Biomedical subjects

T Tobe

Publications and source records attributed to T Tobe.

589 records · Page 33Linked to original sources

PubMedDate not supplied

Glucose intolerance and hyperplasia of islet D-cells after partial hepatectomy in dogs.

Soon after about 40% hepatectomy in dogs, the peripheral blood showed hyperglycemia, similar to that in diabetes, and impaired insulin response in the intravenous glucose tolerance test (IVGTT). Histologically, at this stage, the number of islet D-cells was increased, but there was no rise in portal somatostatin. Thus, in this glucose intolerance after hepatectomy, somatostatin seems to play an important role as a paracrine hormone by inhibiting the secretion of insulin by islet B-cells in the pancreas itself.

Animals↗

PubMedDate not supplied

Effect of surgical stress on glucose-stimulated insulin release from isolated perfused rat pancreas.

To investigate the effect of surgical stress on the endocrine pancreas, we evaluated the changes in glucose-stimulated insulin release from the isolated perfused pancreas 4 and 7 days after laparotomy. Four days after laparotomy, insulin response to a glucose load was poor, and integrated insulin release was significantly less in the first and third phase of stimulation than in the normal rats. At 7 days, however, insulin response to a glucose load was augmented, and the integrated insulin release was significantly increased in all the phases of stimulation. These results indicate that in the early phase after surgical stress there is an impaired insulin response to a glucose load and that in the recovery stage after surgery, there is an augmented insulin response to a glucose load.

Animals↗

PubMedDate not supplied

Splenectomy abolishes antitumor effect of immunotherapy with streptococcal preparation, OK-432, on mouse liver tumors.

In the present study, we investigated the therapeutic effects of oral and subcutaneous administration of OK-432 prior to or following the transplantation of murine liver tumors. In addition, the effect of splenectomy on the antitumor activity of OK-432 was investigated. Mice which received OK-432 orally prior to tumor transplantation exhibited significantly lower tumor weight and significantly improved survival, when compared to the control mice. Prior subcutaneous injection of OK-432 did not show any antitumor activity. On the other hand, both oral and subcutaneous administration of OK-432, subsequent to tumor transplantation, led to a significant improvement of survival and a decrease in the number of lung metastases, although tumor weight was not affected. The anti-tumor effect of OK-432 required the presence of the spleen, since the survival of the mice with liver tumors was not improved by OK-432 if splenectomy and tumor transplantation were performed simultaneously. These results suggest that immunotherapy with OK-432 may beneficial in the treatment of liver tumors and that these effects are dependent on the presence of the spleen.

Animals↗

PubMedDate not supplied

Relationship of in vivo antitumor activities of fluorinated pyrimidines to thymidylate synthase activity and intratumoral concentrations of 5-fluorouracil and uracil.

MOPC-104E plasmacytomas were subcutaneously transplanted into BALB/c mice and after 7 days the mice were administered different fluorinated pyrimidines at 4 times the clinical doses, 5-fluorouracil (5-FU, 15 mg/kg), tegafur (FT, 100 mg/kg) or UFT (FT, 20 mg/kg + uracil, 44.8 mg/kg) daily for 7 days. Tumor growth was most effectively inhibited in the UFT group. The % inhibition of tumor growth on day 14, while not correlating with the concentration of 5-FU in the tumor, negatively correlated with the concentration of uracil, which was lowest in the UFT group. The activity of thymidylate synthase (TS) was measured using a 5-fluoro-deoxyuridine monophosphate (FdUMP) binding assay. The total and free TS activities in the tumor negatively correlated with the % inhibition of tumor growth, and were lowest in the UFT group. However, the % inhibition of TS activity in the tumor, which was about 80% in all 3 groups, did not correlate with the tumor-inhibitory effect. These results suggest that uracil in the tumor may play an important role in the metabolism of fluorinated pyrimidines, and that exogeneously administered uracil may decrease the amounts of uracil and TS in the tumor, and subsequently cause 5-FU accumulation.

Animals↗

PubMedDate not supplied

In vivo inhibitory effect of anticancer agents on human pancreatic cancer xenografts transplanted in nude mice.

