PubMed Health⌕ Search

Biomedical subjects

T Toge

Publications and source records attributed to T Toge.

At least 109 records · Page 6Linked to original sources
PubMed1993

[Mitomycin C and its bioreduction: relevance of NAD(P)H: quinone oxidoreductase activity to mitomycin C-induced DNA damage and cytotoxicity].

Using 4 human cancer cell lines, the relevance of NAD(P)H: quinone oxidoreductase (DT-diaphorase) activity to mitomycin C (MMC)-induced cytotoxicity was investigated. KB cells (oral epidermoid carcinoma) had more than 4 times higher DT-diaphorase activity than PH101 (pancreatic cancer), SH 101 (gastric cancer), or K562 (myelogenous leukemia) cells. The sensitivity to MMC was greatest in KB cells. Concentrations causing 50% inhibition of cell growth (IC50 value: microgram/ml) by 30 min treatment with MMC were 0.4 in KB, 1.1 in PH101, 1.6 in SH 101, and 1.9 in K 562. Treatment with 1.5 micrograms/ml of MMC induced DNA total cross links, and the indices were 0.18 in KB, 0.10 in SH101, 0.09 in SH101, and 0.06 in K 562. When DT-diaphorase activity was inhibited by non-toxic dicoumarol (50 microM), DNA damage and cytotoxic activity induced by MMC were decreased in all cells examined. Especially in KB cells, it was remarkable. Since it was shown that the level of cellular DT-diaphorase activities were correlated with the responses to MMC, we suggest that bioreduction by DT-diaphorase may activate MMC.

Carcinoma, Squamous Cell↗
PubMed1993

[Intra-arterial infusion chemotherapy of cisplatin (CDDP)-lipiodol suspension using implantable injection port for unresectable liver cancer patients].

Intra-arterial CDDP-Lipiodol infusion chemotherapy using an implantable port was effective in 10 unresectable liver cancer patients, including 7 hepatocellular and 3 metastatic cases. CDDP-Lipiodol suspension (10 mg of CDDP/1 ml of Lipiodol) was administered at the dose of 25 mg/m2 of CDDP biweekly from 2 to 9 times. The clinical responses were defined as 4 PR (40%), 5 NC (50%), including 3 MR, and 1 PD (10%). The efficacy rate was 40%. The level of AFP and CEA was reduced in all PR and NC cases except one. Side effects were nausea (70%), low-grade pyrexia (50%), abdominal pain (30%), and liver dysfunction (20%), but they were tolerable and transient.

Carcinoembryonic Antigen↗
PubMed1993

Circadian variation of 5-fluorouracil and cis-platinum toxicity in mice.

Circadian variations of organ specific and lethal toxicities were investigated in female C3H mice following intraperitoneal injection(s) of 5-fluorouracil (5-FU) and/or cis-platinum (CDDP) with different doses at one of the four equidistant time points, viz., 3, 9, 15 and 21 HALO (Hours After Light On). Lethality, peripheral WBC count, spleen size, femoral bone marrow cell population and changes in body weight were analyzed. A single injection of 5-FU (300 mg/kg) showed 45% mortality with 3 HALO and 15% with 9 HALO treatment (p < 0.05); that with CDDP (16 mg/kg) was 80% in 3 HALO and 10% in 9 HALO group (p < 0.01). Peripheral WBC count on the 4th post-treatment day showed that drug induced leukopenia was less severe with 15 HALO dosing compared to the other HALO points (p < 0.01). The reduction in spleen size following treatment was maximum in 3 HALO treated group with both drugs (p < 0.01). The combination therapy of these two drugs also showed circadian variation of toxicity. The results suggest that the toxic effects of chemotherapy are dosing time dependent.

Animals↗
PubMed1992

Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice.

Topoisomerase (topo) I and II are nuclear enzymes which are novel targets of cancer chemotherapy. A new camptothecin (CPT) analog, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyl-oxy-CPT (CPT-11), is a topo-I inhibitor with a higher activity and less toxicity than CPT. To investigate topo-I and -II-targeting chemotherapy in an in vivo model, we studied the effect of sequential or co-treatment using CPT-11 and adriamycin (ADR) a topo-II inhibitor, in 6 human tumor xenografts (2 esophageal, 2 gastric and 2 colon tumor lines). In sequential treatment, adriamycin was administered i.v. 24 hr after CPT-11 treatment, and no antagonistic effect of this treatment schedule was observed. ADR cytotoxicity was potentiated significantly by CPT-11 pretreatment in the case of 2 esophageal and 2 gastric tumor lines and 1 colon tumor line. On the other hand, co-treatment abolished the sensitivity to CPT-11 and ADR in all 6 tumor lines. Moreover, CPT-11 did not significantly enhance the cytotoxicity of other agents tested, including mitomycin C (MMC) and cisplatin (CDDP). Flow cytometry and dot-blot analyses showed that CPT-11 pretreatment induced an increase in the S-phase cell population with an increase of topo-II mRNA expression after 24 and 48 hr, respectively, in the esophageal and colon tumor lines. These results suggest that CPT-11 can modulate topo-11 levels to enhance the effect of topo-II inhibitors in some human tumors, and this suggests a new clinical method of topo-I and -II targeting chemotherapy for human solid tumors.

