Melanocortin-4 receptor antagonist TCMCB07 ameliorates cancer- and chronic kidney disease–associated cachexia
Cachexia, a devastating wasting syndrome characterized by severe weight loss with specific losses of muscle and adipose tissue, is driven by reduced food intake, increased energy expenditure, excess catabolism, and inflammation. Cachexia is associated with poor prognosis and high mortality and frequently occurs in patients with cancer, chronic kidney disease, infection, and many other illnesses. There is no effective treatment for this condition. Hypothalamic melanocortins have a potent and long-lasting inhibitory effect on feeding and anabolism, and pathophysiological processes increase melanocortin signaling tone, leading to anorexia, metabolic changes, and eventual cachexia. We used 3 rat models of anorexia and cachexia (LPS, methylcholanthrene sarcoma, and 5/6 subtotal nephrectomy) to evaluate efficacy of TCMCB07, a synthetic antagonist of the melanocortin-4 receptor. Our data show that peripheral treatment using TCMCB07 with intraperitoneal, subcutaneous, and oral administration increased food intake and body weight and preserved fat mass and lean mass during cachexia and LPS-induced anorexia. Furthermore, administration of TCMCB07 diminished hypothalamic inflammatory gene expression in cancer cachexia. These results suggest that peripheral TCMCB07 treatment effectively inhibits central melanocortin signaling and therefore stimulates appetite and enhances anabolism, indicating that TCMCB07 is a promising drug candidate for treating cachexia.
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The objective of this study was to prepare the liver targeting drug delivery system (TDDS) of artesunate (ART)-loaded polyethylene glycol (PEG)-Poly (D, L-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) modified by glycyrrhetinic acid (GA), and evaluate its in vitro cytotoxicity.Significance: The GA-PEG-PLGA-ART NPs enhanced the in vitro cytotoxicity on HCC cell lines. The development of GA-PEG-PLGA NPs will greatly push the clinical applications of ART as a novel anticancer drug.Methods: The NPs were prepared using solvent evaporation method, and the formulation was optimized through an orthogonal design. In addition,...
PMID: 32976788 [PubMed - as supplied by publisher]
Abstract Long non-coding RNAs (lncRNAs) cancer susceptibility candidate 2 (CASC2) has been characterized as a tumor suppressor in glioma. Although CASC2 may predict the prognosis of glioma patients, the role and mechanism of CASC2 in human glioblastoma remain to be fully illuminated. Expression of CASC2 and miR- 18a was detected using RT-qPCR. Cell growth was evaluated by MTT assay, colony formation assay, and flow cytometry; metastasis and epithelial-mesenchymal transition (EMT) were determined with transwell assay and Western blot, respectively. The target binding between CASC2 and miR-18a was predicted on Starb...
This study represents the first report of miR-214 on global gene expression in the context of HPV. PMID: 32975231 [PubMed - in process]
Conclusion: Faecal M2-PK Quick test has a high sensitivity for detection of colorectal cancer when compared to gFOBT, making it the potential choice for colorectal tumour screening biomarker in the future. PMID: 32972105 [PubMed - as supplied by publisher]
Conclusion: The number of retrieved lymph nodes and the presence of tumor complications were prognostic factors for stage IIA colon cancer but lymphovascular and perineural invasion were not. Sidedness and preoperative CEA could be used as factors to predict the benefit of adjuvant chemotherapy. Currently, it is believed that there is no benefit of AC for stage IIA colon cancer. Further studies are needed to determine the survival benefit of adjuvant chemotherapy in stage IIA colon cancer. PMID: 32972104 [PubMed - as supplied by publisher]
This study aimed to evaluate the relationship between high-output stomas (HOSs), postoperative ileus (POI), and readmission after rectal cancer surgery with diverting ileostomy. Methods: We included 302 patients with rectal cancer who underwent restorative resection with diverting ileostomy between January 2011 and December 2015. HOSs were defined as stomas with ≥2000 mL/day output. We analyzed predictive factors for readmission of these patients. Results: Forty-eight (15.9%) patients had HOSs during the hospital stay, and 41 (13.6%) patients experienced POI. HOSs were strongly associated with POI (45.8 vs. 7.5%, p
Conclusion: Sidedness of colon cancer had a significant and varied prognostic impact in patients with Stage II, III, and liver metastasis after curative resection. PMID: 32972100 [PubMed - as supplied by publisher]
We present a case of synchronous quadruple CRC with 2 lesions previously obscured by ischemic colitis. A 73-year-old woman was admitted to our emergency department. An abdominal computed tomography revealed ischemic colitis and irregular wall thickening of the sigmoid colon and sigmoid-descending junction, suspicious of 2 colon cancers. A colonoscopy examination revealed a fungating mass 20 cm from the anal verge, as well as ischemic colitis spanning the mucosa from the sigmoid colon to the transverse colon. The patient underwent laparoscopic Hartmann procedure. Pathologic examination confirmed both lesions as adenocarcino...