ABSTRACT
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.
ABSTRACT
ObjectiveTo analyze the risk factors of complications after laparoscopic gastrectomy.Methods The clinical data of 76 patients who received laparoscopic gastrectomy at the Tenth Hospital of Tangji University from April 2009 to July 2011 were retrospectively analyzed.All patients were divided into complication group (13patients) and non-complication group (63 patients).Seventeen variables,including gender,age,abdominal surgery history,comorbidities (cardiovascular disease,chronic obstructive pulmonary disease,diabetes mellitus,anemia,hypoproteinemia,pyloric obstruction),palliative operation,operative data ( operation time,blood loss,method of alimentary tract reconstruction),postoperative TNM staging,vascular or nerve invasion and number of lymph nodes dissected were analyzed by using the univariate and Logistic regression analysis to screen out the risk factors of postoperative complications.All data were analyzed using the t test or chi-square test.ResultsThere were 67 patients received laparoscopic curative gastrectomy and 9 received laparoscopic palliative gastrectomy.Sixty-three patients received distal gastrectomy ( including 49 received BillrothⅠgastrectomy and 14 received Billroth Ⅱ gastrectomy) and 13 patients received total gastrectomy + Roux-en-Y esophagojejunostomy).The mean operation time,blood loss,number of lymph nodes dissected were ( 263 ± 72) minutes,( 200 ± 191 ) ml and 17 ±8,respectively.There were 25 patients in TNM stage Ⅰ,18 in stage Ⅱ,27 in stage Ⅲ and 6 in stage Ⅳ.The incidence of complications was high in the old patients,but there was no effect of gender and age on the incidence of complications ( x2 =0.68,2.32,P ＞ 0.05 ).The operation time of the complication group was longer than that of non-complication group,but no significant difference was observed ( t =1.44,P ＞ 0.05 ).Preoperative comobidities (cardiovascular disease,chronic obstructive pulmonary disease,diabetes mellitus,anemia,hypoproteinemia,pyloric obstruction),blood loss and number of lymph node disseeted were not the risk factors of postoperative complications ( x2 =3.20,0.58,0.13,0.26,0.01,0.19,t =0.15,0.83,P ＞ 0.05).The results of multivariate Logistic regression analysis showed that Billroth Ⅱ alimentary tract reconstruction,more comorbidites,and advanced TNM stage were correlated with postoperative complications ( OR =5.54,7.02,2.33,P ＜0.05 ).The accuracy rate of multivariate Logistic regression analysis was 8 i.6％.Conclusion Billroth Ⅱ alimentary tract reconstruction,more comorbidities,and advanced TNM stage are the independent risk factors of complicatioas after laparoscopic gastrectomy.
ABSTRACT
As multidrug resistance related genes and cell factors are discovered one after another,people have a more thorough understanding to the oncological mechanisms of cancer metastasis.Many evidences of the inherent link between the two tips have been found.These researches provide new ideas to further clarify the regulation mechanisms between them.It is revealed that the inherent link maybe occur on the gene expression and transcription,and with complicated regulative factors.Indepth study of the relations between cancer multidrug resistance and metastasis will help to guide the clinical treatment of tumor.