Time filter

Source Type

Medicine Lodge, United States

Okoye E.I.,Houston Methodist Hospital | Bruegl A.S.,Gynecologic Oncology and Reproductive Medicine | Fellman B.,Biostatistics | Luthra R.,University of Texas | Broaddus R.R.,Houston Methodist Hospital
International Journal of Gynecological Pathology | Year: 2016

Endometrial endometrioid carcinomas are related to estrogen excess and express estrogen and progesterone receptors. However, hormone receptor expression can be variable from tumor to tumor, and this variability is not always explained by differences in tumor grade. Variable expression of other biomarkers that may be used in the diagnostic work-up of endometrial cancer has also been noted. We hypothesized that mismatch repair (MMR) defects may contribute to this variability. A total of 411 unselected endometrial carcinomas were evaluated for immunohistochemical expression of DNA MMR proteins and MLH1 methylation. Loss of immunohistochemical expression of MLH1, MSH2, MSH6, or PMS2 was defined as MMR deficient; positive expression was defined as MMR intact. A case-control cohort of 80 Grade 2 endometrioid carcinomas was selected from this set (40 MMR deficient, 40 MMR intact). Cases were matched for histotype, grade, and age. Estrogen receptor, progesterone receptor, CK7, CK20, and Pax-8 immunohistochemistry was evaluated. The median percentage of CK7 + tumor cells was significantly lower in the MMR deficient group compared with the MMR intact group. The mean percentage of tumor cells exhibiting estrogen receptor expression was similar in both the MMR-deficient and MMR intact groups. However, there was greater variability in the MMR-deficient group. Our study shows that MMR defects influence the expression of clinically important biomarkers for endometrioid-type endometrial carcinoma as decreased cytokeratin 7 expression is more commonly associated with MMR deficiency. © 2015 International Society of Gynecological Pathologists. Source

Liu G.,Experimental Therapeutics | Liu G.,Tianjin Medical University | Yang D.,Experimental Therapeutics | Rupaimoole R.,University of Houston | And 21 more authors.
Journal of the National Cancer Institute | Year: 2015

Background: Chemoresistance is a major challenge in cancer treatment. miR-506 is a potent inhibitor of the epithelial-to-mesenchymal transition (EMT), which is also associated with chemoresistance. We characterized the role of miR-506 in chemotherapy response in high-grade serous ovarian cancers. Methods: We used Kaplan-Meier and log-rank methods to analyze the relationship between miR-506 and progression-free and overall survival in The Cancer Genome Atlas (TCGA) (n = 468) and Bagnoli (n = 130) datasets, in vitro experiments to study whether miR-506 is associated with homologous recombination, and response to chemotherapy agents. We used an orthotopic ovarian cancer mouse model (n = 10 per group) to test the effect of miR-506 on cisplatin and PARP inhibitor sensitivity. All statistical tests were two-sided. Results: MiR-506 was associated with better response to therapy and longer progression-free and overall survival in two independent epithelial ovarian cancer patient cohorts (PFS: high vs low miR-506 expression; Bagnoli: hazard ratio [HR] = 3.06, 95% confidence interval [CI] = 1.90 to 4.70, P <. 0001; TCGA: HR = 1.49, 95% CI = 1.00 to 2.25, P = 0.04). MiR-506 sensitized cells to DNA damage through directly targeting the double-strand DNA damage repair gene RAD51. Systemic delivery of miR-506 in 8-12 week old female athymic nude mice statistically significantly augmented the cisplatin and olaparib response (mean tumor weight ± SD, control miRNA plus cisplatin vs miR-506 plus cisplatin: 0.36±0.05g vs 0.07±0.02g, P <. 001; control miRNA plus olaparib vs miR-506 plus olaparib: 0.32±0.13g vs 0.05±0.02g, P =. 045, respectively), thus recapitulating the clinical observation. Conclusions: MiR-506 is a robust clinical marker for chemotherapy response and survival in serous ovarian cancers and has important therapeutic value in sensitizing cancer cells to chemotherapy. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. Source

Hou M.-M.,University of Houston | Hou M.-M.,Chang Gung University | Liu X.,University of Houston | Wheler J.,University of Houston | And 12 more authors.
Anticancer Research | Year: 2014

Background: We evaluated clinical outcomes of patients with metastatic cervical cancer referred to a Phase I Clinical Trials Program. Patients and Methods: We reviewed the electronic medical records of 54 consecutive phase I patients with metastatic cervical cancer over 6.5 years and analyzed the correlation between clinical outcome and potential predictors. Results: All patients had received at least one systemic therapy for metastatic disease before referral. Only two patients declined phase I trial therapy. The median progression-free (PFS) and overall (OS) survivals were 3.6 and 10.6 months, respectively. Patients harboring phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations or phosphatase and tensin homolog loss, and those with more than two sites of metastasis who received more than one prior systemic chemotherapy before the referral had median PFS of 6.7 and 1.8 months, and median OS of 12.6 and 2.9 months, respectively. Conclusion: Patients with more than two metastatic sites who had received more than one prior system therapy had dismal outcomes. An aberrant PI3K pathway was frequently identified and associated with favorable outcome, providing a promising target. Source

Discover hidden collaborations