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Biomedical subjects

S Kodaira

Publications and source records attributed to S Kodaira.

At least 91 records · Page 5Linked to original sources
PubMed1993

Growth of human tumor xenografts in nude mice and mice with severe combined immunodeficiency (SCID).

Twenty-three fresh tumor specimens obtained at surgery and 5 serially transferable human tumor xenografts were implanted subcutaneously into nude mice and mice with severe combined immunodeficiency (SCID) to compare the take rates of the fresh surgical specimens and the growth rates of the transferable strains. The overall take rates were 65% for the SCID mice and 60% for the nude mice, without any significant difference, although colon carcinoma seemed to have higher acceptance in the SCID mice with a take rate of 6/8. All the serially transferable strains were successfully accepted in the SCID mice, their growth rates being essentially identical to those in the nude mice. These results indicate that the SCID mouse can be used as a human tumor xenograft-mouse system as well as the nude mouse.

Adenocarcinoma, Mucinous↗
PubMed1993

The modulation by L-leucovorin of 5-fluorouracil antitumor activity on human colon carcinoma cells in vitro and in vivo.

We investigated the modulating effect of L-leucovorin (LV) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells (C-1) in vitro and human colon carcinoma xenografts (Co-4) in nude mice. The modulating effect of LV on 5-FU reached an optimal concentration of 40-80 micrograms/ml in vitro which was detected by a colorimetric MTT assay. An optimal dose of 200 mg/kg was also observed in the nude mouse system. The modulating effect of LV increased according to the increment of thymidylate synthetase inhibition in vivo. Since the pharmacokinetic pattern of LV in the nude mice administered LV at 200 mg/kg was similar to that in patients treated with LV at a dose of 100 mg/m2, this clinical method of administration was thought to be adequate for modulating the antitumor activity of 5-FU against clinical colon carcinomas.

Adenocarcinoma↗
PubMed1993

[Clinical study on postoperative infections caused by methicillin-resistant Staphylococcus aureus after gastrointestinal surgery].

We studied 308 postoperative infections (216 patients) after gastrointestinal surgery during 1987-1991, to elucidate the incidence of postoperative infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and its correlation to clinical background factors. Results were as follows: (1) MRSAs were isolated from 25.9% out of 216 patients or 22.4% out of 308 infections. (2) The isolation rate of MRSA was significantly high in infectious enterocolitis (64.7%, p < 0.001), intraabdominal infections (52.5%, p < 0.001) and respiratory tract infections (35.3%, p < 0.05). On the other hand, it was significantly low in bacteremias (9.28%, p < 0.001), wound infections (13.6%, p < 0.05) and urinary tract infections (3.33%, p < 0.05). (3) MRSAs were found more frequently in male (p < 0.05), younger patients (p < 0.05) and patients with malignant disease (p < 0.10). Whereas no difference was recognized between patients with or without complication. (4) The isolation rate of MRSA by the kind of antibiotics used after surgery, was 0% (0/20, the 1st generation cephems), 17.2% (10/58, the 2nd generation cephems) and 54.5% (48/88, the 3rd generation cephems). Significant differences were found among each group (p < 0.05, p < 0.001). (5) During 1990-1991 when the 1st generation cephems were used frequently, MRSAs were found significantly lower in frequency than during 1987-1989 (p < 0.05). Especially a marked decrease in the rate of MRSA (51.4% to 8.33%, p < 0.05) was seen among patients after upper gastrointestinal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Disseminated pancreatic polypeptidioma.

Pancreatic polypeptidioma, a pancreatic endocrine tumor, is an extremely uncommon disease and its clinical features and responses to therapy are not well known. We present a 33-year-old woman with disseminated pancreatic polypeptidioma, who subsequently showed various signs and symptoms of metastases, including bone pain, cranial nerve palsy, spinal block, and hematuria, and died 22 months after the presentation. Responses to various therapeutic regimens including hepatic arterial embolization, radiation therapy, systemic chemotherapy, and administration of interferon-alpha or somatostatin analogue, are discussed. Particular note in this case is a prompt response of bone metastases to the radiotherapy.

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

[Problems of randomized controlled study on surgical adjuvant chemotherapy for colorectal cancer in Japan].

There were many clinical trials to evaluate the significance of surgical adjuvant chemotherapy for colorectal cancer, but large-scale randomized controlled study was limited in Japan. From results of these trials, the effectiveness of adjuvant chemotherapy for colorectal cancer remained controversial. In this paper, I described the outline and summarized results of recent randomized controlled study carried out by Japan Cancer Chemotherapy Study Group for Colorectal Carcinoma and discussed various problems (case registration, ineligible cases, statistical method, follow up) of this study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[A study on drinking and problem drinking in tuberculosis patients].

