A 15-gene signature for prediction of colon cancer recurrence and prognosis based on SVM.

Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs.

Prophylactic Administration of Fucoidan Represses Cancer Metastasis by Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs) in Lewis Tumor-Bearing Mice

Background and Objectives 
Human papillomavirus (HPV)-16 infection may be related to non-smoking associated lung cancer. Our previous studies have found that HPV-16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells. In this study, we further investigated the roles of PI3K/Akt and c-Jun signaling pathways in it.


Methods 
Human NSCLC cell lines, A549 and NCI-H460, were stably transfected with pEGFP-16 E6 or E7 plasmids. Western blotting was performed to analyze the expression of HIF-1α, p-Akt, p-P70S6K, p-P85S6K, p-mTOR, p-JNK, and p-c-Jun proteins. VEGF and IL-8 protein secretion and mRNA levels were determined by ELISA and Real-time PCR, respectively. The in vitro angiogenesis was observed by human umbilical vein endothelial cells (HUVECs) tube formation assay. Co-immunoprecipitation was performed to analyze the interaction between c-Jun and HIF-1α.


Results 
HPV-16 E6 and E7 oncoproteins promoted the activation of Akt, P70S6K, P85S6K, mTOR, JNK, and c-Jun. LY294002, a PI3K inhibitor, inhibited HPV-16 oncoprotein-induced activation of Akt, P70S6K, and P85S6K, expression of HIF-1α, VEGF, and IL-8, and in vitro angiogenesis. c-Jun knockdown by specific siRNA abolished HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Additionally, HPV-16 oncoproteins promoted HIF-1α protein stability via blocking proteasome degradation pathway, but c-Jun knockdown abrogated this effect. Furthermore, HPV-16 oncoproteins increased the quantity of c-Jun binding to HIF-1α.


Conclusions 
PI3K/Akt signaling pathway and c-Jun are involved in HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Moreover, HPV-16 oncoproteins promoted HIF-1α protein stability possibly through enhancing the interaction between c-Jun and HIF-1α, thus making a contribution to angiogenesis in NSCLC cells.

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Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.

Survivin, a member of the inhibitor of apoptosis family of proteins (IAPs) that controls cell division, apoptosis, metastasis and angiogenesis, is overexpressed in essentially all human cancers. As a consequence, the gene/protein is considered an attractive target for cancer treatment. Here, we discuss recent findings related to the regulation of survivin expression and its role in angiogenesis, particularly in the context of hypoxia. We propose a novel role for survivin in cancer, whereby expression of the protein in tumor cells promotes VEGF synthesis, secretion and angiogenesis. Mechanistically, we propose the existence of a positive feed-back loop involving PI3-kinase/Akt activation and enhanced β-Catenin-TCF/LEF-dependent VEGF expression followed by secretion. Finally, we elaborate on the possibility that this mechanism operating in cancer cells may contribute to enhanced tumor vascularization by vasculogenic mimicry together with conventional angiogenesis.

https://link.springer.com/content/pdf/10.1186%2Fs12943-015-0467-1.pdf

The twisted survivin connection to angiogenesis

Trametes robiniophila Murr. (Huaier) is a sandy beige mushroom found on the trunks of trees and has been widely used in traditional Chinese medicine (TCM) for ~1,600 years. The anticancer effects of Huaier have attracted increasing worldwide interest in recent years. Accumulating evidence suggests that the anticancer mechanism of Huaier may be associated with various biological activities, such as inhibition of cell proliferation, anti-metastasis, interference with tumor angiogenesis and tumor-specific immunomodula - tory effect. Animal and experimental studies suggest that Huaier is a promising anticancer agent. Further clinical research is warranted to illustrate the untapped chemopre- ventive and therapeutic potential of Huaier either alone or in conjunction with existing therapies.

/pdf/the-anticancer-effect-of-huaier-review-sfktv9dnnn.pdf

The anticancer effect of Huaier (Review).

