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S Inutsuka

Publications and source records attributed to S Inutsuka.

At least 19 recordsLinked to original sources
PubMed1998

Phase II trial of combination chemotherapy with cisplatin, carboplatin and etoposide in stage IIIB and IV small-cell lung cancer. Fukuoka Lung Cancer Study Group.

PURPOSE: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival. METHODS: Previously untreated patients with small-cell lung cancer, with measurable disease, aged < or = 72 years, performance status < or = 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m2 cisplatin on day 1, 100 mg/m2 carboplatin on days 2, 3 and 8, and 50 mg/m2 etoposide on days 1, 2, 3 and 8. RESULTS: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and 14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%, and 43% of patients, respectively. CONCLUSIONS: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer.

Aged↗
PubMed1998

MST-16, a novel derivative of bis(2,6-dioxopiperazine), synergistically enhances the antitumor effects of anthracyclines.

MST-16, a derivative of bis(2,6-dioxopiperazine), is a newly developed anticancer agent that is potentially effective in combination with anthracyclines. It has a structural similarity to ICRF-187. The effects of MST-16 and its active form, ICRF-154, on the cytotoxic activities of six anthracyclines were investigated both in vitro and in vivo. Adriamycin (ADM), therarubicin (THP) and ME2303 (ME) showed synergistic cytotoxicity against colon 26 cells, when combined with MST-16. Epirubicin (EPI) and menogaril (TUT-7) and daunomycin (DM) all had a combination index of less than 1.0 only in the lower fraction affected range and, so there were probably no synergistic interactions between these drugs and MST-16. In colon 26 tumor-bearing mice, a significant delay in tumor growth was noted in the mice treated with ADM (7.5 mg/kg) and MST-16 (750 mg/kg) compared with mice given either drug alone. Similarly, tumor growth in mice treated with THP (10 mg/kg) or ME (10 mg/kg) with MST-16 (750 mg/kg) was significantly delayed. To elucidate the mechanism of synergy between these anthracyclines and MST-16, the concentration of anthracyclines in the treated cells was measured by flow cytometry. No increased intracellular accumulation of ADM. THP or ME was evident even when combined with MST-16. Cell cycle analysis revealed that MST-16 enhanced the accumulation of cells in G2M induced by ADM, THP and ME 1.6, 1.4, and 1.5 times, respectively. We thus conclude that the administration of ADM, THP and ME combined with MST-16 is synergistic and that the mechanism may not include an increase in the intracellular drug uptake but rather an increase in G2M accumulation.

Animals↗
PubMed1998

The relationship between CYP1A1 aryl hydrocarbon hydroxylase activity and lung cancer in a Japanese population.

Because aryl hydrocarbon hydroxylase (AHH) is considered to be responsible for the activation of benzo(a)pyrene and other polyaromatic hydrocarbons in cigarette smoke to carcinogens, it is important to examine CYP1A1 (AHH) activity in the determination of susceptibility to lung cancer. We investigated AHH activity in peripheral mitogen-treated lymphocytes in 108 lung cancer patients and 95 healthy control individuals. Non-induced AHH activity was detectable in all the samples. AHH inducibility (3-methylcholanthrene-induced/non-induced AHH activity) showed a very wide interindividual variation as well as non-induced AHH activity. No significant associations were found between adjusted AHH activity and histologic type of tumor among lung cancer patients. Adjusted AHH inducibility of genotype C [geometric mean and 95% confidence interval (CI); 15.56 and 11.69-20.71] in MspI polymorphism was significantly higher than those of the other two genotypes (P = 0.0001), while no significant difference was observed between genotypes A (4.76 and 3.82-5.93) and B (5.60 and 4.57-6.86). On the other hand, non-induced AHH activity of genotype Val/Val (0.121 and 0.082-0.178 pmol/min/10(6) cells) in isoleucine-valine (Ile-Val) polymorphism was significantly higher than those of genotypes Ile/Ile (0.042 and 0.034-0.052 pmol/min/10(6) cells) and Ile/Val (0.040 and 0.030-0.053 pmol/min/10(6) cells) (P < 0.0001). Even after controlling for age, cigarettes smoked per day and season of the year, high AHH inducibility (7.0 < versus 0 < < or = 3.0: OR and 95 %CI, 12.4 and 2.88-53.4) was an independent risk factor for lung cancer. The data indicate that high AHH inducibility may strongly associate with the susceptibility to lung carcinogenesis.

Adult↗
PubMed1998

[Serum carcinoembryonic antigen doubling time in patients with recurrent gastrointestinal carcinoma and its relationship to tumor biology and life expectancy].

