Systematic analysis competing endogenous RNA coexpression network as a potentially prediction prognostic biomarker for colon adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most common types of colon cancer, represents a major public health issue due to its high incidence and mortality. Competing endogenous RNAs (ceRNAs) hypothesis has generated a great interest in the study of molecular biological mechanisms of cancer progression. The aim of this study was to identify potential prediction prognostic biomarker associated with progression of COAD and illuminate regulatory mechanisms. Two RNA sequencing datasets downloaded from the Genotype-Tissue Expression and TCGA. The differentially expressed RNAs were analyzed. Weighted correlation network analysis was used to analyze the similarity of genes model with a trait in the network. Interactions between lncRNAs, miRNAs, and target mRNAs were predicted by MiRcode, starBase, miRTarBase, miRDB, and TargetScan, and the risk score of mRNAs was established. Based on the identified prognostic signature and independent clinical factors, then the nomogram survival model was built. Totally, we identified 3537 differentially expressed mRNAs, 2379 lncRNAs, and 449 microRNAs. Based on the 8 prognosis-associated mRNAs (CCNA2 + CEBPA + NEBL + SOX9 + DLG4 + RIMKLB + TCF7L1 + TUB), the risk score was proposed. After the independent clinical prognostic factors were identified, the nomogram survival model was built. LncRNA-miRNA-mRNA ceRNA network was built by 68 lncRNAs, 4 miRNAs, and 6 mRNAs, which might serve as prognostic biomarkers of COAD. These findings suggest several genes in ceRNA network might be novel important prognostic biomarkers and potential targets for COAD. CeRNA networks could provide further insight into the mRNA-related regulatory mechanism and COAD prognosis.

Comparative efficacy and safety of antipseudomonal ß-lactams for pediatric febrile neutropenia: A systematic review and Bayesian network meta-analysis.

BACKGROUND: Antipseudomonal ß-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal ß-lactams in pediatric patients remain unclear. The aim of this study was to comprehensively compare the efficacy and side effects of optional antipseudomonal ß-lactams for pediatric FN. METHODS: PubMed, Embase, Medline, and Cochrane Library were systematically searched from their inception to December 18, 2020. Eligible randomized controlled trials in which pediatric FN patients were treated with an empiric monotherapy of antipseudomonal ß-lactams were selected. Data synthesis was performed using WinBUGS 14.0 software and meta packages implemented in R 3.6.2. Random-effects network meta-analysis was performed, and dichotomous data were pooled as odds ratios with 95% confidence intervals. The primary outcome was treatment success without modification; the secondary outcomes were adverse events (AEs), all-cause mortality, and new infections. The GRADE tool was used to assess the quality of the evidence. The protocol was registered with PROSPERO ID CRD42021226763. RESULTS: Eighteen studies with 2517 patients were included. The results showed no statistically significant difference between the optional antipseudomonal ß-lactams in the outcomes of treatment success without modification, all AEs, all-cause mortality, and new infections for pediatric FN. Based on the results of Bayesian rank probability, meropenem was ranked highest among all the treatment options with regard to treatment success without modification benefit; ceftazidime and meropenem were associated with a lower risk of AEs; cefoperazone/sulbactam and piperacillin/tazobactam were associated with a lower risk of mortality, and piperacillin/tazobactam and meropenem were associated with a lower risk of new infections. The quality of evidence was moderate. CONCLUSIONS: Meropenem and piperacillin/tazobactam were found to be better with regard to treatment success without modification, with a comparable safety profile. Therefore, our findings support the use of meropenem and piperacillin/tazobactam as a treatment option for pediatric FN patients.

Clinical efficacy and safety of Huachansu injection combination with platinum-based chemotherapy for advanced non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Huachansu injection (HCS) is a widely used traditional Chinese medicine for advanced non-small cell lung cancer (NSCLC) to alleviate the adverse drug reactions (ADRs) and enhance the clinical efficacy of chemotherapy. OBJECTIVE: To evaluate the efficacy and safety of HCS as an adjunctive treatment to platinum-based chemotherapy (PBC) for advanced NSCLC. METHODS: A systematic review and meta-analysis were conducted according to PRISMA guidelines. A total of nine databases were searched to select randomized controlled trials (RCTs) of HCS plus PBC to treat NSCLC from inception to October 10, 2020. RCTs on HCS plus PBC vs PBC alone for advanced NSCLC were included. Dichotomous data were pooled as risk ratio (RR) with 95% confidence intervals. RCTs compared to HCS plus PBC vs PBC alone were included. Primary outcomes were objective response rate (ORR) and disease control rate (DCR), and secondary outcomes were survival rate, quality of life (QOL), and adverse drug reactions (ADRs). GRADE software was used to access the quality of evidence. RESULTS: A total of 32 RCTs, including 2753 patients, were included. Compared to PBC alone, HCS plus PBC improved the ORR, DCR, 1- and 2-year survival rates, and QOL and alleviated neutropenia, thrombocytopenia, nausea, vomiting, anemia, liver injury, renal injury, and alopecia. CONCLUSIONS: Compared to PBC alone, HCS plus PBC improved the clinical efficacy and alleviated the ADRs in advanced NSCLC patients. Considering the limitations of the included RCTs, high-quality trials with longer follow-ups are needed to further confirm the results.

Aidi injection as adjunctive treatment to gemcitabine-based chemotherapy for advanced non-small cell lung cancer: a systematic review and meta-analysis.