Animals↗
PubMed1992

Prognostic significance of co-expression of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer patients.

The expression of c-erbB-2 oncoprotein and epidermal growth factor receptor (EGFR) was examined by immunocytochemical and radioreceptor assays in 115 patients with primary breast cancer. In 48 of 115 patients (42%), the assays were found to be positive for the expression of c-erbB-2 oncoprotein, and, in 44 of 115 (35%) patients, the assays were positive for the expression of EGFR. There was no correlation between the expression of c-erbB-2 oncoprotein and EGFR. Clinical survey demonstrated that both c-erbB-2 oncoprotein expression and EGFR expression have independent prognostic values. Furthermore, when patients were divided into three groups on the basis of the expression of both c-erbB-2 oncoprotein and EGFR, those who were found to be positive for the expression of both c-erbB-2 oncoprotein and EGFR showed a worse prognosis than other groups. These results suggest that the combination of the expression of both c-erbB-2 oncoprotein and EGFR may be important in selecting patients who have a poor prognosis.

Biomarkers, Tumor↗
PubMed1992

Investigation of suitability of devascularized upper half of the whole stomach as replacement for the esophagus.

One hundred and fifteen patients with esophageal cancer underwent esophageal replacement with the stomach. The patients were divided into group A (52 patients, stomach tube, ante- or retro-sternal route) and group B (54 patients, devascularized upper half of the whole stomach, posterior mediastinal route). The post-operative complications, post operative symptoms and nutritional status were investigated in both groups. Lung complications tended to occur more frequently in group A (28.8% versus 22.2%), showing no significant difference. The incidence of other complications did not show a remarkable difference between either group except for leakage at the site of anastomosis. Major leakage occurred in 11.5% and 5.6%, and minor leakage in 30.8% and 18.5%, respectively. Postprandial fullness, nausea, heart burn and diarrhea were found to be somewhat higher in Group B. Change of oral intake, body weight and other indices of nutritional status were investigated and compared with pre- operative data. The amount of oral intake and levels of serum albumin was higher in group B than in group A between one and 12 months. These results demonstrate the superiority of the devascularized upper half of the whole stomach as an esophageal substitute.

Aged↗
PubMed1992

[Lymphokine-activated killer cell adoptive immunotherapy for cancer treatment and its significance].

New culture system, CDCS-T1, was developed for clinical conduction of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT). Advanced or recurrent cancer patients of digestive tract were treated with AIT with LAK cells generated by CDCS-T1 in combination with plasma exchange. Partial responses were shown in 10 to 20% of patients treated. Long survival was found in some responders, indicating the significance of LAK therapy for cancer treatment. AIT with LAK cell transfer was also conducted in patients with esophageal cancer as postoperative adjuvant therapy. Better restoration of postoperative depression of immunological parameters was found in patients with postoperative LAK cell transfer. It is suggested that postoperative LAK cell transfer is a good candidate for adjuvant immunotherapy for cancer treatment.

Aged↗
PubMed1992

Neuropeptide release from the isolated, perfused, lower esophageal sphincter region of the rabbit and the effect of vasoactive intestinal peptide on the sphincter.

BACKGROUND: The aim was to evaluate the isolated, vascularly perfused, lower esophageal sphincter (LES) as a model for investigating the functional role of neuropeptides such as vasoactive intestinal peptide (VIP). METHODS: At laparotomy the LES was removed along with the distal esophagus, stomach, and left gastric artery and vein. The LES area, isolated from the body of the stomach by a custom-made clamp, was perfused with oxygenated Krebs-Ringer bicarbonate solution (pH 7.4, 38 degrees C) via the left gastric artery. The LES pressure was monitored continuously with a custom-made Dent sleeve catheter. LES pressure and release of neuropeptides were investigated after carbachol and VIP were administered alone or in combination. VIP, calcitonin gene-related peptide (CGRP), and somatostatin were measured in the venous perfusate collected from the left gastric vein. RESULTS: LES tone and contraction frequency were similarly increased by 10 and 100 nmol/L carbachol (increment, 4.0 +/- 0.26 mm Hg with 10 nmol/L carbachol; p less than 0.0003). Perfusion with 10 nmol/L VIP decreased basal tone and completely abolished the contraction induced by 100 nmol/L carbachol. VIP, CGRP, and somatostatin were released from the LES in response to 10 nmol/L carbachol (VIP rose from 55 +/- 13 to 179 +/- 24 pmol/L, CGRP, from 114 +/- 30 to 239 +/- 33 pmol/L, and somatostatin from 15 +/- 2 to 27 +/- 4 pmol/L; all p less than 0.001). CONCLUSIONS: These findings support a role for VIP in the inhibitory reflex of the LES but suggest that other neuropeptides may also be involved. The isolated, perfused LES provides a new tool for investigating neuropeptide interactions.

