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Biomedical subjects

T Todoroki

Publications and source records attributed to T Todoroki.

At least 73 records · Page 4Linked to original sources

Selection of three out of 24 anti-cancer agents in poorly-differentiated gastric cancer cell lines, evaluated by the AUC/delta IC50 ratio.

The purpose of this study was to screen 24 anti-cancer drugs, either in use or in clinical study, using four cell lines, all of which originated from poorly-differentiated gastric cancers. The MTT assay was used at 1, 6, 24 or 72 h exposure times as the chemosensitivity test. We also examined P-glycoprotein expression, mdr-1 gene amplification and the modifier effect of verapamil. All four cell lines generally showed the same chemosensitivity pattern, while GCIY cells showed mdr-1 gene amplification and P-glycoprotein expression, and KATOIII cells showed the multidrug resistant pattern without P-glycoprotein expression. Both cell lines acquired higher chemosensitivity after verapamil addition. All IC50 data (with or without verapamil) were multiplied by exposure time (delta IC50) and compared with the clinical 'area under the concentration curve (AUC)'. SN-38 with/without verapamil, cisplatin with verapamil and pirarubicin with/without verapamil seemed to be the best candidates for poorly-differentiated gastric cancer chemotherapy. Plant alkaloids could also be candidates. With further experiments, we may be able to deduce commonly effective chemotherapy for poorly-differentiated gastric cancer from these drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Intra-arterial 5-FU/intra-venous MTX therapy for metastatic liver lesions].

We have performed intra-arterial 5-fluorouracil (5-FU)/intra-venous methotrexate (MTX) therapy for 4 patients with multiple metastatic liver tumors at out-patient clinic. Primary lesions were of the stomach (one patient, synchronous) and colon (3 patients, two were synchronous and one was metachronous). 5-FU (250-350 mg/day) was continuously infused for two weeks into the hepatic artery through the reservoir using the Baxter Infuser (multi-day type). MTX (100 mg/m2) was infused into the peripheral vein on days 1, 8 and 15. Leucovorin calcium (15 mg) was orally administered three times after MTX infusion. All patients partially responded, and no remarkable side effect was detected. We propose that this new combination therapy, that is intra-arterial 5-FU and intra-venous MTX for metastatic liver cancer, can be useful and safe even for out-patients.

Administration, Oral↗

[Whole abdominal irradiation for peritoneal dissemination of alimentary tract cancers].

Between January 1986 and August 1991, 19 patients with alimentary tract cancers complicated by peritoneal dissemination received whole abdominal irradiation combined with intraperitoneal chemotherapy postoperatively. Using a moving-strip technique of irradiation, 12.0 Gy was delivered in three fractions to the entire abdominal contents with partial liver and kidney shielding. The primary tumor sites were the stomach in 12 patients, the colorectum in five, and the gall bladder in two. Nine patients with gross residual disease also received a limited field boost of 30.6 Gy in 17 fractions after completion of treatment to the whole abdomen. None of the patients failed to complete the planned dose despite acute gastrointestinal toxicity (nausea and vomiting, 84%, diarrhea and cramping, 78%) and acute hematologic toxicity (leukocytopenia, 84%, thrombocytopenia, 68%). Our follow-up study revealed that the actuarial one-year survival rate was 28.4% and the median survival time was 9.0 months. Survival rates at one-year for patients with colorectal and gastric cancer were 75.0% and 16.7%, respectively. Patients with gastric cancer (n = 12) had a poorer outcome than those with colorectal cancer (n = 5) in the present study. One reason for this difference may have been the presence of cancerous pleuritis, which was frequently observed in patients with gastric cancer. Therefore, more intensive treatment to prevent cancerous pleuritis seems to be necessary to improve the efficacy of whole abdominal irradiation.

Abdomen↗

[Immunohistochemical study of VLA integrins in human gastric carcinoma].

Using an immunohistochemical technique, we investigated expression of collagen receptor VLA-2 integrin and laminin receptor VLA-6 integrin in human gastric carcinoma. The expression of VLA integrins was compared in carcinoma of each histologic type and invasion/growth pattern. VLA-2 and VLA-6 were expressed more weakly in undifferentiated carcinoma than in non-cancerous epithelium. Non-localized invasion was observed in 89% of undifferentiated carcinoma. In differentiated carcinoma, expression of VLA-2 was weak in the mucosal layer. In the submucosal layer, however, VLA-2 expression was significantly different according to the invasion/growth pattern (p < 0.01); weak expression of VLA-2 in the localized invasion type and strong expression of VLA-2 in the non-localized type. VLA-6 was strongly expressed in the mucosal and submucosal layers of the differentiated carcinoma, regardless of the invasion/growth pattern. The present study suggested that VLA-6 contributed to the histologic type and VLA-2 affected the invasion/growth pattern of the gastric carcinoma in varied manners according to the histologic type.

