Biomedical subjects

Y Minagawa

Publications and source records attributed to Y Minagawa.

At least 19 recordsLinked to original sources

PubMed2001

Blood flow after intraarterial infusion chemotherapy in a patient with advanced cervical cancer.

We presented a case of locally advanced cervical cancer treated by intraarterial infusion chemotherapy, and evaluated the blood flow of uterine arteries before and after chemotherapy by using a transvaginal ultrasonic color Doppler device. Pulsatility index (PI) of each uterine artery increased after first course of chemotherapy compared to that of before chemotherapy. But PI did not change after second course in spite of a significant reduction in tumor size. Blood flow change assessed by Doppler ultrasound may be a limited but useful parameter for the efficacy of neoadjuvant chemotherapy in patients with cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

The role of topoisomerase I inhibitor in cisplatin-resistant ovarian cancer.

We discussed the role of DNA topoisomerase I (topo I) inhibitor, which is now widely used in clinical practice, in cisplatin-resistant ovarian cancer. Our study showed the synergistic actions between cisplatin and 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of 7-ethyl-10-[4-(1-pyperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), in two cisplatin-resistant cancer cell lines, HeLa/CDDP and KFr cells, but not in each parent cell line, HeLa and KF cells. Furthermore, HeLa/CDDP cells had a collateral sensitivity to SN-38. The levels of topo I protein in the cisplatin-resistant cells did not differ from those of their parent cell lines and were unaffected by exposure to cisplatin. In contrast, topo I enzymatic activity was 2-4 fold higher in the cisplatin-resistant cell lines compared with their respective parent cell lines. A significant correlation between the sensitivity for SN-38 and topo I activity human clear cell carcinoma cell lines, which are known as intrinsically ciasplatin-resistant cancer, was observed. Next, we examined the relationship between topo I activity and sensitivity to second-line chemotherapy consisting of cisplatin and CPT-11. A total of 30 patients with ovarian cancer who had initially undergone chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide (CAP) and exhibited measurable lesions were entered in the study. Tumor samples were obtained in the period between the initial and the second-line chemotherapy. Of those 30 patients, 18 responded to second-line chemotherapy and 12 did not. Topo I activity in tumor samples of responder was significantly greater than that of in nonresponders. In 8 cases whose samples could be obtained before and after CAP, topo I activity significantly increased after CAP therapy. Consequently, the combination therapy with cisplatin and CPT-11 may be effective for patients with cisplatin-resistant ovarian cancer. In addition, topo I enzymatic activity may be a predictor of the sensitivity for topo I inhibitor.

Animals↗

PubMed2000

Sensitivity to paclitaxel is not related to p53-dependent apoptosis in ovarian cancer cells.

We conducted this study to determine whether the sensitivity of ovarian cancer cells to paclitaxel (PTX) relates to cells undergoing p53-dependent apoptosis. Human ovarian adenocarcinoma cell lines (SK-OV-3, KF and KP cells) were used in this study. In SK-OV-3 and KP cells, which have a homozygous deletion of the TP53 gene, wild-type TP53 gene-transduction markedly enhanced the sensitivity to cisplatin (CDDP), but did not enhance the sensitivity to PTX. In all cells, the apoptotic index was increased by CDDP or PTX. After exposure to CDDP, p53 and Bax protein expression increased and Bcl-xL expression decreased in the KF cells and TP53 gene-transducted SK-OV-3 cells. However, these proteins did not change in KP cells. Therefore, the role of p53 in CDDP-induced apoptosis depends upon the cell type. In contrast, TP53 gene status did not correlate with PTX-induced cytotoxicity in any of the cell lines with differing apoptotic pathways. In conclusion, the sensitivity to PTX may not be related to p53-dependent apoptosis in ovarian cancer cells.

Antineoplastic Agents↗

PubMed2000

Prognosis and clinicopathological characteristics of Ib-IIb adenocarcinoma of the uterine cervix in patients who have had radical hysterectomy.