Animals↗
PubMed1991

Clinical significance of the expression of epidermal growth factor and its receptor in esophageal cancer.

The epidermal growth factor receptor (EGFR) level in 56 esophageal cancer tissues was measured by 125I-EGF binding assay to elucidate its role in tumor progression. The survival rate of patients with high EGFR level (more than 50 fmol/mg protein) was significantly lower than that of patients with low EGFR level (less than 50 fmol/mg protein, P less than 0.01), although a correlation between EGFR level and the pathologic findings was not observed. The expression of EGF was examined immunohistochemically using anti-EGF monoclonal antibody in 100 esophageal cancer tissues; EGF-positive tumor cells were detected in 92.0%. The immunoreactivity of EGF was classified arbitrarily into four grades according to the number of stained tumor cells. The expression of EGF significantly correlated with the differentiation of esophageal squamous cell carcinoma (P less than 0.01, by chi-square test). The survival rate of patients with high EGF immunoreactivity (Grade 2 or 3) was much lower than in those with lower grade (0 or 1) tumors, (P less than 0.01). Patients with both high EGFR level and EGF immunoreactivity had a much worse prognosis than if both were low. Furthermore, the mitotic index was higher in groups with both high EGFR and EGF than if both were low (16.39 +/- 5.35 versus 6.90 +/- 3.31). These results suggest that EGF and EGFR in the autocrine system may play an important role in tumor progression in esophageal cancer and their expression could be of prognostic significance.

Antibodies, Monoclonal↗
PubMed1991

Significance of freshly cultured fibroblasts from different tissues in promoting cancer cell growth.

The interactions between human cancer cells and primary cultured human fibroblasts without cell-to-cell contact were investigated using double soft-agar culture. Human fibroblasts obtained from different organs were cultured in monolayers and used after the 3rd or 4th passage. In double soft-agar culture, colony formations of cancer cells in the overlayer were stimulated or inhibited by the presence of various kinds of fibroblast in the underlayer. The growth of all cancer cells tested was always stimulated by the presence of fibroblasts obtained from an organ in which cancer cells had already developed, and inhibited by those from skin. However, fibroblast-conditioned media failed to affect cancer cell growth, either in MTT assay or in soft-agar culture. These results suggest that mutual growth reliance exists between human cancer cells and primary cultured fibroblasts by diffusible factors secreted by both cells (paracrine growth) and that mutual growth enhancement occurs between cancer cells and fibroblasts derived from tissues in which cancer cells had originated.

Adenocarcinoma↗
PubMed1991

The augmentative effect of a protein-bound polysaccharide (PSK) on tumoricidal activity of the soluble factor produced by a streptococcal preparation (OK-432)-activated macrophages.

The enhancement of antitumor activities of the tumoricidal soluble factor (SF) from a streptococcal preparation (OK-432)-activated macrophages by the pretreatment with a protein-bound polysaccharide (PSK) was investigated in tumor-bearing mice. Two-step stimulations with OK-432 at in vivo priming and in vitro eliciting were required for the production of the tumoricidal SF by macrophages, and the tumoricidal activity of the SF apparently correlated with the uptake of OK-432 by macrophages at priming phase. Tumoricidal activity of the SF from OK-432-activated macrophages in proteose-peptone (P-P)-pretreated mice significantly decreased with the development of the tumor, whereas in PSK-pretreated mice did not. Pretreatment of tumor-bearing mice with PSK saved a decrease in the macrophages carrying Iak or asialo GM1 antigens and an increase in wheat germ agglutinin (WGA) receptors. Furthermore, the uptake of OK-432 by macrophages at priming phase was enhanced. The tumoricidal activity of the SF from OK-432-activated macrophages was augmented. Thus, PSK may restore the depressed functions of macrophages, and the combination therapy with PSK and OK-432 may be effective to enhance the production of tumoricidal SF in tumor-bearing mice.

Adjuvants, Immunologic↗
PubMed1991

Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients.

The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL by in vitro additional OK432, interleukin 2 or gamma-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmented in vitro more strongly in patients given IT-OK432 than in those given PO-OK432. Flow cytometric analysis of LNL revealed a decrease in CD4+ cells by PO-OK432 and an increase in CD8+ cells by IT-OK432. An increase in CD4+2H4+ cells and a decrease in CD4+2H4- cells were observed in the patients given OK432, though CD8+CD11+ cells decreased by PO-OK432 while CD8+CD11+ cells increased by IT-OK432. Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432.

