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Z Nihei

Publications and source records attributed to Z Nihei.

At least 37 records · Page 2Linked to original sources

Relationship between intratumoral dihydropyrimidine dehydrogenase activity and gene expression in human colorectal cancer.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for 5-fluorouracil catabolism. In this study, both the enzymatic activity and mRNA level of DPD were estimated in the tumor tissue and adjacent normal mucosa of 51 patients with colorectal cancer. Although no significant difference in enzymatic activity was observed between tumor tissue and normal mucosa (70.4 and 70.7 pmol/min/mg protein, respectively), the mRNA level in normal mucosa was significantly higher than that in tumor tissue (1.37 and 0.39, respectively; P<0.01). A linear relationship was noted between DPD activity and the DPD mRNA level in cancerous tissue (r(s) = 0.714, P<0.001). Thus, the DPD mRNA level as determined by reverse transcription-PCR can be used to indicate the DPD activity of colorectal cancers.

Colorectal Neoplasms↗

[Dihydropyrimidine dehydrogenase gene expression in patients with hepatic metastases from colorectal cancer].

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for 5-FU catabolism. Recently, much interest has been taken in the relation between the antitumor effect of 5-FU and DPD expression in gastrointestinal cancers. In this study, we compared DPD mRNA of 11 hepatic metastatic foci with that of 50 primary foci in colorectal cancer patients. DPD mRNA levels in hepatic metastatic foci were significantly higher than those in primary foci (median DPD/GAPDH ratio 0.79 vs 0.44, p = 0.035). Even in 6 cases available to compare DPD mRNA expression in matched primary and metastatic foci, the same significant difference was obtained (median DPD/GAPDH ratio 0.80 vs 0.36, p = 0.028). Our results suggested that the efficacy of intra-arterial infusion for metastatic liver tumor is mainly due to the fact that the high concentration of 5-FU is enough to overcome the high clearance of 5-FU, which is caused by DPD.

Colorectal Neoplasms↗

[Intra-arterial injection therapy of mitoxantrone for locally advanced breast cancer].

Mitoxantrone (MIT) is a new anthraquinone anticancer agent. We treated 14 patients with locally advanced breast cancer, 3 of which were inflammatory breast cancers, by pre-operative arterial injection of MIT. The treatment protocol was MIT 12 mg/m2 injected into both the internal mammary and the subclavian arteries with oral administration of 5'-DFUR 1,200 mg/day for 20 days. After 2 courses, all tumors were decreased over 50% in size. Down-staging was obtained in all of 8 cases. Mastectomy could be carried out on all patients, without microscopically residual tumor cells. Preoperative arterial injection of MIT might be the treatment of choice for locally advanced breast cancer to perform down-staging, however the survival benefit has remained equivocal. These preliminary results are encouraging to further studies.

Antineoplastic Combined Chemotherapy Protocols↗

Perforation of acalculous cholecystitis associated with localized atherosclerosis: report of a case.

We describe herein the unusual case of a 68-year-old Japanese man who underwent laparotomy for an acute abdomen caused by diffuse peritonitis, which revealed perforation of the gallbladder without any stones. A cholecystectomy was subsequently carried out, and histological examination showed marked atherosclerosis of the gallbladder associated with acute inflammatory changes. It is most likely that circulatory disturbance of the gallbladder wall due to the atherosclerosis played an important role in the events leading to perforation. Acute acalculous cholecystitis is an uncommon condition which is extremely difficult to diagnose preoperatively. The clinicopathological features of this patient are of particular interest and importance in terms of pathogenesis as well as treatment.

Acute Disease↗

Effect of IL-6 on tumor cell invasion of vascular endothelial monolayers.

The effect of interleukin-6 (IL-6) on the invasive capacity of B16-F1 mouse melanoma cells into vascular endothelial monolayers was examined, and an in vitro assay system for the quantitative determination of tumor cell invasiveness, using confocal microscopy with a fluorescence image analyzer, was developed. First, the invasive capacity of B16-F1 mouse melanoma cells against bovine vascular endothelial monolayers was estimated; then, the gap junctional intercellular communication (GJIC) of endothelial cells was examined. Treatment of endothelial cells with IL-6 resulted in a remarkable increase in the invasion of tumor cells into the endothelial monolayer, which was found to be significant from 25 ng/ ml, and peaked at levels of more than 50 ng/ml. This stimulatory effect of IL-6, which was observed from 3 h after the initiation of treatment and lasted for up to 24 h, was abolished by the addition of the anti-IL-6 antibody. Although phase-contrast microscopy did not reveal any morphological changes in the endothelial cells following treatment with 25-200 ng/ml IL-6 for 24 h, the GJIC was observed to be significantly decreased. These findings indicate that the invasive capacity of tumor cells into endothelial cells is affected by IL-6.

