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Biomedical subjects

H Anai

Publications and source records attributed to H Anai.

At least 91 records · Page 5Linked to original sources
PubMed1988

Colorectal carcinoma in vitro is more sensitive to 1-hexylcarbamoyl-5-fluorouracil compared with six other antitumor drugs: carboquone, Adriamycin, mitomycin C, aclacinomycin A, cisplatin, 5-fluorouracil.

The sensitivity to 1-hexylcarbamoyl-5-fluorouracil (HCFU) of 25 colorectal cancer tissues was compared with that of six antitumor drugs: carboquone (CQ), Adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP), and 5-fluorouracil (5-FU), using the in vitro succinate dehydrogenase inhibition (SDI) test. Chemosensitivity was determined to be positive when the succinate dehydrogenase (SD) activity of the drug-exposed cells, at ten times the peak plasma concentration, was decreased to below 50 percent of that of control cells on day 3 of exposure. Decrease in SD activity was remarkable in cases of exposure to HCFU, compared with six other drugs. The sensitivity rates were 32 percent for CQ, 40 percent for ADM, 24 percent for MMC, 28 percent for ACR, 32 percent for DDP, 16 percent for 5-FU, and 68 percent for HCFU. The sensitivity rate for at least one of the six drugs (CQ, ADM, MMC, ACR, DDP, and 5-FU) was 52 percent, but was 80 percent when HCFU was taken into account. Since colorectal cancer tissues are resistant to various antitumor drugs, the chemosensitivity test of HCFU should aid in determining the effects of a particular drug for an individual patient.

Aclarubicin↗
PubMed1988

In situ nick translation method reveals DNA strand scission in HeLa cells following heat treatment.

DNA strand break in HeLa cells induced by heat was detected using the in situ nick translation method. The cells were incubated at 43 degrees C for various times (15, 30, 45, 60, 90 or 120 min) in Lab-Tek tissue culture chamber/slides and were fixed with ethanol/acetic acid on the slide glass. The break sites in DNA were translated artificially in the presence of Escherichia coli DNA polymerase I and 3H-labeled dTTP. The level of break sites in the DNA was visualized by autoradiographic observation of the grains. The DNA strand break appeared as early as 15 min, increased to 10.3-fold at 45 min of 43 degrees C treatment and this level related reciprocally to clonogenicity of the cell. The nick translation method thus provides a rapid in situ assay for determining heat-induced DNA damage of cultured cells, in a semi-quantitative manner.

Bacterial Proteins↗
PubMed1988

Excised human neoplastic tissues are more sensitive to heat than the adjacent normal tissues.

In tissues from patients subjected to gastrectomy or colectomy, the heat sensitivity was determined in the case of 23 neoplastic, 15 gastric, 8 colorectal, and the adjacent normal tissues, using the in vitro succinate dehydrogenase inhibition test. The succinate dehydrogenase (SD) activity of tissue fragments was assayed, following exposure to heat at 43 degrees C (heat treatment) or 37 degrees C (control) for 5, 10, 15 or 20 h. The sensitivity to heat treatment was estimated by the percentage of SD activity of the heat-treated cells, compared to that of control cells. The decrease in SD activity varied in the tumor tissue, following exposure to heat. The SD activity decreased to a greater extent in the tumor tissue than in the adjacent normal tissue, in each case. The mean +/- standard deviation of SD activity, following exposure to heat treatment for 20 h, was 32.1 +/- 14.0% for the tumour tissues and 52.4 +/- 10.4% for the adjacent normal tissues, with a statistically significant difference (p less than 0.01). These results show that the assay of heat sensitivity is meaningful for prediciting the effectiveness of hyperthermia and that hyperthermia has a selectivity for treating a malignant lesion.

Adult↗
PubMed1988

Sensitivity test for 5-fluorouracil and its analogues, 1-(2-tetrahydrofuryl)-5-fluorouracil, uracil/1-(2-tetrahydrofuryl)-5-fluorouracil (4:1) and 1-hexylcarbamoyl-5-fluorouracil, using the subrenal capsule assay.

