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Biomedical subjects

A Ohtsu

Publications and source records attributed to A Ohtsu.

At least 73 records · Page 4Linked to original sources
PubMed1996

Association of p53 protein expression with responses and survival of patients with locally advanced esophageal carcinoma treated with chemoradiotherapy.

Immunohistochemical analysis was performed to determine the clinical role of p53 mutations in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy. The subjects of this study were 20 patients with previously untreated esophageal carcinomas with evidence of T4 disease and/or distant node metastases. Treatment comprised protracted 5-fluorouracil and 2-h cisplatinum infusions along with radiation treatment with a total radiation dose of 60 Gy. Tumor specimens from 18 of the 20 patients were analyzed immunohistochemically. Mutant p53 protein expression in the biopsy materials from the primary tumors was analyzed by immunohistochemical staining using a polyclonal antibody, RSP53. Expression of p53 was detected immunohistochemically in 10 (56%) of the 18 esophageal tumors, the cancer cell nuclei of which were diffusely stained. There were no significant differences between the patient backgrounds of the p53-"positive" and "negative" groups. Four (40%) of the 10 patients with p53 expression achieved overall complete remissions (CRSs) and 7 (70%) of these 10 achieved CRs of their primary tumors. In contrast, none of the 8 p53-negative patients achieved overall CRs and two (25%) achieved CRs of their primary tumors. The CR rates overall and of primary tumors tended to be higher in the p53-positive than negative group, but the differences were not significant. The survival rate for the 10 patients with p53 expression was better than that for the 8 negative ones (P>0.01): their median survival times were 12 and 4.5 months, respectively. Expression of p53 protein may be an indicator of a favorable prognosis in patients with locally advanced esophageal carcinomas treated with concurrent chemoradiotherapy.

Aged↗
PubMed1996

A case of advanced gastric cancer complicated by severe toxicity induced by a combination of tegafur, uracil and mitomycin C, and associated with abnormal pharmacokinetics.

A 60-year-old female patient with gastric cancer and lymph node and liver metastases was treated with a combination of tegafur and uracil (UFT) (375 mg/m2/day) and mitomycin C (MMC) (5 mg/m2 once weekly). On day 15, when diarrhea appeared, chemotherapy was stopped immediately. On day 21, the WBC decreased to 900/microl and high fever developed. Despite treatment with granulocyte colony-stimulating factor and antibiotics, leukopenia persisted and the patient went into septic shock on day 26. On day 34, WBC increased to 5,400/microl and she recovered, with reduction in the size of the lymph node and liver metastases. Pharmacokinetic examination after intravenous injection of low-dose MMC (0.5 mg/m2) showed a markedly high peak plasma concentration (PPC), a large area under the time-versus-concentration curve (AUC) and reduced clearance. Similarly, oral administration of UFT (tegafur 300 mg/body) produced a relatively higher PPC and a larger AUC of 5-fluorouracil (FU). The activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in the metabolism of FU, in peripheral mononuclear cells was within the normal range (0.265 nmol/min/mg). MMC is believed to have played a large part in inducing the severe toxicity observed in this patient. Physicians should be aware of the possibility of severe toxicity during treatment with UFT and MMC, although details of its incidence and mechanism are unclear.

Adenocarcinoma↗
PubMed1995

Expression of integrin alpha 3 in gastric and colorectal cancers: its relation to wall contraction and mode of invasion.

We macroscopically classified 25 gastric and 23 colorectal advanced cancers into "contracted" and "uncontracted" types, and found immunohistochemically that integrin subunit alpha 3 was more frequently expressed in the extracellular matrix (ECM) in the former than in the latter (75%:9/12 vs. 38%: 5/13 in gastric and 86%:6/7 vs. 25%:4/16 in colorectal cancers, respectively). Integrin subunit alpha 3 was also expressed more frequently in cancers producing transforming growth factor-beta (TGF-beta), which is related to ECM deposition, integrin expression and cell mobility, than in those which did not produce TGF-beta (67%:10/15 vs. 40%:4/10 in gastric and 57%:4/7 vs. 38%:6/16 in colorectal cancers, respectively). In addition, integrin subunit alpha 3 was not expressed in 2 benign gastric ulcers combined with gastric cancer elsewhere in the stomach. On the other hand, a retrospective analysis of 107 cases of rectal cancer which recurred after a curative operation revealed that local recurrence was more frequent in "contracted" than "uncontracted" types (44%:11/25 vs. 26%:21/82). These results may suggest that the abundant interstitial fibrosis which leads to remarkable gastric or colorectal wall contraction is a result of the interaction between cancer cells and ECM, along with the expression of integrin and/or the production of TGF-beta. This fibrosis may also be closely related to the mode of gastric and colorectal cancer invasion.

