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Biomedical subjects

H Tanino

Publications and source records attributed to H Tanino.

At least 37 records · Page 2Linked to original sources
PubMed1998

Differential expression of rat brain bcl-2 family proteins in development and aging.

We have previously examined the involvement of the B cell leukemia-2 gene product (Bcl-2) family proteins (Bcl-2, Bcl-x, Bax, Bak, and Bad) in Alzheimer's disease (AD) and found that Bcl-2, Bcl-x, Bak, and Bad were upregulated. As AD is an aging-associated disease, in the present study we examined the developmental and aging-related changes in Bcl-2 family proteins in the rat brain. Immunoblot analyses of brain extracts from embryonic day 19 (E19) to postnatal 96-week-old rats indicated that the Bcl-2 protein level was highest at E19 and decreased after birth. Bcl-x levels remained high from E19 to 96 weeks. Bax levels were high from E19 to 2 weeks and decreased from 4 weeks onward. Bak levels were highest at E19 and decreased abruptly after birth. Bad levels were high from E19 to 2 weeks and decreased abruptly at 4 weeks. The present results suggest that the expression of each Bcl-2 family protein is differentially regulated during development and aging and that the changes in the senescent brains are different from those observed in AD.

Aging↗
PubMed1998

Alteration of myo-inositol monophosphatase in Alzheimer's disease brains.

myo-Inositol monophosphatase (E.C.3.1.3.25) catalyzes the hydrolysis of myo-inositol 1-phosphate in the presence of Mg2+ at a physiologic pH to form free myo-inositol, maintaining a supply that represents the precursor for inositol phospholipid second messenger signaling systems. In the present study the activity and protein level of myo-inositol monophosphatase were investigated in samples from normal human and Alzheimer's disease (AD) postmortem brains. The separation profile on Sephadex G-100 gel filtration chromatography revealed one major form of myo-inositol monophosphatase in crude extracts from both normal human and AD brains. In AD brains myo-inositol monophosphatase activity and its protein level were significantly higher than in control brains. The activity of myo-inositol monophosphatase per enzyme molecule was similar in control and AD brains. These results suggest that myo-inositol monophosphatase is upregulated in AD, probably reflecting compensatory mechanisms concerned with phospholipid metabolism.

Aged↗
PubMed1998

Antitumor spectra of anthracyclines against gastric cancer tissues obtained from surgical specimens with reference to P-glycoprotein expression.

BACKGROUND AND OBJECTIVES: Although the mechanism of P-glycoprotein (Pgp)-related resistance of doxorubicin is known, it has not been clarified for other anthracycline derivatives. We have examined the chemosensitivity of gastric cancer tissues to three anthracyclines in relation to Pgp expression. METHODS: Sixty-six surgical specimens obtained from patients with gastric cancer were subjected to histoculture drug response assay using doxorubicin (DXR), epirubicin (EPI), and 4'-O-tetrahydropyranyldoxorubicin (pirarubicin; THP). The cutoff concentrations used were 15 microg/ml for DXR and EPI and 17 microg/ml for THP. RESULTS: A 50% or more inhibition index (I.I.) was regarded as sensitive, at which the correlation rates were 95.8% (23/24) and 74.2% (49/66) for DXR-EPI and DXR-THP, respectively. Twenty-six specimens were immunohistochemically stained with monoclonal antibody to Pgp, with a positive rate of 53.8% (14/26). In Pgp-positive specimens, all cases were resistant to DXR and 28.6% (4/14) of cases were sensitive to THP, while the antitumor activity of EPI was essentially identical to that of DXR. CONCLUSIONS: The expression of Pgp might affect resistance to DXR and EPI, although THP may partially impair this resistance, suggesting the clinical usefulness of THP in treatment of DXR-refractory gastric carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

myo-Inositol monophosphatase in the brain has zinc ion-dependent tyrosine phosphatase activity.