The chemosensitivity of 20 human neoplastic tissues including 13 gastric and 7 colorectal cancers was tested using 5-fluorouracil (5-FU) and its analogues: 1-(2-tetrahydrofuryl)-5-FU (FT), uracil/FT (UFT) and 1-hexylcarbamoyl-5-FU (HCFU), and the in vivo subrenal capsule (SRC) assay. The relative variation of tumor size (delta TS/TSo) was calculated as follows: delta TS/TS0 = (TS6-TS0/TS0) x 100%, where TS6 was the tumor size on day 6 and TS0 on day 0, and the chemosensitivity was considered to be sensitive when delta TS/TS0 in the treated group was decreased to below -10%. The mean tumor size was -10.9 +/- (SD) 10.9% for 5-FU, -12.3 +/- 17.1% for FT, -18.4 +/- 15.8% for UFT and -17.9 +/- 15.4% for HCFU. The decrease of tumor size was marked when exposed to UFT (p less than 0.01) or HCFU (p less than 0.02), compared with that to 5-FU. Positive correlations were noted between the tumor sizes of 5-FU and its analogues (5-FU vs. FT, r = 0.851; 5-FU vs. UFT, r = 0.746; 5-FU vs. HCFU, r = 0.685). In 9 tissues resistant to 5-FU, 2 (22%) were sensitive to FT, 4 (44%) to UFT, 5 (56%) to HCFU and 7 tissues (78%) to at least one of these analogues. These results suggest that the SRC assay is useful for predicting the effective drug among 5-FU and 5-FU analogues, for individual patients with cancer.

Animals↗
PubMed1988

New cytoskeletal proteins are induced in HeLa cells by Vinca alkaloids.

The effects of Vinca alkaloids, vinblastine, vincristine, and vindesine, on protein synthesis were determined using HeLa cells. Vinblastine at the concentration of 1 microgram/ml induced new proteins, isoelectric points 4.8 and 7.0-7.5 and molecular weights 48 and 92 kd, in the HeLa cells, identified using two-dimensional gel electrophoresis. The 48-kd and the clustered (4-components) 92-kd proteins were also noted in HeLa cells treated with vincristine or vindesine. As most of the 48- and 92-kd proteins were Triton insoluble, they can be considered components of the cytoskeletal structure. Syntheses of these proteins were blocked by actinomycin D, therefore, new messenger RNA synthesis is required for induction. These proteins were not induced by an alkylating agent, antitumor antibiotics, or an antimetabolite. Our findings show that the 48- and the clustered 92-kd proteins are Vinca alkaloid reactive components and can be considered candidates for the elucidation of the antineoplastic effect of Vinca alkaloids.

Carbazilquinone↗
PubMed1988

Sodium succinate enhances the colorimetric reaction of the in vitro chemosensitivity test: MTT assay.

We compared the colorimetric reactions between the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl 2H-tetrazolium bromide (MTT) assay and the succinate dehydrogenase inhibition (SDI) test, in order to evaluate the usefulness of the SDI test for in vitro chemosensitivity testing. The addition of sodium succinate enhanced the colorimetric absorbance at 565 nm in the MTT assay in a dose- and a time-dependent manner, in mouse sarcoma-180 (S-180) cells. At 10 microM of sodium succinate, a dose used in the SDI test, the absorbance of the MTT assay increased by about 2.5-fold in the S-180 cells and in 10 human tumor tissues. The absorbance in the SDI test correlated well with the viable cell number of S-180 cells (r = 0.9993). These results show that the SDI test, using MTT as a tetrazolium salt, has a higher sensitivity for predicting cell viability, compared to the MTT assay.

Animals↗
PubMed1988

UFT is more antineoplastic against gastric carcinoma than 5-fluorouracil, 1-(2-tetrahydrofuryl)-5-fluorouracil and 1-hexylcarbamoyl-5-fluorouracil.

