Hobbssears7584
Backgrounds A number of genetic and biological phenomena imply that tumorigenesis of clear cell renal cell carcinoma (ccRCC) is highly correlated with hypoxia-induced factor-1a (HIF-1α). Recently, research focusing on the post-transcriptional regulation of HIF-1α has provided a new perspective for ccRCC therapy. In this study, we observed the expression pattern of the RNA-binding protein QKI, which could regulate HIF expression in ccRCC both in vitro and in vivo. Methods Tissue microarraywas subjected to immunohistochemistry and tumour cell lines and nude mice were used for in vitro and in vivo assays. QKI overexpression or knockdown was assessed in renal cancer cells. Results The overexpression of QKI inhibited the proliferation of the 786-0 and caki-1 cells, blocked the cells' entry into the S phase, and promoted apoptosis. In ectopic-implantation nude mice model, QKI depletion significantly increased tumor sizes and initiation rates. Tissue microarrays showed that the expression of QKI genes, and especially QKI-6, was significantly decreased in tumor tissues compared with these in normal kidney tissues. Moreover, decreased QKI expression was closely correlated with high tumor grade, poor differentiation, and poor survival. Conclusions QKI may be useful as a novel, independent diagnostic and biological marker for ccRCC. © The author(s).Objectives Ring finger protein 187 (RNF187) was recently demonstrated to be up-regulation and function as a promoter in multiple cancers. However, the roles of RNF187 in osteosarcoma (OS) are unclear. Here, we tried to reveal the clinicopathological and biological roles of RNF187 in OS. Materials and Methods We employed the quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to determine the expression of RNF187 in OS tissues and cells. Migration and invasion capacities were analyzed by wound healing and transwell assays, and colony formation and CCK8 assays were performed to investigate proliferative ability. The functional effects of RNF187 on OS drugs resistance were further determined by CCK8 and western blot assays. Then, the relationship between RNF187 expression and clinical implications was analyzed by tissue microarrays (TMAs) including 51 OS cases. Moreover, the prognostic value was also determined by Kaplan-Meier analysis. Results We reported that RNF187 mRNA wf OS. © The author(s).Purpose Metaplastic breast cancer (BC) is an uncommon yet aggressive histologic subtype of BC. We sought to identify factors associated with its diagnosis and compare the management and outcomes of metaplastic BC with those of other BCs and triple negative invasive ductal carcinoma in particular given how often it has a triple negative phenotype. Patients and Methods We identified women diagnosed with invasive BC in 2010-2014 in the National Cancer Data Base, and used univariate analysis to compare baseline patient and tumor characteristics by BC subtype. Overall survival (OS) was estimated with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to identify independent predictors of OS. Results Of 247,355 cases, 2,084 (0.8%) were metaplastic BC, 55,998 (23%) triple negative BC, and 77% other BC. Relative to non-metaplastic BC, women with metaplastic BC were more likely to be older at diagnosis (median age, 62 vs. 59 years), have ≥1 comorbid conditions (22% vs. 18%), and be on with worse outcomes in metaplastic BC. Extent of surgery affected survival for triple-negative and other BC but not for metaplastic BC. Conclusion Outcomes for metaplastic BC continue to be worse than those for other BC subtypes despite modern treatments. Optimizing systemic therapy options, which was a significant predictor of survival, should be a priority in managing metaplastic BC. © The author(s).Background The Gustave Roussy Immune Score (GRIm-Score) was initially reported to select patients for immunotherapy. Therefore, the purpose of the current retrospective study was to determine whether GRIm-Score, a novel nutritional and inflammatory-based prognostic score, is a useful prognostic marker in patients with esophageal squamous cell carcinoma (ESCC) undergoing surgical resection. Methods A retrospective single institutional study including 372 ESCC patients undergoing surgical resection was performed. The GRIm-Score was simply calculated by lactate dehydrogenase (LDH), neutrophil lymphocyte ratio (NLR) and albumin (ALB). The cancer-specific survival (CSS) was analyzed for the current study with Cox regression analyses with forward stepwise and Kaplan-Meier methods. Results There were 284 (76.3%) men and 88 (23.7%) women with the mean age of 59.3 ± 8.0 years (range 36-80 years). Patient with a high GRIm-Score had poor CSS (10.3% vs. 35.0%, P less then 0.001). The GRIm-Score, in multivariate analyses, instead of NLR, LDH or ALB, was an independent prognostic factor for CSS (P = 0.004). Conclusion The GRIm-Score was an independent prognostic marker in patients with ESCC undergoing surgical resection. Our study is also the first study to discuss the prognostic value of GRIm-Score in patients with resectable ESCC. © The author(s).Background Pancreatic cancer (PC) is a highly malignant tumor with no effective early diagnostic biomarkers. This study was performed to screen and identify serum microRNAs (miRNAs) as noninvasive biomarkers for PC diagnosis. Methods Two upregulated miRNAs were selected by integrated analysis of three independent GEO datasets. Then, the expressions of two miRNAs in serum were determined by quantitative reverse-transcription PCR among 120 PC patients, 40 benign disease controls and 40 healthy controls. The correlation between serum miRNAs and clinical characteristics was analyzed. The diagnostic