Efficacy and safety of docetaxel plus S-1-based therapy in gastric cancer: a quantitative evidence synthesis of randomized controlled trials.

Objective: To systematically evaluate the safety and efficacy of docetaxel plus S-1-based therapy in gastric cancer treatment. Methods: PubMed, Embase, The Cochrane Library, and Web of Science electronic databases were searched for randomized controlled trials on docetaxel plus S-1-based therapy in the treatment of gastric cancer from the establishment of the database to 1 September 2022. Relevant studies were included per pre-defined eligibility criteria, and two researchers independently screened and assessed the included literature using Review Manager v5. Outcome measures and statistics related with efficacy and safety profiles were extracted from the included studies, and Stata v15.1 was used for pooled analysis. Results: Objective response rate (odds ratio = 2.34, 95% CI = [1.32, 4.13], p = 0.003), relapse-free survival (HR = 0.68, 95% CI = [0.58, 0.79], p < 0.001), progression-free survival (HR = 0.81, 95% CI = [0.68, 0.96], p = 0.016), and overall survival (HR = 0.86, 95% CI = [0.79, 0.95], p = 0.002) of docetaxel plus S-1-based therapy (DS-based therapy) in gastric cancer treatment were better than those of the non-DS-based therapy. However, DS-based therapy was associated with increased risk of certain adverse drug effects, such as alopecia, leukopenia, and oral mucositis. Further studies are warranted to validate the efficacy superiority of DS-based versus non-DS-based regimens as per our trial sequential analysis findings. Conclusion: DS-based therapy significantly improves patients' clinical outcomes in gastric cancer, albeit at the cost of increased toxicity. Further RCTs are needed to confirm the efficacy superiority of DS-based regimens.

Long noncoding RNA TCL6 binds to miR-106a-5p to regulate hepatocellular carcinoma cells through PI3K/AKT signaling pathway.

Long noncoding RNAs (lncRNAs) have been reported to dysregulate and involve in the pathology of hepatocellular carcinoma (HCC). Nonetheless, the functional role of lncRNA T cell leukemia/lymphoma 6 (TCL6) and its underlying mechanism in HCC remain unclear. Herein, we analyzed the expression of TCL6 and elucidated its mechanistic involvement in HCC. Bioinformatics analyses indicated TCL6 was evidently downregulated in HCC tissues compared with normal controls. TCL6 was downregulated while microRNA-106a-5p (miR-106a-5p) was upregulated in HCC cell lines. Moreover, knockdown or overexpression of TCL6 significantly raised or diminished the expression level of miR-106a-5p in HCC cells, similar to the effect of miR-106a-5p on TCL6 expression. Functionally, TCL6 inhibited the proliferative, migratory, and invasive potentials of HCC cells as analyzed by cell counting kit-8, scratch wound healing, and transwell assays, respectively. Conversely, miR-106a-5p exerted an opposite effect on the proliferative, migratory, and invasive potentials of HCC. RNA immune precipitation and luciferase reporter assays revealed TCL6 directly bound to miR-106a-5p and luciferase reporter assay verified phosphatase and tensin homolog (PTEN) was a target gene of miR-106a-5p. Mechanistically, TCL6 knockdown evidently reduced PTEN expression at both messenger RNA and protein levels, and miR-106a-5p inhibitor partially rescued this reduction effect in HCC cells. Additionally, western blot assays demonstrated miR-106a-5p downregulation or TCL6 overexpression promoted the protein level of PTEN, and suppressed the phosphorylation level of AKT, the protein level of phosphatidylinositol 3-kinase (PI3K). Collectively, these results revealed TCL6 as a tumor-suppressive lncRNA regulates PI3K/AKT signaling pathway via directly binding to miR-106a-5p in HCC. This mechanism provides a theoretical basis for HCC pathogenesis and a potential therapeutic strategy for HCC treatment.

Long non-coding RNA NKILA inhibited angiogenesis of breast cancer through NF-κB/IL-6 signaling pathway.

