Multidrug resistance of tumor cells has greatly limited the chemotherapy effect. The development of reliable strategies to deal with tumor multidrug resistance is highly desirable for tumor therapy. In this work, a near-infrared II (NIR II) luminogen was rationally designed and prepared, which could act as a photothermal reagent to reverse the drug resistance of tumor cells by reducing the related protein expression, achieving a high inhibition efficiency with the synergistic effect of chemotherapeutic drugs. By the selection of a strong electron-withdrawing unit, the emission peak of the luminogen could reach 973 nm. Moreover, this luminogen shows outstanding photothermal conversion ability and improved thermal stability compared to ICG. Notably, after the photothermal treatment of drug-resistant tumor cells by the NIR II luminogen, the antitumor efficiency of chemotherapeutic drugs, including paclitaxel, cis-platinum, and doxorubicin, was significantly enhanced. The mechanism exploration revealed that drug resistance-related proteins were remarkably reduced, making the cells more sensitive toward drugs. Thus, this strategy demonstrated a promising and reliable approach to reverse the drug resistance of tumor cells for efficient tumor inhibition in the clinic.
Our previous study showed FOXM1 expression was significantly up-regulated in cervical cancer, and was associated with poor prognosis. To clarify miRNAs-FOXM1 modulation pathways, in this study, we investigated the relationships between miR-216b and FOXM1 and the role of miR-216b in cell proliferation and prognosis of cervical cancer patients. Western blotting and qPCR were used to determine expression of FOXM1, cell cycle related factors and miR-216b level. MiR-216b overexpression and inhibited cell models were constructed, and siRNA was used for FOXM1 silencing. Cell proliferation was analyzed by MTT and colony formation assay. Dual luciferase reporter assay system was used to clarify the relationships between miR-216b and FOXM1. Kaplan-Meier survival analysis was used to evaluate prognosis. MiR-216b was down-regulated in cervical cancer cells and tissues, and its ectopic expression could decrease cell proliferation. Western blotting analysis showed miR-216b can inhibit cell proliferation by regulating FOXM1-related cell cycle factors, suppressing cyclinD1, c-myc, LEF1 and p-Rb and enhancing p21 expression. Repressing of miR-216b stimulated cervical cancer cell proliferation, whereas silencing FOXM1 expression could reverse this effect. Western blotting and luciferase assay results proved FOXM1 is a direct target of miR-216b. Survival analysis showed higher level of miR-216b was associated with better prognosis in cervical cancer patients. FOXM1 expression could be suppressed by miR-216b via direct binding to FOXM1 3′-UTR and miR-216b could inhibit cell proliferation by regulating FOXM1 related Wnt/β-catenin signal pathway. MiR-216b level is related to prognosis in cervical cancer patients and may serve as a potential prognostic marker.
Review question / Objective: The aims of this meta-analysis randomised controlled trial is to evaluate the efficacy of PARPis in various cancers, and the efficacy of PARPis in each cancer, efficacy of each PARPi, the difference between the use of PARPis in relapse and newly diagnosis of cancer.Condition being studied: Cancer is the leading cause of death in the world and become major public health problem that persists worldwide for a long time.Based on the data of human epidemiology, every day approximately 4950 people die of cancer in USA[1], and even worse is the fact that there are over 7500 people die of cancer in China[2].Cancer still faces the challenge of high recurrence rate after surgery and conventional chemotherapy which cannot meet the medical requirements of cancer patients for high survival at present, so more and more effective treatment schemes are needed.Molecular targeted therapy has a great potential of scientific research and a revolutionary breakthrough.An increasing number of clinical studies has demonstrated that targeted therapy plays an indispensable role in anti-tumor.Conveniently, some target therapy as oral drugs control the progression or death of cancer just like taking pills to treat hypertensive disorders and some chronic diseases.PARP inhibitor (PARPi), a novel cancer therapy targeting poly ADP ribose polymerase achieves noteworthy therapeutic effects of cancer.