Administration, Oral↗
PubMed1991

mRNA expression of topoisomerase II in human tumors and normal tissues.

The cellular levels of topoisomerase II expression were compared between 10 fresh human tumors and normal tissues to predict the selective anticancer effect of its inhibitors such as adriamycin and VP-16. Topoisomerase II expression was observed in 9 of the 10 tumor tissues (90.0 per cent), 3 of which showed extremely high levels, whereas only 5 of the normal tissues (50.0 per cent) expressed any cellular topoisomerase II and the levels were not higher than those seen in the cancer cells. Six of the 9 positive tumors showed a higher level of topoisomerase II expression than the normal tissues, while the other 3 showed the same level. It can be interpreted from these results that topoisomerase II inhibitors could be effective in cancer patients due to the greater level of this enzyme in tumor cells than in normal tissues. Thus, it is suggested that a comparative analysis of topoisomerase II expression between tumors and normal tissues may be useful for predicting the selective cytotoxicity of topoisomerase II inhibitors in clinical practice.

DNA Topoisomerases, Type II↗
PubMed1991

Clinical significance of P-glycoprotein expression analyzed by immunohistochemical staining in cancer tissues.

P-glycoprotein is a transmembrane protein with increased drug efflux from resistant cells, which is encoded by the MDR1 gene. An overexpression of P-glycoprotein has been reported to correlate with the degree of resistance to anticancer agents, especially to adriamycin. In this study, the expression of P-glycoprotein was analyzed immunohistochemically by using a monoclonal antibody, MRK16 against P-glycoprotein in 18 fresh human tumors. The expression of P-glycoprotein was detected in eight (44 per cent) tumor specimens out of 18 patients. Although six (75.0 per cent) of the 8 P-glycoprotein positive tumors were resistant to adriamycin, the other two tumors showed clinical responses. Furthermore, five (50.0 per cent) of the 10 P-glycoprotein negative tumors exhibited positive clinical responses. These results suggest that P-glycoprotein expression may not be a useful marker to predict intrinsic resistance to adriamycin in fresh human tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Epidermal growth factor receptor expression as a prognostic indicator in breast cancer.

The significance of epidermal growth factor receptor (EGFR) status as a prognostic indicator was investigated by a competitive binding assay in 135 primary breast cancer patients. 55 patients (41%) were EGFR positive and EGFR status was negatively correlated with oestrogen receptor (ER) status (P less than 0.01). 5-year postoperative follow-up showed that relapse-free survival for EGFR positive patients was significantly worse than that for EGFR negative patients (P less than 0.05). There was no difference between the two groups in tumour size, axillary node involvement, age and menopausal status. Analysis by axillary node status demonstrated the poor prognosis of the EGFR positive group in node positive patients. As yet, no difference in prognosis has been seen in node negative patients. A higher frequency of haematopoietic relapse was observed in EGFR positive patients. Simultaneous or sequential EGFR measurements in primary tumour and metastatic sites of 34 patients showed that expression of EGFR was more enhanced in metastatic sites.

Breast Neoplasms↗
PubMed1991

A novel in vitro chemosensitivity test using materials collected by endoscopic biopsy.

The usefulness of chemosensitivity testing of cells collected by endoscopic biopsy using the adenosine triphosphate assay (ATP assay) was investigated for esophageal tumors. Correlation between this chemosensitivity test and other chemosensitivity tests was more than 80% in most combinations. The predictive rate of clinical sensitivity was 77.8% and of clinical resistance was 68.8%. The predictive accuracy was 72.0%. These results will extend the indication and usefulness of chemosensitivity testing in inoperable and preoperable cases.

Adenosine Triphosphate↗
PubMed1991

Expression of cripto, a novel gene of the epidermal growth factor family, in human gastrointestinal carcinomas.

The expression of mRNA for cripto gene, a novel transforming gene of the epidermal growth factor family, was examined in 20 alimentary tract carcinoma cell lines, 60 surgically resected tumor tissues and their adjacent normal mucosas. Although the cripto mRNA was not detected in esophageal carcinomas or in normal mucosas, it was detected in gastric and colorectal carcinomas. In gastric carcinomas, 2.2 kb cripto mRNA was detected in one cell line, all the gastric carcinoma tissues and their adjacent normal mucosas. Of 23 gastric tumor tissues 8 (34.8%) exhibited a higher mRNA level than normal gastric mucosas. cripto mRNA was detected in 2 out of 6 colorectal carcinoma cell lines. Interestingly, 18 (81.8%) out of 22 colorectal carcinoma specimens expressed a higher level of cripto mRNA than that in normal mucosas. The level of the expression was higher than that in gastric carcinoma tissues. The expression was also correlated to tumor stage of colorectal carcinomas.

Adult↗