- LINC01118 Modulates Paclitaxel Resistance of Epithelial Ovarian Cancer by Regulating miR-134/ABCC1. [Journal Article]
- MSMed Sci Monit 2018 Dec 06; 24:8831-8839
- CONCLUSIONS: LINC01118 acted as an oncogene and modulated EOC paclitaxel sensitivity by regulating miR-134/ABCC1.
- Practice patterns of surgery for advanced ovarian cancer: analysis from international surveys. [Journal Article]
- JJJpn J Clin Oncol 2018 Dec 06
- CONCLUSIONS: No visible tumor as the criterion for optimal cytoreduction was preferred in AOC, and aggressive surgery beyond conventional gynecological surgery tended to be performed by other surgeons. Moreover, the preference of neoadjuvant chemotherapy and the positive expectation of preoperative determination of optimal cytoreduction were higher in Europe than in USA.
- Targeted Feature Extraction in MALDI Mass Spectrometry Imaging to Discriminate Proteomic Profiles of Breast and Ovarian Cancer. [Journal Article]
- PCProteomics Clin Appl 2018 Dec 06; :e1700168
- CONCLUSIONS: We obtained robust classification models not confounded by technical variation between MSI measurements. This supports the assumption that the classification of the respective tumor types is based on biological rather than technical differences, and that the selected features are related to the proteomic profiles of the tumor types under consideration. This article is protected by copyright. All rights reserved.
- A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer. [Journal Article]
- CPClin Proteomics 2018; 15:38
- CONCLUSIONS: The PEA assays represent useful tools for identification of new biomarkers for gynecologic cancers. The selected protein assays could be used to distinguish benign tumors from ovarian and endometrial cancer in women diagnosed with an unknown suspicious pelvic mass. The panels could also be used in population screening, for identification of women in need of specialized gynecologic transvaginal ultrasound examination.
- Identification of potential key genes associated with ovarian clear cell carcinoma. [Journal Article]
- CMCancer Manag Res 2018; 10:5461-5470
- CONCLUSIONS: Our research suggests that SPP1 and EPCAM are overexpressed in OCCC compared with normal ovary tissue. Clinical study of large sample is required to evaluate the value of SPP1 and EPCAM in the precision treatment and prognostic influence on OCCC in the future.
- The prognostic roles of mRNAs of the exosomes derived from bone marrow stromal cells in common malignancies: a bioinformatic study. [Journal Article]
- OTOnco Targets Ther 2018; 11:7979-7986
- CONCLUSIONS: Taken together, our findings revealed the prognostic roles of mRNAs of exosomes derived from BMSCs and provided implications for targeted therapy for common malignant neoplasms. However, further studies require large samples and experimental verification.
- Cisplatin-induced immune modulation in ovarian cancer mouse models with distinct inflammation profiles. [Journal Article]
- OOncogene 2018 Dec 05
- The backbone of ovarian cancer treatment is platinum-based chemotherapy and aggressive surgical debulking. New therapeutic approaches using immunotherapy via immune checkpoint blockade, which have de...
The backbone of ovarian cancer treatment is platinum-based chemotherapy and aggressive surgical debulking. New therapeutic approaches using immunotherapy via immune checkpoint blockade, which have demonstrated clinical efficacy in other tumor types, have been less promising in ovarian cancer. To increase their clinical efficacy, checkpoint inhibitors are now being tested in clinical trials in combination with chemotherapy. Here, we evaluated the impact of cisplatin on tumor immunogenicity and its in vivo roles when used alone or in combination with anti-PD-L1, in two novel murine ovarian cancer cell models. The 2F8 and its platinum-resistant derivative 2F8cis model, display distinct inflammatory profiles and chemotherapy sensitivities, and mirror the primary and recurrent human disease, respectively. Acute and chronic exposure to cisplatin enhances tumor immunogenicity by increasing calreticulin, MHC class I, antigen presentation and T-cell infiltration. Cisplatin also upregulates PD-L1 expression in vitro and in vivo, demonstrating a dual, paradoxical immune modulatory effect and supporting the rationale for combination with immune checkpoint blockade. One of the pathways activated by cisplatin treatment is the cGAS/STING pathway. Chronic cisplatin treatment led to upregulation of cGAS and STING proteins in 2F8cis compared to parental 2F8 cells, while acute exposure to cisplatin further increases cGAS and STING levels in both 2F8 and 2F8cis cells. Overexpression of cGAS/STING modifies tumor immunogenicity by upregulating PD-L1, MHC I and calreticulin in tumor cells. Anti-PD-L1 alone in a platinum-sensitive model or with cisplatin in a platinum-resistant model increases survival. These studies have high translational potential in ovarian cancer.