Serum- and glucocorticoid-inducible protein kinase 3 (SGK3), also known as cytokine-independent survival kinase (CISK), encoded by chromosome 8q12.2, is a downstream mediator of phosphatidylinositol 3-kinase (PI3K) oncogenic signaling. As a downstream target of PI3K, SGK3 has been reported to mediate pivotal roles in oncogenic progress in various cancers, including breast cancer, ovarian cancer and hepatocellular carcinoma. Functionally parallel to v-akt murine thymoma viral oncogene homolog (AKT)/protein kinase B, SGK3 serves as a hallmark mediating glycogen synthase kinase-β (GSK3-β), B-cell lymphoma (Bcl)-2-associated death promoter, forkead family of transcription factors, Bcl-extra large, Bcl-2, mammalian target of rapamycin, C-X-C chemokine receptor type 4 (CXCR4) and numerous other molecules in cell proliferation, growth, survival, migration and even tumor angiogenesis. Tumor angiogenesis is recognized as an essential step for tumor growth, invasion and metastasis, and it has become an intriguing target for anticancer drug development for tumor investigators worldwide. An abundance of experiments have been performed to investigate the role of the phosphoinositide 3-kinase (PI3K)/AKT pathway in regulating tumor angiogenesis. The mechanism of angiogenesis regulated by the PI3K/AKT pathway is, to a certain extent, clear. Although a number of SGK3 target molecules, including CXCR4 and GSK3β, have demonstrated potential roles in promoting angiogenesis, the exact association between angiogenesis and SGK3 remains unclear. Thus, we hypothesize that SGK3, parallel to AKT, may also be important in mediating angiogenesis. Identifying the role of SGK3 in tumor angiogenesis will certainly present a novel perspective on the malignant transformation of tumors, as well as a target for tumor therapy.
Chemo-resistance is a leading cause of tumor relapse and treatment failure in patients with ovarian cancer. The identification of effective strategies to overcome drug resistance will have a significant clinical impact on the disease. The protein and mRNA expression of GOLPH3L in ovarian cancer cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. 177 human ovarian cancer tissue samples were analyzed by IHC to investigate the association between GOLPH3L expression and the clinicopathological characteristics of ovarian cancer patients. Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of GOLPH3L in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of GOLPH3L promotes chemoresistance in ovarian cancer cells. The expression of GOLPH3L was markedly upregulated in ovarian cancer cell lines and tissues, and high GOLPH3L expression was associated with an aggressive phenotype and poor prognosis with ovarian cancer patients. GOLPH3L overexpression confers CDDP resistance on ovarian cancer cells; however, inhibition of GOLPH3L sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. Additionally, GOLPH3L upregulated the levels of nuclear p65 and phosphorylated inhibitor of nuclear factor Kappa-B kinase-β and IκBα, thereby activating canonical nuclear factor-κB (NF-κB) signaling. Our findings suggest that GOLPH3L is a potential therapeutic target for the treatment of ovarian cancer: targeting GOLPH3L signaling may represent a promising strategy to enhance platinum response in patients with chemoresistant ovarian cancer.
Background: To investigate whether circulating tumor cells (CTCs) are detectable in patients with gestational choriocarcinoma (GC) and evaluate the prognostic value of CTC enumeration.
