The present clinicopathologic study and meta-analysis showed that HIF-1α overexpression is associated with poor survival of cervical cancer and emphasized the importance of HIF-1α as a predictor for cervical cancer.

BackgroundThe tumor immune microenvironment has clinicopathological significance in predicting prognosis and therapeutic efficacy. We aimed to develop an immune signature to predict distant metastasis in patients with nasopharyngeal carcinoma (NPC).MethodsUsing multiplexed quantitative fluorescence, we detected 17 immune biomarkers in a primary screening cohort of 54 NPC tissues presenting with/without distant metastasis following radical therapy. The LASSO (least absolute shrinkage and selection operator) logistic regression model used statistically significant survival markers in the training cohort (n=194) to build an immune signature. The prognostic and predictive accuracy of it was validated in an external independent group of 304 patients.ResultsEight statistically significant markers were identified in the screening cohort. The immune signature consisting of four immune markers (PD-L1+ CD163+, CXCR5, CD117) in intratumor was adopted to classify patients into high and low risk in the training cohort and it showed a high level of reproducibility between different batches of samples (r=0.988 for intratumor; p<0.0001). High-risk patients had shorter distant metastasis-free survival (HR 5.608, 95% CI 2.619 to 12.006; p<0.0001) and progression-free survival (HR 2.798, 95% CI 1.498 to 5.266; p=0·001). The C-indexes which reflected the predictive capacity in training and validation cohort were 0.703 and 0.636, respectively. Low-risk patients benefited from induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) (HR 0.355, 95% CI 0.147 to 0.857; p=0·021), while high-risk patients did not (HR 1.329, 95% CI 0.543 to 3.253; p=0·533). To predict the individual risk of distant metastasis, nomograms with the integration of both immune signature and clinicopathological risk factors were developed.ConclusionsThe immune signature provided a reliable estimate of distant metastasis risk in patients with NPC and might be applied to identify the cohort which benefit from IC+CCRT.

Background Circular RNA hsa_circ_0061395 (circ_0061395) has been reported to accelerate the advancement of hepatocellular carcinoma (HCC). However, the regulatory mechanism by which circ_0061395 modulates the progression of HCC is unclear. Methods The morphology and size of exosomes were analyzed by transmission electron microscope (TEM) and nanoparticle-tracking analysis (NTA). Protein levels were detected by western blotting. Expression levels of circ_0061395, microRNA (miR)-877-5p, and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) mRNA were assessed by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, invasion, migration, cell cycle progression, and apoptosis were analyzed by cell counting kit-8 (CCK-8), plate clone, transwell, or flow cytometry assays. The targeting relationship between circ_0061395 or PIK3R3 and miR-877-5p was verified using the dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. Xenograft assay was performed to confirm the biological function of circ_0061395 in HCC. Results Circ_0061395 was upregulated in HCC tissues, serum, cells, and serum-derived exosomes. Circ_0061395 silencing decreased tumor growth in vivo, and induced cell cycle arrest, apoptosis, repressed proliferation, invasion, and migration of HCC cells in vitro. MiR-877-5p was downregulated while PIK3R3 was upregulated in HCC. Circ_0061395 regulated PIK3R3 expression via competitively binding to miR-877-5p. MiR-877-5p inhibitor overturned circ_0061395 knockdown-mediated influence on malignant behaviors of HCC cells. PIK3R3 overexpression reversed the suppressive influence of miR-877-5p mimic on malignant behaviors of HCC cells. Conclusion Circ_0061395 facilitated HCC progression via regulating the miR-877-5p/PIK3R3 axis, providing a new perspective on the advancement of HCC.

Alantolactone (Ala) is a sesquiterpene lactone that can be isolated from many herbal plants belonging to Asteraceae. Besides the antimicrobial activities against bacteria, fungi and viruses, Ala has also demonstrated significant antiinflammatory effects in various models by inhibiting NF-κB and MAPKs to decrease the pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. The antitumor effects of Ala have been demonstrated in vitro and in vivo via inducing intrinsic apoptosis, oxidative stress, ER stress, cell cycle arrest and inhibiting autophagy and STAT3 phosphorylation, which are also involved in its combination or synergy with other antitumor drugs. Ala also has neuroprotective activity through attenuating oxidative stress and inflammation, besides its modulation of glucose and lipid metabolism. This review summarizes the recent advances of the pharmacological effects of Ala, including anti-inflammatory, antitumor, antimicrobial, neuroprotective activities, as well as the underlying mechanisms.Ala might be employed as a potential lead to develop drugs for multiple diseases.