AIMS: The aim of the present study was to evaluate the outcome of patients with stage lb-IIb cervical adenocarcinoma treated with radical hysterectomy, and to determine the clinicopathological characteristics of those patients. METHODS: A total of 255 patients with cervical carcinoma stage Ib-IIb (57 adenocarcinoma and 198 squamous cell carcinoma) who had undergone radical hysterectomy were included in this study. Patient survival distribution was calculated using the Kaplan-Meier method. RESULTS: The estimated 5-year survival rate for patients with adenocarcinoma was significantly poorer than that for patients with squamous cell carcinoma (77.9% vs 91.7%). The survival rate in stage Ib patients did not differ between two groups (95.8% vs 94.4% respectively). The incidence of lymph node involvement was significantly higher in patients with adenocarcinoma than in those with squamous cell carcinoma (31.6% vs 14.8%). Among patients receiving post-operative radiotherapy, the survival rate for adenocarcinoma (71.1%) was significantly poorer than that for squamous cell carcinoma (90.0%). When patients underwent radical hysterectomy, the survival rate for stage II patients with adenocarcinoma was significantly poorer than that for patients with squamous cell carcinoma. CONCLUSIONS: The higher incidence of lymph node involvement and lower response to post-operative radiotherapy are considered to be factors of poorer prognosis in cervical adenocarcinoma.

Adenocarcinoma↗

PubMed2000

Alteration of a p53 gene status affects outcome of patients with recurrent ovarian cancer.

The aim of this longitudinal study was to examine whether and how the p53 gene is altered in patients with recurrent ovarian cancer and to determine the significance of p53 mutation in recurrent tumors. The primary and recurrent tumors were examined in 15 patients who had recurrent epithelial ovarian cancer, and whose primary tumor contained a wild-type p53 gene. The interval between cytoreductive surgery and the appearance of recurrence ranged from 5. 2 to 63.6 months (mean 23.4 months). Mutations in the p53 gene were screened by polymerase chain reaction single strand conformation polymorphism analysis and determined by cycle sequencing. Mutation of the p53 gene in the recurrent tumor was found in 7 of the 15 patients (46.7%). Estimated 3- and 5-year survival rates were 57.1 and 0%, respectively, for patients with p53 gene mutation detected in the recurrence tumor, and 75.0% and 37.5% for patients without the mutation (p = 0.0155). The interval between cytoreductive surgery and the appearance of recurrence did not differ between those groups (549.7 +/- 102.2 vs. 832.9 +/- 283.8 days). Mean survival time after recurrence was significantly better in the patients without mutation (438.6 +/- 56.4 vs. 873.0 +/- 157.5 days, p = 0.0125). The present study suggests that p53 gene mutation frequently occurs in recurrent ovarian cancer and that alteration of p53 gene status affects salvage chemotherapy. This phenomenon affects the prognosis of recurrent disease and may predict outcome.

Aged↗

PubMed2000

Cellular efflux pump and interaction between cisplatin and paclitaxel in ovarian cancer cells.

OBJECTIVE: The aim of this study was to evaluate the combination effect of paclitaxel (PTX) and cisplatin (CDDP) and to determine the mechanisms of interaction between these agents. METHODS AND RESULTS: We used human ovarian adenocarcinoma cell lines, namely a parent cell line (KF), a CDDP-resistant cell line (KFr) and a PTX-resistant cell line (KFTx).The combination effect of PTX and CDDP was synergistic on KF and KFTx and additive on KFr. The incidence of anaphase or telophase, evaluated by immunofluorescence microscopy, decreased with PTX and significantly decreased with PTX and CDDP in KF and KFTx. The concentration of PTX, which was measured by high-performance liquid chromatography, was higher in KF and KFTx cells treated with a combination of PTX and CDDP than those treated with PTX alone. Multidrug resistance gene mRNA appeared in KFTx and its expression decreased after exposure to PTX and CDDP. After exposure to CDDP, the expression of multidrug resistance-associated protein (MRP) and the concentration of glutathione increased in KF, but not in KFr or KFTx. MRP expression slightly increased in KF and KFTx after exposure to PTX. In contrast, its expression decreased in KFr. CONCLUSION: The present study suggests that CDDP enhances PTX accumulation and that the interaction of these agents is synergistic in CDDP-sensitive cells.

Adenocarcinoma↗

PubMed1999

Topoisomerase-I activity and response to second-line chemotherapy consisting of camptothecin-11 and cisplatin in patients with ovarian cancer.

