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Background: Overexpression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and glutathione-S-transferase pi (GSTpi) is associated with drug resistance in acute myeloid leukemia (AML). The short-term effects of drug exposure on their expression levels were investigated., Materials and Methods: HL-60 cells and drug-resistant sublines were cultured with or without daunorubicin (DNR) and cytarabine (Ara-C). At several time-points the expression levels of P-gp, BCRP and GSTpi were determined., Results: After exposure to Ara-C, P-gp mRNA rapidly increased in all the cell lines. P-gp protein was detected in the sensitive cells after 8 h exposure to Ara-C. GSTpi mRNA increased in the resistant cells, but no change in BCRP mRNA was observed. Exposure to DNR revealed rapidly increased P-gp and GSTpi mRNA in the resistant cells., Conclusion: Ara-C rapidly increases P-gp mRNA and protein expression in sensitive and resistant cells, and GSTpi mRNA in resistant cells, in vitro. This may be of clinical importance during AML induction chemotherapy.

Aim: Multidrug resistance (MDR) is closely correlated to an unfavorable prognosis in various human cancers. However, the clinical significance of the expression of MDR-related proteins p-glycoprotein (PGP), glutathione-s-transferases (GST-pi), topoisomerase-II (Topo-II) and lung resistance protein (LRP) in primary gastric cardiac adenocarcinoma (PGCA) remains unclear. In this present study, the total of the four kinds of MDR-related proteins mentioned above were detected by using immunohistochemistry, and their clinical significance in chemoresistance were also investigated., Methods: This retrospective study included 69 resected specimens from patients with PGCA. The expression of PGP, GST-pi, Topo-II and LRP in formalin-fixed paraffin-embedded tissue sections was determined by a labelled streptavidin-biotin immunohistochemical technique, and the results were analyzed in correlation with clinicopathological data. None of these patients received chemotherapy prior to surgery., Results: The positive rates of expression of PGP, GST-pi, Topo-II and LRP in malignant tissues (49.2%, 75.4%, 68.1% and 58%, respectively) were all higher than that of the normal tissues(0, 30%, 20% and 0, respectively, P < 0.01). PGP expression in tumors that had metastasized was significantly more frequent than in tumors that had not metastasized (67.5% vs 24.1%, P < 0.01). The expression of PGP was closely related with clinicopathologic staging (staging 1/2 vs 3/4, 28.6% vs 58.3%, P < 0.05). No significant correlation was shown between PGP and increasing differentiated degree (40%, 42.4% and 61.5%, P > 0.05). GST-pi expression status progressively increased with increasing differentiated degree (40%, 75.8% and 88.5%, P < 0.05) and clinicopathologic stage (staging 1/2 vs 3/4, 57.1% vs 83.3%, P < 0.05). In addition, a significant positive correlation was also observed between GST-pi and lymphatic metastasis (with vs. without metastasis, 87.5% vs 58.6%, P < 0.05). The expression of Topo-II was associated with increasing differentiated degree (33.3%, 69.7 and 80.7%, P < 0.01). No significant differences with Topo-II expression were found in relation to the clinicopathologic stage (staging 1/2 vs 3/4, 57.1% vs 72.9%, P > 0.05) and lymphatic metastasis (with vs. without metastasis, 65.0% vs 72.4%, P > 0.05). Moreover, a significant difference with the expression of LRP was found in relation to the clinicopathologic stage (staging 1/2 vs 3/4, 38% vs 66.6%, P < 0.05), and lymphatic metastasis (with vs without metastasis, 70.0% vs 41.4%, P < 0.05). Comparing the well, moderately and poorly differentiated cohort, a non-statistical increasing trend towards LRP expression status was noted (50.0%, 54.5% and 65.3%, respectively, P > 0.05). Besides, the co-expression of all four tested MDR-related proteins also existed. The positive rates of co-expression of PGP and GST-pi, PGP and Topo-II, PGP and LRP, GST-pi and Topo-II, LRP and GST-pi, LRP and Topo-II, PGP, GST-pi, Topo-II and LRP in malignant cells were 23.2%, 15.9%, 11.6%, 13.0, 26.1, 7.24, 5.8, respectively., Conclusions: MDR-related proteins PGP, GST-pi, Topo-II alpha and LRP are involved in multiple mechanisms of drug resistance in PGCA. Combined determination of PGP, GST-pi, Topo-II and LRP may be prospectively valuable for optimizing the chemotherapy regimes, developing high quality anti-cancer drugs, and further predicting the outcomes of those patients with PGCA.