The sensitivity of human gastric cancer tissue to 5-fluorouracil (5-FU) and its analogues 1-(2-tetrahydrofuryl)-5-fluorouracil (FT), UFT and 1-hexylcarbamoyl-5-fluorouracil (HCFU) was determined, using the in vivo subrenal capsule (SRC) assay. The relative variation of tumor size (delta TS/TS0) was calculated as follows: delta TS/TS0 = (TS6-TS0/TS0) x 100%, where TS6 was the tumor size on day 6 and TS0 on day 0. The chemosensitivity was considered to be positive when delta TS/TS0 in the treated group decreased to below -10%. For their cytotoxic effects, 5-FU analogues are converted to 5-FU and positive correlations were noted between the tumor sizes of 5-FU and its analogues (5-FU vs. FT, r = 0.737; 5-FU vs. UFT, r = 0.653; 5-FU vs. HCFU, r = 0.709), in gastric tissues from 22 patients. The means +/- SD of tumor size were -8.5 +/- 11.5% for 5-FU, -8.3 +/- 16.0% for FT, -18.1 +/- 15.8% for UFT and -13.7 +/- 13.4% for HCFU. Decrease in tumor size was marked in case of exposure to UFT, compared with that to 5-FU (p less than 0.001), FT (p less than 0.001) and HCFU (p less than 0.05). 18% were sensitive to UFT and resistant to 3 other drugs. Thus, UFT proved to be the most effective among 5-FU and its analogues for decreasing the size of gastric cancer tissues.

Animals↗
PubMed1988

[Human colorectal carcinoma is more sensitive to HCFU than 5-FU and tegafur in in vitro and in vivo drug sensitivity tests].

The sensitivity of human colorectal cancer to 5-fluorouracil (5-FU) and its derivatives: 1-(tetrahydro-2-furyl)-5-FU (tegafur) and 1-hexylcarbamoyl-5-FU (HCFU) was determined by in vitro succinate dehydrogenase inhibition (SDI) test and in vivo subrenal capsule (SRC) assay. Using the SDI test with 25 colorectal cancer specimens, the succinate dehydrogenase (SD) activity decreased to 73.6 +/- 17.8% for 5-FU-treated cells and 37.2 +/- 17.0% for HCFU-treated cells, compared to that of control cells. The chemosensitivity-positive rates were 16% for 5-FU and 68% for HCFU. Using the SRC assay with 7 colorectal cancer specimens, the relative variation of tumor size, which was calculated by delta TS/TS0 = (TS6-TS0)/TS0 X 100 (%), decreased to -12.6 +/- 10.1% for 5-FU, -14.9 +/- 12.4% for tegafur and -23.9 +/- 14.2% for HCFU, and the inhibition of tumor growth following exposure to HCFU was evident. The chemosensitivity-positive rates were 49% for 5-FU, 57% for tegafur and 71% for HCFU. Our results show that HCFU is more effective to colorectal cancer than 5-FU and FT-207, and the chemosensitivity test of HCFU will be useful in determining the effective drug for the treatment of colorectal cancer.

Animals↗
PubMed1988

Chemosensitivity differences between primary and metastatic lesions of clinical gastric cancer.

An in vitro chemosensitivity test, the succinate dehydrogenase inhibition (SDI) test, was used to examine 16 pairs of samples obtained simultaneously from primary and metastatic lesions of clinical gastric cancer. Concerning the metastases, 11 were in the lymph nodes and five in the liver. The chemosensitivities of metastatic lesions against six anti-tumour drugs, carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), and 5-fluorouracil (5-FU), differed from those in the primary lesions, and there were no correlations of chemosensitivities between the primary and the metastatic lesions against these drugs, except for DDP. The lymph nodes were more sensitive to CQ, ADM, MMC, DDP, ACR and 5-FU, while the liver was less sensitive than the primary lesions to CQ, ADM, MMC, DDP, and ACR. Our findings indicate that in patients with lymph node metastasis, there is a sensitivity to anti-tumour drugs, while in cases of liver metastasis, drug treatment may be less effective. We propose that chemosensitivity testing should be done when attempting to design anti-tumour drugs.

Antineoplastic Agents↗
PubMed1987

The ATP assay is more sensitive than the succinate dehydrogenase inhibition test for predicting cell viability.