1. myo-Inositol monophosphatase (E.C. 3.1.3.25) hydrolyzes inositol monophosphate to form free myo-inositol, the precursor for the inositol phospholipid second-messenger signaling systems. The biochemical properties of the enzyme were examined in detail. 2. The enzyme exhibited significant hydrolytic activity only on phosphotyrosine among physiological substrates tested in the presence of Zn2+ ions in an acidic environment. 3. The enzyme was recognized and immunoprecipitated with polyclonal antibodies developed against the Zn2+-dependent tyrosine phosphatase of bovine brain. 4. These results indicate that myo-inositol monophosphatase exhibits Zn2+-dependent tyrosine phosphatase activity in an acidic environment and has immunological identity with a Zn2+-dependent tyrosine phosphatase.

Acid Phosphatase↗
PubMed1998

Characterization of high- and low-molecular weight zinc-dependent acid phosphatases in bovine liver.

We have purified two forms of Zn2+-dependent acid phosphatase (Zn2+-APase) from bovine liver, both of which require Zn2+ to hydrolyze the substrate p-nitrophenyl phosphate in an acidic environment. The apparent molecular weights of these two forms of Zn2+-APase were estimated to be about 100,000 and 62,000 by gel filtration, and about 44,000 and 31,000 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, respectively. The low-molecular weight (LMW) Zn2+-APase catalyzed the hydrolysis of myo-inositol-1-phosphate in the presence of 3 mM Mg2+ at physiological pH, but the high-molecular weight (HMW) enzyme did not. The LMW-Zn2+-APase of bovine liver was recognized by polyclonal antibodies developed against the Zn2+-APase of bovine brain, but the HMW-Zn2+-APase was not.

Acid Phosphatase↗
PubMed1997

Analysis of the early postoperative serum carcinoembryonic antigen time-course as a prognostic tool for bronchogenic carcinoma.

BACKGROUND: The serum kinetics of carcinoembryonic antigen (CEA) after resection of lung carcinoma are not well characterized. Its prognostic implications remain unclear. This study was designed to clarify the correlation between postoperative CEA time-course and patient prognosis. METHODS: The authors analyzed early postoperative CEA time-course in 31 lung carcinoma patients using nonlinear least square analysis with the following three equations: Equation 1: C(t) = C(0); Equation 2: C(t) = C(0)exp(-kt); and Equation 3: C(t) (C(0)PLAT)exp(-kt) + PLAT, in which t: postoperative day; C(t): postoperative CEA; PLAT: postoperative CEA at plateau; C(0): CEA at postoperative Day zero; and k: rate constant of elimination. The equation that yielded the least Akaike's information criterion was adopted as the best fitting regression equation for each patient. When Equation 3 was adopted, postoperative CEA production (PROD) was calculated as PLAT multiplied by k. RESULTS: Equations 1, 2, and 3 were adopted for 16 (Group 1), 0, and 15 (Group 2) patients, respectively. In Group 1, no decrease in serum CEA level after surgery was detected and CEA production appears to have been little or none. In Group 2, biologic CEA half-life was 1.1 +/- 0.7 days and was not useful for predicting patient prognosis. Tumor recurrences were observed in 9 of the Group 2 patients 19 +/- 9 months postoperatively and there was no significant difference in PLAT or PROD between patients with and without recurrence. Early recurrence within 6 months after surgery was recognized in 5 (early-REC) of the 15 Group 2 patients, in whom there was a tendency for PLAT to be higher than in the other 10 patients without recurrence (early-NON) (early-REC: 3.8 +/- 4.9 ng/mL; early-NON: 1.5 +/- 1.1 ng/mL; P = 0.08). PROD was significantly higher in early-REC than in early-NON (early-REC: 3.5 +/- 4.2 ng/mL/day; early-NON: 0.8 +/- 0.4 ng/mL/day; P < 0.05). CONCLUSIONS: Although PROD is more sensitive than PLAT, both parameters appear to be useful as prognostic tools for predicting early recurrence after resection of lung carcinoma. This is probably because they represent the number of residual tumor cells immediately after surgery.

Adult↗
PubMed1997

[Induction chemotherapy based on histoculture drug response assay for a patient with advanced thymic cancer--a case report].