The expression of survivin, an inhibitor of apoptosis can be seen in most tumors and is correlated with the angiogenic factor vascular endothelial growth factor (VEGF). But little is known about their contribution in small-cell lung cancer (SCLC). This study was designed to investigate the expression of survivin and VEGF in SCLC, and to explore their correlation with clinical-pathological feature and prognosis. Forty-five patients with pathological histology of SCLC were entered into this study. Forty-five cases of matched adjacent non-tumor samples and 10 samples of operated patients with benign lung tumor were also included as control. The expression of survivin and VEGF was detected by immunohistochemistry (IHC, SP). These two sets of data were processed and tested for correlation with major patients' characteristics, and overall survival. The correlations between survivin and VEGF expressions and the clinical-pathological features were evaluated by chi-square test. The correlation between survivin and VEGF expressions was analyzed by Spearman's rank correlation test; the overall survival was analyzed by the Kaplan-Meier method; and the relationship between clinical and pathological features and overall survival was analyzed by the Cox proportional hazard models. Positive expression rate of survivin and VEGF was significantly higher in SCLC than those of adjacent non-tumor tissues and benign lung tumor tissues (73.3 vs. 15.6 vs. 0 %, P < 0.05) and (75.6 vs. 20 vs. 0 %, P < 0.05), respectively. Survivin and VEGF expressions were significantly associated with lymph node metastasis (P = 0.003, 0.011) and clinical stage (P = 0.006, 0.021). The expression of survivin was significantly coincident with the expression of VEGF (r = 0.644, P = 0.000). The median overall survival in survivin positive group and VEGF positive group was significantly shorter than those in survivin negative and VEGF negative group, respectively (log-rank P = 0.000). Moreover, multivariate analysis showed that survivin expression (HR 0.224; 95 % CI 0.074-0.675; P = 0.008) and VEGF expression (HR 0.172; 95 % CI 0.054-0.559; P = 0.003) were statistically independent predictive factors of poorer prognosis for SCLC patients. Our results indicated that survivin and VEGF were over-expressed in small-cell lung cancer, each of them may be an independent poor prognostic factor.

Over-expression of survivin and VEGF in small-cell lung cancer may predict the poorer prognosis

Introduction: The efficacy and safety of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) remain unresolved, and relevant meta-analyses are lacking. Additionally, mepolizumab has been evaluated in far fewer patients, and the evidence is unclear. We conducted a meta-analysis to identify evidence gaps that will guide future investigation of therapies targeting interleukin (IL)-5 signaling (anti-IL-5Rα or anti-IL-5) for CRSwNP. Methods: We performed a systematic review and meta-analysis that were registered with PROSPERO (No. CRD42021276867). A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Library on September 2, 2021. Only randomized controlled trials (RCTs) assessing anti-IL-5 treatments (anti-IL-5Rα or anti-IL-5) in adult patients for CRSwNP were included. Results: Seven RCTs with 799 patients evaluating the efficacy and safety of treatments targeting IL-5 pathway (benralizumab [anti-IL-5Rα], mepolizumab, and reslizumab [anti-IL-5]) were included. The overall pooled meta-analysis showed that anti-IL-5 treatments were associated with a significantly better nasal polyp score (weighted mean difference [WMD]: −0.71; 95% confidence interval [CI]: [−0.87, −0.55]; p < 0.00001). Anti-IL-5 treatments were associated with a significantly better nasal congestion score (WMD: −1.73; 95% CI: [−2.29, −1.16]; p < 0.00001). Anti-IL-5 treatments were associated with a significantly better Sino-Nasal Outcome Test (SNOT-22) score (WMD: −11.30; 95% CI: [−14.77, −7.83]; p < 0.00001). The overall pooled meta-analysis showed that anti-IL-5 treatments were associated with a significantly better University of Pennsylvania Smell Identification Test (UPSIT) score (WMD: 2.09; 95% CI: [0.42, 3.77]; p = 0.01). Anti-IL-5 treatments significantly reduced the loss of smell score in the overall pooled meta-analysis (WMD: −1.38; 95% CI: [−1.97, −0.79]; p < 0.00001). In the overall pooled meta-analysis, anti-IL-5 treatments showed no difference with the placebo in the risk of adverse events (AEs; risk ratio [RR]: 1.01; 95% CI: [−0.93, 1.09]; p = 0.83) and serious AEs (SAEs; RR: 0.73; 95% CI: [0.40, 1.34]; p = 0.32). Conclusion: This systematic review and meta-analysis identified that anti-IL-5 treatments significantly improved the size of nasal polyps, health-related quality of life, and sense of smell in moderate to severe CRSwNP, and they were safe and well tolerated.

Efficacy and Safety of Anti-Interleukin-5 Therapies in Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Ding-Yi Liu

Papers

Over-expression of survivin and VEGF in small-cell lung cancer may predict the poorer prognosis

Efficacy and Safety of Anti-Interleukin-5 Therapies in Chronic Rhinosinusitis with Nasal Polyps: A Systematic Review and Meta-Analysis of Randomized Controlled Trials