BACKGROUND: The present study was done to determine if carcinoembryonic antigen (CEA) concentration doubling time can predict the course of disease in patients with adenocarcinoma of the gastrointestinal tract and characterize tumor biology. METHODS: CEA doubling times were determined from semilogarithmic plots of CEA concentration time courses in 20 patients with recurrent gastric cancer and 17 with recurrent colorectal cancer. RESULTS: Gastric and colorectal carcinomas showed mean CEA doubling times of 229 days and 85 days, respectively. There were no significant differences with regard to patient age, tumor size, gross appearance and histological differentiation. However, women had shorter CEA doubling times than did men. Flow cytometric analysis showed that tumors with a higher proportion of cells in S-phase (> or = 15%) had significantly shorter CEA doubling times than those with a lower S-phase fraction (< 15%). There was a significant correlation between the CEA doubling time and the length of survival after the initial CEA concentration increase in patients with recurrent gastric and colorectal carcinomas. CONCLUSIONS: CEA doubling time predicts life expectancy in patients with adenocarcinoma of the gastrointestinal tract. Differences in survival time are closely associated with variations in the biological aggressiveness of individual tumors.

Aged↗
PubMed1997

The appearance of a normal appendix on barium enema examination does not rule out a diagnosis of chronic appendicitis: report of a case and review of the literature.

We report herein the rare case of a 15-year-old girl with chronic appendicitis in whom the appendix was clearly depicted by a barium enema (BE) examination. The patient presented with a 4-month history of diffuse abdominal pain and tenderness in the lower abdomen. Neither computed tomography nor ultrasonography showed any abnormal findings in the lower abdomen or pelvic cavity. Furthermore, BE examination depicted an appendix filled with the contrast medium. However, at elective surgery, she was found to have chronic appendicitis which was later confirmed histologically. Following this case report, a discussion on the value and limitations of BE examination for the diagnosis of acute and chronic appendicitis is presented.

Abdominal Pain↗
PubMed1997

Phase II trial of dose intensification with cisplatin and carboplatin plus vindesine in patients with inoperable non-small cell lung cancer.

We conducted a phase II trial of a regimen that combined cisplatin (CDDP), carboplatin (CBDCA), and vindesine (VDS) in previously untreated patients with non-small cell lung cancer (NSCLC) to evaluate the efficacy and safety of the regimen. Thirty-five patients with inoperable NSCLC entered the study. Cisplatin (CDDP 80 mg/m2) was administered on day 1, and CBDCA 100 mg/m2 and VDS 2 mg/m2) were administered on days 2, 3, and 8. We observed one complete response (CR) and 16 partial responses (PR), with a total response rate of 49% [95% confidence interval (CI) 31-66%]. The overall median survival was 58 weeks; the 1-year survival rate was 60%, and the 2-year survival rate was 23%. Major toxicities were hematologic; leukopenia of grades 3 and 4 occurred in 66% patients, and thrombocytopenia occurred in 23%. Therefore, the dose-intensified regimen of CDDP, CBDCA, and VDS was active in treating patients with inoperable NSCLC, with demonstration of a favorable median survival time.

Adult↗
PubMed1997

Potentiation of the cytotoxicity of carboquone by flavone acetic acid combined with hyperthermia.

Flavone acetic acid (FAA) has shown the effectiveness of vasoactive drugs in the selective reduction of tumor blood flow. A FAA-mediated decrease in tumor blood flow may produce sufficient hypoxic conditions within the tumor. Carboquone (CQ), a naturally occurring prototype bioreductive alkylating agent like mitomycin C (MMC), has been shown to be selectively more cytotoxic toward hypoxic tumor cells. We have reported enhancement of the combined antitumor effects of MMC plus FAA and hyperthermia (HT). In this study, we examined the combined effects of FAA, CQ and HT. In vitro, although HT (43 degrees C, 60 min) reduced the colonogenicity to 0.58 in CQ (0.01 microg/ml) alone, the combined cytotoxicity of CQ and HT was not enhanced with exposure to FAA at a concentration of 100 microg/ml. In vivo, the tumor growth time, calculated as the time required to reach twice the initial tumor volume, for CQ (2 mg/kg) alone, FAA (150 mg/kg) alone, CQ+FAA, CQ+HT (43 degrees C, 15 min), FAA+HT and FAA+CQ+HT was 6.1, 5.1, 7.1, 8.0, 7.6 and 13.4 days, respectively. A significant enhancement of antitumor effects by trimodality therapy with CQ, FAA and HT was observed, when compared to the treatment with CQ and FAA (p < 0.05). The possible mechanisms of an increased antitumor response achieved with the combination of CQ, FAA and HT may be explained in the following way: the FAA-mediated decrease in tumor blood flow produced sufficient hypoxic conditions within the tumor, and these resulted in a significant increase of the antitumor effects of CQ and HT.

