ABSTRACT
OBJECTIVE: Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. METHODS: NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. RESULTS: ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. CONCLUSIONS: ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK cell-based immunotherapeutic approaches for the treatment of ovarian cancer.
Subject(s)
Interleukin-15/agonists , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/immunology , Proteins/pharmacology , Animals , Ascites/immunology , Ascites/pathology , Female , Humans , K562 Cells , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Lymphocyte Activation/drug effects , Mice , Mice, Inbred NOD , Mice, SCID , Recombinant Fusion Proteins , Xenograft Model Antitumor AssaysABSTRACT
We report our learning experience in simulated and real surgical tasks with a new voice-controlled robotic endoscope manipulator: an industrial robot with the tool-holder arm modified to support the optic and camera. The manipulator control-card programs have been rewritten to meet the needs of endoscopic surgeons. For this preliminary work, systems engineers with an additional monitor monitored, recorded, and compared the percentage effectiveness and precision of the responses of the robotic and human assistant to successive oral commands during the several different experimental surgical tasks. Simultaneously, to help develop this voice-commanded system for future, more precise robotic manipulation of surgical instruments, they measured the cartesian and spherical coordinates of successive positions of the optic. In unexpectedly difficult experimental conditions, the tireless robot proved more precise and effective than the demonstrably fatigable human: the steadier screen images of the robotic manipulations helped the surgeon tie knots in 7-0 sutures.
Subject(s)
Endoscopy/methods , Robotics/instrumentation , Animals , Equipment Design/methods , Humans , Models, Animal , Robotics/methods , Stomach/surgery , Suture Techniques , Swine , User-Computer Interface , Video-Assisted Surgery/instrumentation , Video-Assisted Surgery/methods , VoiceABSTRACT
We treated a series of 30 patients who had a Nyhus type II, III, or IV inguinal hernia without associated pathology by laparoscopic surgery using 2-mm surgical instruments and a modified preperitoneal Dulucq technique. A 30 degrees optic was used, and the repair was reinforced by an accordion-folded, polypropylene mesh introduced through a 10-mm optic needleport. There were no postoperative complications, and all patients were discharged 24 hours after operation. At 6 months there has been no recurrence of hernia. It was evident that the 2-mm procedure produced less surgical trauma.