Pancreatic cancer is one of the neoplasms resistant to chemotherapy. In the present study human pancreatic cancer xenografts (3 adenocarcinomas and 1 cystoadenocarcinoma) were subcutaneously transplanted in nude mice and after the tumors grew to 100-300 mm3, the mice were intraperitoneally administered with mitomycin C (MMC), adriamycin (ADR), 5-fluorouracil (5-FU), carboquone (CQ), cisplatinum (CDDP), nimustine chloride (ACNU) or DWA2114R at 1/3 LD50 on days 0.4, and 8. The tumor sizes on day 12 were compared with those on day 0. MMC and CQ significantly inhibited the tumor growth of 3 lines, and ACNU, CDDP and ADR inhibited the growth of 1 line. Further, 5-FU, futrafur, carmofur, UFT and L-phenylalanine mustard (L-PAM) were orally administered to mice into which 1 adenocarcinoma line had been transplanted. While none of fluoropyrimidines inhibited tumor growth, L-PAM at 4 mg/kg significantly inhibited growth, although it was accompanied by severe body weight loss. In the present study several agents significantly inhibited tumor growth, but none of them could induce the regression of the tumor when used singly. These results suggest that CQ, ACNU, CDDP and L-PAM may be applied to the chemotherapy of pancreatic cancer. However, the effect of a single agent is restricted and the development of new combination treatments is urgently required.

Adenocarcinoma↗

PubMedDate not supplied

In vitro and in vivo antineoplastic activity of a new platinum antineoplastic agent, (R)-(-)-1,1-cyclobutanedicarboxylate (2-aminomethylpyrrolidine)-platinum (II) (DWA2114R) on freshly separated human tumor cells and human tumor xenografts transplanted in nude mice--a comparison with cis-diammine-dichloroplatinum (CDDP).

The in vitro antimetabolic effect of a newly synthesized platinum antineoplastic agent, DWA2114R, on 72 fresh human tumors was compared with that of cis-platinum (CDDP). DWA2114R is reported to have a lower nephrotoxicity than CDDP, but is as strong an inhibitor of DNA synthesis as CDDP. In vitro IC50 was assessed in 10 tumors; the IC50 of DWA2114R ranged between 9.2 and 107 microM (mean +/- S.D., 45.9 +/- 36.6) and that of CDDP ranged between 0.9 and 40 microM (18.3 +/- 15.1). DWA2114R had an antitumor spectrum similar to that of CDDP. Primary esophageal and pancreatic cancers were sensitive to DWA2114R, and cells separated from malignant effusion or metastatic lymph nodes were more sensitive than those from primary lesions. Nude mice were transplanted with 3 kinds of human tumor xenografts (esophageal, pancreatic and bile duct cancer lines), and were then treated with CDDP or DWA2114R at 4 times the clinical doses. CDDP significantly inhibited the growth of all the 3 lines, and DWA2114R inhibited the growth of 2 of the lines. The effect of DWA2114R on body weight was smaller than that of CDDP. These results suggest that DWA2114R may be less potent than CDDP but may be useful as a new platinum antineoplastic agent with lower grade of side effects than CDDP.

Adenocarcinoma↗

PubMedDate not supplied

Binding and internalization of human immunoglobulin G conjugated with melphalan (K18) to human tumor cell lines.

The binding and internalization of melphalan-conjugated human immunoglobulin G (K18) to human tumor cell lines were studied using 14C-K18 (IgG conjugated with 14C-melphalan) and were compared with those of 14C-melphalan. K18 and melphalan dose-dependently bound to tumor cells, and the saturation binding analysis revealed a receptor-mediated binding of K18 but not of melphalan, to tumor cells. Intracellular distribution of 14C-K18 differed from that of 14C-melphalan, but a DNA unwinding experiment using a hydroxylapatite column showed that 14C-melphalan or 14C-K18 bound to DNA. These results suggest that after being bound to receptors K18 may be internalized in a macromolecular form and degraded into peptide binding melphalan. Moreover, the quantity of K18 that bound to 7 different human tumor cell lines was significantly larger than those that bound to lymphocytes of normal donors. These results suggest that K18 may be beneficial for cancer chemotherapy.

Antineoplastic Agents↗

PubMedDate not supplied

The inhibitory effect of a conjugate of human immunoglobulin G and melphalan, K18, on DNA synthesis of human tumor cells.

K18 is a conjugate of human immunoglobulin G and melphalan and has been reported to accumulate selectively in the tumor. In the present study, the in vitro antitumor effect of K18 was assessed in a total of 107 fresh human tumors by DNA synthesis (3H-thymidine incorporation) inhibition assay, and compared with that of other drugs. Human tumor cells showed a variety of sensitivities to K18: gastric, breast, pancreatic, liver or ovarian cancer cells were comparatively sensitive to K18, while esophageal or colorectal cancers were insensitive. These results suggest that the conjugation of melphalan with IgG did not reduce the antitumor activity of melphalaln and that K18 may be applied in cancer chemotherapy instead of melphalan.

DNA, Neoplasm↗

PubMedDate not supplied

Selective accumulation of a new antineoplastic agent, K-18 (human immunoglobulin conjugated melphalan), in Ehrlich carcinoma transplanted in mice.