The aim of the present study was to clarify the relationship between topoisomerase-I (topo-I) activity and sensitivity to second-line chemotherapy consisting of cisplatin and camptothecin-11 (CPT-11) in patients with ovarian cancer. Thirty Japanese women with relapsed epithelial ovarian cancer who received treatment at Tottori University Hospital or Kurume University Hospital between 1992 and 1997 were included in this study. All patients had initially undergone chemotherapy consisting of cisplatin, doxorubicin and cyclophosphamide (CAP). All subjects exhibited measurable lesions and received second-line chemotherapy consisting of 50 to 60 mg/m(2) CPT-11 on days 1, 8 and 15 and 60 mg/m(2) cisplatin on day 1. Tumor samples were obtained in the period between initial and second-line chemotherapy. Topo-I activity was assayed by relaxation of supercoiled plasmid substrate DNA. Of the 30 patients, 18 responded to second-line chemotherapy and 12 did not. We found no significant difference in patient characteristics in responders and non-responders. The interval from the end of the initial course of chemotherapy to the beginning of the second-line chemotherapy did not significantly differ in the 2 groups. The minimum amount of extraction showing complete DNA relaxation in non-responders was significantly greater than that in responders (201.7 +/- 92.5 vs. 124.1 +/- 59.4 ng; p = 0.0164). In 8 cases whose samples could be obtained before and after CAP, the amount of protein significantly decreased after CAP therapy (286.4 +/- 142.1 vs. 138.5 +/- 97.8 ng; p = 0.0294). Topo-I activity, which is enhanced by CAP therapy, can play an important role in sensitivity to CPT-11.

Adult↗

PubMed1999

Chemosensitivity and p53-dependent apoptosis in epithelial ovarian carcinoma.

BACKGROUND: Although p53 gene mutation frequently is observed in ovarian carcinoma, the function of the p53 gene in chemosensitivity has not been defined conclusively. The objective of the current study was to elucidate the relation between chemotherapy-induced apoptosis through the p53 pathway and chemosensitivity to ovarian carcinoma. METHODS: Tumor samples were obtained from 24 patients with epithelial ovarian carcinoma before and after chemotherapy with cisplatin, doxorubicin, and cyclophosphamide. Mutations in the p53 gene were screened by polymerase chain reaction-single-strand conformation polymorphism analysis and determined by cycle sequencing. Expression of the p53, Bax, and bcl-2 proteins and proliferating cell nuclear antigen (PCNA) were determined by immunohistochemical staining. Apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling method. RESULTS: Of the 24 patients, 12 responded to chemotherapy and 12 did not. p53 gene mutation was observed in ten nonresponders and two responders. The incidence of p53 protein expression in tumors with the gene mutation was 58% (7 of 12) and was 17% (2 of 12) in tumors without the gene mutation. A significant reverse correlation between apoptotic index (AI) and labeling index (LI), determined by the percentage of PCNA positive cells, was observed in tumors after chemotherapy. AI was found to increase significantly after chemotherapy in tumors with the wild-type p53 gene (3.84 +/- 1.64 vs. 7.13 +/- 5.23) but LI did not change in either tumor type. The expression of Bax protein was significantly greater in tumors with the wild-type p53 gene after chemotherapy. bcl-2 protein expression did not relate to p53 gene status before or after chemotherapy. CONCLUSIONS: The current study suggests that p53-dependent apoptosis in tumors is strongly related to the chemosensitivity in epithelial ovarian carcinoma.

Apoptosis↗

PubMed1999

Significance of cytoreductive surgery including bowel resection for patients with advanced ovarian cancer.

The aim of this study was to determine the significance of bowel resection in advanced ovarian cancer. A total of 64 women with stage IIIc or IV epithelial ovarian cancer, who consecutively received primary treatment between 1991 and 1995, were entered in this prospective study. The outcome of the patients undergoing bowel resection was evaluated. Thirty-nine patients underwent cytoreductive surgery at initial surgery. Of them, 16 patients could undergo optimal operation without bowel resection. Twenty-three patients received bowel resection at initial surgery. Of these 23 patients, 16 underwent optimal operation and 7 did not. Among 25 patients judged as inoperable cases at initial surgery, 21 responded to chemotherapy and underwent second surgery. Of 21 patients receiving second surgery, 15 underwent optimal operation (7 without bowel resection and 8 with bowel resection). The 3-year survival rate for 24 patients undergoing optimal operation with bowel resection (46.8%) was not significantly different from that for 23 patients without bowel resection (59.1%). Postoperative complications were seen in 8 patients (21.6%) of the patients receiving bowel resection and 3 (13.0%) of those without bowel resection. Cytoreductive surgery including bowel resection is effective for an improvement of the survival in patients with advanced ovarian cancer, if an optimal operation can be performed.