Carcinoma↗

Dependence of the thymidylate synthase inhibition rate on the interval after the last administration of tegafur in sigmoid colon cancer patients.

The thymidylate synthase (TS) inhibition rate was measured after tegafur (FT) administration (1.5 g/day, at least 10 days) in 7 sigmoid colon cancer patients. The TS inhibition rate decreased as the interval between the time of the last administration and the time of the tumor resection increased longer. This study provides basic data for considering methods of drug administration and assessment of modification, for example, by leucovorin.

Adenocarcinoma↗

Cell proliferation kinetics of the bile duct epithelium of the rat.

Cell proliferation kinetics of the extrahepatic bile duct were studied by flash and cumulative labelling methods and immunohistochemical techniques. We compared the cell kinetics of the epithelium of the intra- and extra-pancreatic bile ducts and of the bile duct of the ampulla in rats administered intraperitoneally with bromodeoxyuridine (BrdUrd). After a single injection of BrdUrd (flash labelling), labelled cells appeared in the lower portion of the downgrowths of the epithelium in the intra- and extra-pancreatic bile ducts. A gradual accumulation of the labelled cells at the surface epithelium was observed during the cumulative labelling. After cumulative labelling the labelled cells gradually decreased in number and were finally confined to the degenerative cell zone of the surface epithelium 30 days later. Similarly, after a single injection of BrdUrd, the labelled cells in the bile duct of the ampulla appeared at the lower half of the crypt from where they migrated to the upper portion during cumulative labelling. These findings indicate that epithelial cells of the bile duct are renewed at the lower portion of the downgrowths of the epithelium, or crypt, and shed from the surface epithelium or upper portion of the fold. The labelling indices reached 23.83 +/- 7.47% in the intra-pancreatic bile duct, 14.74 +/- 7.99% in the extra-pancreatic bile duct and 43.42 +/- 4.40% in the bile duct of the ampulla at the end of 70 h cumulative labelling. The fluctuating values of the labelling index were higher in the bile duct of the ampulla than in the intra- or extra-pancreatic bile ducts. These results indicate that the bile-duct epithelium undergoes a slower renewal rate than the other parts of the gastrointestinal tract, and that the renewal time of the epithelial cells is shorter at the bile duct of the ampulla than at the intra- or extra-pancreatic bile ducts.

Animals↗

[Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) in carcinoma at the confluence of the main hepatic ducts and its relationship to expression of CEA, CA19-9 and EGF receptor].

The Distribution pattern and proportion of the positive cells of proliferating cell nuclear antigen (PCNA) were examined immunohistochemically to study the proliferative activities of 33 cases of carcinoma found at the confluence of the main hepatic ducts. Expressions of CEA, CA19-9 and EGF receptor (R) were further examined with serial histological sections and comparatively analyzed with the result of PCNA staining and the clinico-pathological features of the carcinoma. PCNA positive cancer cells were observed in greatest abundance at the deeply infiltrated region of the carcinoma. CEA and CA19-9 were also expressed most strongly in this region and a stromal staining pattern was predominant. However, negative or apical staining patterns of CEA and CA19-9 were more frequent in the surface or the lateral spreading regions of the carcinoma, where the PCNA positive cancer cells were fewer in number. EGFR expression was rarely observed in the present study.

Adenocarcinoma↗

Long-term survivors after salvage surgery combined with radiotherapy for recurrence of stage IV main hepatic duct cancer--report of two cases.

Main hepatic duct cancer is notorious for its poor prognosis and frequent locoregional failure of therapy even after curative resection. In this paper, two cases of recurrent carcinoma of the stage IVA main hepatic duct are presented. One patient had local failure 13 years after curative resection of the tumor and the other had regional failure 18 months after combination treatment with non-curative resection and intra-operative radiation therapy. Recurrent tumors were successfully treated with combined resection and postoperative radiation therapy or with combined intra-operative radiation therapy and postoperative radiation therapy. The patients are well 16.9 and 6.3 years, respectively, after primary tumor resection. We briefly review a number of other reports of salvage treatment in patients with recurrent carcinoma of the main hepatic ducts and discuss the results with particular reference to the advantage of salvage therapy for the main hepatic duct cancer.