Drinking and problem drinking were studied in 43 tuberculosis patients with the following results. The results of the KAST (Kurihama Alcoholism Screening Test) revealed that 10% of the patients were severe problem drinkers (diagnosed as alcohol dependent syndrome), 7% of the patients had drinking problems and 17% were potential problem drinkers. These percentages are higher than those of the general adult population. In the cases having higher KAST scores, the time between the onset of subjective symptoms and the first medical examination were long, but the time between the first medical examination and diagnosed tuberculosis was short. Severe tuberculosis patients showed higher KAST scores. It was assumed that tuberculosis patients who drink too heavily or are problem drinkers, were apt to put off consulting a physician, and as a result, the condition of tuberculosis would be more severe when they finally did see a physician. In the field of tuberculosis prevention and medical treatment, professionals should pay more attention to drinking and alcoholism. The need to stay sober is important in both preventing relapses and supporting recovery from tuberculosis.

Adult↗
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

Pharmacokinetic analysis of antibody localization in human colon cancer: comparison with immunoscintigraphy.

The biodistribution and imaging characteristics of the 111In-labeled anti CEA monoclonal antibody ZCE-025 were studied in five patients with suspicion of colorectal carcinoma. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimen, making a comparison with whole-body imaging with a gamma camera. ZCE-025 localization in tumors was demonstrated by gamma-camera imaging in 4 of the 5 patients, corresponding to surgical findings. Persistent accumulation of 111In in the lymph nodes was observed in one patient, whereas surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon carcinoma. Analysis of individual plasma by size exclusion HPLC showed two radioactivity peaks, labeled antibody and free DTPA. No transchelation of 111In to circulating transferrin was observed. The blood clearance was fitted to a two-compartment equation and its half-lives were found to be 10.8 +/- 8.7 h and 69.5 +/- 21.8 h for t1/2 alpha and t1/2 beta, respectively. Total urinary excretion averaged 0.3% of the injected dose/h with a small patient to patient variation. At 24 hrs postadministration the predominant radiolabeled species in urine was free DTPA. Thereafter, radioactivity in urine was partly present as a low molecular weight catabolic product. No apparent correlation between CEA content and uptake of 111In-ZCE-025 in tumors resected by surgery could be found. How 111In-labeled antibody is accumulated into tumors as well as into some nontumor tissues needs further study.

Aged↗
PubMed1992

High human IgG levels in severe combined immunodeficient mouse reconstituted with human splenic tissues from patients with gastric cancer.

We implanted normal peripheral blood lymphocytes (PBL) from healthy donors and splenic tissues from patients with gastric cancers into the severe combined immunodeficient (SCID) mouse, demonstrating that SCID mouse with splenic tissue can produce a high level of human immunoglobulin G (IgG). The normal PBLs at 10(7) and 10(8)/mouse were implanted intraperitoneally, and three splenic tissues with a size of 3 x 3 x 3 mm from gastric cancer patients were inoculated subcutaneously into the bilateral backs of the mice. At 2, 4, 6 and 8 weeks after inoculation, mice were killed, and the human IgG was assessed by an ELISA method. SCID mice with splenic tissue revealed high human IgG levels from 2 weeks after inoculation and approximately 2 mg of IgG per ml was observed at 8 weeks post-implantation, while the IgG levels in mice treated with PBLs were limited. Since the half life of the extrinsic human IgG was 10.2 days, the high level of human IgG in the SCID mice was supposed to be produced by human plasma cells in the splenic tissue from gastric cancer patients. This model was thought to be adequate for evaluating human immunological functions in vivo.

Animals↗
PubMed1992

[Investigation on central venous catheter related sepsis].

We made an investigation on central venous catheter related sepsis (CRS) in recent 5 years (1987-1991). The incidence of CRS was high; 16.0% (125 out of 782 cases) or 13.1% (135 out of 1029 catheters). CRS occurred frequently during 2-3 weeks after catheter insertion. The incidence of CRS was not affected by the kind of disease (malignant or benign), complication (diabetes, liver cirrhosis, collagen disease) operation or administration of antibiotics. Eight percent out of 91 organisms isolated from culture of catheter tips were so-called resistant strains; multi-drug resistant Staphylococci (16), Pseudomonas aeruginosa (5), fungi (49), etc. Complications (shock, acute renal failure, secondary pneumonia, fungal endophthalmitis) broken out in 18 patients (14.4% out of 125 CRS). Fungi were isolated from 14 out of 18 complicated cases, furthermore fungi were isolated alone in 11 cases. No complication were seen among cases from which gram positive cocci were isolated alone. Body temperature and white blood cell count of complicated cases were significantly higher than those of uncomplicated cases. The duration until removal of catheter from outbreak of fever in complicated cases was significantly longer than that in uncomplicated cases.