Histoculture drug response assay (HDRA) was applied to a biopsy specimen of advanced thymic cancer from a 68 years-old male patient. HDRA revealed that the tumor was not sensitive to CDDP but highly sensitive to 5-FU, ADM and MMC, which were administered as induction chemotherapy. The tumor regressed to 14% of the pretreatment size and was able to be completely resected with right and left brachiocephalic veins, superior vena cava, pericardium, right phrenic nerve and a part of right lung. Histologically, only a few small cancer nests remained in the fibrous tissue. The patient is alive and disease free 32 months after surgery. This result suggests that HDRA is useful to select anticancer agents which are sensitive to a rare kind of carcinoma such as thymic cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Dual modulation by l-leucovorin and recombinant human interferon alpha 2a of 5-fluorouracil antitumor activity against the human colon carcinoma xenograft Co-4.

We investigated the dual modulation by l-leucovorin (LV) and recombinant human interferon-alpha 2a (IFN-alpha 2a) of 5-fluorouracil (5-FU) antitumor activity against human colon carcinoma cells (Co-4) using a nude mouse system. 5-FU was administered intraperitoneally (IP) at 10 or 90 mg/kg. 5-FU (10 mg/kg) was administered daily for 10 days, and 90 mg/kg was administered once. LV was administered IP 1 and 0 h before 5-FU treatment at 200 mg/kg. IFN-alpha 2a was administered subcutaneously (SC) daily for 14 days at 60,000 IU/mouse. When 5-FU was administered at 10 or 90 mg/kg with these two modulators, the antitumor effect was increased significantly, with T/C ratios of 18.1 and 6.1, respectively. These modulatory effects were assessed as synergistic, without associated severe side effects or death during the experimental period. LV augmented the antitumor activity of 5-FU through increment of thymidylate synthetase (TS) inhibition, and IFN-alpha 2a showed a modulatory effect in elevating the intratumoral concentration of fluorouridine without change in TS inhibition. These results suggest that 5-FU antitumor activity against human colon carcinoma could be significantly potentiated without severe side effects by these two modulators, which possess different modes of action.

Animals↗
PubMed1995

In vivo antitumor activity of hexamethylmelamine against human breast, stomach and colon carcinoma xenografts.

We have evaluated the antitumor activity of Altretamine (hexamethylmelamine, HMM) on human carcinoma xenografts serially transplanted in nude mice. Five human breast carcinoma xenografts, MX-1, T-61, MCF-7, R-27 and Br-10, were inoculated subcutaneously into female nude mice. Two human stomach carcinoma xenografts, SC-1-NU and St-4, and three human colon carcinoma xenografts, Co-3, Co-4 and Co-6, were inoculated subcutaneously into male nude mice. One pellet of 17 beta-estradiol (0.1 mg/mouse) was inoculated subcutaneously in the mice transplanted with MCF-7 when the tumors were inoculated. HMM was administered per os daily for 4 weeks. MX-1 and T-61 tumors regressed completely after treatment with HMM at a dose of 75 mg/kg (the maximum tolerated dose: MTD) for MX-1 and 25 mg/kg for T-61. Br-10 was sensitive, whereas MCF-7 and R-27 were resistant to HMM at its MTD. HMM exerted the most potent antitumor effect against T-61. Against MX-1, it exerted an antitumor effect equivalent to that of cisplatin or cyclophosphamide. In addition, this agent was effective against all stomach and colon carcinoma xenografts, in particular St-4 (T/C% = 10.7: the mean tumor weight of treated group/the mean tumor weight of control group) and Co-3 (T/C% = 31.5%) which are insensitive to presently available agents. HMM seems worthy of further clinical investigation as a candidate agent to treat breast, stomach, colon and other carcinomas.

Altretamine↗
PubMed1994

Synergistic antitumor activity of combination chemotherapy with mitomycin C and cisplatin against human gastric cancer xenografts in nude mice.

