The mRNA expression of BRCA1, ERCC1, TUBB3, PRR13 genes and their relationship with clinical chemosensitivity in primary epithelial ovarian cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer.</p><p><b>METHODS</b>Primary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated.</p><p><b>RESULTS</b>The BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673±2.143, and clinical-sensitive group -1.436±2.594 (P=0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529±1.982 and clinical-sensitive group -3.188±2.601 (P=0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P=0.074), and the TUBB3 expressions between the two groups were also not significantly different (P=0.619). When the intercept point value BRCA1 mRNA expression logarithm was -0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively.</p><p><b>CONCLUSIONS</b>BRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer.</p>

Application of ATP-tumor chemosensitivity assay in primary epithelial ovarian cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the predictive value of the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in the chemotherapy applied in primary epithelial ovarian cancer (PEOC), and to analyze if the neoadjuvant chemotherapy have any influence on the postoperative chemosensitivity.</p><p><b>METHODS</b>ATP-TCA results from 61 PEOC specimens were analyzed retrospectively. Patients were divided into sensitive group and resistant group according to the ATP-TCA results. Sensitive index (SI) was applied to analyze the ATP-TCA results. The correlation between in vitro results and clinical outcome was assessed by univariate and multivariate analysis.</p><p><b>RESULTS</b>SI set at > 250 had the highest test sensitivity, specificity, positive and negative predictive value of 91.6%, 73.9%, 84.6% and 85.0%, respectively. The ATP-TCA results had significant correlation with clinical outcome (chi(2) = 26.9, P < 0.001). Patients with tumors shown to be resistant had a higher risk of recurrence in comparison with those who were tested as sensitive (P = 0.030, OR = 0.033, 95%CI 0.002 approximately 0.724). The median progression-free survival (PFS) and overall survival (OS) of in vitro-sensitive patients were 26 months and 39 months, respectively, significantly longer than those in the in vitro drug-resistant group of patients (PFS 10 months and OS 25 months) (both P < 0.01). Neoadjuvant chemotherapy had a significant correlation with the clinical chemoresistance (chi(2) = 15.214, P < 0.001).</p><p><b>CONCLUSION</b>ATP-TCA assay may effectively predict the chemosensitivity of primary ovarian cancer, and predict the early recurrence of the tumor.</p>

Application of ATP-tumor chemosensitivity assay in recurrent epithelial ovarian cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the value of adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in individualized treatment of recurrent epithelial ovarian cancer (REOC), and to evaluate the correlation between the in vitro chemosensitivity assay and clinical drug sensitivity.</p><p><b>METHODS</b>Sixty-nine REOC specimens were tested by ATP-TCA assay retrospectively. The patients were divided into strong sensitive, moderate sensitively and resistant groups according to the ATP-TCA assay results. The clinical results were evaluated according to imaging and serum CA125 analysis. The correlation between in vitro ATP-TCA assay and clinical outcome was statistically analyzed by χ(2) test. The progression free survival (PFS) and overall survival (OS) of each group were analyzed using Kaplan-Meier method.</p><p><b>RESULTS</b>The results of ATP-TCA assay had significant correlation with clinical outcome. The clinical chemotherapy outcome became better with increased drug sensitivity in vitro (χ(2) = 9.066, P = 0.004). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate for ATP-TCA method to predict the clinical chemotherapy sensitivity of REOC were 87.5%, 45.9%, 58.3%, 80.9% and 65.2%, respectively. The mean PFS of strong sensitive group, moderately sensitive group and resistant group were 187.1 days, 195.0 days and 60.3 days, respectively. The mean OS were 476.7, 335.7 and 237.5 days, respectively, following the start of TCA-directed therapy. The PFS and OS of the two sensitivity groups in vitro were significantly longer than that of the in vitro-resistant group (P < 0.01).</p><p><b>CONCLUSION</b>The results of ATP-TCA assay are well correlated with clinical treatment responses. The assay may be an important and useful method for individualized chemotherapy for recurrent ovarian cancer.</p>