Antigens, CD↗
PubMed1995

[Recent advances in chemotherapy for advanced gastric cancer: from the standpoint of survival advantages].

Recently, there have been many reports indicating higher response rates in combination chemotherapies for advanced gastric cancer. Since 1990, several randomized controlled trials (RCT) have been reported, which showed evidences of survival impacts in such cases. Patients treated with chemotherapy obtained significant survival advantages over those with best supportive care in three RCTs. The RCT from EORTC also resulted in more significant survival prolongation in FAMTX than in FAM, and FAMTX should be a reference arm for new regimens. Some RCTs are now under way to establish a standard therapy for advanced gastric cancer. From the analysis of long-term results of Japanese studies, 3% of entry cases survived longer than 5 years with no evidence of disease by chemotherapy. Chemotherapy for gastric cancer should be evaluated with survival advantages or rate of long-term survivors in future studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Concurrent chemotherapy and radiation therapy for locally advanced carcinoma of the esophagus.

A pilot study was undertaken to clarify the efficacy of concurrent chemoradiotherapy against locally advanced esophageal carcinoma. The 20 patients in this study had previously untreated esophageal carcinoma with evidence of T4 disease and/or distant node metastases. Chemotherapy consisted of protracted infusion of 5-fluorouracil at a dose of 400 mg/m2/day on days 1-5 and 8-12, combined with a 2-h infusion of cisplatinum at 40 mg/m2 on days 1 and 8. Radiation treatment for the mediastinum was administered 5 days per week for 3 wk at 2 Gy/day, along with chemotherapy. These schedules were repeated twice to give a total radiation dose of 60 Gy. For patients who responded, two additional courses of chemotherapy were administered. Five of the 20 patients had UICC stage III disease and 15 had stage IV. Seventeen (85%) of the 20 patients exhibited an objective response, including 6 (30%) complete responses. Local control was excellent with 10 (50%) complete responses. Toxic effects were severe. Major toxicities were leukocytopenia of grade 3 or more in 45% of the patients and esophagitis, including four perforations. There were two treatment-related deaths. The median survival time was 9 mo (range: 2 to 34+). Concurrent chemotherapy and radiotherapy was effective even for locally advanced esophageal carcinoma, but was associated with significant toxicity.

Aged↗
PubMed1994

Detection of point mutations in the K-ras oncogene at codon 12 in pure pancreatic juice for diagnosis of pancreatic carcinoma.

BACKGROUND: Mutations in the K-ras oncogene at codon 12 are detected at a remarkably high frequency in pancreatic carcinomas and are believed to be a critical event in oncogenesis. The authors attempted to detect K-ras mutations in DNA obtained from pure pancreatic juice collected endoscopically, as a novel diagnostic approach to pancreatic carcinoma. METHODS: K-ras mutations were examined using the two-step polymerase chain reaction (PCR) combined with restriction enzyme digestion, followed by nonradioisotopic single-strand conformation polymorphism (SSCP) analysis. RESULTS: Specific mutations of the K-ras gene at codon 12 were found in six of nine (67%) duct cell carcinomas, all of which were negative by cytodiagnosis of the same pure pancreatic juice. K-ras mutations were not detected in the pancreatic juice from 14 healthy control subjects, 10 patients with chronic pancreatitis, or 3 patients with islet cell tumors. CONCLUSIONS: Detection of K-ras mutation at codon 12 in pancreatic juice is highly specific for diagnosing pancreatic duct cell carcinoma and may be a valuable diagnostic modality for pancreatic carcinoma and for differentiating chronic pancreatitis from carcinoma.

Adenocarcinoma↗
PubMed1994

Phase II study of protracted infusional 5-fluorouracil combined with cisplatinum for advanced gastric cancer: report from the Japan Clinical Oncology Group (JCOG).