Animals↗
PubMed1997

Possible role of indoor environment and coal combustion emission in lung carcinogenesis in Fuyuan County, China.

Fuyuan Country, in Yunnan Province, China has an extremely high lung cancer mortality both in males and non-smoking females. Out of 5768 deaths, 588 patients died of malignant diseases. Lung cancer was the number one cause of death among malignant diseases both in males and females. The rate of lung cancer death to the whole of malignant diseases was 56.2% for males and 55.0% for females. Indoor soot and combustion emission derived from smoky coal produced in northern Fuyuan exhibited high mutagenic activities against Salmonella typhimurium TA98 strain in Ames test. Resected lung tissues derived from the patients with lung cancer in Fuyuan contained significantly higher concentrations of benzo(a)pyrene than those in Japan, both in males and females (i.e., 608.7 +/- 477.1 pg/dry weight for samples of the patients in Fuyuan, 180.1 +/- 104.5 for Japanese non-smokers, and 207.5 +/- 98.8 for Japanese heavy smokers, respectively). These results suggest that mutagenic chemicals contained in coal as well as indoor environment may have a great influence on lung carcinogenesis in Fuyuan, Yunnan Province, China.

Air Pollution, Indoor↗
PubMed1997

[Expression of CD44 standard and CD44 variant 6 in human lung cancer].

We immunohistochemically examined the expression of CD44 standard (CD44 st) and CD44 variant 6 (CD44 v6) in 112 cases of primary lung cancer, and their relationship to the clinical milieu, including the clinical stage. In 46 cases of squamous cell carcinoma, expression of CD44 st was observed in 45.7% of the cases, and expression of CD44 v6 was observed in 60.9%. In 43 cases of adenocarcinoma, positive staining of CD44 st and CD44 v6 was seen in 2.3% and 4.7% of the cases, respectively. None of 21 small cell carcinomas was positive for CD44 st or CD44 v6. In squamous cell carcinomas, the expression of CD44 st and CD44 v6 was observed at a rate significantly higher than in other histologic type. Most specimens positive for CD44 st stained positively for CD44 v6. Therefore, it seems likely that the CD44 expression observed in squamous cell carcinoma of the lung was a variant CD44 containing the domain encoded by variant exon 6. The expression of CD44 v6 was not related to the clinical stage. Significant association between CD44 v6 and differentiation of squamous cell carcinoma was seen; 2/7 (28.6%) for poorly differentiated, 19/31 (61.3%) for moderately differentiated, and 7/8 (87.5%) for well differentiated squamous cell carcinomas (p = 0.02 by trend test). It was previously reported that CD44 st and CD44 v6 were expressed in both normal bronchial epithelium and squamous cell metaplasia. These results suggest that the expression of CD44 v6 in squamous cell carcinoma of the lung may reflect the immunohistochemical characteristics of the tissue from which such carcinoma emerge.

Adenocarcinoma↗
PubMed1996

The relationship between aryl hydrocarbon hydroxylase and polymorphisms of the CYP1A1 gene.

We examined the relationship between aryl hydrocarbon hydroxylase (AHH) and the frequency of a MspI mutation in the 3'-flanking region of cytochrome P450 (CYP) 1A1 (MspI polymorphism) and another mutation in exon 7 (Ile-Val polymorphism) in 84 healthy male subjects in Fukuoka, Japan. AHH inducibility (3-methylcholanthrene (MC)-induced AHH activity/non-induced AHH activity) was correlated with the MspI polymorphism (P < 0.0001) and age class (P = 0.015), whereas no correlation was found for the Ile-Val polymorphism (P = 0.509). Age-adjusted AHH inducibility (mean +/- SE) of the predominant homozygote (genotype A), the heterozygote (genotype B) and a homozygote rare allele (genotype C) genotypes was 4.89 +/- 0.36, 4.82 +/- 0.29 and 13.61 +/- 1.44, respectively. The genotype C showed much higher AHH inducibility than genotypes A and B (P < 0.001), while no significant difference was observed between genotypes A and B. Non-induced AHH activity was also correlated with these polymorphisms. The AHH activity of a homozygous mutant Val/Val genotype (0.076 +/- 0.010 pmol/min/10(6) cells) was significantly higher (P < 0.05) than that of the wild-type homozygous Ile/Ile (0.044 +/- 0.004 pmol/min/10(6) cells) and heterozygous Ile/Val (0.047 +/- 0.007 pmol/min/10(6) cells) genotypes. Our study suggests that the genotypes C and Val/Val, which are more frequent in smoking-related lung cancer, are closely related with high AHH inducibility and high non-induced AHH activity, respectively. Thus, the positive relationship between AHH inducibility and lung cancer is supported by our study. If our results are confirmed and the assessment of genotype becomes feasible on a population basis, identification of smokers who have genetically high susceptibility to lung cancer (genotype C or Val/Val) may become important for the prevention of lung cancer.