OBJECTIVE: The relationship between NF-κB Interacting lncRNA (NKILA) and angiogenesis in breast cancer has never been studied. Our study aimed to investigate effect of NKILA on proliferation, migration, apoptosis, as well as angiogenesis in breast cancer. METHODS: NKILA was over-expressed in MDA-MB-231 cells by transfection of pcDNA3.1-NKILA vector. Cell viability, apoptosis and migration were measured by MTT, flow cytometry and wound healing assays, respectively. Angiogenesis of human umbilical vein endothelial cells (HUVEC) was measured using tube formation assay. The expression levels of NKILA, IL-6, VEGFA, VEGFR, apoptosis and epithelial-mesenchymal transition (EMT) and NF-κB/IL-6 signaling-related markers were determined using qRT-PCR or Western blotting. RESULTS: Cell viability and migration of MDA-MB-231 cells were significantly inhibited, while cell apoptosis was obviously promoted by overexpression of NKILA. Overexpression of NKILA could also inhibit the phosphorylation of IκBα and the nuclear transposition of p65, as well as induce cell apoptosis-related proteins and inhibit epithelial-mesenchymal transition-related proteins. Cell viability and migration of HUVEC were also significantly inhibited when treated with supernatant of cells overexpressed NKILA or treated with BAY11-7028. Exogenous IL-6 significantly increased the cell viability and migration of HUVEC, and overexpression of NKILA could reverse these effects induced by IL-6. Overexpression of NKILA significantly inhibited the protein levels of IL-6 and VEGFA in supernatant, as well as VEGFR in HUVEC, thus inhibited the angiogenesis of HUVEC. NKILA also reversed the above effects on protein levels of IL-6 and VEGFA in supernatant and angiogenesis induced by exogenous IL-6. CONCLUSION: Overexpression of NKILA could inhibit cell proliferation, migration and promote apoptosis of breast cancer cells. It could also inhibit cell proliferation, migration and angiogenesis of HUVEC through inhibiting IL-6 secretion via NF-κB signaling pathway.

Current perspectives of SA-4-1BBL in immune modulation during cancer.

A recombinant co-stimulatory molecule capable of inducing multiple effects on varied immune cells when present in its soluble active form is termed as SA-4-1BBL. It has been reported to influence innate, adaptive, and regulatory immune cells. Recent studies confirmed its engagement with receptor, 4-1BB leading to collection of interleukin-2 (IL-2) that in turn overcomes Treg suppression. Further, a vast number of pre-clinical studies reported its therapeutic efficacy in the form of adjuvant subunit in cancer vaccines. Furthermore, it is also observed that it contributes significantly towards communication bridge of CD4 and NK cells. On the other hand, depletion of either NK or CD4 cells negated SA-4-1BBL's antitumor protection. The present review article is focused on the current updates of this molecule pertaining to the filed of cancer therapeutics or cancer preventives.

[Effect of Acanthopanax senticosus injection on the activities of human tumor necrosis factor and natural killer cell in blood in the patients with lung cancer].

OBJECTIVE: To study the effect of Acanthopanax senticosus injection (ASI) on the activities of human tumor necrosis factor (TNF) and natural killer cell (NKC) in the patients with lung cancer and the underlying mechanism. METHOD: 73 cases with lung cancer were randomly divided into two groups, namely, the treatment group (n = 39) and observation group (n = 34); 61 cases with or without other diseases were respectively divided into control A (n = 30) and B (n = 31) groups. The patients in treatment group were injected with ASI for 21 days. The activities of human TNF and NKC and the levels of IgG, IgA and IgM were detected respectively. RESULT: After injection with ASI the activity of TNF-alpha in treatment group was comparable with that in the two control groups and was significant lower that that in observation group. The activity of TNF-beta and the levels of IgA, IgG and IgM were significantly higher than those in observation group and two control groups (P < 0.01). The activity of NKC was also remarkably higher than observation and two control groups. CONCLUSION: ASI can regulate the cellular immunity and factor, indicating that ASI can be used as an assistant drug to regulate the function of cellular immunity in the patients with lung cancer.