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T Todoroki

Publications and source records attributed to T Todoroki.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Chemotherapy for primary bile duct cancer].

The prognosis for patients with bile duct cancer (BDC) is still dismal, because of the high incidence of postresection recurrence and frequency of unresectable tumors. Chemotherapy has been applied over 20 years with anticipation of enhanced response rate together with minimal adverse effects and prolonged survival. Despite the scarcity of experiences with chemotherapy dedicated to BDC, some efficacy of chemotherapy on BDC has been indicated by this review of the literature. Chiefly, the administered drugs to unresectable BDC were 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin-C (MMC). Systemic chemotherapy, employing those drugs as single agents or as a combination like FAM (5-FU + ADM + MMC), was most commonly administered. The collective response rate was 18.6% (13/70), including a higher response rate of 29% (4/14) by FAM. Regional chemotherapy by hepatic arterial infusion has been expected to be more effective from the view point of blood supply, however, only a few trials have been reported as long as BDC. The series from the literature show a collective response rate of 50% (3/6) for hepatic arterial infusion therapy. The total number of patients (n = 16) treated by intra-ductal chemotherapy is too small to estimate clinical efficacy despite a relatively high collective response rate of 43.8% (7/16). This paper should encourage further investigation of chemotherapy for BDC.

Antineoplastic Agents↗
PubMed1996

[Evaluation of reserved hepatic function in patients with hepatobiliary tumor by 99mTc-GSA: effect of hyperbilirubinemia and usefulness of regional reserved hepatic functional imaging].

The evaluation of the reserved hepatic function was performed by 99mTc-galactosyl serum albumin (99mTc-GSA) in seventy patients with hepatobiliary tumor. The dynamic study was performed to evaluate global reserved hepatic function following the intravenous bolus injection of 99mTc-GSA, and the hepatic single photon emission computed tomography (SPECT) was obtained to assess the regional reserved hepatic function. The functional hepatic index (LHL15) was derived from liver time-activity data, and it was compared with serum total-bilirubin level, serum albumin level and plasma disappearance rate of indocyanine green (ICG15). In the patients with hepatocellular carcinoma, LHL15 value agreed well with ICG15 value, serum total-bilirubin level, and serum albumin level. Moderate or severe hepatic dysfunction was observed at 65.4% of these patients. In the patients with cholangiocellular carcinoma, a discrepancy of LHL15 value and ICG15 value was observed. Increment of the ICG15 value was correlated with that of the serum total-bilirubin level, whereas the correlations was not observed between the LHL15 value and the serum total-bilirubin level. These results indicate that 99mTc-GSA scintigraphy can evaluate the reserved hepatic function without the embellishment of jaundice. This method is useful for assessing the global and regional reserved hepatic function.

Aged↗
PubMed1995

Mutations of p16Ink4/CDKN2 and p15Ink4B/MTS2 genes in biliary tract cancers.

p16Ink4 and p15Ink4B are cyclin-dependent kinase 4 inhibitors and link to the regulation of cell cycle in mammalian cells. The genes encoding these inhibitors are located at 9p21, which is a frequent site of allelic loss in various types of tumors. Twenty-five primary biliary tract cancers were examined for somatic mutations in p16Ink4/CDKN2, p15Ink4B/MTS2, p53, and K-ras genes and allelic loss of 9p21 by microsatellite analysis. Four biliary tract cancer cell lines were analyzed for homozygous deletions and point mutations. We found frequent homozygous deletions in p16Ink4/CDKN2 and p15Ink4B/MTS2 genes in the biliary tract cancer cell lines. Each cancer cell line had alteration of either p16Ink4/CDKN2, p15Ink4B/MTS2, or p53 genes. In primary tumors, 16 of 25 (64%) biliary tract cancers had point mutations in the p16Ink4/CDKN2 gene. These include 14 missense and 2 silent mutations. The frequency of mutations in gall bladder cancer and hilar bile duct cancer were 80% (8 of 10) and 63% (5 of 8), respectively. Each of codons 1, 80, and 111 was changed in two cases of these cancers. One of three intrahepatic bile duct cancers, one of two common bile duct cancers, and one of two ampullary cancers had mutations in the p16Ink4/CDKN2 gene. In contrast, no mutation in the p15Ink4B/MTS2 gene, one base change in the K-ras gene, and one loss of heterozygosity at the IFN alpha locus in 25 cancers and one base change in the p53 gene in 19 cancers were observed. These results suggest that p16Ink4/CDKN2, rather than p15Ink4B/MTS2 or p53 genes, and its inactivation may be important in biliary tract carcinogenesis.

Base Sequence↗
PubMed1995

The functional hepatic volume assessed by 99mTc-GSA hepatic scintigraphy.

The accuracy of measurement of the functional hepatic volume by single photon emission computed tomography (SPECT) with 99mTc-galactosyl serum albumin (99mTc-GAS) was evaluated. 99mTc-GSA planar scintigraphic images were obtained dynamically and the hepatic SPECT imaging was then performed in 25 patients with hepatobiliary tumors. The patients were divided into 4 groups with normal hepatic function, and mild, moderate and severe hepatic dysfunction. The functional hepatic volume determined by SPECT was compared with the morphological hepatic volume determined by compute tomography. The ratio of the hepatic volumes obtained by the two methods was calculated. The mean hepatic volume ratio was 96.6 +/- 2.3% in the normal hepatic function group and 95.9 +/- 2.2% in the mild dysfunction group (n.s.). In both the moderate and severe hepatic dysfunction groups, the hepatic volume ratio was smaller than that in the normal group (87.9 +/- 5.2%, p < 0.0001, and 71.9 +/- 7.6%, p < 0.0001, respectively). There was a linear correlation between the hepatic volume ration and various indices of reserve hepatic function, such as LHL15 (r = 0.83, p < 0.0001), HH15(r = 0.74, p < 0.0001), and ICG15 (r = 0.75, p < 0.0005). These results indicate that the hepatic volume ratio is proportional to the severity of hepatic dysfunction, and suggest that the functional hepatic volume measured with 99mTc-GSA faithfully reflects the functioning hepatocyte mass. 99mTc-GSA scintigraphy and hepatic SPECT therefore provide information regarding global and regional reserve hepatic function.

Adult↗
PubMed1995

Induction of human autologous cytotoxic T lymphocytes on formalin-fixed and paraffin-embedded tumour sections.

Human autologous tumour-specific cytotoxic T lymphocytes (CTL) were generated from peripheral blood on small formalin-fixed paraffin-embedded sections of a gastric cancer. The CTL killed live target cells at an effector/target ratio of 1 within 24 hours and showed the same target specificity as those induced on live cancer cells. The killing activity of the CTL lasted for more than four months in culture and was inhibited by antibodies against CD8 and MHC-class I. These results suggest that adoptive immunotherapy of tumours will be possible with CTL induced on a stable source of tumour antigen.

Adenocarcinoma↗
PubMed1995

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↗
PubMed1995

[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↗
PubMed1995

[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↗
PubMed1994

[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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

[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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