Carbon nanoparticle-assisted natural orifice specimen extraction surgery with left colic artery preservation: a retrospective study.

Introduction: Natural orifice specimen extraction surgery (NOSES) has been widely regarded as a new technology in minimally invasive surgery. Meanwhile, carbon nanoparticles have been increasingly used for lymph node tracing in colorectal cancer surgery. Aim: To evaluate the effectiveness and feasibility of carbon nanoparticle-assisted natural orifice specimen extraction surgery with left colic artery preservation for total laparoscopic colorectal resection. Material and methods: We retrospectively reviewed the medical records of 83 patients diagnosed with sigmoid colon cancer or mid- and upper-rectal cancer from October 2017 to June 2020. These patients were divided into the NOSES group who underwent left colic artery preservation NOSES, being injected with a carbon nanoparticle suspension under colonoscopy the day before surgery, and the LA group, who underwent left colic artery preservation laparoscopic surgery. Surgical outcomes were retrospectively analyzed. Results: The mean number of harvested lymph nodes (p < 0.001) in the NOSES group was higher than in the LA group. Conversely, as regards pain score (p < 0.001) and postoperative hospital stay (p = 0.035), the LA group has higher mean values. The incidence of perioperative complications (p = 0.385) was 5.3% for the NOSES group compared to 13.3% for the LA group. Conclusions: Preoperative colonoscopic injection of a carbon nanoparticle suspension is a feasible and practical solution to dissect lymph nodes surrounding the inferior mesenteric artery without affecting the left colic artery in patients with colorectal cancer and about to receive NOSES. Moreover, NOSES combined with this approach leads to less postoperative pain and shorter hospital stays.

Synergistic antitumor effect of Andrographolide and cisplatin through ROS-mediated ER stress and STAT3 inhibition in colon cancer.

Colon cancer is one of the most leading death-causing cancers in the world. Cisplatin has been widely used as the first-line treatment of cancer. However, its clinical application is limited by the side effects or acquired drug resistance. Hence, it is of vital clinical significance to develop novel agents that synergize with cisplatin and decrease its side effects. The aim of this study was to investigate whether Andrographolide (AP) synergistically potentiates the anti-tumor effect of cisplatin on colon cancer cells. Here, we found that AP synergizes with cisplatin in exerting anticancer activity in colon cancer cells. Further studies showed that AP potentiates cisplatin-induced endoplasmic reticulum stress and STAT3 inhibition through increasing intracellular ROS. Notably, pre-treatment of NAC, a ROS scavenger, reversed apoptosis induced by combined treatment of AP and cisplatin, while relieving the activation of endoplasmic reticulum stress as well as STAT3 inhibition. These findings indicated that ROS plays a pivotal role in mediating synergistic anticancer effects of AP and cisplatin on colon cancer cells. Overall, this study presents a potential new therapeutic strategy for the treatment of colon cancer.

Let-7a Inhibits Tumor Metastasis by Regulating TGF-ß/Smad Signaling in the Colorectal Adenocarcinoma Cell Line LS-174T.

BACKGROUND/AIM: Colorectal adenocarcinoma has a poor prognosis due to its propensity for metastasis. It has been experimentally demonstrated that the microRNA (miRNA) let-7a can effectively inhibit tumor proliferation and metastasis by regulating the transforming growth factor (TGF)-ß signaling pathway; however, limited research has been conducted in the area of on colorectal cancer. Herein, we aimed to clarify the role and regulation of let-7a in a colorectal adenocarcinoma cell line (LS-174T). MATERIALS AND METHODS: LS-174T cells were transfected to express let-7a. Let-7a miRNA expression was detected by quantitative real-time polymerase chain reaction (RT-qPCR). Cell growth was assessed by methyl thiazolyl tetrazolium (MTT) assay; invasion and migration were examined by Matrigel invasion and wound healing assays. The expression levels of matrix metalloproteinase (MMP)-2, phosphorylated Drosophila mothers against decapentaplegic 2 (p-SMAD2), and TGF-ß1 were analyzed by western blotting. The mRNA expression levels of TGFB1 were also analyzed by RT-qPCR. RESULTS: Overexpression of let-7a resulted in significant inhibition of LS-174T cell proliferation in vitro. The invasion and migration abilities of the cells overexpressing let-7a were decreased, compared to the control group and miR-negative control group. Transfection of LS-174T cells with let-7a resulted in down-regulation of MMP-2, as well as of TGF-ß1 and p-SMAD2 protein expression. Moreover, TGF-ß1 mRNA levels were reduced following let-7a overexpression. CONCLUSION: Let-7a inhibited the growth and metastasis of colonic mucinous adenocarcinoma cells, at least partially, by regulating the TGF-ß/Smad signaling pathway.