Adult↗

PubMed1999

Cisplatin-resistant HeLa cells are resistant to apoptosis via p53-dependent and -independent pathways.

Since HeLa cells possess very little functional p53 activity, they could be originally resistant to genotoxic stress-induced apoptosis. Therefore, it is likely that the drug-resistant cells derived from HeLa cells are more resistant to apoptosis. The aim of this study was to determine whether cisplatin-resistant cells derived from HeLa cells have an apoptosis-resistant phenotype. A cisplatin-resistant cell subline, HeLa/CDDP cells, showed a 19-fold resistance to cisplatin compared with the parent cells. The subline showed a collateral sensitivity to paclitaxel. An equitoxic dose (IC50) of cisplatin produced DNA fragmentation in HeLa cells but not in HeLa/CDDP cells. Transfection of wild-type p53 gene enhanced the cytotoxicity of cisplatin and cisplatin-induced apoptosis in HeLa cells but not in HeLa/CDDP cells, although it caused p53 overexpression in both cell lines. The expression of caspase 1 (interleukin-1beta-converting enzyme, ICE) mRNA and the overexpression of bax protein were observed only in HeLa cells. Paclitaxel-induced DNA fragmentation appeared less in HeLa/CDDP cells than in HeLa cells. p53 gene transfection did not affect the extent of DNA fragmentation in either cell line, suggesting that paclitaxel may induce p53-independent apoptosis. These findings suggest that HeLa/CDDP cells may have an acquired phenotype that is resistant to p53-dependent and -independent apoptosis.

Antineoplastic Agents↗

PubMed1998

Glutathione concentration may be a useful predictor of response to second-line chemotherapy in patients with ovarian cancer.

BACKGROUND: No useful predictor of resistance or sensitivity to second-line chemotherapy is known for ovarian cancer. The objective of this prospective study was to determine the utility of tumor glutathione S-transferase-pi (GST-pi) expression or glutathione (GSH) concentration in predicting ovarian cancer patients' responses to second-line chemotherapy. METHODS: Tumor samples were obtained from 26 patients with relapsed epithelial ovarian cancer 3-4 weeks before the initiation of second-line chemotherapy with etoposide (daily on Days 1-5) and cisplatin (on Day 5). The expression of GST-pi in tumor samples was determined by immunohistochemical staining and Western blot analysis. GSH concentration was measured by an enzymatic assay. RESULTS: The response rate was 38.4%. The estimated 3-year survival rate for the responders (66.7%) significantly exceeded that for the nonresponders (9.1%). Expression of GST-pi by immunohistochemical staining was more frequently observed in nonresponders (2 of 10 responders vs. 11 of 16 nonresponders). Western blot analysis detected GST-pi in all cases. There was no significant difference in the relative density values of the GST-pi Western blot analysis between the two groups. The mean value of GSH concentration in nonresponders was significantly higher than in responders (18.4 +/- 9.7 vs. 7.5 +/- 8.2 microg/mg protein). GSH concentration was below the cutoff point (10.3 microg/mg protein) in all responders except one. CONCLUSIONS: Second-line chemotherapy consisting of etoposide and cisplatin is effective in the treatment of relapsed epithelial ovarian cancer. In addition, tumor concentration of GSH may be a useful predictor of the response to this therapy.

Adult↗

PubMed1998

Indication and efficacy of radiation therapy following radical surgery in patients with stage IB to IIB cervical cancer.