A new combined cancer chemotherapy regimen of mitomycin C (MMC) and cisplatin (DDP) showed synergistic antitumor activity against human gastric cancer xenografts St-40 and SC-1-NU in BALB/c nu/nu mice. The drugs were administered intraperitoneally at doses of 2 or 4 mg/kg for MMC and 3 or 6 mg/kg for DDP, respectively. To clarify the schedule-dependent antitumor activity of MMC and DDP against St-40 and SC-1-NU, different sequential therapies were conducted. Simultaneous administration of these agents showed the highest antitumor activity against SC1-NU among the three regimens used, whereas the sequence of MMC followed by DDP showed higher antitumor activity than the reverse sequence against St-40. The intratumoral concentration of platinum was significantly increased in St-40 treated with the sequence MMC to DDP, in comparison with the sequence DDP to MMC. The maximum tolerated dose (MTD) of this combination was 4 mg MMC plus 6 mg DDP per kg in all the combinations, and these MTDs were 2/3 of the corresponding values for their single use. Since this combination increased the antitumor activity of each single agent without any increase in their toxicity, it would appear to be useful clinically.

Adenocarcinoma↗
PubMed1993

A suitable model for experimental liver metastasis of human colon cancer xenografts using mice with severe combined immunodeficiency.

Studies on liver metastasis of human colon cancer are limited because of a lack of suitable animal models. In this study, the usefulness of mice with severe combined immunodeficiency (SCID), which congenitally lack functional T and B lymphocytes, was evaluated in comparison with currently available nude mice. Three human colon cancer xenografts transplantable into nude mice were disaggregated enzymatically to obtain tumor cell suspensions, and implanted intrasplenically into SCID and nude mice. The incidence of splenic tumorigenesis and of liver metastases were significantly greater in SCID mice for all xenografts, in comparison with nude mice. In total, 33 of 36 SCID mice and 17 of 43 nude mice developed liver metastases. On the basis of this result, we conclude that SCID mice would be a more suitable model than nude mice for studying liver metastasis of human colon cancer.

Adenocarcinoma↗
PubMed1993

Colorimetric chemosensitivity testing using sulforhodamine B.

A colorimetric chemosensitivity test was investigated using sulforhodamine B (SRB), which stains protein synthesized by cells, as an end-point marker. Four cultured cell lines, 9 human tumor xenografts serially transplanted into nude mice, and 14 fresh surgical specimens were subjected to this assay. The optimal conditions for the assay were 3-5 x 10(4) cells per well in a 96-microplate, an SRB concentration of 4%, and an incubation time of more than 10 minutes. When mitomycin C, doxorubicin, cisplatin, and 5-fluorouracil were assessed by the SRB assay, the concentration-effect curves revealed a sharp slope between plateaux at low and high concentrations, suggesting that this assay has an excellent sensitivity which can assess the effect of drugs as "all or none." Although this high sensitivity resulted in good reproducibility of the assay for cultured cell lines, the predictive rate of the SRB assay for the chemosensitivity of human tumor xenografts in vivo was limited to 63.9%. As a result, this SRB assay is thought to be useful for evaluating the chemosensitivity of cultured cells as all or none, since it can assess directly cellular protein synthesis, which is one of the most important parameters of cell renewal, with excellent sensitivity.

Animals↗
PubMed1993

Experimental cancer chemotherapy using a liver metastatic model of human colon cancer transplanted into the spleen of severe combined immunodeficient mice.

We have developed a liver metastatic model of human colon cancer using severe combined immunodeficient (SCID) mice. Liver metastases were observed in all the SCID mice on day 28 after intrasplenic injection with 5 x 10(6) dissociated tumor cells of COL-2-JCK, a human colon cancer strain serially transplanted in nude mice. When this model was applied for chemotherapeutic experiments, 5-fluorouracil (5-FU) demonstrated significant antitumor effects in preventing liver metastases, whereas the efficacy of 5-FU was limited in the currently used sc-ip chemosensitivity assay in nude mice. When the human LDH-5 isozyme was evaluated in the homogenized metastatic liver tissue of SCID mice, a good correlation was obtained between the liver tumor weights and LDH-5 isozyme, suggesting that it could be a promising quantitative indicator for metastases. This model would be useful for further studies on the treatment of liver metastases of colon cancer.