Analysis of Variance↗

Gastrointestinal autonomic nerve tumor with giant abscess. A case report and literature review.

We report a gastrointestinal autonomic nerve tumor of the stomach with a giant abscess. The patient had fever and pain and was found to have anemia and an abdominal mass. X-ray and endoscopic examination showed a gastric submucosal tumor with a fistula to the gastric lumen. Partial gastrectomy was performed and no metastasis was found. On gross examination, the excised tumor was seen to be a submucosal solid tumor with a giant abscess. Alpha streptococci and anaerobic gram-negative rods were cultured from the pus of the abscess. The tumor resembled a gastric myogenic tumor composed of spindle cells, partly showing storiform and epithelioids. Tumor cells showed positive staining for vimentin and neuron-specific enolase but were negative for desmin, alpha-smooth muscle actin, and S-100 protein. Ultrastructural examination showed remarkable interdigitation of cytoplasmic processes with neurosecretory granules between the tumor cells. This lesion was similar to previously described gastrointestinal autonomic nerve tumors. Gastrointestinal autonomic nerve tumors are a rare, distinct subtype of gastrointestinal stromal tumors; although several cases of focally necrotic tumors have been reported, there has been only one report of the tumor with an abscess, as in our case.

Abscess↗

[Combination therapy with 5'-DFUR, MMC and CDDP in patient with far advanced gastric cancer: report of a case].

A 48-year-old man was referred to our hospital for a Borrmann 3 type advanced gastric cancer. Endoscopic biopsy disclosed poorly differentiated adenocarcinoma. Ultrasonography and CT scan revealed left hydronephrosis. Endoscopic retrograde cholangiography detected a stenosis of common bile duct at the hepatic hilum due to lymph nodal metastasis, and laparoscopy revealed peritoneal dissemination. Because the tumor was diagnosed as not for curative resection, the patient was treated by 4 courses of combination therapy with 5'-DFUR, MMC and CDDP. No adverse effect of chemotherapy was observed. As a result, lymph nodal metastasis and peritoneal dissemination were reduced. Curative intent total gastrectomy was performed, together with pancreatico-splenectomy, left hemicolectomy, cholecystectomy, and extended lymph nodal dissection. The patient is well and alive with no sign of recurrence 2 years after operation.

Adenocarcinoma↗

Mutations of the transforming growth factor-beta type II receptor gene are strongly related to sporadic proximal colon carcinomas with microsatellite instability.

BACKGROUND: Mutations of the transforming growth factor-beta type II receptor gene (TGF-beta RII) have been found in several replication error-positive sporadic colorectal carcinomas and hereditary nonpolyposis colorectal carcinoma cell lines. The aim of this study was to clarify the role of TGF-beta RII in sporadic colorectal carcinogenesis. METHODS: The authors screened for mutations at simple repeated sequences in the TGF-beta RII gene by polymerase chain reaction-single strand conformation polymorphism. They also examined genomic instability, using five microsatellite DNA markers in 69 sporadic colorectal carcinomas. When the carcinomas exhibited the TGF-beta RII mutations, the authors screened further for mutations in two DNA mismatch repair genes, hMSH2 and hMLH1. RESULTS: Seven of the 69 cancers (10%) showed one or two A deletions in TGF-beta RII and resultant frameshift mutations in nucleotide positions 709-718 containing a (A) 10 repeated sequence; but none of these appeared in the corresponding normal DNA, indicating a somatic mutation. All of the seven cancers were located in the proximal colon; there were none in the distal colon (P < 0.01). On the other hand, 22 of the 69 carcinomas (32%) showed the replication error-positive phenotype. The frequency of replication errors in proximal colon carcinomas was higher than that in distal colon carcinomas (P < 0.05). All 7 cancers with TGF-beta RII mutations showed replication errors. One of them revealed a nonsense mutation at codon 413, and 1 revealed a loss of heterozygosity in hMSH2. CONCLUSIONS: These data indicate that mutations of TGF-beta RII are strongly related to proximal colon carcinomas with microsatellite instability and that the mechanism of carcinogenesis in some proximal colon carcinomas is similar to that in hereditary nonpolyposis colorectal carcinoma.