Expression of retinoic acid receptor-beta mRNA and p16, p53, Ki67 proteins in esophageal carcinoma and its precursor lesions / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression of retinoic acid receptor-beta (RAR-beta) mRNA and p16, p53, Ki67 proteins in squamous-cell carcinoma of the esophagus and its precursor lesions in a high risk population.</p><p><b>METHODS</b>A total of 397 tissue specimens were collected from individuals with normal mucosa (NM, n = 25), mild dysplasia (MiD, n = 69), moderate dysplasia (MoD, n = 106), severe dysplasia (SD, n = 51), carcinoma in situ (CIS, n = 78), and squamous-cell carcinoma (SC, n = 68). Expression of RAR-beta mRNA was detected by in situ hybridization, and that of p16, p53 and Ki67 proteins by immunohistochemistry.</p><p><b>RESULTS</b>The frequencies of RAR-beta mRNA expression in NM, MiD, MoD, SD, CIS and SC were 96.0%, 89.9%, 67.9%, 68.6%, 62.8%, and 63.2%, respectively. The frequencies of p16 expression were 88.0%, 71.0%, 64.2%, 51.0%, 53.8% and 52.9%; those of p53 expression were 4.0%, 39.1%, 57.5%, 52.9%, 67.9% and 69.1%; those of Ki67 expression were 0, 40.6%, 61.3%, 58.8%, 59.0% and 75.0%, respectively.</p><p><b>CONCLUSION</b>There are no significant differences in four biomarkers expression between carcinoma of the esophagus and its precursor lesions.</p>

Correlation between ATP bioluminescence tumor chemosensitivity assay and clinical response in ovarian cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the correlation between results of ATP bioluminescence tumor chemosensitivity assay (ATP-TCA) of human ovarian cancer specimens in vitro and clinical chemo-therapeutic responses of patients.</p><p><b>METHODS</b>Thirty-four freshly taken ovarian cancer specimens (28 cases) and ascites (6 cases) and 9 chemotherapeutic drugs were tested in vitro for cancer chemosensitivity by ATP-TCA.</p><p><b>RESULTS</b>Among the 34 ovarian cancer cases, the efficacy of ATP-TCA is 94.0%, the sensitivity, the specificity, the positive and negative predicting values, and an overall predicting value in vitro and vivo were 90.0%, 91.7%, 94.7%, 84.6% and 90.6%, respectively.</p><p><b>CONCLUSION</b>The results of ATP-TCA assay are correlated well with clinical treatment responses. The assay may be an important and useful method for individual-based chemotherapy of cancers.</p>

Expression of a plant associated human cancer antigen in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression of a glycoprotein of plant origin in normal, benign and malignant breast tissues.</p><p><b>METHODS</b>Expression of a plant glycoprotein was examined in 5 samples of normal breast tissues, 20 fibro-adenoma and 136 breast cancer by SABC immunohistochemical staining and the results were analyzed by SPSS statistics software.</p><p><b>RESULTS</b>No positive staining was detected in normal breast tissues (0/5). Weak staining was observed in 4 of 20 (20.0%) breast fibro-adenoma. Positive staining was demonstrated in 116 out of 136 (85.3%) breast cancer specimens. The differences were statistically significant. The expression of plant-associated human cancer antigen was related to pathological grade (P < 0.05), tissue invasiveness (P < 0.01) and recurrence (P < 0.05), but not to patients' age, tumor size and c-erbB-2 expression.</p><p><b>CONCLUSION</b>The plant glycoprotein studied may be a human cancer-associated antigen which might be a potential marker of breast cancer.</p>

Heterogeneity of human breast cancer cells and their biological behavior / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the heterogeneity of human breast cancer cells, their influence on biological behavior of tumor cells and clinical implications.</p><p><b>METHODS</b>The subpopulations of MCF-7 breast cancer cells were isolated by Percoll gradient centrifugation. DNA content and cell cycle distribution were detected with flow cytometry. Tumor chemosensitivity analysis was performed with MTT assay.</p><p><b>RESULTS</b>Heterogeneity was observed in DNA content and cell cycle distribution among four subpopulations of breast cancer cells, which were related to their proliferation ability and chemosensitivity results.</p><p><b>CONCLUSION</b>Hereditary instability and intrinsic characteristics of most tumor cells, not only lead to tumor progression and heterogeneity but also cause the loss of monoclonality and the generation of subclones. Further study on some profiles of tumor heterogeneity such as DNA content, cell cycle distribution and their influence on tumor proliferation and chemosensitivity may very well improve the clinical treatment.</p>