ABSTRACT
Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.
ABSTRACT
Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.
ABSTRACT
Objective To summarize the experience of one case of anastomotic leakage after simultaneous pancreas-kidney transplantation (SPK ) with enteric drainage .Methods One case of type 2 diabetes mellitus complicated with end-stage nephropathy undergoing SPK was retrospectively analyzed .Iliac venous systemic circulation was employed for pancreatic venous reflux ,transplanted pancreas exocrine via enteric drainage and side-to-side anastomosis between donor pancreaticoduodenum and recipient jejunum . Pancreatoduodenal anastomotic leakage occurred at 12 days post-operation .During re-operation ,Roux-en-Y anastomosis was established between donor pancreaticoduodenum and recipient jejunum .And the relevant domestic and foreign literatures were searched .Results The follow-up time was 3 month after a second operation .Recipient pancreas and kidney transplantation survived well . There was no onset of enteric leakage .The incidence of anastomotic leakage varies greatly between different transplantation centers both at home and abroad .The incidence ranged from 3 .6％ to 11 .3％ .And the risk of pancreatic loss was as high as 54 .6％ .Conclusions As a severe postoperative complication ,anastomotic fistula after SPK may cuase abdominal infection . Even after reparing enteric fistula , the risk of leakage remains high . Roux-en-Y anastomosis is other therapeutic option .