Aged↗

Chronological changes in bone mineral content following gastrectomy.

Recent advances in the modalities of quantitatively assessing bone mineral content have resulted in an increasing awareness of metabolic bone disease as a late complication following gastrectomy. In this study, 98 postgastrectomy patients were examined by quantitative computed tomography (QCT). The bone mineral density index (BMDI), defined as 100 x (measured bone mineral density divided by that of age- and sex-matched controls), was used to evaluate the actual effect of gastrectomy on bone disorders. The BMDI values following gastrectomy were 80.4 +/- 27.3, with no significant difference between men and women, or between total and distal gastrectomy. Moreover, no significant differences were observed between the BMDI values within 6 months, being 92.6 +/- 37.3, and those 6 months to 1 year post gastrectomy, being 79.6 +/- 31.2; however, a significant and sharp decrease to 70.5 +/- 36.0 was evident after 1-2 years. The regression coefficient of the BMDI measured within 2 years postoperatively was lower than that measured after 2 years. These findings suggest that the influence of gastrectomy on bone metabolism is induced within 2 years, after which the bone mineral content decreases in accordance with physiological nature. Thus, we conclude that the treatment for bone disease resulting from gastrectomy would only be effective if initiated within a short period after surgery.

Adult↗

The positive relationship between the expression of CD44 variant 6 and prognosis in colorectal cancer.

CD44 variant 6 (CD44 v6) is well known as a useful marker of tumor progression; however, its relationship to prognosis has not yet been elucidated. In this study, we investigated the expression of CD44 v6 in colorectal cancer to analyze its relationship to hepatic metastasis as well as to prognosis. Tumor tissues were obtained from 42 patients with colorectal cancer who underwent curative resection with follow-up periods ranging from 5.9 to 71.3 months. There were 21 patients (50%) whose tumors were positive for CD44 v6, with no significant difference between colon and rectal cancer. CD44 v6 staining was significantly related to Dukes' classification as well as to hepatic metastasis. The 5-year survival rate was significantly higher in patients with CD44 v6 negative cancer (84%) than in those with CD44 v6 positive cancer (31%). Thus, we concluded that CD44 v6 could be a reliable prognostic indicator, as well as a predictor of metastatic potential after curative surgery for colorectal cancer.

Biomarkers, Tumor↗

Frequent microsatellite instabilities and analyses of the related genes in familial gastric cancers.

Microsatellite instability or replication error seems to be related to defective DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2, which have been identified as causative genes of hereditary nonpolyposis colorectal cancers (HNPCC). Recently, it was reported that mutations at the simple repeated sequences in the transforming growth factor-beta type II receptor (TGF-beta RII) gene occurred in replication error-positive colorectal cancers. To determine genetic alterations in familial gastric cancers (FGC, we examined replication error using eight microsatellite DNA markers, and screened mutations in the hMSH2, hMLH1 and TGF-beta RII genes in six cases from four FGC kindreds. Moreover, hMTH1, a human homolog of the bacterial mutT gene, was also screened. Four of six (67%) cancers showed the replication error-positive phenotype, indicating that microsatellite instability is highly associated with not only HNPCC, but also FGC. No germline mutation was found in the whole coding sequences of hMSH2 and hMTH1, or in the conservative regions of hMLH1 in any patient, while one cancer DNA showed a somatic mutation at codon 682 (threonine to alanine) in hMSH2. No alteration was found at the small repeated sequences in TGF-beta RII in FGC tumor DNA. These results indicate that the carcinogenetic process of FGC may be different from that of HNPCC.

Adaptor Proteins, Signal Transducing↗

[A case of nonresectable advanced gastric cancer responding to combined chemotherapy with 5'-DFUR, CDDP, and MMC].