// Minzhi Hou 1, 3, * , Zhiqiang Cheng 2, * , Hongwei Shen 3, * , Shanyang He 3 , Yang Li 1 , Yunping Pan 4 , Chongjin Feng 4 , Xinlin Chen 5 , Yang Zhang 6 , Millicent Lin 7 , Liantang Wang 1 , Zunfu Ke 1 1 Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 2 Department of Pathology, ShenZhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, P.R. China 3 Department of Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 4 Department of Stomatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Province Guangdong, P.R. China 5 Department of Preventive Medicine and Biostatistics, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China 6 Biomedical Engineering, University of Texas at El Paso, El Paso, Texas, USA 7 Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging (CIMI), California NanoSystems Institute (CNSI), University of California, Los Angeles, California, USA * These authors have contributed equally to this work Correspondence to: Zunfu Ke, e-mail: kezunfu@126.com Keywords: CTHRC1, epithelial-mesenchymal transition, epithelial ovarian cancer, β-catenin Received: May 04, 2015 Accepted: September 21, 2015 Published: October 03, 2015 ABSTRACT Collagen triple helix repeat-containing 1 (CTHRC1) is aberrantly overexpressed in multiple malignant tumors. However, the expression characteristics and function of CTHRC1 in epithelial ovarian cancer (EOC) remain unclear. We found that CTHRC1 expression was up-regulated in the paraffin-embedded EOC tissues compared to borderline or benign tumor tissues. CTHRC1 expression was positively correlated with tumor size ( p = 0.008), menopause ( p = 0.037), clinical stage ( p = 0.002) and lymph node metastasis ( p < 0.001) and was also an important prognostic factor for the overall survival of EOC patients, as revealed by Kaplan-Meier analysis. CTHRC1 increased the invasive capabilities of EOC cells in vitro by activating the Wnt/β-catenin signaling pathway. We showed that ectopic transfection of CTHRC1 in EOC cells up-regulated the expression of EMT markers such as N-cadherin and vimentin, and EMT-associated transcriptional factor Snail. Knockdown of CTHRC1 expression in EOC cells resulted in down-regulation of N-cadherin, vimentin, Snail and translocation of β-catenin. Collectively, CTHRC1 may promote EOC metastasis through the induction of EMT process and serve as a potential biomarker for prognosis as well as a target for therapy.
To explore the potential clinical value of platelet parameters in early pregnancy in predicting gestational diabetes mellitus (GDM).A total of 1188 singleton pregnant women were included in the regular antenatal examination and delivered in the First Affiliated Hospital of Sun Yat-Sen University from January 2016 to December 2018, who had no pre-pregnancy diabetes, no factors leading to elevated blood glucose level, no medical complications and no other obstetrical complications. Blood routine examination was performed at the 11-13+6 gestational weeks. All pregnant women underwent 75 g OGTT directly at the 24-28th gestational weeks. And they were divided into GDM group (n = 192) and non-GDM group (n = 996). Binomial Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the ability of first-trimester platelet parameters to predict GDM, that is the sensitivity and specificity of platelet parameters at the optimal critical value.There were significant differences in platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and plateletcrit (PCT) between the GDM group and the normal group (p＜.05). After adjusting for the related factors such as maternal age, parity and pregestational body mass index (BMI), the MPV and PCT were correlated with the incidence of GDM (p＜.05). The area under the curve (AUC) of MPV was 0.577; 95% confidence interval (CI) 0.533-0.621 and that of PCT was 0.628. 95%CI 0.582-0.674. PLT and PDW were not correlated with GDM.MPV and PCT in early pregnancy are potential indicators in predicting gestational diabetes mellitus.
Gestational choriocarcinoma (GC) is a highly aggressive tumor. In our study, we systematically investigated EpCAM/CD147 expression characteristics in patients with GC and assessed the role of circulating tumor cells (CTCs) in predicting chemotherapy response and disease progression. GC tissues were positive for either epithelial cellular adhesion molecule (EpCAM) or CD147, and all samples exhibited strong human chorionic gonadotropin (HCG) expression. Among all the recruited patients (n = 115), 103 had at least 1 CTC in a 7.5-mL peripheral blood sample, and the percentage of patients with ≥4 CTCs in a particular FIGO stage group increased with a higher FIGO stage (p < 0.001). Furthermore, the pretreatment CTC count was related to tumor size (r = 0.225, p = 0.015) and the number of metastases (r = 0.603, p < 0.001). A progression analysis showed that among the 115 included patients who qualified for further examination, 52 of the 64 patients defined as progressive had ≥4 pretreatment CTCs, while only 7 of the 51 non-progressive patients had ≥4 pretreatment CTCs (p < 0.001). In multivariate analysis, CTCs (≥4) remained the strongest predictor of PFS when other prognostic markers, FIGO score and FIGO stage were included. Moreover, based on the chemotherapy response, patients with ≥4 CTCs were more likely to be resistant to chemotherapy than those with <4 CTCs (P < 0.001). These findings demonstrates the feasibility of CTC detection in cases of GC by adopting EpCAM/CD147 antibodies together as capturing antibodies. The CTC count is a promising indicator in the evaluation of biological activities and the chemotherapy response in GC patients.
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