A phase II study of protracted infusional 5-fluorouracil (5FU) combined with cisplatin (CDDP) was conducted in patients with advanced gastric carcinoma. 55 previously untreated patients, including 40 patients with measurable disease, were treated with 5FU (800 mg/m2, days 1-5, protracted infusion) and CDDP (20 mg/m2, days 1-5, drip infusion). Objective tumour responses were observed in 17/40 (43%) patients with measurable disease. Median survival was 7 months. WHO grade 3 or 4 leucopenia occurred in 10/55 patients (18%) and grade 3/4 thrombocytopenia was observed in 4 patients (7%). A randomised trial including this regimen is now underway in a JCOG study.

Adult↗
PubMed1993

Small cell carcinoma of the esophagus with an esophago-mediastinal fistula successfully treated by chemoradiation therapy and intubation: a case report.

A case of esophageal small cell carcinoma with cervical node metastases and an esophago-mediastinal fistula was treated successfully by chemoradiotherapy. The fistula, after irradiation, was handled successfully by esophageal intubation, followed by infusional 5-fluorouracil and cisplatinum chemotherapy, resulting in the closure of the fistula. Two courses of concurrent chemoradiotherapy, followed by additional cisplatinum and etoposide chemotherapy, were administered. The tumor, including the cervical lymph node metastases, disappeared completely after the treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Translocation t(8;16)(p11;p13) in neonatal acute monocytic leukaemia.

A recent report demonstrated that t(8;16) (p11;p13) may be linked to acute monocytic leukaemia (AMoL) of differentiated subtype (M5b) with active haemophagocytosis by leukaemic cells. Only two cases of neonatal AMoL with t(8;16) (p11;p13) have been reported; M5b with haemophogocytosis and M5a. We report a case of neonatal AMoL (M5b) with t(8;16)(p11;p13), but haemophagocytosis by the leukaemic cells was not detected.

Chromosomes, Human, Pair 16↗
PubMed1991

An early phase II study of 5-fluorouracil combined with cisplatinum as a second line chemotherapy against metastatic gastric cancer.

Twenty-two patients with measurable metastatic gastric cancer, refractory to prior chemotherapy, were treated with a combination chemotherapy of 5-fluorouracil (5FU) and cisdiamminedichroloplatinum (II) (CDDP). 5FU was continuously infused for five consecutive days at a dose of 800 mg/m2/day, and CDDP was given intravenously for five days at a dose of 20 mg/m2/day over 30 min every four weeks. All patients had received only one regimen of prior chemotherapy, and 10 of the 22 had been pretreated with combination of etoposide, doxorubicin and CDDP (EAP). It was possible to evaluate 20 of the 22 patients treated for response and toxicity. Nine of the 20 patients achieved a partial response, the response rate being 45% (23-67% with 95% confidence limits). The nine patients who responded included three who had been pretreated with EAP, indicating that 5FU + CDDP can be used as a second line chemotherapy against gastric cancer, even when the initial intensive chemotherapy, such as EAP, has failed to obtain or maintain a response. High grade toxicities (WHO grade 3 or 4) of leukocytopenia, thrombocytopenia and stomatitis were seen in 20, 25 and 40%, respectively. No treatment-related death was, however, observed. The above results suggest that 5FU + CDDP could be promising in a phase II trial with a large number of cases.

Adenocarcinoma↗
PubMed1991

Anticataractogenic property of gamma-glutamylcysteine ethyl ester in an animal model of cataract.

The anticataractogenic potential of gamma-glutamylcysteine ethyl ester was investigated in model cataracts induced by L-buthionine sulfoximine. Subcutaneous injection of the ester (0.625-2.5 mmol/kg) effectively inhibited cataractogenesis in suckling mice. Treatment of mice with L-buthionine sulfoximine alone resulted in a marked reduction of the glutathione content in the eyes. This deprivation of glutathione was mitigated, to a significant degree, by coadministering gamma-glutamylcysteine ethyl ester. In an experiment with rat lens in culture, gamma-glutamylcysteine ethyl ester was found to elevate the lenticular level of glutathione. These results indicate that gamma-glutamylcysteine ethyl ester is able to permeate across biomembranes and serves as an excellent precursor for glutathione biosynthesis, thereby exerting its anticataractogenic activity.