Animals↗
PubMed1993

Significance of in vitro attachment of human colon cancers to extracellular matrix proteins in experimental and clinical liver metastases.

The attachment of 7 human colon cancer lines transplantable into nude mice, and primary tumors and liver metastases from 30 patients with colon cancer to 4 extracellular matrix proteins (EMPs)--Matrigel, laminin, fibronectin, and type IV collagen--was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H (MTT) assay. Cancer cells from the 4 established tumor lines which produced experimental liver metastases in vivo showed significantly greater attachment to each EMP than those from the other 3 tumor lines which did not. Although there were no significant differences between attachment to EMPs of cancer cells from 15 clinical primary tumors with liver metastases and those without, attachment to each EMP of cells derived from liver metastases was significantly greater than that of the cells from the corresponding primary tumors in 8 cases for which liver metastases and primary tumors were examined simultaneously. Attachment to EMPs, which could be determined simply and rapidly using the MTT assay, is thus considered a significant factor in experimental and clinical liver metastases of human colon cancers.

Animals↗
PubMed1993

Synergistic antitumor activity of mitomycin C and cisplatin against gastric cancer cells in vitro.

The synergistic antitumor activity of mitomycin C (MMC) and cisplatin (DDP) against the gastric cancer cell lines MKN-28 and MKN-45 was assessed in vitro using the MTT assay. The synergism of the two agents was evaluated in terms of the interaction index (I.I.). The sequence of MMC followed by DDP showed higher antitumor activity than the reverse sequence against MKN-28 and MKN-45, and the intracellular concentration of platinum was significantly increased in MKN-45 by preincubation with MMC, suggesting that MMC modulates cellular permeability to DDP or the ability of DDP to intercalate DNA. Since these two antitumor agents show different types of toxicity clinically, i.e., myelotoxicity by MMC and nephrotoxicity by DDP, this combination chemotherapy could be advantageous by providing synergistic antitumor activity without increased toxicity.

Adenocarcinoma↗
PubMed1993

A metastatic model of human colon cancer constructed using cecal implantation of cancer tissue in nude mice.

COL-2-JCK, a human colon cancer xenograft line able to be transplanted into nude mice, was implanted in the subserosal layer of the cecum, either as cancer tissue or as a single cell suspension. When cancer tissue was used for the cecal implantation, 100% extensive local tumor growth and a high incidence of metastases to the regional lymph nodes, peritoneum, liver, and lung was observed. In contrast, when the cell suspension of this line was injected into the cecal wall, no metastases were observed, with significantly reduced local tumor growth. The use of cancer tissue maintaining the original cancer tissue structure is therefore considered imperative for allowing full expression of the biological characteristics of cancer cells. This nude mouse model using the cecal implantation of cancer tissue should thus prompt further study on the biology of human colon cancer.

Animals↗
PubMed1993

Enhancement of antitumor activity of cisplatin on human gastric cancer cells in vitro and in vivo by buthionine sulfoximine.

An attempt was made to evaluate the enhancement of the antitumor activity of cisplatin (DDP) by buthionine sulfoximine (BSO) in vitro and in vivo. In the in vitro study, pre-treatment with BSO (5, 10 and 25 mM) increased the antitumor activity of DDP against the gastric cancer cell lines MKN-28 and MKN-45, whereas BSO alone exhibited only slight antitumor activity (inhibition rate, 20-30%). In the in vivo study, the antitumor effects of DDP against human gastric cancer xenografts St-15 and SC-1-NU in BALB/c nu/nu mice were enhanced pretreatment with BSO, which was administered intraperitoneally at a dose of 500 mg/kg according to a schedule of qd x 3. BSO alone showed no antitumor effects against these tumors in nude mice. The side effects (assessed in terms of death rate and body weight loss) associated with the maximum tolerated dose of DDP (9 mg/kg) were not increased by BSO pretreatment. As BSO increased the antitumor activity of DDP without a corresponding increment of its toxicity, BSO appears to be a promising agent for further study.

Animals↗