Emerging evidence suggests that mesenchymal stem cells (MSCs) are often recruited to tumor sites but their functional significance in tumor growth and disease progression remains elusive. Herein we report that prostate cancer (PC) cell microenvironment subverts PC patient adipose-derived stem cells (pASCs) to undergo neoplastic transformation. Unlike normal ASCs, the pASCs primed with PC cell conditioned media (CM) formed prostate-like neoplastic lesions in vivo and reproduced aggressive tumors in secondary recipients. The pASC tumors acquired cytogenetic aberrations and mesenchymal-to-epithelial transition (MET) and expressed epithelial, neoplastic, and vasculogenic markers reminiscent of molecular features of PC tumor xenografts. Our mechanistic studies revealed that PC cell-derived exosomes are sufficient to recapitulate formation of prostate tumorigenic mimicry generated by CM-primed pASCs in vivo. In addition to down-regulation of the large tumor suppressor homolog2 (Lats2) and the programmed cell death protein 4 (PDCD4), a neoplastic transformation inhibitor, the tumorigenic reprogramming of pASCs was associated with trafficking by PC cell-derived exosomes of oncogenic factors, including H-ras and K-ras transcripts, oncomiRNAs miR-125b, miR-130b, and miR-155 as well as the Ras superfamily of GTPases Rab1a, Rab1b, and Rab11a. Our findings implicate a new role for PC cell-derived exosomes in clonal expansion of tumors through neoplastic reprogramming of tumor tropic ASCs in cancer patients.
The implementation of guidelines and proctoring recommendations is necessary to protect surgeons, proctors, institutions and, above all, the patients who are associated with the institutional introduction of a robot assisted radical prostatectomy program. With no current guidelines we anticipate this article will serve as a catalyst of interorganizational discussion to initiate regulatory oversight of surgeon certification and proctorship.
To our knowledge this review represents the largest multi-institutional experience of robotic dismembered pyeloplasty with long-term followup. Robotic pyeloplasty appears to be safe, durable and efficacious for primary and secondary ureteropelvic junction obstruction with or without concomitant stone extraction, and for patients with a solitary kidney.
Ureteral stents are an integral part of urological practice. However, stents that migrate, fragment or are forgotten pose a management and legal dilemma. Our series consists of 31 patients, 22 with forgotten stents that were left indwelling for more than 6 months (mean 22.7) and 9 migrated stents. Of the forgotten stents 15 (68%) were calcified, 10 (45%) were fragmented, and 3 (14%) were calcified and fragmented. Procedures to render the patient stent-free were ureteroscopy in 16 (52%), percutaneous nephroscopy in 8 (26%), cystoscopic electrohydraulic lithotripsy in 6 (19%), extracorporeal shock wave lithotripsy in 10 (32%), open cysto-litholapaxy in 1 (3%) and simple nephrectomy in 1 (3%). Multiple procedures were required in 6 patients (19%). Management of such complicated ureteral stents requires a multimodal therapeutic approach incorporating the latest in extracorporeal shock wave lithotripsy and endourological techniques. These patients are at increased risk for loss of renal function. A computerized tracking registry of ureteral stents may help prevent this urological travesty.
Classic laparoscopic donor and hand assisted laparoscopic donor nephrectomies appear to be safe procedures for harvesting kidneys. The recipient graft function is similar in the laparoscopic and open surgery groups.
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