A 39-year-old man was referred for epigastric fullness and a mass in the umbilical region. A giant mass was palpated in the epigastric region, while a mass 1 cm in diameter with a hemorrhagic tendency was felt in the umbilical region. Fluoroscopy of the upper gastrointestinal tract and gastroscopy revealed a Borrmann 3 tumor in the upper part of the gastric corpus. The tumor was found by CT scanning to be growing clearly across the wall of the stomach, and the invasion to the transverse colon was suspected by the enema. The tumor was unresectable because of the extensive tumor invasion of the abdominal wall. Therefore, the patient received 2 courses of combined chemotherapy with 5'-DFUR, CDDP, and MMC. As a result, the tumor in the epigastric region was reduced dramatically, and it became unpalpable 6 months after treatment. At the same time, the tumor in the umbilical region disappeared. Both CT scanning and upper gastrointestinal radiography disclosed tumor reduction, and sufficient oral ingestion became possible. The administration of 5'-DFUR has since been continued as maintenance therapy. Aside from transient anorexia and slight leukopenia, the patient developed no symptoms during the treatment period. At present. 2 years and 9 months after starting chemotherapy, the patient is in good health.

Adult↗

[Vascular tumor].

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Hemangiosarcoma↗

Experiences with the linear cutter technique for performing Roux-en-Y anastomosis following total gastrectomy.

The use of stapling devices for performing gastro-intestinal anastomosis has recently gained wide acceptance. In fact, since 1991, we have been using linear cutter devices for performing the Roux-en-Y anastomosis, transection of the duodenum, and closure of the jejunal stump (except following esophagojejunostomy), and are no longer employing hand-sewn procedures. In this report, the linear cutter technique used after total gastrectomy is described and the differences in anastomotic leakage, morbidity, operating time, and reconstruction time are evaluated in comparison with those following hand-sewn anastomoses. A total of 22 patients undergoing total gastrectomy within a 2-year period were randomized into two groups of 11, to have reconstruction performed by either a stapled or hand-sewn Roux-en-Y anastomosis. One patient from the stapled group died of acute myocardial infarction 6 days after the operation. Anastomotic leakages from the esophagojejunostomy region occurred in 18% of the patients in the stapled group, but fortunately no leakage was apparent from the Y-anastomosis when the linear cutter technique was used. The most obvious significance was the short mean reconstruction time in the stapled group of 19.1 +/- 3.56 min (P < 0.01) being 31 min shorter than that of the hand-sewn group (n = 11). Thus, we proposed that the linear cutter technique is a safe technique for performing anastomosis following total gastrectomy, which would significantly reduce the reconstruction time.

Adenocarcinoma↗

Comparison by carcinoembryonic antigen doubling time of hepatic injection and infusion for unresectable hepatic metastasis from colorectal cancer.

This study explored the efficacy of hepatic arterial therapy, comparing both injection and infusion of 5-fluorouracil (5-FU) in prolonging the survival of 92 patients with recurrent unresectable hepatic metastasis from colorectal cancer. With respect to pretreatment carcinoembryonic antigen doubling time (CEA-DT), 56 patients were treated with intra-arterial injection, and 36 with intra-arterial infusion. In 21 patients with a CEA-DT of less than 40 days, the cumulative survival of patients treated with arterial injection was significantly longer than that of patients treated with arterial infusion. In 45 patients with a CEA-DT of 40-80 days, the survival curves of patients did not differ from each other. Of the remaining 26 patients with a CEA-DT of more than 80 days, those treated using arterial infusion had an excellent prognosis, in contrast to those treated using arterial injection, with statistical significance. CEA-DT may be useful when choosing a chemotherapy regimen, and may help to accurately establish the prognosis of patients with unresectable hepatic metastasis from colorectal cancer.

Adult↗

Expression of endothelin-1 immunoreactivity in breast cancer.

This study performed immunohistochemical staining for human ET-1, utilizing avidinbiotin-peroxidase complex detection to examine 47 surgically resected primary breast cancers. Positive immunoreactivity was demonstrated in 19 of the 47 breast cancers (40.4%). There was no significant relationship between the expression of ET-1 and clinicopathological findings. A significant difference was found between ET-1 positive and negative groups in the incidence of recurrence and distant metastasis (P < 0.05). The 5-year overall survival rate was significantly poorer in patients with ET-1-positive cancer (84.2%), compared to 96.4% in patients with ET-1 negative cancer (P < 0.01). The 5-year disease-free survival rate was significantly poorer in patients with ET-1-positive cancer (73.7%) compared to 96.4% in patients with ET-1-negative cancer (P < 0.05). These results suggest that the expression of ET-1 could be used as a possible indicator for predicting the metastatic potential of breast cancer.

Adult↗