utility of miRNAs was compared to CA19-9 using receiver operating characteristic curve analysis. Results We discovered miR-1290 and miR-1246 were upregulated in PC patients through GEO datasets analysis. Serum miR-1290 and miR-1246 expression levels were elevated in PC patients compared to all controls and dramatically decreased after tumor resection (all P less then 0.001). The area under the curve (AUC) for miR-1290 was larger than miR-1246 and CA19-9 (miR-1290 0.91; miR-1246 0.81; CA19-9 0.82). The combined diagnosis of individual or both miRNAs with CA19-9 was more effective for discriminating PC from all controls than the single CA19-9 assay (miR-1290+CA19-9 0.96, miR-1246+CA19-9 0.93, miR-1290+miR-1246+CA19-9 0.97). The abundance of serum miR-1290 and miR-1246 was associated with tumor stage and size respectively and logistic modeling proved that both of them were independent risk factors for PC. Conclusion Serum miR-1290 and miR-1246 might be promising biomarkers for PC diagnosis and the combined detection of CA19-9, together with miR-1290 or miR-1246, could improve the diagnostic accuracy of PC. © The author(s).MicroRNA-183(miR-183) is abnormally expressed in many kinds of tumors. It participates in the initiation and development of tumors. There are many pathways regulate the expression of miR-183. The action mechanism of miR-183 in cancer is very extensive, and contradictory conclusions are often drawn. It was upregulated in 18 kinds of cancer, downregulated in 6 kinds of cancer. In addition, there are seven types of cancer, both upregulated and downregulated reports can be found. Evidence showed that miR-183 can not only directly play the role of oncogene or antioncogene, but also regulate the expression of other oncogene or antioncogene in different cancer types. In this review, we discuss the regulator of miR-183 and summarized the expression of miR-183 in different cancers. We also counted the target genes of miR-183 and the functional roles they play. Furthermore, we focused on the roles of miR-183 in cell migration, cell invasion, epithelial-mesenchymal transition (EMT) and microangiogenesis, which play the most important roles in cancer processes. It sheds light on the likely reasons why miR-183 plays different roles in various cancers. In addition, miR-183 and its downstream effectors have the potential to be promising prognostic markers and therapeutic targets in cancer. © The author(s).Background Nanocrystallization is a promising field for the development of new drugs. This study aims to present the use of nanocrystallization via intraperitoneal nanoaerosol therapy (INAT) for the treatment of peritoneal metastases. Methods A continuous aerosol generation device was used to aerosolize a highly concentrated doxorubicin solution within a dry CO2 environment. The produced nanoaerosol was directed into an ex vivo abdominal model and collision of aerosol particles with placed samples was subject to further analysis via scanning-electron microscopy (SEM). SEM detected structural changes of particles caused by migration to different locations. Results It was possible to visualize the contact of doxorubicin aerosol particles with the surface. Larger particles as well as particles closer to the aerosol generation chamber collided with the glass sample creating liquid drops, while smaller particles with more distance to the aerosol chamber collided as highly concentrated nanocrystals. The amount of nanocrystal particles outweighed the amount of fluid aerosol particles by far. Conclusions Under optimal conditions, the formation of nanocrystals via aerosol creation device is possible. While a wide range of possible applications of nanocrystals is conceivable, surface coating with drug particles is especially interesting as it may serve as an alternative to conventional liquid intraperitoneal chemotherapy. Further studies are required to investigate nanocrystallization of chemotherapeutic solutions as well as its physical and pharmacological properties and side effects. © The author(s).Imbalance of redox homeostasis may be responsible for the resistance of cancer to chemotherapy. Currently, increasing studies demonstrated that vitamin K3 (VK3), which promoted the production of ROS, had potential to be developed as an anti-tumor agent. We found SKOV3/DDP cells with high levels of p62 were insensitive to VK3 compared with SKOV3 cells. read more Furthermore, Nrf2 downstream antioxidant genes such as HO-1(heme oxygenase 1) and NQO1 (NAD (P) H quinone oxidoreductase 1) were upregulated in SKOV3/DDP cells with VK3 treatment, which indicated VK3 activated Nrf2 signaling in SKOV3/DDP cells. Moreover, co-localization of p62 and Keap1 was also observed. Suppression of p62 expression increased the apoptosis induced by VK3, and the expression of Nrf2, HO-1 and NQO1 were all downregulated in SKOV3/DDP cells. Our results suggested that overexpressed p62 may protect cells from oxidative damage caused by VK3 through activating Keap1/Nrf2 signaling in ovarian cancer. © The author(s).The identification of driver mutations in epidermal growth factor receptor, anaplastic lymphoma kinase, the BRAF and ROS1 genes and subsequent successful clinical development of kinase inhibitors not only significantly improves clinical outcomes but also facilitates the discovery of other novel driver mutations in non-small cell lung cancer. These driver mutations can be categorized into mutations in or near the kinase domain, gene amplification or fusion. In this review, BRAF V600E, EGFR and HER-2 exon 20 mutation, FGFR1-4, K-RAS, MET, neuregulin-1, NRTK, PI3K/AKT/mTOR, RET and ROS1 gene aberration and their therapeutics will be discussed. © The Author(s), 2020.