OBJECTIVE: To determine the role of radiation therapy following radical surgery in patients with cervical cancer. METHOD: A total of 104 patients with International Federation of Gynecology and Obstetrics stage IB to IIB cervical cancer who underwent radical hysterectomy and pelvic lymph node dissection at Tottori University Hospital between 1988 and 1994 were entered in this study. The criteria for postoperative radiotherapy included positive lymph node involvement, compromised surgical margin, parametrial extension, or deep stromal invasion of cervix with less than 3 mm of distance from serosa. Postoperative radiotherapy consisted of 10-20 Gy whole pelvis and an additional parametrial dose with a midline block to deliver a total of 44-50 Gy to the pelvic side wall. RESULTS: Sixty-two patients (59.6%) who met the criteria received postoperative radiotherapy. Lymph node metastasis was most frequent in stage IIB followed by stage IIA and then stage IB (36.7, 22.2, and 10.7%, respectively). Parametrial extension was observed 8.7% of patients with stage IB and 27.7% of those with stage IIA. The estimated 5-year survival rate for patients undergoing surgery alone was 97.6% and that for patients receiving postoperative radiotherapy was 82.7% (P = 0.038). Multivariate analysis showed that lymph node metastasis and parametrial extension were major prognostic factor, but the survival rate did not relate to depth of stromal invasion. CONCLUSION: Postoperative radiotherapy may improve the survival of patients with cervical cancer exhibiting lymph node metastasis or parametrial extension.

Adult↗

PubMed1998

Radical surgery following neoadjuvant chemotherapy for patients with stage IIIB cervical cancer.

BACKGROUND: We conducted a phase II trial of radical surgery following neoadjuvant chemotherapy in patients with stage IIIB cervical cancer. METHODS: A total of 26 patients with stage IIIB cervical cancer were entered in this study. Patients were treated with a chemotherapeutic regimen consisting of intraarterial infusion of cisplatin and intravenous infusion of other anticancer agents, to a maximum of 3 courses. If the results of the evaluation indicated that surgery was feasible, radical surgery, including complete removal of pelvic vessels, partial resection of adjacent organs, and pelvic and paraaortic lymphadenectomy, was performed. Patients whose tumors showed no response received radiotherapy. We evaluated operability, survival rate, toxicities, and complications. Additionally, we examined prognostic variables by multivariate analysis in the patients treated by radical surgery. RESULTS: Eighteen patients (69.2%) underwent radical surgery. The remaining eight patients received radiation therapy. The 3-year disease-free survival rate was 72.2% in patients who received surgery and 25.0% in those who received radiotherapy. Multivariate analysis did not show any independent prognostic factors in the patients who underwent surgery. CONCLUSION: Radical surgery following neoadjuvant chemotherapy may be feasible in two thirds of patients with stage IIIB cervical cancer; therefore, phase III trials can be recommended.

Adult↗

PubMed1998

Alteration of telomerase activity associated with development and extension of epithelial ovarian cancer.

OBJECTIVE: To assess telomerase activity associated with the development and extension of epithelial ovarian cancer and to investigate the relationship between p53 gene status and telomerase activity. METHODS: A total of 53 samples (41 epithelial ovarian cancers, five borderline epithelial tumors, four benign adenomas, and three surface epithelia) were examined for telomerase activity by the polymerase chain reaction (PCR) -based telomeric repeat amplification protocol assay. Mutations in the p53 gene were determined by PCR-single strand conformation polymorphism analysis. RESULTS: Telomerase activity was detected in 33 of 41 epithelial ovarian cancers and in three of five borderline malignancies but was not detectable in either benign tumors or normal surface epithelium. The mean (+/-standard deviation [SD]) intensity of telomerase activity in cancers was significantly higher than that in borderline malignancies (10.6+/-8.2 versus 3.6 4+/-1.3). The positivity of telomerase activity did not correlate with any clinical findings, but the intensity (+/-SD) of telomerase activity was significantly higher in tumors with lymph node involvement (12.2+/-8.3 versus 3.8+/-1.1). Mutations of the p53 gene were observed in 44% of ovarian cancers; p53 gene status did not relate to telomerase activity. Multivariate analysis showed that the intensity of telomerase activity was not an independent factor for prognosis of patients with ovarian cancer. CONCLUSION: Telomerase activity may be associated with development and extension of epithelial ovarian cancer.

Adenocarcinoma, Mucinous↗

PubMed1998

A newly developed adenovirus-mediated transfer of a wild-type p53 gene increases sensitivity to cis-diamminedichloroplatinum (II) in p53-deleted ovarian cancer cells.

A new recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) was developed and the combination effect of p53 gene transfer and cis-diamminedichloroplatinum (II) (CDDP) was examined in an ovarian cancer cell line, SK-OV-3, with deletion of the p53 gene. AxCAp53 showed a high efficiency of gene transduction and increased sensitivity to CDDP in the SK-OV-3 cells. It was found that the sensitivity of the cells to CDDP correlated with the amount of infectious units of virus per cell of AxCAp53 which correlated with p53 protein expression. The results suggest that the combination of CDDP and AxCAp53 may be a potential strategy for the therapy of CDDP-resistant ovarian cancer.