Animals↗
PubMed1991

Glutathione and glutathione-related enzymes in human cataractous lenses.

Glutathione and its related enzymes were measured for normal and cataractous human lenses. Glutathione decreased progressively with the development of cataracts. This decrease was more pronounced in the nucleus than in the capsule-epithelia of cataractous lenses. Glutathione reductase in nuclear extracts was relatively unchanged during cataract progress, while glutathione synthetase was significantly low in the advanced stages of cataracts. gamma-Glutamylcysteine synthetase was not measurable in the nuclei of cataractous lenses.

Aged↗
PubMed1991

A long-term survivor of metastatic gastric cancer treated by chemotherapy: case report.

A long-term survivor of advanced gastric cancer with multiple metastases to the liver treated by chemotherapy is described. Chemotherapy comprising a combination of uracil and tegafur with mitomycin C achieved a complete response in the patient which lasted for approximately four years. Four years after initiation of the chemotherapy, a unique form of cancer recurrence occurred on the skin, showing infiltrative erythema. Cancer metastases developed further despite more treatment, and the patient died of generalized metastasis four years six months after the initiation of chemotherapy. It is significant that, at autopsy, no cancer cells were revealed in the primary lesion or in the liver which had been present before the initial chemotherapy.

Adenocarcinoma↗
PubMed1989

Inhibition of colony formation of drug-resistant human tumor cell lines by combinations of interleukin-2-activated killer cells and antitumor drugs.

The cytotoxicity of interleukin-2-activated killer (LAK) cells with or without anticancer drugs against cell lines with acquired drug resistance was evaluated in vitro by colony assay. Human non-small cell lung cancer cell lines, PC-9 and PC-14, human leukemia cell line, K-562, and their sublines resistant to cisplatin (CDDP), PC-9/CDDP and PC-14/CDDP, and to adriamycin (ADM), K-562/ADM, were used as target cells. PC-9/CDDP demonstrated a marked increase in susceptibility to killing by both peripheral blood lymphocytes (PBL) and LAK cells, as compared to the parental cell line, PC-9. The cytotoxicity of PBL and LAK cells against PC-14/CDDP and K-562/ADM was similar to that against their parental cell lines. Moreover, the combination of LAK and CDDP had a synergistic effect on PC-14 and PC-14/CDDP.

Adenocarcinoma↗
PubMed1988

Induction of angiogenic response by chemically stable prostacyclin analogs.

Angiogenic activities of several chemically stable prostacyclin analogs (isocarbacyclins and 7-fluoro prostacyclin) were evaluated by the chick embryo chorioallantoic membrane assay. These compounds showed potent angiogenic activity at very low concentration (0.1 micrograms/egg 1.0 micrograms/egg), whereas naturally occurring prostaglandins such as prostacyclin and PGE1 were almost ineffective up to 1 microgram/egg. Pretreatment of chorioallantoic membranes with dexamethasone or indomethacin inhibited the angiogenic response induced by these chemically stable prostacyclin analogs. These results indicate that these prostacyclin analogs induce the angiogenic response of chick chorioallantoic membranes via a mechanism involving activation of inflammatory cells, as well as through their direct angiogenic activity.

Allantois↗
PubMed1985

Effects of a novel fatty acid derivative [(7E)-8-(2-naphthyl)-5,6-trans-5,6-methano-7-octenoic acid] on arachidonic acid metabolism in cultured cells.

The effects of a novel synthetic fatty acid derivative (TEI-8005:(7E)-8-(2-naphthyl)-5,6-trans-5, 6-methano-7-octenoic acid) on arachidonic acid metabolism in some cultured cells were studied. The compound significantly stimulated prostaglandin (especially prostacyclin) biosynthesis in cultured vascular cells and gastric mucosal epithelial cells, and inhibited lipoxygenase product formation in n-butyrate-treated mastocytoma. In aortic smooth muscle cells in which cyclooxygenase activity was reduced, it strongly stimulated prostaglandin formation in young cells with reduced cyclooxygenase activity but had less effect in aged cells. These result indicated that TEI-8005 enhanced prostaglandin formation in cells with either normal or reduced cyclooxygenase activity.

Aging↗