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Background: Laparoscopic distal pancreatectomy (LDP) showed advantage of perioperation outcomes for benign and low-grade tumor of the pancreas. The application of LDP for pancreatic ductal adenocarcinoma (PDAC) didn't gain popular acceptance and the number of LDP for PDAC remains low. We designed a case-matched study to analysis the short- and long-term outcomes of the patients undergoing either Laparoscopic distal pancreatectomy or open distal pancreatectomy for PDAC.Method: From 2003 to 2013, 17 patients were underwent LDP and 34 patients were underwent ODP for PDAC were matched by tumor size, age and body mass index (BMI). The two groups' demographic information, perioperative outcomes and survival data were compared.Results: Baseline characteristics were comparable between the LDP and ODP groups. The intraoperative blood loss, first flatus, first oral intake and postoperative hospital stay were significantly less in LDP group than ODP group (50 ml vs400ml, P = 0.000; 3d vs 4d, P = 0.001; 3d vs 4d, P = 0.003; 13d vs 15.5d, P = 0.022). The mean operation time, overall postoperative morbidity and postoperative pancreatic fistula rates were similar in the two groups. 5 patients (29.4 %) in LDP group and 7 patients (20.6 %) in ODP group underwent extended resections. There were no significant differences in tumor sizes (3.5 cm vs 3.9 cm, P = 0.664) and number of harvested lymph nodes (9 vs8 P = 0.534). The median overall survival for both groups was 14.0 months. Cox proportional hazards analysis showed extended resections, R1 resection, perineural invasion and tumor differentiation were associated with worse survival.Conclusion: LDP is technically feasible and safe for PDAC in selected patients and the short-term oncologic outcomes were not inferior to ODP in this small sample study. However the long-term oncologic safety of LDP for PDAC has to be further evaluated by multicenter or randomized controlled trials. [ABSTRACT FROM AUTHOR]

Y-320, a novel immune-modulator, inhibits IL-17 production by CD4 + T cells stimulated with IL-15. Its use in autoimmune diseases such as rheumatoid arthritis has been documented. However, no studies have be conducted to evaluate its application in cancer treatment either as mono or combined therapy. This study demonstrated that while Y-320 had little effect on multidrug resistance (MDR) cell lines, it induced remarkable injury to MDR tumor cells when concurrently administered with other chemotherapeutic agents. Concomitant use of Y-320 with a low dose of paclitaxel significantly sensitized MDR tumors by inducing G2/M phase arrest and apoptosis. Further analyses indicated that Y-320 was a substrate of P-glycoprotein (P-gp). It could inhibit P-gp efflux function without altering P-gp expression, and subsequently reverse P-gp mediated drug resistance in MDR cells. The co-administration of Y-320 and paclitaxel suppressed tumor growth remarkably with an inhibition rate of 77.1% compared to 6.5% in the paclitaxel monotherapy group in vivo . This co-treatment did not increase extra complications in MDR tumor xenograft models. Particularly, no significant changes in body weight and hepatorenal serology were observed with the co-treatment. In conclusion, our results confirm that Y-320 is a promising chemotherapy sensitizer for the first time. The co-administration of Y-320 and chemotherapeutic agents might be an effective and low-toxicity chemotherapeutic regime for the MDR tumor patients., Competing Interests: None., (AJTR Copyright © 2020.)

Side-effects and resistance substantially limit the efficacy of chemotherapy. One possible solution to this persistent problem would be co-administration of targeted therapy and chemotherapy to achieve synergistic anti-cancer effects without extra toxicity. Here, we reported that LY2228820, a selective inhibitor of p38-MAPK signaling pathway, could induce synergistic anti-cancer effects with anti-microtubule (AMT) chemotherapy both in vitro and in vivo . In drug-resistant cancer cells, treatment with either LY2228820 or AMT drug alone was compatible with viability, while co-administration of both led to dramatic cytotoxicity, G2/M arrest and apoptosis. Moreover, co-treatment with LY2228820 notably improved the effectiveness of paclitaxel without exhibiting adverse effects in vivo . Mechanistic studies showed that LY2228820 sensitized cancer cells to AMT agents independent of P-gp. LY2228820 did not influence either the expression or the function of P-gp. Instead, it could inhibit p38-HSP27 signaling axis by down-regulating p-HSP27. Furthermore, LY2228820 blocked the p-HSP27 mediated protective response against AMT drugs in tumor cells, resulting in mitochondrial instability and the activation of mitochondrial death pathways. This P-gp-independent regime containing LY2228820 and AMT agents could produce synergistic anti-cancer effects without extra systematic toxicity. Our study offers a novel strategy for improving the therapeutic efficacy of AMT drugs by achieving a better balance between efficacy and toxicity. This new combination regime could be advantageous in patients who show little response to the maximal dosage of AMT chemotherapy, as well as those unable to tolerate the systematic toxicity of these agents in clinic., Competing Interests: None., (AJCR Copyright © 2019.)

The prognosis of advanced hepatocellular carcinoma (HCC) patients remains extremely poor, partially due to the development of acquired resistance to sorafenib and chemotherapy. Cabazitaxel, a semisynthetic taxane, has been approved for the therapy of docetaxel-resistant prostate cancer. However, no studies have been performed on the effect of cabazitaxel on HCC, and whether cabazitaxel remains sensitive in chemotherapy-resistant and sorafenib-resistant HCC cells is not clear. Our results demonstrate that cabazitaxel is highly toxic to HCC cell lines in a time- and dose-dependent manner by inducing G2/M phase arrest and apoptosis in vitro. Cabazitaxel also significantly suppresses HCC tumor growth in vivo. In chemotherapy-resistant HCC cell Huh-TS-48 with P-gp-overexpression, cabazitaxel shows less cross-resistant to other chemotherapeutic agents. The resistance fold of cabazitaxel, doxorubicin, paclitaxel, docetaxel and vinorelbine is 1.53, 8.60, 38.58, 15.53 and 18.06 respectively. Furthermore, sorafenib-resistant HCC cell SK-sora-5 is still sensitive to cabazitaxel. The IC50 values of cabazitaxel after 72 h exposure for parental cell SK-hep-1 and resistant cell SK-sora-5 are 0.84 and 0.73 nM. The results indicate that cabazitaxel is a potential agent to treat HCC after developing chemotherapy resistance caused by overexpression of P-gp and acquired resistance to sorafenib, and might improve prognosis in advanced HCC patients., Competing Interests: None.