This study evaluates the curative effects laparo-scopic hysterectomies performed to treat uterine fibroids and determined the impact of the procedures on ovarian blood supply. A total of 124 patients with uterine fibroids admitted and treated in our hospital from December 2014 to December 2015 participated in the study. Two groups of 62 patients each were formed according to different operating plans; one group of patients underwent abdominal (open) panhysterectomy and were set as the control group; with the other group of patients were treated with laparoscopic hysterectomy and were set as the observation group. Ovarian endocrine function tests and blood supply changes were measured in both groups before the operation and one month after it, and the clinical conditions of all the patients were followed up for 24 months after surgery. Our results showed the duration of operation, amount of bleeding and time to recovery after the procedure were significantly lower in the patients in the observation group (P<0.05). Also, compared with preoperative conditions, the levels of PRL, FSH, E2, LH and other ovarian function markers in both groups were significantly lower one month after the operation, but the levels of the patients in the observation group were still significantly higher than those of the patients in the control group (P<0.05). Likewise, the surgeries affected the ovarian blood supply in patients of both groups, as evidenced by the lower levels of PI, RI, Vmin, Vmax and other blood supply indexes observed by Doppler ultrasound a month after the operations. However, the impact of the surgery on the ovarian blood supply was less marked in the patients in the observation group as their levels remained higher than those of patients in the control group (P<0.05). The numbers of patients with completely healed abdominal muscular layers in the observation group were always significantly higher than those of patients in the control group, at every different time point examined (1, 4, 8 and 12 months after surgery) (P<0.01). At the end of the 24 months of the follow-up period, the recurrence rate of fibroids for patients in the observation group was 4.8%. In our hands, the laparoscopic hysterectomy procedure to treat uterine fibroids showed the usual advantages over the abdominal open hysterectomy, like small trauma, short surgical procedure and rapid postoperative recovery, but it also proved to cause a significantly smaller impact on ovarian blood supply and should be considered whenever uterus preservation is a priority.
Background: Recent advances in the field of cancer immunotherapy have identified CD8 + T cell responses against tumor-specific mutations as a key driver of tumor regression and overall survival.ADXS-NEO is a personalized Listeria monocytogenes (Lm)-based immunotherapy designed to target a patient's mutation-derived tumor-specific neoantigens. The objective of this study is to demonstrate the feasibility of using the ADXS-NEO platform to target tumor-specific point mutations and control tumor growth by generating neoantigen-specific T cell responses using a pre-clinical mouse tumor model. Methods:Whole-exome sequencing of the MC38 mouse tumor cell line identified 2870 unique nonsynonymous mutations. The netMHCcons algorithm was used to predict 137 potential neoantigens. We validated 20 immunogenic neoantigens either by peptide immunization followed by ELISPOT or by the presence of CD8 + T cells recognizing the neoantigen peptide following checkpoint inhibitor treatment.Two ADXS-NEO vectors were constructed; Lm20, targeting 20 validated immunogenic neoantigens, and Lm19, targeting most of the non-validated NSMs.Results: Both Lm19 & Lm20 significantly slowed tumor growth in C57BL/6 mice compared to control. An accumulation of ADXS-NEO-specific TILs was observed in tumor bearing mice treated with either Lm19 or Lm20. Examination of the tumor microenvironment in Lm19 or Lm20 treated mice revealed a decrease in the frequency and absolute number of Tregs, TAMs, MDSCs, and PD1 high exhausted CD8 + T cells as well as an increase in the frequency and absolute number of effector CD8 + T cells, relative to control.Conclusion: ADXS-NEO is a potent immunotherapy capable of driving immune responses against tumorspecific mutations and leading to tumor control in mice.
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