patient, who did not show peritoneal dissemination at the operation but was positive for trypsinogen-1 mRNA detection, later died of the recurrence of peritoneal dissemination. CONCLUSIONS: These results indicated that trypsinogen protein and trypsinogen-1 mRNA frequently expressed in peritoneal dissemination as well as primary tumors in gastric cancer and detection of trypsinogen-1 mRNA expression was a useful method for early diagnosis in peritoneal dissemination of gastric cancer.

Adenocarcinoma↗

PubMedDate not supplied

Anomalous pancreaticobiliary ductal junction without bile duct dilatation in gallbladder cancer.

BACKGROUND/AIMS: Anomalous pancreaticobiliary junction is a rare anomaly but is a risk factor for primary carcinoma of the gallbladder. To define the relationship between anomalous pancreaticobiliary junction, especially if it is not associated with common bile duct dilatation, and gallbladder carcinoma, we retrospectively reviewed data of 126 patients with gallbladder carcinoma. METHODOLOGY: All these patients had undergone direct cholangiography either by endoscopic retrograde cholangiopancreaticography or percutaneous transhepatic cholangiography. RESULTS: Among 126 patients with gallbladder cancer, 23 patients (18.3%) exhibited anomalous pancreaticobiliary junction. Patients with anomalous pancreaticobiliary junction were younger (mean age: 54 +/- 9.1 years) than patients without anomalous pancreaticobiliary junction (mean age: 65 +/- 9.7 years). The incidence of gallstones in patients with anomalous pancreaticobiliary junction (17%) was significantly lower than in those without this anomaly (64%) (P < 0.01). Among the 23 patients with anomalous pancreaticobiliary junction, 12 patients (52%) had no bile duct dilatation and, 11 patients (48%) had bile duct dilatation in the form of fusiform or cylindrical dilatation. However, no cases with severe cystic dilatation were found. Patients of anomalous pancreaticobiliary junction without common bile duct dilatation had more advanced disease and poor prognosis than those with common bile duct dilatation. CONCLUSIONS: The present study revealed that gallbladder cancer in the patients of anomalous pancreaticobiliary junction without common bile duct dilatation was diagnosed at advanced stage and the prognosis was very poor. Therefore, if a minor abnormality is detected in the wall of acalculous gallbladder on ultrasonography, direct cholangiography should be done to exclude this anomaly.

Adult↗