Adult↗
PubMed1995

Effectiveness of extended lymphadenectomy in noncurative gastrectomy.

PURPOSE: We examined the efficacy of extended lymph node dissection for prolonging survival in macroscopically or histologically proven incurable gastric cancer. PATIENTS AND METHODS: We analyzed clinico-pathologic data on 119 patients with serosally invasive gastric cancer who underwent noncurative gastrectomy, with respect to the relation between the extent of lymphadenectomy and survival benefit. RESULTS: The 5-year survival rate was significantly higher among patients treated with extensive lymphadenectomy (R2/3) compared to simple gastrectomy (R1). Extensive lymphadenectomy significantly prolonged survival time even after noncurative gastrectomy in cases where there was no evidence of hepatic metastasis, peritoneal seeding, or extensive nodal metastasis beyond the tertiary lymph node, and regardless of the extent of direct invasion to adjacent organs. CONCLUSIONS: Gastrectomy combined with extended lymphadenectomy and/or resection of adjacent organs is recommended for gastric cancer patients without distant metastasis, even when the operation is histologically noncurative. Gastrectomy and perioperative intensive chemotherapy are called for when patients have distant metastasis.

Adenocarcinoma↗
PubMed1995

Effect of lymph node dissection on the prognosis in patients with node-negative early gastric cancer.

BACKGROUND: Our objective was to evaluate the long-term benefit of R2/3 lymph node dissection compared with that of R1, even in node-negative cases. METHODS: We analyzed clinicopathologic data on 373 surgically treated patients with early gastric cancer and without microscopic nodal involvement. RESULTS: Five- and 10-year survival rates for patients treated with R2/3 gastrectomy were 97.3% and 95.4%, respectively. These values were significantly higher than the 90.1% and 81.1% noted for R1 gastrectomy (p < 0.01). Although no difference was found in morbidity and mortality, the incidence of death from a recurrence of the gastric cancer was significantly higher in patients treated with R1 gastrectomy than those with R2/3. Multivariate analysis with the Cox's proportional hazard model revealed patients' age and R2/3 gastrectomy to be independent prognostic factors in patients with node-negative early gastric cancer. CONCLUSIONS: These data show that prophylactic lymph node dissection can potentially prolong the survival time of patients with node-negative early gastric cancer by preventing a recurrence of the gastric cancer.

Age Factors↗
PubMed1994

Laser flow cytometric studies on the intracellular accumulation of anthracyclines when combined with heat.

The effects of heat on intracellular accumulation of anthracyclines were investigated by laser flow cytometry analysis. Sarcoma-180 cells were exposed to Adriamycin (ADM), epirubicin (EPIR), daunomycin (DM), THP-Adriamycin (THP), ME-2303 (ME) and KRN-8602 (KRN) at 37 degrees C and at higher temperatures. There was a dose-dependent increase in the fluorescence intensity of all drugs at 37 degrees C, but heat varied the fluorescence intensity of each drug. At 43 degrees C the cellular fluorescence of ADM and EPIR increased by approximately 200%, but for DM the increase was 110-130%. The cellular fluorescence of THP and ME was little affected by heat, and heat reduced that of KRN to 80-90%. Each drug showed was unique in the relationship between drug exposure time and the fluorescence intensity at 37 degrees C and 43 degrees C. Cytotoxicity determined by the MTT assay was enhanced with heat in the cases of ADM and EPIR, but not with DM, THP, ME, or KRN. Thus, ADM and EPIR are expected to show enhanced antitumor activities when given in combination with hyperthermia.

Animals↗
PubMed1994

Effect of gastrectomy on the pharmacokinetics of tegafur, uracil, and 5-fluorouracil after oral administration of a 1:4 tegafur and uracil combination.