Acid-responsive nanoparticles as a novel oxidative stress-inducing anticancer therapeutic agent for colon cancer.

OBJECTIVE: Nanoparticles can efficiently carry and deliver anticancer agents to tumor sites. Mounting evidence indicates that many types of cancer cells, including colon cancer, have a weakly acidic microenvironment and increased levels of reactive oxygen species. The construction of nano drug delivery vehicles "activatable" in response to the tumor microenvironment is a new antitumor therapeutic strategy. METHODS: Cinnamaldehyde (CA) was designed to link directly with dextran to form a polymer through an acid cleavable acetal bond. Herein, a novel pH-sensitive drug delivery system was constructed with co-encapsulated 10-hydroxy camptothecin (HCPT). Dynamic light scattering (DLS) analysis, transmission electron microscopy (TEM) analysis, and release kinetics analysis of HCPT-CA-loaded nanoparticles (PCH) were conducted to investigate the physical and chemical properties. The cellular uptake signatures of the nanoparticles were observed by confocal microscopy and flow cytometry. Cell viability, cell scratch assay, apoptosis assay, and colony formation assay were performed to examine the potent antiproliferative and apoptotic effects of the PCH. The antitumor mechanism of the treatment with PCH was evaluated by Western blotting, flow cytometry, and TEM analysis. The pharmacokinetics of PCH were examined in healthy Sprague Dawley rats within 6 hours after sublingual vein injection. We lastly examined the biodistribution and the in vivo anticancer activity of PCH using the xenograft mouse models of HCT116 cells. RESULTS: Both HCPT and CA were quickly released by PCH in an acidic microenvironment. PCH not only induced cancer cell death through the generation of intracellular reactive oxygen species in vitro but also facilitated the drug uptake, effectively prolonged drug circulation, and increased accumulation of drug in tumor sites. More attractively, PCH exhibited excellent therapeutic performance and better in vivo systemic safety. CONCLUSION: Overall, PCH not only utilized the tumor microenvironment to control drug release, improve drug pharmacokinetics, and passively target the drug to the tumor tissue, but also exerted a synergistic anticancer effect. The acid-responsive PCH has enormous potential as a novel anticancer therapeutic strategy.

Marital status and survival in patients with rectal cancer: An analysis of the Surveillance, Epidemiology and End Results (SEER) database.

BACKGROUND: Marital status has been validated as an independent prognostic factor for survival in several cancer types, but is controversial in rectal cancer (RC). The objective of this study was to investigate the impact of marital status on the survival outcomes of patients with RC. METHODS: We extracted data of 27,498 eligible patients diagnosed with RC between 2004 and 2009 from the Surveillance, Epidemiology and End Results (SEER) database. Patients were categorized into married, never married, divorced/separated and widowed groups.We used Chi-square tests to compare characteristics of patients with different marital status.Rectal cancer specific survival was compared using the Kaplan-Meier method,and multivariate Cox regression analyses was used to analyze the survival outcome risk factors in different marital status. RESULTS: The widowed group had the highest percentage of elderly patients and women,higher proportion of adenocarcinomas, and more stage I/II in tumor stage (P < 0.05),but with a lower rate of surgery compared to the married group (76.7% VS 85.4%). Compared with the married patients, the never married (HR 1.40), widowed (HR 1.61,) and divorced/separated patients (HR 1.16) had an increased overall 5-year mortality. A further analysis showed that widowed patients had an increased overall 5-year cause-specific survival(CSS) compared with married patients at stage I(HR 1.92),stage II (HR 1.65),stage III (HR 1.73),and stage IV (HR 1.38). CONCLUSION: Our study showed marriage was associated with better outcomes of RC patients, but unmarried RC patients, especially widowed patients,are at greater risk of cancer specific mortality.