Thiazolidinedione, a peroxisome proliferator-activated receptor-gamma ligand, inhibits growth and metastasis of HT-29 human colon cancer cells through differentiation-promoting effects.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands inhibit the growth of PPAR-gamma expressing cancer cells through terminal differentiation. However, there are few studies examining the effect of a PPAR-gamma ligand on metastatic potential of cancer cells in an animal model and the underlying molecular mechanisms. We have recently developed a rectal cancer xenograft animal model in which anti-tumor and anti-metastatic efficacy of agents can be evaluated.

Impact of the biliary diversion procedure on carcinogenesis in Barrett's esophagus surgically induced by duodenoesophageal reflux in rats.

Objective: To determine whether the elimination of bile reflux in the established esophagojejunostomy model of Barrett's esophagus (BE) will reduce or eliminate the risk of developing esophageal adenocarcinoma.

Summary Background Data: Reflux of duodenal juice as well as gastric acid plays an important role in the pathogenesis of BE and adenocarcinoma. Duodenoesophageal reflux (DER) per se induces these diseases without carcinogen.

Disposition kinetics of taxanes after intraperitoneal administration in rats and influence of surfactant vehicles.

Rats were intraperitoneally administered 40 mg x kg(-1) of paclitaxel or docetaxel dissolved in various drug solutions. The drug solutions were prepared using 20 mL of saline, adding 4.2% Cremophor EL (crEL) for paclitaxel (TXL), and 1.

FR901228, a novel histone deacetylase inhibitor, induces cell cycle arrest and subsequent apoptosis in refractory human pancreatic cancer cells.

Histone deacetylase (HDAC) inhibitors have antiproliferative activity against human cancer cells via cell cycle arrest, differentiation, and apoptosis. However, no report has focused on the apoptotic potential of HDAC inhibitors in refractory human pancreatic cancer. This study was designed to examine the apoptotic potential of FR901228, a novel HDAC inhibitor, in five human pancreatic cancer cell lines: Capan-1, BxPC-3, HPAF, Panc-1, and MIAPaCa-2.

[Sentinel node navigation surgery in early-stage gastric carcinoma: a limited gastric resection with lymphatic basin dissection in sentinel node-negative patients].

The high accuracy of sentinel node biopsy in clinical T1 gastric cancer leads to the idea of excluding conventional D2 from node-negative patients. The question now arises of what to do when sentinel nodes are missed during surgery and micrometastases are over looked in frozen tissue sections. To avoid and correct a mistaken diagnosis, surgeons should remove the lymphatic basin even in the case of negative sentinel nodes, because the basin is exclusively associated with the involved nodes.

5-Fluorouracil, methotrexate, leucovorin, CDDP and epirubicin (FEPMTX): a wide-spectrum regimen of salvage chemotherapy for high-grade advanced gastric cancer.

Background/aims: Twenty-one patients with primary stage IV gastric cancer were treated with a wide-spectrum regimen, designated as FEPMTX therapy to establish an effective salvage chemotherapy.

Methodology: FEPMTX therapy consisted of 5-fluorouracil and the triple biochemical modulators in addition to epirubicin. The schedule comprised 3 days continuous administration of 5-fluorouracil (350 mg/m2/day) and; methotrexate (MTX; 35 mg/m2) on day 1, calcium leucovorin (LV; 30 mg/m2) on day 2 and 3, cisplatin (CDDP; 30 mg/m2) and epirubicin (20 mg/m2) on day 3 every 2 weeks in principle.

A new scoring system for peritoneal metastasis in gastric cancer.

Background: The degree of peritoneal metastasis (PM) of gastric cancer has been classified into four grades (P0, P1, P2, and P3) in the Japanese Classification of Gastric Carcinoma, First English Edition. However, the PM category in this version was so ambiguous in terms of volumetry that it was unlikely to estimate PM status correctly. We have developed a new volume scoring system for PM, modifying Sugarbaker's classification.

Angiotensin converting enzyme-independent, local angiotensin II-generation in human pancreatic ductal cancer tissues.

Hypovascularity is an outstanding characteristic of pancreatic ductal cancer by diagnostic imaging: most pancreatic ductal cancers are hypovascular or avascular, and tumor vessels are seldom seen on angiography. However, we found that the vasculature was not always poor on angiography of surgically resected specimens of locally advanced pancreatic ductal cancers. To elucidate these controversial findings, we focused on angiotensin II, a vasoconstrictor which is directly produced from angiotensinogen at acidic pH by active trypsin.