The effects of gastrectomy on the pharmacokinetics of UFT, a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, were examined in 26 patients with macroscopic Stage I gastric cancer. In all, 200 mg UFT (in terms of tegafur) was given to 17 patients who underwent partial gastrectomy (9 cases of Billroth I reconstruction, 8 cases of Billroth II reconstruction) and to 9 patients who underwent total gastrectomy with modified Roux-en-Y reconstruction. Before the operation, the area under the curve (AUC) for tegafur, uracil, and 5-fluorouracil (5-FU) was 79.28 +/- 26.88, 4.41 +/- 1.78, and 0.51 +/- 0.20 micrograms h ml-1, respectively. Partial (Billroth I and II) and total gastrectomy did not alter the AUC of tegafur, and partial gastrectomy using the Billroth I and II methods decreased the AUCs of uracil and 5-FU during the first 2 weeks postoperation. However, plasma levels of uracil and 5-FU reverted to preoperative values at 3 months postsurgery. Our findings show that when UFT is prescribed for patients treated in the early postoperative period following partial gastrectomy for cancer, dose increases and the timing of administration should be given close attention.

Administration, Oral↗
PubMed1993

Kumacone II: an adapter to aid in the placement of a purse-string suture in very low anterior rectal resection.

We have designed an adapter called the "Kumacone II", being a bottle-shaped rubber device which greatly aids in placing a purse-string suture, even at the lowest level near the anorectal junction of the rectum. When this adapter is used, performing the anastomosis is much less time-consuming and not as much training is needed as for low anterior resection using conventional manual suturing. In a clinical study, the incidence of leakage and incontinence was nil in five out of five patients.

Anal Canal↗
PubMed1993

Postoperative PSK and OK-432 immunochemotherapy for patients with gastric cancer.

We evaluated the effects of chemotherapy given postoperatively with and without immunomodulators on the survival of patients who had undergone resection for gastric cancer. We conducted a retrospective survey of data on 963 Japanese patients treated at our department of surgery between 1965 and 1987. Data related to the duration of postoperative survival were calculated for those who received chemotherapy, i.e. an individualized combination of various agents given with or without the immunomodulators PSK, a protein extract of the fungus Coriolus versicolor, and/or OK-432, a preparation of an attenuated strain of Streptococcus (immunochemotherapy). Postoperative immunochemotherapy was more often prescribed for patients with advanced disease. The survival of patients who received immunochemotherapy was shorter than that of patients who received only chemotherapy. In a subgroup of patients adjusted for disease stage, the survival of those on chemotherapy versus immunochemotherapy did not differ significantly at any stage. For optimal results, a protocol for postoperative immunochemotherapy needs to be designed and investigated prospectively and according to the stage of gastric cancer. The stage III gastric cancers seem amenable to a favorable response.

Adjuvants, Immunologic↗
PubMed1993

Inhibition of PHA induced mononuclear cell proliferation by FK506 in combination with cyclosporine, methylprednisolone, 6-mercaptopurine and mycophenolic acid.

In vitro inhibition of human peripheral blood mononuclear cell (PBMC) proliferation by immunosuppressive drugs has been shown to correlate with clinical outcomes in kidney transplant patients. The aim of our study was to analyse the degree of variability of in vitro interactions of FK506 (FK) with combinations of cyclosporin A (CyA), methylprednisolone (MP), 6-mercaptopurine (6ME), and mycophenolic acid (MPA) using phytohaemagglutinin (PHA) stimulated PBMCs. Our hypotheses were: that a wide range of interindividual variation would be detected; and that certain combinations of drugs would have a synergistic inhibitory effect on PHA stimulated PBMCs. Cells were cultured in supplemented RPMI 1640 for 65 hours at 37 degrees C in humidified 5% CO2 - 95% air and proliferative responses measured by 3H-thymidine incorporation over a further 24 hours. Inhibition of PBMC proliferation was assessed over 10 FK concentrations ranging from 1 x 10(-8) to 10 micrograms/ml using both volunteer controls (n = 51) and dialysis patients (n = 23). A wide range of interindividual variability of FK inhibition occurred throughout the range of FK concentrations tested, becoming less variable at the higher concentrations. The interactions of FK with CyA, MP, 6ME and MPA were assessed using PBMCs from 12 volunteer controls. For FK at 1 x 10(-8) micrograms/ml; CyA, MP, 6ME and MPA were used at 0.01 microgram/ml. For FK at 1 x 10(-7) micrograms/ml; CyA, MP, 6ME and MPA were used at 0.1 microgram/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporine↗