GM-CSF-miRNA-Jak2/Stat3 Signaling Mediates Chemotherapy-Induced Cancer Cell Stemness in Gastric Cancer.

Chemotherapy serves as the first choice in clinic to treat advanced gastric cancer. However, emerging evidence indicated the induction of drug resistance and cancer stem cells occasionally by chemotherapy, which seriously limit the therapeutic effects, but the regulatory mechanism remains unclear. Here we treated two human gastric cancer cell lines SGC7901 and BGC823 with 5-Fluorouracil (5-Fu) or Cisplatin (DDP) in vitro. The survived cells showed significant increase of drug resistance, cell stemness and cytokine GM-CSF expression and secretion. As such, GM-CSF was applied to stimulate gastric cancer cells, followed by the subpopulation of CD133 + CSC analysis, sphere formation assay and stemness genes expression analysis. As a result, CSCs showed induction by GM-CSF treatment. A gastric cancer animal model further indicated that the gastric cancer cells significantly promoted tumor growth after GM-CSF treatment in vivo. High-throughput miRNA and mRNA sequencing analyses identified a subset of miRNAs and mRNAs under regulation of both 5-Fu and GM-CSF in gastric cancer cells, including upregulation of miR-877-3p and downregulation of SOCS2. Targeted overexpression or knockdown of miR-877-3p in gastric cancer cells revealed the oncogenic function of miR-877-3p in regulating gastric cancer by suppressing target gene SOCS2. Jak2/Stat3 signaling pathway, as a downstream target of SOCS2, showed activation in vitro and in vivo after treatment with miR-877-3p or GM-CSF. Our findings not only revealed a novel mechanism through which chemotherapy induced CSCs in gastric cancer via GM-CSF-miRNA-Jak2/Stat3 signaling, but also provided an experimental evidence for appropriate dose reduction of adjuvant chemotherapy in treatment of cancer patients.

Acupuncture for the relief of hot flashes in breast cancer patients: A systematic review and meta-analysis of randomized controlled trials and observational studies.

OBJECTIVE: To critically assess the effectiveness and safety of acupuncture for treating hot flashes (HFs) among breast cancer (BC) patients, and to get much more highly compelling evidence then to guide clinical practice. METHODS: Comprehensive systematic literature searches were carried out for identifying randomized controlled trials and observational studies (OSs) published before January 2015. The meta-analysis (MA) was performed by Review Manager 5 software if data could be merged routinely, if not descriptions would be given. RESULTS: A total of 18 studies were eligible ultimately. With respect to HFs frequency, the MA during treatment showed a significant difference (MD = -1.78, 95% confidence intervals [95% CIs]: -3.42--0.14), but no statistical differences were observed when posttreatment or follow-up period. While electroacupuncture versus applied relaxation, they both helped to promote HFs markedly but did not reveal statistically significance between them. Referring to Kupperman's index, all the treatment brought out great assistance when compared with baseline conditions, and there was significant difference between real acupuncture sham acupuncture (posttreatment: MD = -4.40, 95% CI: -6.77--2.03; follow-up: MD = -4.30, 95% CI: -6.52--2.08). In terms of OS, 7 prospective single arm studies focused on exploring the efficacy of traditional acupuncture, and all revealed moderate or great benefit for BC patients suffering from HFs. CONCLUSIONS: Acupuncture still appeared to be an efficacious therapeutic strategy, especially for the less/no side effects. Because of its widespread acceptance and encouraging effectiveness for improving HFs, much more high-quality studies are in need urgently.

Physiological characterization, transcriptomic profiling, and microsatellite marker mining of Lycium ruthenicum.

Lycium ruthenicum is a perennial shrub species that has attracted considerable interest in recent years owing to its nutritional value and ability to thrive in a harsh environment. However, only extremely limited transcriptomic and genomic data related to this species can be found in public databases, thereby limiting breeding research and molecular function analysis. In this study, we characterized the physiological and biochemical responses to saline-alkaline mixed stress by measuring photochemical efficiency, chlorophyll content, and protective enzyme activity. We performed global transcriptomic profiling analysis using the Illumina platform. After optimizing the assembly, a total of 68 063 unique transcript sequences with an average length of 877 bp were obtained. Among these sequences, 4096 unigenes were upregulated and 4381 unigenes were down-regulated after saline-alkaline mixed treatment. The most abundant transcripts and over-represented items were assigned to gene ontology (GO) terms or Kyoto Encyclopedia of Genes and the Genomes (KEGG) categories for overall unigenes, and differentially expressed unigenes were analyzed in detail. Based on this set of RNA-sequencing data, a total of 9216 perfect potential simple sequence repeats (SSRs) were identified within 7940 unigenes with a frequency of 1/6.48 kb. A total of 77 primer pairs were synthesized and examined in wet-laboratory experiments, of which 68 loci (88.3%) were successfully amplified with specific products. Eleven pairs of polymorphic primers were verified in 225 individuals from nine populations. The inbreeding coefficient and the polymorphism information content value ranged from 0.011 to 0.179 and from 0.1112 to 0.6750, respectively. The observed and expected heterozygosities ranged from 0.064 to 0.840 and from 0.115 to 0.726, respectively. Nine populations were clustered into three groups based on a genetic diversity study using these novel markers. Our data will be useful for functional genomic investigations of L. ruthenicum and could be used as a basis for further research on the genetic diversity, genetic differentiation, and gene flow of L. ruthenicum and other closely related species.