Protease-activated receptor-2 expression and the role of trypsin in cell proliferation in human pancreatic cancers.

Protease-activated receptor (PAR)-2 is a G protein-coupled receptor that is activated by trypsin. The purpose of this study was to examine PAR-2 expression and the role of trypsin in cell proliferation in human pancreatic cancer cells. All four pancreatic cancer cell lines studied, from well to undifferentiated types, AsPC-1, BxPC-3, Panc-1, and MIAPaCa-2, had significant levels of PAR-2 mRNA detected by reverse transcription-polymerase chain reaction, and showed a band of about 55 kDa corresponding to the known molecular weight of PAR-2: AsPC-1, BxPC-3 and Panc-1 showed a strong band, and MIAPaCa-2 showed a weak one.

Expression of vascular endothelial growth factor D is associated with lymph node metastasis in human colorectal carcinoma.

Objective: Expression of vascular endothelial growth factor (VEGF)-D by tumors is associated with metastasis to lymph nodes in mice. However, there are few reports concerning the clinical significance of VEGF-D protein in human carcinoma.

Methods: After confirming production of VEGF-D by eight colorectal carcinoma cell lines, we investigated relationships between the expression of VEGF-D protein, lymph node metastasis and postoperative survival in 83 colorectal carcinoma patients.

Sentinel lymph node navigation surgery for pancreatic head cancers.

Recently, sentinel lymph node (SN) concept has been validated for gastrointestinal and breast cancers. Our previous study has shown that the No. 13 posterior pancreaticoduodenal lymph node group constitutes the major regional drainage site from primary tumors in the pancreatic head, and that the status of these nodes predicts that of the No.

Mapping sentinel nodes in patients with early-stage gastric carcinoma.

Background: Nodal status in gastric carcinoma is related not only to prognosis but also to the extent of nodal dissection. However, a method for accurate assessment of nodal status during operation has not been established. This study aimed to map the sentinel nodes of gastric carcinoma and to estimate the clinical usefulness of sentinel node biopsy.

Regeneration of small intestinal mucosa after acute ischemia-reperfusion injury.

To determine whether c-Fos and c-Jun are involved in the repair of small intestinal mucosa after ischemia-reperfusion (I/R), we investigated the mechanism of regeneration following acute I/R injury in rats by evaluating changes in DNA synthesis, fractional synthesis rate (FSR) of proteins, and alkaline phosphatase (ALP) activity. Furthermore, we examined the sequential expression of c-Fos and c-Jun using western blot analysis and immunohistochemical staining. Proliferating cell nuclear antigen (PCNA) labeling index (LI) demonstrated that the LI of the I/R group at 2 and 6 hr after reperfusion was significantly higher than that of the controls.

[Intrinsic angiotensin II-generating system in human pancreatic cancer tissues].

To clarify whether an intrinsic angiotensin II-generating system exists in human advanced pancreatic cancer tissues, we measured angiotensin II concentration and angiotensin converting enzyme (ACE) activity in tissues of normal pancreas, pancreatic cancers, colon cancers and hepatocellular carcinomas. After the surgically resected specimens were homogenized, angiotensin II concentration and ACE activity in tissues were measured using the florisil method and Kasahara's method, respectively. Tissue angiotensin II levels in pancreatic cancers (n = 13) were significantly higher than those of normal pancreas (n = 7), colon cancers (n = 7), or hepatocellular carcinomas (n = 7).

[Pharmacologic study of intraperitoneal paclitaxel in gastric cancer patients with peritoneal dissemination].

This study was designed to evaluate the pharmacokinetics and toxicity of paclitaxel administered via an intraperitoneal (i.p.) route for patients with gastric cancer.

[Pharmacologic study of intraperitoneal docetaxel in gastric cancer patients with peritoneal dissemination].

This study was designed to evaluate the pharmacokinetics and toxicity of docetaxel administered via an intraperitoneal (i.p.) route for patients with gastric cancer.

Outcome of ratio of lymph node metastasis in gastric carcinoma.

Background: The purpose of this study was to clarify the outcome of the ratio of the metastatic lymph nodes (RML) in gastric cancer patients.