CONTEXT: Aidi injection is one of the most commonly use antitumor Chinese medicine injections for advanced non-small cell lung cancer (NSCLC). It is made from the extraction of Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. OBJECTIVE: To evaluate the efficacy and safety of Aidi injection in combination with gemcitabine-based chemotherapy (GBC) for advanced NSCLC. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and VIP were searched for relevant randomised controlled trials (RCTs) comparing Aidi injection plus GBC treatment with GBC alone in NSCLC, from inception up to October 2020. The primary outcomes were objective response rate (ORR), and disease control rate (DCR). Secondary outcomes were quality of life (QOL) and adverse drug reactions (ADRs). The quality of evidence was rated using the GRADE approach. This study was registered with PROSPERO: CRD42021221225. RESULTS: In total, 54 RCTs involving 4318 NSCLC patients were included in this meta-analysis. Compared with GBC alone, Aidi injection plus GBC significantly improve ORR (risk ratios [RR] = 1.38, 95% confidence interval [CI] 1.29-1.48), DCR (RR = 1.15, 95% CI 1.12-1.19), QOL (RR = 1.71, 95% CI 1.54-1.89), and reduced the risk of gastrointestinal toxicity, thrombocytopenia, neutropenia, liver injury, renal injury, and anaemia. The evaluation results of the evidence ranged from moderate to low. CONCLUSIONS: Current moderate evidence revealed that Aidi injection as an adjunctive treatment to GBC was associated with superior benefits in patients with advanced NSCLC and alleviate toxicities. High-quality RCTs are needed to further confirm the results.

Anti-invasive effect and pharmacological mechanism of genistein against colorectal cancer.

Colorectal cancer (CRC) refers to a deadly carcinoma following potent invasiveness and metastasis in advanced stage. Unfortunately, existing anti-CRC medicine is insufficient for chemotherapy in addition to adverse effects. Consequently, the candidate natural ingredient for treating CRC needs to be further developed. Our previous experiments report that genistein exerts beneficial effects to inhibit CRC cells via an antiproliferative mechanism. Based on the metastatic characteristics of staging CRC, anti-invasive and antimetastatic pharmacological activities using genistein remain uninvestigated. The scientific purpose of this study was to disclose the antimetastatic mechanism by using human and cell culture/nude mice samples, followed by biochemical tests and immunoassays. In human study, these CRC cases resulted in increased transforming growth factor beta-1 (TGF-ß1) levels, long noncoding RNA (lncRNA) TTTY18 expressions, followed with up-regulated Ki-67, serum and glucocorticoid regulated kinase 1 (SGK1), AktSer473 expressions. In a study in vitro, genistein-dosed CRC cells showed suppressed cell viability, promoted cell apoptosis, reduced Ki-67 positive cells, reduced cellular migration, down-regulated expressions of TTTY18, SGK1, AktSer473 , p38 MAPKTyr323 . In a further study in vivo, genistein-dosed tumor-bearing nude mice exhibited visibly reduced body mass, lowered tumorous TGF-ß1 and TTTY18 contents. In addition, intracellular numbers of SGK1, AktSer473 , p38 MAPKTyr323 positive cells were reduced dose-dependently. Collectively, these human and experimentative findings reveal that genistein pharmacologically exerts the potential antimetastatic CRC effects, possibly through a molecular mechanism of inhibiting TTTY18/Akt pathway in CRC cells.

Clinical characteristics of colorectal cancer patients and anti-neoplasm activity of genistein.

BACKGROUND: Epidemiologically, the disease incidence of colorectal cancer (CRC) ranks the third among all malignant tumors, and its mortality is the second following lung cancer. If unmanaged, CRC will develop fatal invasiveness and metastasis. However, existing chemotherapy is limitedly effective to treat metastatic CRC. Genistein, a functional phytoestrogen, is found with potent pharmacological activity against cancer cells. Therefore, this study was designed to characterize the clinical signatures of human CRC and to conduct anti-CRC experiments using genistein. METHODS: Briefly, the plasma, tumor, non-tumor samples of CRC patients were harvested for biological experiments, followed by analysis of clinical data. A pharmacological study in vitro of genistein for treating CRC cells was conducted accordingly. RESULTS: In diagnostic data, molecular tumor biomarkers in CRC patients were detected in plasma samples, consistent with pathological and imaging diagnoses of CRC. Notably, carcinomatous expressions of miR-95, serum glucocorticoid kinase 1 (SGK1), B-cell lymphoma-2 (Bcl-2), extracellular regulated protein kinase 1 (Erk1) in human CRC were notably elevated when compared to those in non-tumor controls. In pharmacological experiments using cell culture model, genistein-treated CRC cells resulted in reduced cellular viability, elevated lactate dehydrogenase (LDH) content, increased apoptotic cells and TdT mediated dUTP nick end labeling (TUNEL)-positive cells following a dose-dependent manner. Interestingly, down-regulated expressions of endogenous miR-95, SGK1, Bcl-2, Erk1 were observed after genistein treatments in a dose-dependent way. CONCLUSIONS: Collectively, the current clinical data indicate pathological markers of miR-95, SGK1, Erk1 in human CRC cases, and further experimental findings reveal that anti-CRC pharmacological mechanism using genistein was implicated in suppression of cellular miR-95, SGK1, Erk1 expressions. Together, genistein may be a promising bioactive compound for treating CRC.