- DHS (trans-4,4'-dihydroxystilbene) suppresses DNA replication and tumor growth by inhibiting RRM2 (ribonucleotide reductase regulatory subunit M2). [Journal Article]
- OOncogene 2018 Dec 05
- DNA replication machinery is responsible for accurate and efficient duplication of the chromosome. Since inhibition of DNA replication can lead to replication fork stalling, resulting in DNA damage a...
DNA replication machinery is responsible for accurate and efficient duplication of the chromosome. Since inhibition of DNA replication can lead to replication fork stalling, resulting in DNA damage and apoptotic death, inhibitors of DNA replication are commonly used in cancer chemotherapy. Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the biosynthesis of deoxyribonucleoside triphosphates (dNTPs) that are essential for DNA replication and DNA damage repair. Gemcitabine, a nucleotide analog that inhibits RNR, has been used to treat various cancers. However, patients often develop resistance to this drug during treatment. Thus, new drugs that inhibit RNR are needed to be developed. In this study, we identified a synthetic analog of resveratrol (3,5,4'-trihydroxy-trans-stilbene), termed DHS (trans-4,4'-dihydroxystilbene), that acts as a potent inhibitor of DNA replication. Molecular docking analysis identified the RRM2 (ribonucleotide reductase regulatory subunit M2) of RNR as a direct target of DHS. At the molecular level, DHS induced cyclin F-mediated down-regulation of RRM2 by the proteasome. Thus, treatment of cells with DHS reduced RNR activity and consequently decreased synthesis of dNTPs with concomitant inhibition of DNA replication, arrest of cells at S-phase, DNA damage, and finally apoptosis. In mouse models of tumor xenografts, DHS was efficacious against pancreatic, ovarian, and colorectal cancer cells. Moreover, DHS overcame both gemcitabine resistance in pancreatic cancer and cisplatin resistance in ovarian cancer. Thus, DHS is a novel anti-cancer agent that targets RRM2 with therapeutic potential either alone or in combination with other agents to arrest cancer development.
- IL-6 mediates platinum-induced enrichment of ovarian cancer stem cells. [Journal Article]
- JIJCI Insight 2018 Dec 06; 3(23)
- In high-grade serous ovarian cancer (OC), chemotherapy eliminates the majority of tumor cells, leaving behind residual tumors enriched in OC stem cells (OCSC). OCSC, defined as aldehyde dehydrogenase...
In high-grade serous ovarian cancer (OC), chemotherapy eliminates the majority of tumor cells, leaving behind residual tumors enriched in OC stem cells (OCSC). OCSC, defined as aldehyde dehydrogenase-positive (ALDH+), persist and contribute to tumor relapse. Inflammatory cytokine IL-6 is elevated in residual tumors after platinum treatment, and we hypothesized that IL-6 plays a critical role in platinum-induced OCSC enrichment. We demonstrate that IL-6 regulates stemness features of OCSC driven by ALDH1A1 expression and activity. We show that platinum induces IL-6 secretion by cancer-associated fibroblasts in the tumor microenvironment, promoting OCSC enrichment in residual tumors after chemotherapy. By activating STAT3 and upregulating ALDH1A1 expression, IL-6 treatment converted non-OCSC to OCSC. Having previously shown altered DNA methylation in OCSC, we show here that IL-6 induces DNA methyltransferase 1 (DNMT1) expression and the hypomethylating agent (HMA) guadecitabine induced differentiation of OCSC and reduced - but did not completely eradicate - OCSC. IL-6 neutralizing antibody (IL-6-Nab) combined with HMA fully eradicated OCSC, and the combination blocked IL-6/IL6-R/pSTAT3-mediated ALDH1A1 expression and eliminated OCSC in residual tumors that persisted in vivo after chemotherapy. We conclude that IL-6 signaling blockade combined with an HMA can eliminate OCSC after platinum treatment, supporting this strategy to prevent tumor recurrence after standard chemotherapy.
New Search Next
- Diffusion-weighted imaging and diffusion kurtosis imaging for early evaluation of the response to docetaxel in rat epithelial ovarian cancer. [Journal Article]
- JTJ Transl Med 2018 Dec 05; 16(1):340
- CONCLUSIONS: DWI and DKI parameters, especially K, are superior for imaging tumor size for the early detection of the response to DTX chemotherapy in induced rat EOC.