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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 73 records · Page 4Linked to original sources
PubMed1993

Alteration in proliferative and endocrine responsiveness of human mammary carcinoma cells by prototypic tumor-suppressing agents.

The experiments performed in this study were designed to establish that (1) acquisition of anchorage-independent growth, a biological characteristic of tumorigenically transformed phenotype, can be modulated by prototypic tumor-suppressing agents, and (2) modulation of growth is influenced by the metabolic competence of the cells to biotransform estradiol, MCF-7 human breast carcinoma cells exhibited linear cell proliferative kinetics with a 41-hour population doubling time, and a 15% colony-forming efficiency in 0.33% agar. Indole-3-carbinol (13C), a naturally occurring tumor-suppressive agent; tamoxifen (TAM), an antiestrogenic agent; and 4-hydroxytamoxifen (4-OHTAM), a metabolite of TAM, demonstrated 73.7%, 72.5%, and 89.9% suppression in anchorage-independent growth of MCF-7 cells, respectively. At the metabolic level, 13C and 4-OHTAM induced 2.3-fold (P < 0.0001) and 1.3-fold increase (P = 0.001) relative to their own controls in the extent of 2-hydroxylation of estradiol. The results indicate that growth inhibition by 13C, TAM, and 4-OHTAM may in part be due to altered estradiol metabolism in MCF-7 cells. Thus, anchorage-independent growth and altered biotransformation of estradiol may constitute useful cellular and endocrine markers to evaluate the biological response of chemosuppressive agents.

Antineoplastic Agents↗
PubMed1993

Increased chemiluminescence and ulcer development in the low blood flow state of the gastric tube for esophageal replacement.

Peptic ulcers in the gastric tube for esophageal replacement develop in spite of reduction of acid secretion after truncal vagotomy and often result in serious conditions such as bleeding and perforation. Thirteen cases of gastric tube ulcers were detected endoscopically from 1985 to 1990 in our hospital. Most of these ulcers developed within 20 cm of the anastomosis (esophagogastrostomy), which was an especially hypoxic and ischemic area. Ischemic change due to decreased blood supply is suggested as a causative factor in ulcer development. Recent studies indicate that chemiluminescence (ChL) activity may increase even in the low-flow hypoxic condition. Therefore, we investigated the ChL of regional blood in the hypoxic gastric tube in dogs. The ChL activity of the blood sample collected from the ischemic region in the gastric tube significantly increased after construction of the gastric tube, compared with systemic blood from the femoral vein, and the number of leukocytes decreased in the ischemic region. We believe that oxygen radicals derived from neutrophils adhering to the vascular endothelium may play an important role in the damage to endothelial cells of the gastric tube and suggest the possibility of their causative effects in the process of ulcer formations.

Anastomosis, Surgical↗
PubMed1993

Enhancement of antitumor activity of cisplatin on human gastric cancer cells in vitro and in vivo by buthionine sulfoximine.

An attempt was made to evaluate the enhancement of the antitumor activity of cisplatin (DDP) by buthionine sulfoximine (BSO) in vitro and in vivo. In the in vitro study, pre-treatment with BSO (5, 10 and 25 mM) increased the antitumor activity of DDP against the gastric cancer cell lines MKN-28 and MKN-45, whereas BSO alone exhibited only slight antitumor activity (inhibition rate, 20-30%). In the in vivo study, the antitumor effects of DDP against human gastric cancer xenografts St-15 and SC-1-NU in BALB/c nu/nu mice were enhanced pretreatment with BSO, which was administered intraperitoneally at a dose of 500 mg/kg according to a schedule of qd x 3. BSO alone showed no antitumor effects against these tumors in nude mice. The side effects (assessed in terms of death rate and body weight loss) associated with the maximum tolerated dose of DDP (9 mg/kg) were not increased by BSO pretreatment. As BSO increased the antitumor activity of DDP without a corresponding increment of its toxicity, BSO appears to be a promising agent for further study.

Animals↗
PubMed1993

Revaluation of endoscopic laser therapy for treatment of early cancer in the stomach.

The efficacy and safety of the endoscopic laser therapy for eradication of early cancer in the stomach was revaluated in fourty-eight patients. In 37 of the 42 patients (88%) treated with the laser therapy alone, the procedure was effective and the complete eradication was confirmed at the end of the follow-up period. In seven of fourteen patients with the incomplete treatment, residual cancer cells were successfully removed by repeated laser therapy. The endoscopic mucosal resection was effective in 21 of the 30 patients (70%) with the early gastric cancer. Interestingly, six of the eleven cases with incomplete treatment with the endoscopic mucosal resection underwent the laser therapy and the complete eradication was achieved in all patients. Although the endoscopic mucosal resection is now the main method for the endoscopic treatment of the early gastric cancer, these data favor offering the endoscopic laser therapy as the combined method with the mucosal resection therapy.

