P-Glycoprotein (P-gp), an efflux transporter, plays a crucial role in drug pharmacokinetic properties (ADME), and is critical for multidrug resistance (MDR) by mediating the active transport of anticancer drugs from the intracellular to the extracellular compartment. Here we reported an original database of 1273 molecules that are categorized into P-gp inhibitors and noninhibitors. The impact of various physicochemical properties on P-gp inhibition was examined. We then built the decision trees from a training set of 973 compounds using the recursive partitioning (RP) technique and validated by an external test set of 300 compounds. The best decision tree correctly predicted 83.5% of the inhibitors and 67.0% of the noninhibitors in the test set. Finally, we applied naive Bayesian categorization modeling to establish classifiers for P-gp inhibitors. The Bayesian classifier gave average correct prediction for 81.7% of 973 compounds in the training set with leave-one-out cross-validation procedure and 81.2% of 300 compounds in the test set. By establishing multiple decision trees and Bayesian classifiers, we evaluated the impact of molecular fingerprints on classification by the prediction accuracy for the test set, and we found that the inclusion of molecular fingerprints improves the prediction obviously. As an unsupervised learner without tuning parameters, the Bayesian classifier employing fingerprints highlights the important structural fragments favorable or unfavorable for P-gp transport, which provides critical information for designing new efficient P-gp inhibitors.
Uptake of 18F-FDG on PET or PET/CT either before or after treatment has a promising value of both predicting survival outcomes for patients with cervical cancer and identifying patients for more aggressive treatment.
ObjectiveTo define genetic profiling of homologous recombination (HR) deficiency in Chinese ovarian cancer patients.Methodswe have applied next-generation sequencing to detect deleterious mutations through all exons in 31 core HR genes. Paired whole blood and frozen tumor samples from 50 Chinese women diagnosed with epithelial ovarian carcinomas were tested to identify both germline and somatic variants.ResultsDeleterious germline HR-mutations were identified in 36% of the ovarian cancer patients. Another 5 patients had only somatic mutations. BRCA2 was most frequently mutated. Three out of the 5 somatic mutations were in RAD genes and a wider distribution of other HR genes was involved in non-serous carcinomas. BRCA1/2-mutation carriers had favorable platinum sensitivity (relative risk, 1.57, p<0.05), resulting in a 100% remission probability and survival rate. In contrast, mutations in other HR genes predicted poor prognosis. However, multivariate analysis demonstrated that platinum sensitivity and optimal cytoreduction were the independent impact factors influencing survival (hazards ratio, 0.053) and relapse (hazards ratio, 0.247), respectively.Conclusionour results suggest that a more comprehensive profiling of HR defect than merely BRCA1/2 could help elucidate tumor heterogeneity and lead to better stratification of ovarian cancer patients for individualized clinical management.
Background. We conducted this prospective, randomized, double-blind, placebo-controlled study to evaluate the effects of transcutaneous electric acupoint stimulation (TEAS) on the quality of recovery (QoR) and postoperative analgesia after gynecological laparoscopic surgery. Methods. 74 American Society of Anesthesiologists physical status (ASA) I or II patients undergoing gynecological laparoscopic surgery were randomly allocated to TEAS or control groups. The primary outcome was the quality of recovery, which was assessed on the day before surgery and 24 h after surgery using a 40-item questionnaire. Secondary outcomes included postoperative pain scores, the incidence of postoperative nausea and vomiting (PONV), duration of postanesthesia care unit (PACU) stay, and patient's satisfaction. Results. The TEAS group had higher QoR scores than control group upon 24 h after surgery (177 versus 165; P < 0.001). Compared with the control group, postoperative pain scores and the cumulative number of opioids administered were lower in the TEAS group patients (P = 0.04). TEAS reduced the incidence of PONV and dizziness, as well as duration of PACU stay. Simultaneously, the patient's satisfaction scores were higher in the TEAS group (P = 0.002). Conclusion. Preoperative TEAS enhances QoR, improves postoperative analgesia and patient's satisfaction, alleviates postoperative side effects, and accelerates discharge after general anesthesia for gynecological laparoscopic surgery.
(Abstracted from Fertil Steril 2019;112:283–290)
Despite a widespread increase in the use of preimplantation genetic testing (PGT), there remains inconclusive examination of maternal and neonatal outcomes after pregnancy achieved through in vitro fertilization (IVF) with PGT. It has been proposed that abnormal placentation may occur at a higher rate in pregnancies after PGT due to the removal of trophectoderm cells during biopsy, leading to higher rates of preeclampsia and restricted fetal growth.
Objective: To evaluate the influence of insemination methods on outcomes of preimplantation genetic testing for aneuploidy (PGT-A) by assessing PGT-A results in embryos that derived from conventional in vitro fertilization (IVF) versus intracytoplasmic sperm injection (ICSI) in sibling oocytes. Design: Retrospective cohort study. Setting: Single academic IVF center.
BackgroundB-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) might be an appropriate biomarker in the management of epithelial ovarian cancer (EOC). However, the biological role of BMI1 and its relevant molecular mechanism needs further elaboration. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is an excellent genome-editing tool and is scarcely used in EOC studies.MethodsWe first applied CRISPR/Cas9 technique to silence BMI1 in EOC cells; thereafter we accomplished various in vivo and in vitro experiments to detect biological behaviors of ovarian cancer cells, including MTT, flow cytometry, Transwell, real-time polymerase chain reaction and western blotting assays, etc.; eventually, we used RNA sequencing to reveal the underlying molecular traits driven by BMI1 in EOC.ResultsWe successfully shut off the expression of BMI1 in EOC cells using CRISPR/Cas9 system, providing an ideal cellular model for investigations of target gene. Silencing BMI1 could reduce cell growth and metastasis, promote cell apoptosis, and enhance the platinum sensitivity of EOC cells. BMI1 might alter extracellular matrix structure and angiogenesis of tumor cells through regulating Focal adhesion and PI3K/AKT pathways.ConclusionBMI1 is a potential biomarker in EOC management, especially for tumor progression and chemo-resistance. Molecular traits, including BMI1 and core genes in Focal adhesion and PI3K/AKT pathways, might be alternatives as therapeutic targets for EOC.Electronic supplementary materialThe online version of this article (10.1186/s13048-018-0406-z) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.