Adenocarcinoma↗

PubMed1998

[A case of complete mediastinal goiter located in the retrotracheal region: review on reported cases from 1986 to 1997 in Japan].

A 66-year-old man was admitted to our hospital as a result of an abnormal shadow which was observed on his chest X-ray. A chest CT scan and chest MRI revealed an upper mediastinal tumor. The tumor was located in the retrotracheal region and resected completely following a thoracotomy. Histological examination of the tumor revealed follicular adenoma of the thyroid gland. Complete mediastinal goiter is a relatively rare lesion, with only 59 cases (including our case) in Japan prior to 1997. Only two cases were reviewed, in which the tumors were located in the retrotracheal region, out of the 59 cases in Japan.

Adenoma↗

PubMed1998

Gamma-glutamyl cysteine synthetase up-regulates glutathione and multidrug resistance-associated protein in patients with chemoresistant epithelial ovarian cancer.

Cellular detoxification, such as that mediated by the glutathione (GSH) system, is involved in the metabolism of various cytotoxic agents. Little is known, however, about the clinical relevance of cellular detoxification in chemoresistance. To elucidate the relevance of the GSH system to the resistance to chemotherapy observed in patients with ovarian cancer, we assayed the expression of mRNA encoded by the multidrug resistance-associated protein (MRP) and gamma-glutamyl cysteine synthetase (gamma-GCS) genes, as well as the level of GSH protein in 32 patients with epithelial ovarian cancer after chemotherapy. Tumors of 14 of the 32 patients responded to chemotherapy, whereas 18 did not. The levels of MRP and gamma-GCS transcripts in tumors from nonresponders were each about 2-fold higher than in responders. In contrast, the level of GSH did not differ between the two groups. We observed coordinated expression of gamma-GCS mRNA and GSH protein levels, and between gamma-GCS and MRP in nonresponders, but not in responders. Expression of MRP-encoded mRNA did not correlate to GSH level, however, in either group. These results suggest that gamma-GCS may up-regulate GSH and MRP expression in tumors unresponsive to chemotherapeutic agents, and that the GSH system may be involved in the mechanism of chemoresistance in ovarian cancer.

ATP-Binding Cassette Transporters↗

PubMed1997

Glutathione S-transferase-pi expression and glutathione concentration in ovarian carcinoma before and after chemotherapy.

BACKGROUND: To clarify the role of glutathione (GSH) in the chemotherapy resistance of ovarian carcinoma, the authors examined the expression of glutathione S-transferase-pi (GST-pi) and the concentration of glutathione in tumors before and after chemotherapy in the same patients. METHODS: The cohort for this study comprised 20 patients with ovarian carcinoma who had residual disease after primary surgery. These patients received two to three courses of postoperative chemotherapy, then underwent surgery for a second time. Chemotherapy consisted of 50 mg/m2 cisplatin, 40 mg/m2 doxorubicin, and 400 mg/m2 cyclophosphamide. The expression of GST-pi in tumors was determined by immunohistochemical staining and Western blot analysis. GSH concentration was measured by an enzymatic assay. RESULTS: Of the 20 patients, 10 responded to chemotherapy and 10 did not. Immunohistochemical staining for GST-pi was positive in 3 tumors among the 10 responders and in 7 tumors among the 10 nonresponders, but Western blot analysis detected GST-pi expression in all tumors. Among the responders, GST-pi after chemotherapy increased in one patient, was unchanged in two patients, and decreased in seven patients. Among nonresponders, GST-pi increased in six patients, was unchanged in one patient, and decreased in three patients. The ratio of GST-pi density in tumors after chemotherapy to GST-pi density before chemotherapy was significantly higher in nonresponders than in responders (2.0 +/- 1.1 vs. 0.6 +/- 0.4). The concentration of GSH in tumors was widely distributed, but it was found that the ratio of GSH concentration in each tumor after chemotherapy to GSH concentration before chemotherapy was significantly higher for nonresponders than for responders (3.0 +/- 1.3 vs. 0.6 +/- 0.3). CONCLUSIONS: Increased levels of GST-pi expression after chemotherapy are linked to drug resistance in patients with ovarian carcinoma.

Aged↗