Adult↗
PubMed1993

Carbohydrate antigens and liver metastasis in colorectal cancer.

A comparative immunohistochemical study was performed to analyse the expression of cancer-associated carbohydrate antigens by primary and metastatic lesions of colon cancer. We used monoclonal antibodies which reacted with Lea, Lex and Tn as well as their sialylated derivatives. Twenty-one primary lesions in patients without metastasis and 26 primary and metastatic lesions in patients with liver metastasis were studied. Sialyl Lea was expressed by 57% of the primary lesions of patients without metastasis, 65% of the primary lesions of patients with metastasis and 73% of their liver metastases. Sialyl Lex was expressed by 60% of the primary lesions of patients with and without metastasis as well as by approximately 80% of the liver metastases. Sialyl Lea and sialyl Lex showed strong expressions in the liver metastases, significantly greater than in the primary lesions. The findings indicate the increased expressions of sialyl Lea and sialyl Lex to be correlated with liver metastasis of colorectal cancer.

Adenocarcinoma↗
PubMed1993

Anastomotic leakage after colorectal cancer surgery: a risk factor for recurrence and poor prognosis.

In order to discover the incidence of recurrence and prognosis of patients with anastomotic leakage after colorectal surgery, 980 colorectal cancer patients who underwent anastomosis at Keio University Hospital between 1970 and 1990 were examined. Thirty-three patients (leakage group) out of the 980 exhibited anastomotic leakage. The incidence of local recurrence in the leakage group was significantly higher than in the no leakage group (P < 0.01). The disease-free survival rate of the leakage group was significantly lower than that of the no leakage group in Dukes' A, B patients (P < 0.01), but was not so in Dukes' C, D patients. These results suggested that anastomotic leakage after colorectal cancer surgery might enhance the incidence of local recurrence and make the prognosis poor.

Aged↗
PubMed1993

Splenic abscess associated with colon cancer: a case report.

The present report describes a case of colon cancer which presented with a rare complication of splenic abscess. A 52-year-old Japanese man with diarrhea, fever and chills was admitted to our hospital. He complained of fever, with chills at night, and abdominal pain occurring during the last month. The origin of the fever was investigated, and Escherichia coli grew from a blood culture. Multilocular splenic abscesses and wall thickening of the descending colon were revealed by CT scan, magnetic resonance imaging and ultrasound. A cancer of the descending colon was found by barium enema and colonoscopy. A curative resection was performed and the pathological report revealed the splenic abscess to have developed from a direct extension of, and perforation by, the carcinoma of the descending colon.

Abscess↗
PubMed1993

[Targeting therapy using monoclonal antibody directed against growth factor receptors].

Targeting therapy is expected to be a new effective anti-cancer treatment in near future. Major advances are achieved by considerable effort in this area. Monoclonal antibodies that recognize tumour-associated antigens were conjugated to chemotherapeutic drugs, toxins and radionuclides with various procedures. To apply this new therapy for clinical use, many problems still remain to be clarified. These problems consist of human anti-mouse antibody, antigenic heterogeneity and low tumour uptake. By our experiment, growth factor receptor was an ideal target for targeting therapy and immunoconjugate directed against growth factor receptor showed selective cytotoxicity to cancer cells with expression of growth factor receptor. Moreover, cytotoxic effect was positively correlated with expression level of growth factor receptor.

Animals↗
PubMed1992

High in vitro-in vivo correlation of drug response using sponge-gel-supported three-dimensional histoculture and the MTT end point.

The in vitro sponge-gel-supported three-dimensional histoculture chemosensitivity assay (Hoffman assay) allows the in vivo-like culture of human tumors. In this study, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) end point was applied to the Hoffman assay in an attempt to increase in vitro-in vivo correlation. The chemosensitivities of 16 human tumor lines were determined in vitro by the histoculture assay, and retrospectively correlated to their in vivo chemosensitivity as xenografts in nude mice. The in vitro test was considered to be positive if tumor-cell MTT reduction activity was lowered by more than 50%. The cutoff drug concentrations to determine sensitivity in vitro were determined for mitomycin C, doxorubicin, 5-fluorouracil and cisplatin. Using these cutoff drug concentrations in vitro we found, as a function of time of exposure, a strong correlation between serum drug concentrations found in nude mice given maximum tolerated doses and drug concentrations found in the histoculture media in vitro, thereby establishing a relationship between the amounts of drugs to which tumors were exposed in vivo and in vitro. The overall correlation rate of the efficacy results of the drug-response assay to in vivo chemosensitivities was 89.8%, with 90.0% true-positive and 89.7% true-negative rates, 81.7% sensitivity and 94.6% specificity, thereby indicating potential clinical use for tumor histoculture with the MTT end point.