Adenocarcinoma↗

Therapeutic gain of local and radical resection combined with postoperative radiation for murine fibrosarcomas.

Resection of 8-mm fibrosarcomas (FSaII) growing in the right leg of syngeneic C3H/Sed mice was performed under a dissecting (x8) microscope. Local and radical resection achieved 20% (5/25) and 48% (12/25) tumor control, respectively. TCD80s (average dose expected to control 80% of irradiated tumors) for radiation alone given as one fraction per day for 5 consecutive days were 73.1 and 118.0 Gy for the microscopic and 8-mm tumors, respectively. Radiation therapy started at 4 or 7 days following local or radical resection enhanced both the local tumor control and the treatment-related morbidity represented by leg shortening. From enhancement ratios (ERs) for tumor control (TCD80 for radiation alone/TCD80 for postoperative radiation) and for leg shortening (dose for 5-mm leg shortening for radiation alone/postoperative radiation) values, therapeutic gain factors (TGFs) were derived as ER tumor/ER leg shortening. These were 1.3 and 1.4 for local and radical resection followed by radiation started on the 7th postoperative day, respectively. Corresponding figures for radiation started on the 4th postoperative day resulted in 1.2 for both resection procedures.

Animals↗

[Effects of traditional Chinese medicines (dai-saiko-to, sho-saiko-to and hachimi-zio-gan) on spontaneously diabetic rat (WBN/Kob) with experimentally induced lipid and mineral disorders].

To clarify the therapeutic effects of several traditional Chinese medicines to improve disorders of carbohydrate, lipid and mineral metabolism, spontaneously diabetic rats (WBN/Kob) were treated with Vit. D2, 1 x 10(5) I.U./kg b.w./day, for 4 days, and then fed a hyperlipidemic diet containing traditional Chinese medicines for 6 weeks. The following results were obtained: 1) In the diabetic rats, the 3 traditional Chinese medicines further decreased the blood glucose level at 120 min after glucose loading in the glucose tolerance test. 2) The drugs increased the inorganic phosphate in the liver and normalized mineral metabolic disorder. 3) Hachimi-zio-gan decreased the cholesterol content in the kidney, and Sho-saiko-to decreased the cholesterol content in the elastin fraction (elastin-cholesterol) of the kidney. Such experimental results suggest that traditional Chinese medicines may be effective against the pathological conditions of diabetes mellitus that involve disorders of lipid and mineral metabolism.

Animals↗

Early extramedullary plasmacytoma confined to the lamina propria of the gastric mucosa: case report.

A case of early gastric plasmacytoma in a 51-year-old woman is reported. The demonstration of monotypic IgM-kappa immunoglobulin in biopsy specimens by an immunoperoxidase technique contributed to the histological diagnosis. The patient had non-ulcerative lesions (of approximately 15 x 16 cm) of a superficially spreading type of gastric plasmacytoma. Extensive histological analysis of the resected stomach showed the IgM-kappa monoclonal proliferation of plasmacytic tumor cells to infiltrate merely into the lamina propria of the gastric mucosa and not to extend deeply into the submucosa, proper muscle and serosa of the stomach.

Female↗

[Histopathological evaluation of the radiosensitizing effects of an intratumoral injection of BrdU for rectal cancer].

We delivered preoperative radiotherapy with intratumoral injection (ITI) of radiosensitizer, 5-bromodeoxyuridine for patients with locally advanced cancer originating in lower rectum. We identified immunohistochemically the tumor cells that incorporated BrdU, and evaluated the radiosensitizing effect of BrdU histopathologically. (1) BrdU-labeled nuclei of cancer cells were identified in twenty-three cases out of 24 (96%). Mean labeling index was 18.5%, and tended to decrease as time progressed. (2) The parameters representing volume of residual tumor nests (Tumor Nest Index) or degrees of tumor extension (Depth of Extramural Tumor and Depth of Extramural Fibrosis) for patients with ITI were compared to those for patients without ITI. Those parameters tended to decrease when ITI was combined with radiotherapy. However, the difference was not significant statistically. Intratumorally injected BrdU can incorporate with cancer cells, but a methodological invention is required for yielding clinically measurable radiosensitization.