The succinate dehydrogenase inhibition (SDI) test and the adenosine triphosphate (ATP) assay, are both used for in vitro human tumor chemosensitivity testing. We exposed HeLa cells to various concentrations of mitomycin C for 1, 2 or 3 days and found that the decrease in number of viable cells correlated with that of succinate dehydrogenase (EC 1.3.99.1) activity and that of intracellular ATP level of the viable cells. In the dead cells, the ATP level was extensively decreased, but the succinate dehydrogenase activity remained at a level of 24% of that of mitomycin C-untreated viable cells, even on day 3. Thus, the ATP level better reflected the cell viability. In clinical situations, the succinate dehydrogenase activity and the ATP level are assayed in whole cells following exposure to anticancer drugs, therefore the activity remaining in the dead cells must be taken into consideration for the chemosensitive prediction with the SDI test, but not with the ATP assay. This higher sensitivity of the ATP assay will enable a more accurate prediction of cell viability.

Adenosine Triphosphate↗
PubMed1987

1-Hexylcarbamoyl-5-fluorouracil is more cytostatic than 5-fluorouracil against human tumors in vitro.

The sensitivity of HeLa cells and 15 human tumors, including eight gastric cancers, five colorectal cancers and two lung cancers to 1-hexylcarbamoyl-5-fluorouracil (HCFU) was compared with that to 5-fluorouracil (5-FU) in vitro. HeLa cells were doubly sensitive to HCFU, as compared to 5-FU. After the HeLa cells had been treated with 5-FU or HCFU at 77 microM for 1-5 h, the intracellular levels of 5-FU and HCFU were determined, using gas chromatographic-mass spectrometric methods. The level of HCFU plus 5-FU in the HCFU-treated cells was twice as high as the level of 5-FU in the 5-FU-treated cells. The sensitivity to HCFU in 15 tumor tissues varied with the tissue; however, all tissues tested were more sensitive to HCFU than to 5-FU, assessed using the succinate dehydrogenase inhibition test. These results suggest that the hexylcarbamoyl structure facilitates the rapid uptake of HCFU through the cell membrane. HCFU may prove to be more effective for treating each individual patient with a malignant lesion.

Antineoplastic Agents↗
PubMed1987

Comparison between succinate dehydrogenase inhibition test and subrenal capsule assay for chemosensitivity testing.

The chemosensitivity result of the succinate dehydrogenase inhibition (SDI) test was compared with that of the subrenal capsule (SRC) assay in 23 human tumor tissues exposed to adriamycin (ADM), mitomycin C (MMC), cisplatin (DDP) and 5-fluorouracil (5-FU). The chemosensitivity was considered as positive when the succinate dehydrogenase (SD) activity of the drug-exposed cells was decreased to below 50% of that of control cells on day 3 in the SDI test, and the tumor size on day 6 was decreased to below -10% of that on day 0 in the SRC assay. Correlation rates between the decrease of SD activity in the SDI test and the decrease of tumor size in the SRC assay, using 23 evaluable cases in both assays, were r = 0.717 for ADM, r = 0.699 for MMC, r = 0.796 for DDP and r = 0.735 for 5-FU. The correlations of the chemosensitivity results were 73.9% for ADM, 73.9% for MMC, 82.6% for DDP and 60.9% for 5-FU. A positive correlation was noted between the in vitro and in vivo chemosensitivity results. This SDI test can serve as an effective tool for chemosensitivity testing.

Animals↗
PubMed1987

Carboquone alters the protein synthesis of Chinese hamster V79 cell.

The effect of carboquone (CQ) on protein synthesis in Chinese hamster V79 cells was determined. While the syntheses of higher molecular weight proteins decreased, the relative level of a 43-kilodalton (kd) protein increased following exposure to CQ at the concentration of 0.5 microgram/ml, in a time-related fashion, determined using one-dimensional gel electrophoresis. Using two-dimensional gel electrophoresis, the 43-kd protein may be actin protein, and the syntheses of another two proteins of 8.5/45 and 4.8/270 (designated isoelectric point/molecular weight, kd) were increased in the CQ-treated V79 cells. These changes of the proteins induced by CQ in V79 cells were noted in HeLa cells. Three CQ-induced proteins are candidates for the elucidation of the antineoplastic effect of CQ.