Animals↗
PubMed1992

Increased drug resistance of cultured human cancer cell lines in three-dimensional cellular growth assay using collagen gel matrix.

We have conducted a three-dimensional cellular growth assay using collagen gel matrix with an endpoint of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay, on four human gastric and colonic cancer cell lines. Three-dimensionally growing cells in collagen gel matrix were 2- to 180-fold more resistant to mitomycin C, doxorubicin, 5-fluorouracil, and cisplatin than those in monolayer culture, and these resistances were increased further when the cells increased their three-dimensionality. Furthermore, the influence of fibroblasts in the collagen gel matrix on the chemosensitivity of cancer cells was less than that in monolayer culture. Since this new assay using collagen gel matrix with an endpoint of the MTT assay was able to detect the increase of drug resistance of human cancer cell lines by three-dimensional cellular growth using a simple and convenient procedure, it was considered to be more useful than conventional monolayer cultures for evaluating the chemosensitivity of cancer cells.

Adenocarcinoma↗
PubMed1992

Targeting cancer chemotherapy using a monoclonal antibody (NCC-LU-243) conjugated with mitomycin C.

Two kinds of immunoconjugate (T-3M and T-11M) of murine monoclonal antibody with mitomycin C (MMC) were developed using spacers containing a disulfide (T-3M) or thiocarbamate (T-11M) bond. A murine monoclonal antibody (NCC-LU-243) raised against a human small cell lung carcinoma cell line, Lu-24, in nude mice, is an IgG2a monoclonal antibody that recognizes a 145-kDa protein on the cell surface membrane. T-3M and T-11M showed affinity for the LU-243 antigen-positive H-69 cell line but not for the antigen-negative Lu-65 cell line in vitro. In the in vitro MTT assay, the order of efficacy of these compounds was T-11M > T-3M > MMC against antigen positive H-69 and T-11M = MMC > T-3M against antigen-negative K562. When antigen-positive H-69 was transplanted into nude mice for in vivo assay, the maximum tolerated dose of T-3M was twice as high than that of the parent compound MMC. Furthermore, T-3M showed higher antitumor activity against antigen-positive H-69 than MMC conjugated with a non-specific rabbit IgG in vivo. When the maximum tolerated doses of T-3M and MMC were administered to H-69-bearing nude mice, the effect of T-3M was superior to that of MMC, whereas no differences were observed between the antitumor activity of T-3M and MMC against antigen- negative MX-1, a human breast carcinoma. These two immunoconjugates of monoclonal antibody with mitomycin C are thought to be useful for targeting cancer chemotherapy against human small cell lung carcinomas.

Animals↗
PubMed1992

Histopathological development of gastric tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

The development of carcinoma was examined in male Wistar rats (n = 120) exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (83 micrograms/ml) for 16 weeks. After MNNG administration, rats were investigated by endoscopic observation, visualization of microvascular structure, and estimation of lectin binding sites. Changes of bile reflux to the stomach was observed endoscopically at 24 weeks as well as the development of gastric mucosal erosions. Protruding and expansive ulcerating carcinomas developed at 36 weeks and had a microvascular pattern similar to that of human adenocarcinoma. Estimation of lectin binding site and pattern was useful to evaluate the malignant potential of cell proliferation. We postulate that endoscopic observation is valuable in investigating the development of gastric carcinoma, and microvascular structure and lectin binding pattern may be useful to demonstrate the mechanism of growth of gastric carcinoma.

Animals↗
PubMed1992

Demonstration of bicarbonate secretion in rat duodenal brush border membrane vesicles.

This study was designed to characterize the mechanisms available for bicarbonate transport across the apical membrane using rat duodenal brush border membrane vesicles (BBMVs), including the morphological findings. BBMVs were purified using a double Mg2+ precipitation technique. Electron microscopy of the final pellet showed only membrane material without contaminating organelles of cytoskeletal aggregates. BBMVs were enriched 15.1 +/- 3.2-fold in A-lp and 12.5 +/- 2.4-fold in LAP. The time course of 36Cl uptake into BBMVs demonstrated a good response curve and equilibrated to the intravesicular space over 120 min. In this present study, these BBMVs were purified and showed a stabilized structure. Therefore, these results suggest that this model was useful for studying HCO3- secretion and ulcer etiology.