[Shift of Microbial Communities During the CO2-Brine-Sandstone Interaction Process].

In this study, the dynamic variation of the structure, functionality and biodiversity of indigenous microorganism during the CO2-brine-sandstone interaction process was investigated using MiSeq sequencing techniques. The results indicated that some kinds of indigenous microorganisms could grow well under the extreme condition induced by CO2-injection. After injection of CO2, the species of indigenous microorganisms tended to be single and the relative abundance of Proteobacteria reached up to 99.77% after 6 months. The dominant species varied as follows:Pseudomonas sp., Citrobacter sp. and Brevundimonas sp.. Meanwhile, some special genera such as Bacillus sp., Hydrogenophaga sp. and Rhizobium sp. with functionality of iron-reducing and denitrification were found in this study, which may have a potential effect on the capture and storage of CO2. In addition, the Shannon index decreased from 5.3302 to 1.9465 after injection of CO2, suggesting that the biodiversity reduced significantly. Function and main metabolites analysis of bacteria in the CO2-brine-sandstone interaction process showed that bacteria like Bacillus sp., Citrobacter sp. and Pseudomonas sp. could enhance CO2 solubility-trapping process. Bacteria metabolisms could accelerate the dissolution of feldspar and chlorites, and facilitate the formation of transition-state calcite and siderite. Otherwise, the great variation was mainly attributed to the change of condition driven by CO2-brine-sandstone interactions, such as pH and the chemical composition of brine water(anion and cation), etc.

Comparison of hepatic resection and transarterial chemoembolization for solitary hepatocellular carcinoma.

AIM: To compare the outcomes of hepatic resection and transarterial chemoembolization (TACE) for solitary hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer (BCLC) staging system. METHODS: A consecutive sample of 540 patients with solitary HCC who underwent liver resection (n = 312) or TACE (n = 128) were included in the present study. Baseline characteristics, tumor characteristics, and post-operative complications were compared between the two groups. The Kaplan-Meier method was used for long-term survival analysis. Independent prognostic predictors were identified using the Cox proportional hazards model (univariate and multivariate analyses). RESULTS: The TACE and liver resection groups had similar baseline demographic and clinicopathological characteristics. The TACE group showed a significantly lower rate of major complications than the liver resection group (3.9% vs 17.4%, P < 0.001). Univariate and multivariate analyses indicated that TACE did not contribute to poor overall survival compared with liver resection; however, a solitary tumor diameter of greater than 6 cm should be considered a risk factor for poor overall survival (HR = 1.328, 95%CI: 1.002-1.783, P = 0.048). The liver resection and TACE groups had comparable overall survival rates at 1 year, 3 years, and 5 years (86.2%, 62.8%, and 44.0% vs 88.3%, 59.8%, and 40.6%, respectively, P = 0.419). In cases with tumor diameters equal to or less than 6 cm, the liver resection group showed a survival benefit compared with the TACE group at 1 year, 3 years, and 5 years (P = 0.030). The 1-, 3-, and 5-year overall survival rates of HCC cases with tumor diameters of more than 6 cm were similar among the liver resection and TACE groups (P = 0.467). CONCLUSION: A tumor diameter of 6 cm should be the cutoff for deciding between liver resection and TACE.

Patients with spontaneously ruptured hepatocellular carcinoma benefit from staged surgical resection after successful transarterial embolization.

BACKGROUND: Surgical resection of spontaneously ruptured hepatocellular carcinoma (HCC) after successful transarterial embolization (TAE) remains controversial. The aim of this study was to investigate its efficacy in a series of cases. MATERIALS AND METHODS: We retrospectively examined ruptured HCC cases from Jan 2000 to Dec 2008; all of these 126 cases received TAE as the initial therapy. Subsequently, 74 cases received staged surgical resection, and the remaining 52 cases underwent repeated TACE. The baseline demographic data, tumor characteristics, and long term survival were recorded and compared. RESULTS: The demographic and baseline characteristics were comparable between the hepatic resection and TACE groups; furthermore, no significant difference in the tumor characteristics was detected between the two groups. The differences in in-hospital, 30- day and 90-day mortality between the two groups were not significant (P>0.05). However, the 1-, 3-, and 5-year overall survival rates were 85.1%, 63.5%, and 37.8%, respectively, in the hepatic resection group, which were significantly higher than those in the TACE group (69.2%, 46.2%, and 17.3%, respectively, P=0.004). Univariate and multivariate analyses indicated that these patients benefitted from hepatic resection compared with TACE with respect to long-term outcomes. CONCLUSIONS: Staged hepatic resection after TAE is an effective treatment that results in superior long-term survival to repeated TACE.