Animals↗
PubMed1987

Poorly differentiated human gastric carcinoma is more sensitive to antitumor drugs than is well differentiated carcinoma.

The chemosensitivities of 41 poorly differentiated gastric cancer tissues were compared with that of 16 well differentiated tissues, using the in vitro succinate dehydrogenase inhibition test. These human tissues obtained at the time of surgery were exposed to six different antitumor drugs: carboquone (CQ), adriamycin (ADM), mitomycin C (MMC), aclacinomycin A (ACR), cisplatin (DDP) and 5-fluorouracil (5-FU). The chemosensitivity was determined as positive when the succinate dehydrogenase (SD) activity of the drug exposed cells was decreased to below 50% of that of control cells, on day 3 of exposure. Decrease in SD activity was remarkable in the poorly differentiated tissues, compared to the well differentiated tissues, exposed to ADM, MMC, DDP and 5-FU. The sensitive rates were higher in the poorly differentiated tissues than in the well differentiated tissues, against all six antitumor drugs. Sixty-three per cent of the poorly differentiated tissues were sensitive to more than three antitumor drugs, in an identical tissue, but the rate was only 19% in the well differentiated tissues. The resistant rates to all drugs tested were 20% in the poorly differentiated and 31% in the well differentiated tissues. This would indicate that patients with a poorly differentiated gastric cancer will probably show a better response to antitumor drugs, compared to those with a well differentiated type.

Aclarubicin↗
PubMed1987

[Chemosensitivity testing for 5-FU and 5-FU derivatives using subrenal capsule assay].

An evaluation was made, using in vivo subrenal capsule (SRC) assay, of the chemosensitivity of 12 human neoplastic tissues including 7 gastric cancers, 2 colo-rectal cancers, 2 lung cancers and 1 breast cancer, exposed to 5-fluorouracil (5-FU) and the 5-FU derivatives: tegafur (FT), UFT and hexylcarbamoyl-5-FU (HCFU). The relative variation of tumor size (delta TS/TS0) was calculated as follows: delta TS/TS0 = (TS6-TS0)/TS0 X 100 (%), where TS6 was the tumor size on day 6 and TS0 that on day 0, and more than a 10% decrease of delta TS/TS0 in the treated group was considered as positive for chemosensitivity. Delta TS/TS0 was decreased to -10.9 +/- 11.3% (mean +/- standard deviation) for 5-FU, -13.0 +/- 16.4% for FT, -19.8 +/- 18.2% for UFT and -18.8 +/- 15.1% for HCFU, and the inhibition of tumor growth following exposure to 5-FU correlated well with that following exposure to 5-FU derivatives (5-FU vs. FT, r = 0.659; 5-FU vs. UFT, r = 0.864; 5-FU vs. HCFU, r = 0.729). However, the sensitivity of each tumor varied; for example, the chemosensitivity was positive for 5-FU derivatives, but negative for 5-FU, in some tissues. The SRC assay appears to be useful for selecting sensitive drugs from 5-FU and 5-FU derivatives for individual cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Comparison between the succinate dehydrogenase inhibition test and ATP assay for in vitro chemosensitivity testing].

The predicted level of cell viability was compared between the succinate dehydrogenase inhibition (SDI) test and the adenosine triphosphate (ATP) assay, both of which are used for in vitro human tumor chemosensitivity testing. After HeLa cells had been exposed to various concentrations of 5-FU for 1, 2, 3 or 4 days, the decrease occurring in viable cell number correlated with that of succinate dehydrogenase (EC 1.3.99.1) activity and that of the intracellular ATP level of the viable cells. In dead cells, the ATP level was extensively decreased, but the succinate dehydrogenase activity remained at a level of 11% of that of 5-FU-untreated viable cells, even on day 4. The cell viability correlated well with the intracellular ATP level, as compared with the succinate dehydrogenase activity. The activity remaining in dead cells must thus be taken into consideration for the prediction of chemosensitivity in the SDI test, but not in the ATP assay.

Adenosine Triphosphate↗