Colon 26 adenocarcinoma cells can induce severe cancer cachexia experimentally, and the mechanism may be partially due to the enhanced TNF-alpha and IL-6 in tumor-bearing animals, which is controlled by NF-kappaB. Low dose of indomethacin alleviates the cachexia, decreases the activation of NF-kappaB and the serum levels of TNF-alpha and IL-6, and prevents body weight loss and muscle atrophy, while no further effect is gained by a higher dosage.
Optimization of care in gastrectomy can shorten postoperative hospital stay and provides multiple beneficial outcomes, including hastening the return of gut function, without increasing morbidity.
AIMTo investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes.METHODSThis is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy (RG), laparoscopic gastrectomy (LG), open gastrectomy (OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided.RESULTSThe present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients (RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery (P = 0.42) and stage of the disease (P = 0.16). Intraoperative blood loss was significantly lower in the LG (95.93 ± 119.22) and RG (117.91 ± 68.11) groups compared to the OG (127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG (27.78 ± 11.45), LG (24.58 ± 13.56) and OG (25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay (P < 0.0001). A similar complications rate was found (P = 0.13). The leakage rate was not different (P = 0.78) between groups.CONCLUSIONLaparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.
Background
Aberrant changes in epigenetic mechanisms such as histone modifications play an important role in cancer progression. PRMT1 which triggers asymmetric dimethylation of histone H4 on arginine 3 (H4R3me2a) is upregulated in human colorectal cancer (CRC) and is essential for cell proliferation. However, how this dysregulated modification might contribute to malignant transitions of CRC remains poorly understood.
Methods
In this study, we integrated biochemical assays including protein interaction studies and chromatin immunoprecipitation (ChIP), cellular analysis including cell viability, proliferation, colony formation, and migration assays, clinical sample analysis, microarray experiments, and ChIP-Seq data to investigate the potential genomic recognition pattern of H4R3me2s in CRC cells and its effect on CRC progression.
Results
We show that PRMT1 and SMARCA4, an ATPase subunit of the SWI/SNF chromatin remodeling complex, act cooperatively to promote colorectal cancer (CRC) progression. We find that SMARCA4 is a novel effector molecule of PRMT1-mediated H4R3me2a. Mechanistically, we show that H4R3me2a directly recruited SMARCA4 to promote the proliferative, colony-formative, and migratory abilities of CRC cells by enhancing EGFR signaling. We found that EGFR and TNS4 were major direct downstream transcriptional targets of PRMT1 and SMARCA4 in colon cells, and acted in a PRMT1 methyltransferase activity-dependent manner to promote CRC cell proliferation. In vivo, knockdown or inhibition of PRMT1 profoundly attenuated the growth of CRC cells in the C57BL/6 J-ApcMin/+ CRC mice model. Importantly, elevated expression of PRMT1 or SMARCA4 in CRC patients were positively correlated with expression of EGFR and TNS4, and CRC patients had shorter overall survival. These findings reveal a critical interplay between epigenetic and transcriptional control during CRC progression, suggesting that SMARCA4 is a novel key epigenetic modulator of CRC. Our findings thus highlight PRMT1/SMARCA4 inhibition as a potential therapeutic intervention strategy for CRC.
Conclusion
PRMT1-mediated H4R3me2a recruits SMARCA4, which promotes colorectal cancer progression by enhancing EGFR signaling.
To better understand the impact of undernutrition, nutritional risk, and nutritional treatment on the clinical outcomes of hospitalized cancer patients in China, the authors conducted a multicenter, cross-sectional study with 2248 cancer patients from 20 hospitals from January to June 2010. The authors defined 19.7% and 26.8% patients as undernourished at baseline and reassessment, respectively. Patients with gastrointestinal malignancies had a higher rate of undernutrition than other patients. The nutritional risk rate was 24.6% and 40.2% at baseline and reassessment, respectively. For patients with nutritional risk, the relative risk (RR) of adverse events (AEs) significantly increased with and without nutritional treatment. In comparison with the nonnutritional treatment subgroup, patients who received enteral nutrition (EN) or total parenteral nutrition (TPN) significantly reduced the RR of AE development. The RR of AEs for EN and TPN were 0.08 (95% CI: 0.01-0.62) and 0.56 (95% CI: 0.33-0.96), respectively. Separated nutrient infusion increased the risk of AEs. The authors concluded that undernutrition and nutritional risk are general problems that impact the outcomes of hospitalized cancer patients in China. Higher NRS2002 scores are related to AE risk but not weight loss. In nutritional treatment, EN and TPN can significantly reduce the risk of AEs.
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