Objective: To evaluate the relationship between combined multigene detection and response to chemotherapy and prognosis in epithelial ovarian carcinomas (EOCS)., Methods: A total of 80 ovarian tissue samples taken from the surgical specimens of patients with EOCS of our hospital in the last two decades who had received chemotherapy after surgery were paraffin-embedded. The samples were divided into 2 groups, good prognosis group (patients who survived more than 2 years, n = 46) and poor prognosis group (patients who survived less than 2 years, n = 34). The expression levels of ToPo-II, Ki-67, MGMT, PCNA, p27, p53, p16, P-gp, LRP, GST-pi, bcl-2, C-myc, Fas, bax, MSH2, MRP and BCRP were investigated by the combination of tissue arrays and immunohistochemical streptavidin-biotin peroxidase (SP) method in all samples. Data were analysed with SPSS 12.0 for windows., Results: There were statistically significant differences in the positive expression levels of P-gp, BCRP, MGMT, MSH2, p27 and p16 (62%, 50% and 50% in poor prognosis group vs 33%, 28% and 28% respectively, P < 0.05) in the good prognosis group, suggesting that the positive expression levels of P-gp, BCRP, MGMT, MSH2, p27 and p16 were related to the response to chemotherapy and prognosis in EOCS. And the positive expression of P-gp, BCRP and MSH2 (43%, 54% and 43%) indicated poor prognosis, while the positive expression of MGMT, p27 and p16 (18%, 29% and 24%, P < 0.05) indicated good prognosis. Cox multigene expression analysis confirmed that the positive expression levels of MRP, C-myc, LRP, p16, p27, MGMT, ToPo-II, P-gp and GST-pi were related to the response to chemotherapy and prognosis in EOCS. And the positive expression of MRP, C-myc, LRP, ToPo-II, P-gp and GST-pi indicated poor prognosis, while the positive expression of MGMT, p27 and p16 indicated good prognosis. Combined multigene detections were conducted among P-gp, BCRP, MGMT, MSH2, p27 and p16, and there were statistically significant differences in the positive coexpression of P-gp plus MGMT in the two groups (P < 0.05); indicating that the combined multigene expression were related to the response to chemotherapy and prognosis in EOCS. The predictive value to response to chemotherapy and prognosis of the positive coexpression of P-gp plus MGMT was 70%., Conclusions: By univariate and multivariate analyses, the positive expression of P-gp, MGMT, p27 and p16 are related to the response to chemotherapy and prognosis in EOCS. The combined multigene expression of P-gp plus MGMT are related to the response to chemotherapy and prognosis and could predict prognosis more effectively.

This study was purposed to investigate the relationship of expressions of gluthatione-S-transferase-pi (GST-pi), multidrug resistance protein-1 (MRP-1), lung resistance protein (LRP) with multidrug resistance of acute leukemia (AL), the correlation between 3 kinds protein expressions and the correlation of their protein expression with clinical features of AL patients. The S-P immunohistochemical staining method was used to determine the expressions of GST-pi, MRP1 and LRP proteins in 80 AL patients and 30 normal subjects. The results showed that there was the correlation between GST-pi, MRP1, LRP protein expression and chemotherapy resistance, meanwhile CR rates of patients with positive expression of those proteins were lower than that of patients with negative expression (P<0.05), so those protein expressions may be accounted for poor prognosis. There was the positive relationship between expression of GST-pi and MRP1 in refractory group (r=0.851, P<0.01). It is concluded that co-examination of GST-pi and MRP1 has greater significance than examination of one kind of protein in evaluating poor prognosis of leukemia patients. LRP protein expression increase obviously when WBC counts >or= 10 x 10(9)/L (63.6%, P<0.05), therefore LRP protein has great judging value for evaluating drug resistance and prognosis of acute leukemia patients whose peripheral blood WBC counts were high.

Objective: To explore the expression of multidrug resistance gene 1 ( MDR1), glutathione-S-transferases-pi (GST-pi) in osteosarcoma and soft tissue sarcoma tissues from 34 patients and their correlation with chemotherapy resistance., Methods: MDR1 and GST-pi expressions were analyzed by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) and flow cytometry (FCM) at mRNA and protein levels, respectively. Chemotherapy sensitivity on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were detected by MTT assay., Results: The nonsensitive rates on adriamycin, cisplatinum, fluorouracil, mitomycin C, dacarbazine, vincristine, methotrexate in tumor tissues were 41.18%, 17.7%, 47.1%, 50.0%, 76.5%, 61.8% and 52.9%, respectively. The expression of P-glycoprotein (P-gp) and GST-pi in tumor tissues was 1.54 and 2.58 (relative fluorescence intensity). Chi2 analysis showed that there was a positive correlation between P-gp expression and drug resistance on ADM, GST-pi expression and resistance on ADM, DDP and MMC (P < 0.05). There was not seen obvious correlation between expression of MDR1, GST-pi and age, gender, pathological type, tumor size in osteosarcoma and soft tissue sarcoma patients (P > 0.05). The expression of GST-pi was increased in patients receiving preoperative chemotherapy. The rate of postoperative recurrence was higher in patients with higher GST-pi expression level than those with lower GST-pi expression level before operation (P < 0.05)., Conclusion: Individual differences exist in chemotherapy sensitivity and expression of MDR1 and GST-pi in osteosarcoma and soft tissue sarcomas patients. Chemotherapy can induce up-regulation of GST-pi protein expression. Primary high expression of GST-pi is the main mechanism of resistance of osteosarcoma and soft tissue sarcomas to chemotherapy and is related to poor prognosis.