Candida↗
PubMed1991

Clinical usefulness of chemosensitivity testing using the MTT assay.

The results of in vitro chemosensitivity testing using the MTT assay of tumor cells from 140 patients were analyzed with reference to the clinical antitumor effects of the chemotherapy. One hundred and twenty-four (88.6%) of 140 specimens were successfully tested by the method of Mosmann (J Immunol Methods 65:55-63, 1983) with some modifications. When the results of the assay were compared with the clinical effects of chemotherapy in 22 patients with remaining measurable tumor lesions, the overall prediction rate was 86.4% (19/22). Among 31 patients with stage III-V gastric and colorectal carcinomas without remaining measurable tumor lesions, the survival rate of nine patients treated with drugs shown to be effective in the assay was significantly (P less than 0.05) better than that of 22 patients treated with drugs shown to be ineffective.

Adult↗
PubMed1991

Antitumor activity of fluoropyrimidines and thymidylate synthetase inhibition.

Experimental chemotherapy with 5-fluorouracil (5-FU; 60 mg/kg), 1-hexylcarbamoyl-5-fluorouracil (HCFU; 70 mg/kg), 3-(3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)benzoyl)-1-ethoxym ethyl-5- fluorouracil (BOF-A2; 30 mg/kg) and UFT (20 mg/kg as tegafur with uracil at a molar ratio of 1:4) was performed using human gastric (H-111) and colon (Co-4) carcinoma strains in nude mice. 5-FU was administered ip with a q4d x 3 schedule and the other agents were given po daily for three weeks. Concentrations of 5-FU in the serum and the tumor were assessed by gas chromatography-mass fragmentography, two hours or 12 days (5-FU) after the last treatment, and thymidylate synthetase (TS) was assayed according to the method of Spears et al. using the same schedule. The antitumor activity of the agents was assessed in terms of the actual tumor weight at the end of the experiment. HCFU was effective against both strains and 5-FU was effective against Co-4, although the other agents were ineffective against either strain. Statistically significant correlations were found between the serum and tumor concentrations of 5-FU and antitumor activity. Statistically significant correlations were also observed between the antitumor activity and TS inhibition rate (TSIR) and the activity of free thymidylate synthetase (TSfree), with higher TSIR and lower TSfree resulting in higher antitumor activity. Therefore, TSIR and TSfree were thought to be promising indicators for predicting the antitumor activity of fluoropyrimidines.

Adenocarcinoma↗
PubMed1991

[Immunoscintigraphy of colorectal cancer with 111In labeled anti-CEA monoclonal antibody (ZCE-025)].

Clinical trials with 111In labeled anti-CEA monoclonal antibody (ZCE-025) was initiated. Five patients with colorectal cancer suspected were given an intravenous injection of 1 mg of 111In labeled ZCE-025. Planar and SPECT images were obtained 24 and 72 hours after injection. Surgical operation was performed on all patients between 7 and 10 days post injection. Of 4 primary sites, all were clearly visualized. Intrahepatic metastasis was visualized as higher activity than normal liver in one of two patients. In one patient whose imaging was negative, no residual cancer was found at surgery. Persistent accumulation of 111In in the lymph nodes was also observed in one patient. Surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon cancer. No side effects were encountered, although HAMA were detected in all 5 patients by 4 weeks after the administration of ZCE-025. Immunoscintigraphy appears useful in distinguishing recurrent tumor from postoperative granuloma. Further investigation directed to the causes of 111In accumulation in tumor-free lymph nodes is required.

Aged↗
PubMed1991

[Establishment of transplantable human colon cancer cell lines, chemosensitivity of colon carcinomas and the serially transplantable strains with MTT assay].

Three human colon carcinoma xenografts serially transplantable into nude mice were established and named Co-6, Co-7, and Co-8. The chemosensitivity of these stains were assessed by MTT assay of the fresh surgical specimens (primary MTT assay) and the serially passaged xenografts (xenografts MTT assay), in vivo chemosensitivity test in nude mice (nude mouse system) and clinical responses. Drugs used for the experiments are mitomycin C (MMC), adriamycin (ADM), 5-fluorouracil (5-FU) and cisplatin (DDP). The primary MTT assay revealed true negative with MMC and 5-FU on Co-7 and Co-8 cases. The chemosensitivity of the tumor cells seemed to be increased in the xenografts MTT assay and nude mouse system, in which MMC and DDP were evaluated to be positive on Co-6 and Co-7. However, the chemosensitivity pattern of the tumor cells seemed to be stable in these chemosensitivity tests, indicating better to choose the agent with the highest inhibition rate among various tested agents, even when none have an inhibition rate equal to or more than 50%.

Animals↗