The absorption of K-18 (human IgG conjugated melphalan) through the intestine and its selective accumulation in the tumor were studied. After oral administration of 14C-melphalan and 14C-K-18 to ICR mice with subcutaneously transplanted Ehrlich carcinoma, K-18 was detected at the tumor site by autoradiogram after 48 hrs, but melphalan was not. Immunofluorescence study showed that orally administered K-18 was absorbed from the intestine via both the portal and the lymphatic route. Moreover, immunoperoxidase staining revealed K-18 in cytoplasm of tumor cells, but not in bone marrow cells. These results demonstrate the absorption of K-18 from the intestine after oral administration and its selective affinity for tumor tissue.

Animals↗

PubMedDate not supplied

Antitumor activity of orally administered streptococcal preparation, OK-432 on murine solid tumors and its absorption from the gut.

OK-432 is an immunopotentiator which is normally administered by injection. In the present study, the antitumor activity of orally administered OK-432 on various solid tumors and the absorption of OK-432 from the gut were studied. Orally administered OK-432 inhibited the growth of Meth-A and BAMC-1 fibrosarcomas which had been subcutaneously transplanted in BALB/c mice. Autoradiograms of mice which had been administered 14C-labelled OK-432 orally demonstrated the absorption of OK-432 from the gut, and about 6% of orally administered OK-432 was absorbed 24 hrs after its administration. Moreover, an immunofluorescent study using an anti-OK-432 antibody revealed specific fluorescence in the mesenteric lymph node of mice which had been orally administered with OK-432. These results suggest that oral administration of OK-432 may be a beneficial immunotherapy.

Administration, Oral↗

PubMedDate not supplied

In vivo inhibitory effect of a conjugate of immunoglobulin G and melphalan, K18, on human tumors transplanted in nude mice.

Various human tumor lines, including gastric, colonic, esophageal, pancreatic, lung and breast cancer, were transplanted in nude mice, and the effect of K18 (IgG conjugated melphalan) on them was assessed and compared with that of melphalan. Melphalan (1 mg/kg) or K18 (100 mg/kg) were administered to mice for 28 days. The tumor growth was significantly inhibited in 5 out of 6 tumors by both agents, although only the esophageal line was insensitive to both agents. Significant loss of body weight was observed in mice after treatment. K18 had no influence on body weight. These results suggested that K18 may be useful in cancer chemotherapy.

Animals↗

PubMedDate not supplied

Postoperative radiation therapy for esophageal cancer.

The value of postoperative radiation therapy (RT) was investigated in 77 patients with esophageal cancer resected between 1977 and 1986. Surgical resection was palliative in 13 of these patients. Although seven of them underwent postoperative irradiation to the residual tumor, all of the patients died within one year. Following potentially curative resection performed in 64 patients, 31 patients received 50 Gy of postoperative RT to the lower neck and the mediastinum (group Ia), seven were unable to receive full-dose postoperative RT (group Ib), and 26 were not treated with postoperative RT (group II). The 5-year survival rate estimated by the Kaplan-Meier method was 54% for group Ia, 29% for group Ib, and 33% for group II, with the difference between groups Ia and II being significant (p less than 0.025). The local recurrence rate in the mediastinum was lower in group Ia than in group II. Prophylactic postoperative RT for esophageal cancer is a safe and effective regimen for patients with resected disease.

Adult↗

PubMedDate not supplied

Combined treatment using radiotherapy for carcinoma of the pancreas involving the adjacent vessels.

The prognosis of pancreatic duct carcinoma is determined mainly by the degree of local invasion, particularly of the portal system and/or associated arteries supplying the carcinoma. Intraoperative (25-36.5 Gy of betatron) and/or external (14.4-25.6 Gy, preoperatively, and 24-61.2 Gy, postoperatively, using lineac photon beams) radiotherapy was combined with pancreatectomy or by-pass surgery for patients with pancreatic carcinoma involving the surrounding vessels but with no distant metastases. Twelve- and 24-month survival rates were 25.9% and 3.2%, respectively, in patients with pancreatectomy (n = 35) and 6.4% and 0%, respectively, in patients with by-pass operations (n = 32). However, in patients with combined surgery and radiotherapy the prognosis was markedly improved to 12- and 24-month survival rates of 33.5% and 20.1%, respectively, for patients with pancreatectomy (n = 13) and rates of 25% and 13%, respectively, for patients with by-pass operations (n = 8). Moreover, radiotherapy produced a significant advantage for local control of pain in patients with unresectable pancreatic carcinoma. This suggests that combined treatment using radiotherapy will be a valuable therapeutic improvement for patients presenting advanced pancreatic carcinoma with vessel involvement.

Carcinoma, Intraductal, Noninfiltrating↗