Methods: The postoperative survival of 650 patients with gastric cancer who underwent D2 curative gastrectomy was analyzed with regard to the RML. The location, number, and RML in the N1 station and in all (N1 and N2) stations were analyzed.

Essential role for nuclear factor kappaB in ischemic preconditioning for ischemia-reperfusion injury of the mouse liver.

Background: Ischemic preconditioning protects various organs from subsequent ischemic insult, but the precise mechanisms underlying this phenomenon remain undefined. To investigate the molecular mechanism by which ischemic preconditioning exerts its protective effect, we examined the activity of the transcription factor nuclear factor (NF)-kappaB and subsequent inflammatory gene expression.

Methods: Mice were used for total hepatic ischemia-reperfusion experiments after subcutaneous transposition of the spleen.

Diagnostic laparoscopy, serum CA125, and peritoneal metastasis in gastric cancer.

Background And Study Aims: Peritoneal metastasis is a crucial factor for the prognosis in gastric cancer, but its diagnosis is difficult before laparotomy. We report on the utility of laparoscopy and its indications in the detection of peritoneal metastasis in gastric cancer.

Patients And Methods: A total of 39 patients with gastric cancer underwent laparoscopy and peritoneal cytology investigation in our department, between April 1992 and April 2000.

Long-term survival of a patient with primary papillary serous carcinoma of the peritoneum treated by subtotal peritonectomy plus intraoperative chemohyperthermia.

We report the long-term survival of a patient with primary papillary serous carcinoma of the peritoneum, treated by subtotal peritonectomy combined with continuous hyperthermic peritoneal perfusion. After subtotal peritonectomy and continuous hyperthermic peritoneal perfusion, early postoperative intraperitoneal chemotherapy with cisplatin and three cycles of cisplatin-based intravenous chemotherapy were administered. The patient currently remains alive 23 months after surgery.

Thiazolidinedione, a peroxisome proliferator-activated receptor-gamma ligand, modulates the E-cadherin/beta-catenin system in a human pancreatic cancer cell line, BxPC-3.

Activation of peroxisome proliferator-activated receptor (PPAR)-gamma induces terminal differentiation and growth inhibition associated with G1 cell cycle arrest in some cancer cells. The multifunctional molecule beta-catenin performs important roles in intercellular adhesion and signal transduction. However, no report has focused on actions of PPAR-gamma in regulating the E-cadherin/beta-catenin system.

Role of MMP-7 in the formation of peritoneal dissemination in gastric cancer.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7) is an important matrix-degrading enzyme that has a large role in the invasion and metastasis of cancer. To discover the mechanism of the formation of peritoneal dissemination in gastric cancer, we studied the mRNA and protein expression of MMP-7 in primary gastric cancers and peritoneal dissemination.METHODS: MMP-7 expression in primary gastric cancers (136 patients) was studied by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and the results were compared with chinicopathological parameters.

Thymidine phosphorylase and dihydropyrimidine dehydrogenase levels in primary colorectal cancer show a relationship to clinical effects of 5'-deoxy-5-fluorouridine as adjuvant chemotherapy.

Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR, doxifluridine), an intermediate metabolite of capecitabine, to 5-fluorouracil (5-FU). While dihydropyrimidine dehydrogenase (DPD) catalyzes 5-FU to inactive molecules. We investigated TP and DPD levels in tumor tissue to assess their clinical significance as indicators for selecting colorectal cancer patients for 5'-DFUR adjuvant chemotherapy.

Expression of insulin-like growth factor-2, c-MET, matrix metalloproteinase-7 and MUC-1 in primary lesions and lymph node metastatic lesions of gastric cancer.

Background/aims: Lymph node metastases are thought to be formed as lymphatic flow, so the first metastasis is formed in the lymph node nearest the primary tumor and then further lymph node metastases are formed continuously down stream. In this study of gastric cancer, we evaluated whether IGF-2 (insulin-like growth factor-2), c-MET (hepatocyte growth factor receptor), MMP-7 (matrix metalloproteinase-7) and MUC-1, which are associated with nodal metastasis from primary tumor, are concerned with metastasis from nodal metastatic lesion to other nodes.

Methodology: Tissue specimens were obtained from 146 patients who underwent gastrectomy at the Department of Surgery II of Kanazawa University between 1989 and 1997.