Animals↗
PubMed1992

Production of human immunoglobulin G reactive against human cancer in tumor-bearing mice with severe combined immunodeficiency reconstituted with human splenic tissues.

Splenic tissues derived from patients with gastric cancer were implanted into mice with severe combined immunodeficiency (SCID) and then the mice were challenged with COLO-205, a human colon cancer cell line. Production of human immunoglobulin G (IgG) reactive against the COLO-205 cells was detected by enzyme-linked immunosorbent assay in sera from the reconstituted and tumor-bearing SCID mice. The titers of the reactive IgG relative to total IgG in the sera of SCID mice began to increase from one week after implantation of the tumor cells, and became 10- to 100-fold higher than that in the donor's serum by 3-4 weeks. This model using implantation of human cancer cells in SCID mice reconstituted with human splenic tissues would facilitate further studies of human cancer immunology.

Animals↗
PubMed1992

Recombinant human interferon-alpha 2a increases hormone receptor level of a human breast carcinoma xenograft in nude mice and enhances the anti-proliferative activity of tamoxifen.

The effect of recombinant human interferon-alpha 2a (rhIFN-alpha 2a) on the hormone receptor level and antitumor activity of tamoxifen (TAM) was investigated in nude mice using ZR-75-1, an estrogen receptor (ER)-positive, and progesterone receptor (PgR)-negative human breast carcinoma xenograft. ER levels (maximum binding sites) of tumors treated with rhIFN-alpha 2a at a dose of 6 x 10(5) U/mouse/day for 1 or 3 wk were not significantly different from the control, whereas those with rhIFN-alpha 2a at a dose of 6 x 10(4) U/mouse/day for 1 or 3 wk were higher than the control (3.9- to 4.4-fold) with a significant difference at P < 0.01. The increase of ER by rhIFN-alpha 2a was investigated using a sucrose density gradient method. The peak was only seen at 8S in both rhIFN-alpha 2a-treated tumor and control ER, and the sedimentation patterns were almost the same, suggesting that both ERs were essentially equivalent. On the other hand, PgR of all the treated groups could be detected, while that of the control group was undetectable. The antitumor effect of the combination treatment of rhIFN-alpha 2a and TAM was compared with those of single treatments. While rhIFN-alpha 2a at a dose of 6 x 10(5) U/mouse/day and TAM did not show a combination effect, rhIFN-alpha 2a at a dose of 6 x 10(4) U/mouse/day and TAM showed a synergistic combination effect, and ER was decreased to the threshold of detection by the combination treatment. These findings indicated that a low dose of rhIFN-alpha 2a increased the ER levels of ER-positive human breast cancer in vivo as well as in vitro and enhanced the anti-proliferative effect of TAM, and the newly synthesized ER was essentially the same as the original ER.

Animals↗
PubMed1992

[Problems in multidisciplinary treatment from the standpoint of clinical characteristics in human cancers].

We investigated the amplification and expression of oncogenes in human gastric and breast cancers. The biological malignancy of the cases with oncogene amplification/expression was higher than that of the cases without amplification/expression. Moreover, the case with amplification/expression of oncogene was found to be highly correlated with distant organ metastasis. In strongly suggests the necessity of postoperative adjuvant therapy. In addition, these data will have to be taken into consideration as deciding on the way of operation and therapy.

Breast Neoplasms↗
PubMed1992

[Rapid detection of mecA gene by nested PCR for diagnosis of methicillin resistance in Staphylococcus aureus].

In recent years, the most common causative organism of hospital infections has been methicillin resistant Staphylococcus aureus (MRSA). The major mechanism of beta-lactam resistance in MRSA is attributed to the production of a specific penicillin binding protein (PBP2'), which is a product of mecA gene, with extremely low binding affinities to beta-lactams. In the present study, we have established a rapid identification method of MRSA by sensitive detection of mecA gene using nested PCR. Nested PCR method amplifying the target DNA in two steps enhanced the efficiency of the second round amplification. By means of this method, mecA gene was successfully detected in clinical samples, such as blood, pus, sputum and feces within 3-4 hrs. Rapid diagnosis of MRSA-bacteremia is particularly important for prevention of sever systemic infection. There are some strains of S. aureus which possess mecA gene in spite of low minimal inhibitory concentration of DMPPC. In these strains expression of mecA gene is induced by contact of beta-lactams and they obtain methicillin resistance. Using nested PCR method, these latent MRSA are rapidly and certainly detectable. This method should be useful for early and effective detection of MRSA hospital infections.

Cross Infection↗