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T Shimomatsuya

Publications and source records attributed to T Shimomatsuya.

28 records · Page 2Linked to original sources

[In vitro chemosensitivity assay using a double-layer-agar system: human tumor cloning assay and thymidine incorporation assay].

Human tumor cloning assay (HTCA) and thymidine incorporation assay (TIA) were both performed using a double-layer-agar system with continuous exposure of cells to standard anticancer drugs. The rate of evaluable assays was 44% (280 of 638 tumor samples) in HTCA and 48% (216 of 452) in TIA. When the tumor samples were restricted to the gastric and colorectal cancers, it was significantly higher in TIA than HTCA (p < 0.01). HTCA was 95% reliable for predicting in vivo resistance and 52% reliable for in vivo sensitivity, whereas TIA was 88% reliable for in vivo resistance and 44% for in vivo sensitivity. These results seem to suggest that it is unnecessary to select just clonogenic tumor cells among whole tumor cell population in assessing chemosensitivity of human tumors. The current study also indicates that chemotherapy with in vitro sensitive drugs assessed by TIA produced longer survival of the patients with stage III or IV gastric cancer. Most of clinical correlation trials including this study, however, have been performed retrospectively. The prospective study is necessary to determine whether drug selection by in vitro assays is superior to that by an experienced oncologist. In addition, further studies on pharmacokinetics of anticancer drugs are required to solve some other problems inherent to the current chemosensitivity assays.

Antineoplastic Agents↗

In vitro growth ability and chemosensitivity of gastric and colorectal cancer cells assessed with the human tumour clonogenic assay and the thymidine incorporation assay.

A human tumour cloning assay (HTCA) has been performed on 191 samples of gastric and 152 samples of colorectal cancers, and a thymidine incorporation assay (TIA) on 178 samples of gastric and 109 samples of colorectal cancers. The rate of evaluable assays was significantly higher in the TIA than in the HTCA (P less than 0.01). In terms of in vitro growth potential in the two assays, gastric cancer cells were less active than the colorectal cancer cells (P less than 0.05). In frequency of in vitro sensitivity to drugs, gastric cancer was more chemosensitive than colorectal cancer in both assays. The in vitro/in vivo correlations of high resistance-predictive ratios and low sensitivity-predictive ratios were similar in both assays. The results indicate that the TIA is more applicable than the HTCA to screening of active agents against fresh gastrointestinal cancers.

Colorectal Neoplasms↗

Proliferative activity of human tumors: assessment using bromodeoxyuridine and flow cytometry.

Cell kinetics of human carcinoma xenografts and human solid tumors were evaluated by means of two-color flow cytometry using single sampling at appropriate time intervals after bromodeoxyuridine (BrdU) labeling. The tumors were resected several hours after the administration of BrdU, and flow cytometry was used to measure the DNA content and BrdU incorporation. Once the BrdU labeling index (LI) and DNA synthesis time (Ts) were obtained, the potential doubling time (Tpot) was calculated from these values. In 11 xenografts, the cell kinetic data were compared with the actual tumor doubling time (Td), and a good correlation between Tpot and Td was obtained (r = 0.91, P less than 0.005). In a clinical study, 33 patients with gastric cancer, colorectal cancer, lung cancer, or other solid tumors were analyzed. Aneuploid tumors had a significantly higher LI value (P less than 0.01) and a shorter Tpot than diploid tumors. The cell loss rate of human tumors ranged from 40% to 80%. These cell kinetic parameters therefore accurately indicated the level of proliferative activity of human tumors.

Animals↗

[Etiological consideration of neonatal gastric rupture: assumption of possible association with gastric volvulus and gastroesophageal reflux].

Spontaneous gastric rupture of the newborn infant can be lethal. While the etiology of this problem is unknown, pneumatic rupture of the stomach seems the most logical explanation. The rupture mostly occurs in the anterior wall of the fundus near or on the greater curvature with in the first seven days of life. Three such patients have been managed during the past 5 years. These patients are presented in detail. X-ray films of those 3 patients, of a case of gastroesophageal reflux, and of some reported cases of impending gastric rupture are also presented in an effort to better understand the pathogenesis of this gastric catastrophe. (1) Clinical findings of a double air fluid level in the upper stomach at the upright position found in one case and of the direction of advancement of the nasogastric tube enable us to consider the gastric organoaxial volvulus as an etiological factor. (2) Plain x-ray and barium study films of the case of gastroesophageal reflux and of the reported cases of impending gastric rupture also suggest some degree of gastric volvulus as the cause of corresponding diseases. (3) Fluid accumulation in the fundus is facilitated by gastric organoaxial rotation and the fluid-filled fundus acts as a barrier to prevent eructation. Retention of feeds occurs as a result of air accumulating at the pyloric end. In such situation of a fluid trap syndrome, tremendous intragastric pressures enough to cause rupture may result when vomiting occurs.