Objective: To study the expression and clinical significance of P-gp, GST-pi and Topo II alpha in gastric and colorectal cancers., Methods: The expression of P-gp, GST-pi and Topo II alpha in 83 cases with gastric or colorectal cancer were examined by immunohistochemistry S-P., Results: The positive expression rates of P-gp, GST-pi, Topo II alpha in normal tissue and gastric and colorectal cancers were 69.9%, 65.1%, 50.6% and 83.1%, 85.5%, 45.8%, respectively. The positive rates of P-gp and GST-pi in gastric and colorectal cancer were significantly higher than those in normal gastric and colorectal tissue (P < 0.05). The expression of Topo II alpha in poorly differentiated cancers was significantly higher than that in well-and moderately differentiated cancers. There was no correlation between other items and clinicopathological parameters (P > 0.05)., Conclusion: P-gp, GST-pi and Topo II alpha play important role in multidrug resistance. Their mechanisms of drug resistance were different. The detection of expression of P-gp, GST-pi and Topo II alpha has an important guiding significance in chemotherapy for gastric and colorectal cancers.

Objective: To study the correlation of expression implication of MDR genes (GST-pi and Topo II) and MDR gene-coded product (Pgp) with prognosis in laryngopharyngeal malignant melanoma., Method: Using immunohistochemical S-P method,expression of GST-pi, Topo II and Pgp was detected in 28 cases of laryngopharyngeal malignant melanoma. The relationship between GST-pi, Topo II, Pgp and clinicopathological features, prognosis of the tumors were also analyzed., Result: The positive rates of Pgp, GST-pi and Topo II were 35.7%, 57.1% and 46.4% respectively in 28 cases of laryngopharyngeal malignant melanoma, without significant difference (P > 0.05). The positive rates of Pgp, GST-pi and Topo II were not correlated with sex,age, size of tumor and Clark's grade, Breslow's grade (P > 0.05), but AJC grade and prognosis (P < 0.05)., Conclusion: Expression of Pgp,GST-pi and Topo II may be the chief mechanism of multi-drug resistance. Detection of multi-drug resistance genes is of necessity and feasibility when predicting the effect of chemotherapy.

Objective: To discuss the guiding significance of multidrug resistance (MDR) gene expression for monitoring the clinical effectiveness of chemotherapy upon cancer, and to analyze the MDR1 and glutnthione-s-transferase(GST-pi) mRNA expression rates in primary breast cancer, and their correlation with the clinical outcome and prognosis., Methods: The mRNA expression levels of MDR1 in 16 cases with malignant pleural effusion and ascites and 102 cases of solid tumors were measured using semiquantitative RT-PCR assay. The MDR1 and GST-pi mRNA expression rates in 84 cases of breast cancer, out of the 102 cases of solid tumors, were also studied in the same way., Results: (1) An average coincidence rate of 84.5% was found between the mRNA expression level of MDR1 and the clinical response to chemotherapy in the 16 cases with malignant pleural effusion and ascites and 18 cases of solid tumors. (2) The positive rate of MDR1 mRNA expression in primary breast cancer tissue was 79.7%, with the medium and high levels as high as 33.3%, while the positive rate of GST-pi mRNA expression was 33.3%, with the medium and high expression levels being as low as 4.8%. There was a highly significant difference between the two groups (P < 0.01). The positive rates of MDR1 mRNA in the group having received chemotherapy before surgery and the group not receiving chemotherapy before surgery were 87.8% and 68.6% respectively, showing a lymph nodes and in the group without metastases in axillary lymph nodes were 89.1% and 68.4% respectively, indicating a significant difference (P < 0.05). The positive rates of GST-pi mRNA in the group suffering distant metastases and the group not suffering distant metastases were 71.4% and 20.6% respectively, showing a significant difference (P < 0.05). The GST-pi mRNA expression rates in the estrogen receptor (ER)- and progesterone receptor (PR)-positive groups were higher than those in the ER- and PR-negative groups, indicating a significant difference (P < 0.05) ., Conclusion: The mRNA expression level of MDR1 has a relatively high correlation with the clinical response to chemotherapy, and thus can be used to monitor the effectiveness of chemotherapy. MDR1 is the main drug resistance mechanism in breast cancer. Chemotherapy before surgery induces MDR1 mRNA expression. MDR1 e xpression and GST-pi mRNA expression serve as a significant prognostic indicator for breast cancer, thus having guiding significance for assessing prognosis.