The online version of this artivle has a Supplementary Appendix. BackgroundNovel therapies capable of targeting drug resistant clonogenic MM cells are required for more effective treatment of multiple myeloma. This study investigates the cytotoxicity of natural killer cell lines against bulk and clonogenic multiple myeloma and evaluates the tumor burden after NK cell therapy in a bioluminescent xenograft mouse model. Design and MethodsThe cytotoxicity of natural killer cell lines was evaluated against bulk multiple myeloma cell lines using chromium release and flow cytometry cytotoxicity assays. Selected activating receptors on natural killer cells were blocked to determine their role in multiple myeloma recognition. Growth inhibition of clonogenic multiple myeloma cells was assessed in a methylcellulose clonogenic assay in combination with secondary replating to evaluate the self-renewal of residual progenitors after natural killer cell treatment. A bioluminescent mouse model was developed using the human U266 cell line transduced to express green fluorescent protein and luciferase (U266eGFPluc) to monitor disease progression in vivo and assess bone marrow engraftment after intravenous NK-92 cell therapy. ResultsThree multiple myeloma cell lines were sensitive to NK-92 and KHYG-1 cytotoxicity mediated by NKp30, NKp46, NKG2D and DNAM-1 activating receptors. NK-92 and KHYG-1 demonstrated 2-to 3-fold greater inhibition of clonogenic multiple myeloma growth, compared with killing of the bulk tumor population. In addition, the residual colonies after treatment formed significantly fewer colonies compared to the control in a secondary replating for a cumulative clonogenic inhibition of 89-99% at the 20:1 effector to target ratio. Multiple myeloma tumor burden was reduced by NK-92 in a xenograft mouse model as measured by bioluminescence imaging and reduction in bone marrow engraftment of U266eGFPluc cells by flow cytometry. ConclusionsThis study demonstrates that NK-92 and KHYG-1 are capable of killing clonogenic and bulk multiple myeloma cells. In addition, multiple myeloma tumor burden in a xenograft mouse model was reduced by intravenous NK-92 cell therapy. Since multiple myeloma colony frequency correlates with survival, our observations have important clinical implications and suggest that clinical studies of NK cell lines to treat MM are warranted. Haematologica 2012;97(7):1020-1028. doi:10.3324/haematol.2011 ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n
Fertility awareness is associated with time to seek treatment, ethnicity, and level of education among new patients seeking medical treatment. This study demonstrates the need to educate women of reproductive age and identifies particular patient populations in Canada that would most benefit from further education about infertility.
Abbreviations: SROC, summary receiver-operating characteristics; TOLAC, trial of labor after cesarean section; VBAC, vaginal birth after cesarean section. AbstractIntroduction: Cesarean section rates are increasing with a decrease in the rate of trial of labor after cesarean section. The objective of this study was to systematically review the predictive characteristics of sonographic measurement of lower uterine segment thickness for uterine rupture during labor. Material and methods:The review was carried out in agreement with PRISMA and SEDATE guidelines. MEDLINE, EMBASE, ClinicalTrials.gov and Cochrane Library were searched from 1990 until November 2018. Quality of included studies was assessed using the QUADAS-2 tool. Data were extracted to construct 2 × 2 tables from each study comparing ultrasound measurement with uterine defect at time of delivery. The data were plotted as a summary receiver-operating characteristic (SROC) curve using the hierarchical SROC model. Results: Twenty-eight observational cohort studies met the selection criteria for inclusion. Sonographic lower uterine segment thickness was measured at a gestational age of 36-40 weeks in women with a previous cesarean section. The risk of bias and concerns regarding applicability were low among most studies. The sonographic measurement was correlated with either delivery outcome or lower uterine segment thickness at the time of repeat cesarean section. The cut-off value for lower uterine segment thickness ranged from 1.5 to 4.05 mm across all studies. An association between thin lower uterine segment measurement and uterine dehiscence and uterine rupture was shown in 27 and four studies, respectively. Nineteen studies were included in a meta-analysis with a subgroup analysis by ultrasound methodology. In the subgroup using the ultrasound methodology associated with uterine rupture, the cutoff value is more precise (2.0-3.65 mm) among these 12 studies. There were 18 cases (1.0%) of uterine rupture, 120 (6.6%) of uterine dehiscence and 1674 (92.4%) women with no uterine defect. The SROC curve showed a sensitivity of 0.88 (95% CI 0.83-0.92) and specificity of 0.77 (95% CI 0.70-0.83). The negative likelihood ratio was 0.11 (95% CI 0.08-0.16) and the diagnostic odds ratio was 34.0 (95% CI 18.2-63.5). Conclusions:Lower uterine segment thickness >3.65 mm, measured using a standardized ultrasound technique, is associated with a lower likelihood of uterine rupture. | 831SWIFT eT al.
This study evaluates a novel technique of laparoscopic ovarian transposition performed by Gynecologic Oncologists prior to pelvic radiation for gynecologic cancer. A retrospective review was completed of all patients that underwent laparoscopic ovarian transposition from February 2007 to June 2017 at one tertiary care cancer. The technique involves salpingectomy, followed by retroperitoneal dissection to move the ovaries lateral to the hepatic and splenic flexures of the colon. Normal ovarian function was defined by the absence of vasomotor symptoms, FSH and menstrual history (if menstruating). The radiation dose to the ovary was calculated through dose volume histograms from three-dimensional image planning. Ten patients had laparoscopic ovarian transposition, of which, eight patients received post-operative external beam radiation to the pelvis (45–59.4 Gy). Four had additional brachytherapy (35.5–40 Gy). Median age and follow up were 29 years (18–37), and 20 months (6–103). Nine patients had cervical and one had vaginal cancer. Four patients were treated with primary radiation, three had radical trachelectomy with adjuvant radiation, and three had radical hysterectomy with one of three receiving adjuvant radiation. No patients developed vasomotor symptoms (0/8 (95% CI 0–19%)). FSH was normal in 2/2 patients. Menses continued post-radiation in 5/7 women who retained their uterus. The median radiation dose to the right and left ovary was 0.51 (0.23–1.1) Gy and 0.53 (0.23–1.1) Gy, respectively. Laparoscopic ovarian transposition with mobilization to the hepatic and splenic flexures of the colon achieves preservation of ovarian function in women prior to pelvic radiation.
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