Female↗

[Experimental study of hemodynamic changes following superior mesenteric arterial injection of various contrast media].

Following the superior mesenteric arterial injection of three contrast media, [38% Meg/Na Amidotrizoate, 76% Meg/Na Amidotrizoate, Iopamidol (370 mg l/ml)], and isotonic saline, we measured and analyzed the changes of superior mesenteric arterial blood flow rate for 10 minutes continuously in 6 dogs by means of electromagnetic flow meter. Blood volume change of superior mesenteric arterial blood flow was calculated by integration of blood flow. After injection of the agents, superior mesenteric arterial flow increased and returned to control level. The duration was influenced by the agent's osmolality. Therefore, volume change was analyzed because it is concurrent index of flow and duration. Correlation between volume change (increase) of superior mesenteric arterial blood flow and the agent's osmolality was shown. (r = 0.985, p less than 0.01). Increased blood volume of local arterial blood flow appears to be a desirable index for estimating vasodilatory effect of contrast media.

Animals↗

[An in vitro drug screening assay, scintillation assay, and its clinical application].

We have developed an in vitro drug screening test by scintillation assay with which we can assess the chemosensitivity of solid human tumors during the 5 days following tumor resection. We are able to evaluate 62% (271/439) of the human tumors' chemosensitivity results. Seventy-seven of these cases were examined for in vitro-in vivo correlations. In 14 of 33 in vitro sensitivity cases (42%) we found clinical responses. And, in 41 of 44 in vitro resistance cases (95%) we found progressive disease. These in vitro-in vivo correlations with the scintillation assay were similar to those in other reports with different types of chemosensitivity assay. The true-positive accuracy of these tests averaged 50%, while the true-negative accuracy averaged 90%. We think that tumor cell heterogeneity is one of the main reasons for low true positive accuracy in the drug screening assays. In some studies we implanted human tumors into nude mice. The resulting xenografts demonstrated that fresh human tumors are composed of heterogeneous subpopulations of cells with varying chemosensitivities and varying DNA indexes. This heterogeneic nature of human tumor cells means that a single biopsy specimen may not comprehensively define the chemosensitivity of a patient disease.

Drug Screening Assays, Antitumor↗

Treatment of cystic hygroma and lymphangioma with the use of bleomycin fat emulsion.

Of the several types of treatment for cystic hygromas and lymphangiomas, surgical excision has been the preferred treatment. However, there is a high recurrence rate because lymphangiomas tend to infiltrate the surrounding tissues. Bleomycin in a microsphere-in-oil (S/O) emulsion was used in this study as a sclerosing agent for lymphangiomas. Experimental studies using domestic rabbits showed that the bleomycin emulsion caused more marked fibrotic changes at the injection site than other formulations, such as a blank emulsion and bleomycin solution. In clinical trials, 27 of 33 patients received bleomycin S/O emulsion injected directly into the tumors with satisfactory results. Histologic pictures of the clinically resected specimens confirmed the findings of the experimental studies. Comparative studies of treatments between bleomycin S/O emulsion and surgery indicated that injection therapy of bleomycin S/O emulsion would be more beneficial than surgical excisions.

Animals↗

Detection of P-glycoprotein in solid tumors by flow cytometry.

P-glycoprotein (P-gp) detection by FCM (flow cytometry) was correlated with P-gp detection by immunohistochemical staining or Western blotting in K562 cell lines variably resistant to doxorubicin (DOX). A strong correlation was noted between the flow cytometric data and the degree of resistance assessed by thymidine incorporation assay (TIA). Of the human carcinomas tested, 37.5% were P-gp positive by flow cytometry. The flow cytometry data correlated strongly with the immunohistochemical staining (p < 0.001). Thirteen of the 15 P-gp positive tumors were resistant to DOX and vincristine (VCR) on TIA. Thus, P-gp detection by FCM correlates strongly with tumor sensitivity to DOX and VCR (p < 0.001).

ATP Binding Cassette Transporter, Subfamily B, Mem↗