Adenocarcinoma↗

[Computed tomographic evaluation of thickness of perirectal fascia in rectal cancer treated by preoperative radiotherapy--diagnostic value for prediction of local recurrence].

Perirectal fascia was examined by computed tomography before and after preoperative radiotherapy in thirty-six patients with rectal cancer. CT measurement showed that perirectal fascia tend to increase in thickness during preoperative radiotherapy in proportion to tumor extension into perirectal fat tissue. The fascial thickening more than 7 mm after preoperative radiotherapy was suggestive of local recurrence to develop. Preoperative or intraoperative boost irradiation would be recommended for such high-risk patients.

Adenocarcinoma↗

Comparative study of Vibrio cholerae non-O1 isolated from 2 rivers according to antibiotics and metals susceptibility.

Vibrio cholerae non-O1 was isolated at six locations on each of two different rivers in 1984 and 1985. A study of the strains isolated from these rivers according to antibiotic and metal susceptibility and the incidence of resistant strains produced the following results. 1) Tests to determine susceptibility to eight antibiotics (chloramphenicol, tetracycline, streptomycin, kanamycin, ampicillin, gentamicin, nalidixic acid and polymyxin-B) indicated that there was virtually no difference in the susceptibility of strains isolated from the two rivers. Of the 115 environmental strains, 81 (70.4%) showed resistance to one or more drugs. However, no strains were resistant to gentamicin. There was considerable variation in the concentration of susceptibility to polymyxin-B, and for this reason it was difficult to determine the resistance concentration. 2) 64.3% (74/115) of the strains isolated from the two rivers showed ampicillin resistance and produced beta-lactamase. 3) 67.9% (55/81) of all resistant strains were resistant only to ampicillin, while 16.0% (13/81) were resistant to ampicillin and nalidixic acid. The rate of resistance to these substances was higher than to the other drugs. 4) The incidence of resistant strains differed according to environmental conditions along the two rivers. These variations appear to reflect the influence of environmental conditions in the catchment areas. 5) There was no metallic contamination in either the Sagami River, which has good water quality, or the Sakai River, which is heavily polluted. This meant that there was no variation in the metal susceptibility of the isolated strains according to differences in the degree of water pollution. Furthermore, none of the strains showed resistance to metals.

Anti-Bacterial Agents↗

[Establishment and characterization of a human scirrhus type gastric cancer cell line, GCIY, producing CA19-9].

A human gastric cancer cell line, designated GCIY, was established from ascites of a patient with scirrhus type gastric cancer. Doubling time of this cell line was 55 hours. The karyotype indicated that these cells were human cells and the chromosome number varied widely, the mode being 57. GCIY cells were of moderate size and showed monolayer arrangement. They had a large nucleus and a clear nucleolus. Papanicolaou staining showed that they had the characteristics of adenomatous epithelia. They could be subcutaneously transplanted into nude mice, and they histologically resembled the original tumor. They were immunohistochemically recognized by anti-CA19-9 antibody and weakly by anti-CA125, CEA and alpha FP antibodies. Cultured medium also contained CA19-9, CA125, CEA and alpha FP.

Adenocarcinoma, Mucinous↗

Influence of lead on the host's defence mechanisms (I)--Influence of lead on antibody production.

To clarify the influence of lead on the host's defense mechanisms, antibody production in mice pretreated with lead was tested using the hemagglutination titer against SRBC (Sheep Red Blood Cells) and HRBC (Hamster Red Blood Cells) as indicator and the following results were obtained. 1. When mice were pretreated intraperitoneally with lead one day or six days before immunization and then immunized with SRBC, which is known as a strong antigen, antibody developed smoothly in the first immunization showing the same tendency as that of the control group. After the booster immunization, antibody production was markedly suppressed in the group of mice pretreated with lead six days before the immunization. When mice were immunized with HRBC, which is known as a weak antigen, antibody production was very poor in the first immunization, but after the booster immunization, the antibody titers rose rapidly in the group pretreated one day before the immunization. However, the titers of the group pretreated with lead 6 days before the immunization was considerably suppressed, showing the same tendency as that of mice immunized with SRBC. 2. When mice received intraperitoneally three or six doses of lead before immunization with SRBC or HRBC, antibody titer of these groups were somewhat lower than that of the control group. 3. When mice were pretreated intravenously with lead one day or six days before immunization with SRBC or HRBC, the antibody production ability was not remarkably damaged, showing almost the same titer as in the control group.

Animals↗