67 research outputs found
Microbuckling of Fibrous Matrices Enables Long Range Cell Mechanosensing
No full textWhen biological cells migrate, divide, and invade, they push and pull on individual fibers of the matrix surrounding them. The resulting fiber displacements are neither uniform nor smooth; rather, displacements localize to form dense fibrous bands that span from one cell to another. It is thought that these bands may be a mechanism by which cells can sense their neighbors, but this hypothesis remains untested, because the mechanism for band formation remains unknown. Using digital volume correlation, we measure the displacements induced by contractile cells embedded in a fibrous matrix. We find that cell-induced displacements propagate over a longer range than predicted by linear elasticity. To explain the long-range propagation of displacements, we consider the effect of buckling of individual matrix fibers, which generates a nonlinear stress-strain relationship. We show that fiber buckling is the mechanism that causes the displacements to propagate over a long range and the bands to form between nearby cells. The results thus show that buckling of individual fibers provides a mechanism by which cells may sense their distant neighbors mechanically
Abstract 721: Minimally invasive test and composite biomarker for early detection of serous ovarian carcinoma
No full textAbstract
Background: Current screening programs for early detection of high grade epithelial ovarian cancer (HGOvC) among high-risk populations have failed to show improvement in HGOvC mortality, therefore these women are offered risk-reducing bilateral salpingo-oophorectomy (RRBSO) at 35- 40 years. Stratification of high-risk population, especially BRCA mutation carriers, may enable personalized risk counseling and individualization of timing of RRBSO. In most cases, the precursor lesions of HGOvC arise in the epithelium of the fallopian tube (FT) fimbriae rather than intra-peritoneally. It is therefore plausible that proteins, RNA or DNA from early-stage tumor cells may be identifiable in fluid samples obtained from the lumen of the gynecological tract, thus making it possible to identify curable, early stage lesions.
Aims: (1) Test the feasibility of uterine lavage as a minimally invasive test for early detection of ovarian cancer, and (2) Identify novel early-detection biomarkers in the uterine lavage fluid (UtLF).
Methods: We developed a method for sampling of gynecologic tract fluid termed uterine lavage fluid (UtLF), which is a simple, reproducible, low-cost office procedure that can be performed routinely during gynecologic follow-up visits. We have already collected UtLF from 140 HGOvC patients and control women undergoing gynecologic surgical procedures for non-malignant indications. Deep proteomic profiling of UtLF is performed by isolation of microparticles from body fluids, followed by solubilization, trypsin digestion and high resolution mass spectrometric (MS) analysis (on the Q-Exactive MS). Machine learning algorithms have been used to extract a classifier that can predict the diagnosis of ovarian cancer.
Results: Uterine lavage appears to be a feasible, low burden procedure. The MS approach has identified thousands of proteins in each UtLF specimen, in a high throughput manner. The label-free quantification algorithm (MaxQuant) enables a quantitative comparison between samples from cases and controls. We have derived a 20-protein classifier with an area under the curve (AUC) of Receiver Operating Characteristics (ROC) curve of 0.91 at 20% error. The composite biomarker has been applied to an independent validation set with a negative predictive value (NPV) of 92% and positive predictive value (PPV) of 45%.
Conclusions: A minimally invasive technique of uterine lavage to collect unique diagnostic samples, coupled with state-of-the-art proteomics methods, results in a highly sensitive and specific composite biomarker which may be developed in to a screening tool for early detection of serous ovarian cancer in high-risk populations.
Citation Format: Keren Bahar-Shany, Georgina D. Barnabas, Limor Helpman, Ariella Yakobson-Siton, Tamar Perri, Ram Eitan, Jacob Korach, Tamar Geiger, Keren Levanon. Minimally invasive test and composite biomarker for early detection of serous ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 721. doi:10.1158/1538-7445.AM2017-721</jats:p
Conservative Treatment of a Vesicocervical Fistula Resulting from Shirodkar Cervical Cerclage
No full textMenopausal hormone therapy for BRCA-mutation carriers: attitudes of Israeli healthcare providers before and after a brief educational intervention
No full text
Author response
No full textDevelopment of uterine endometrial receptivity for implantation is orchestrated by cyclic steroid hormone-mediated signals. It is unknown if these signals are necessary for oviduct function in supporting fertilization and preimplantation development. Here we show that conditional knockout (cKO) mice lacking estrogen receptor α (ERα) in oviduct and uterine epithelial cells have impaired fertilization due to a dramatic reduction in sperm migration. In addition, all successfully fertilized eggs die before the 2-cell stage due to persistence of secreted innate immune mediators including proteases. Elevated protease activity in cKO oviducts causes premature degradation of the zona pellucida and embryo lysis, and wild-type embryos transferred into cKO oviducts fail to develop normally unless rescued by concomitant transfer of protease inhibitors. Thus, suppression of oviductal protease activity mediated by estrogen-epithelial ERα signaling is required for fertilization and preimplantation embryo development. These findings have implications for human infertility and post-coital contraception
Сomparative Analysis of Belarusian and German Phraseological Units and Paremias with Bible Anthroponyms
No full textУ артыкуле апісваюцца ў супастаўляльным аспекце выяўленыя з фразеалагічных і парэміялагічных слоўнікаў беларускія і нямецкія ўстойлівыя адзінкі з біблейскімі кампанентамі, якія абазначаюць уласныя імёны і прозвішчы чалавека (Адам, Ева, Каін, Ісус Хрыстос, Марыя, Іосіф, Фама, Іуда, Пётр, Павел (Саўл), Абрам, Мафусаіл, Ной, Іарэд, Лаван, Якаб, Валтасар, Гог, Понцый Пілат, Корах, Вельзевул, Давід, Голіаф, Йонатан, Валаам) і іх дэрываты. Вызначаюцца поўныя эквіваленты ў абедзвюх мовах. Асобна падаюцца ўстойлівыя выразы, якія сустракаюцца толькі ў беларускай мове ці маюць месца выключна ў нямецкай мове. Упершыню ажыццяўляецца іх колькасны падлік і вызначаецца роля ў папаўненні фразеалагічнага і парэміялагічнага фондаў абедзвюх моў. Гэта робіць магычымым разгледзець уплыў Бібліі на носьбітаў беларускай і нямецкай моў, а таксама вызначыць агульныя і адметныя рысы ў моўных карцінах абодвух народаў і іх менталітэтах.= The article describes in a comparative aspect Belarusian and German set expressions with the Bible components: personal names and surnames (Adam, Eve, Cain, Jesus Christ, Maria, Joseph, Thomas, Judas, Peter, Paul (Saul), Abram, Methuselah, Noah, Iared, Lavan, Jacob, Belshazzar, Gog, Pontius Pilate, Korach, Beelzebub, David, Goliath, Jonathan, Balaam) and their derivatives, identified on the material of actual phraseological and paremiological dictionaries. The full equivalents are determined in the two languages. Set expressions that are found only in Belarusian and only in German are given separately. For the first time their quantity is counted and their role in the phraseological and paremiological funds replenishing of the two languages is determined. It makes possible to consider the influence of the Bible on Belarusian and German speakers and also determines the similarities and differences in the linguistic pictures of the world and the mentality of the two peoples
Efficacy and Safety of Bevacizumab-Containing Therapy in Newly Diagnosed Ovarian Cancer: ROSiA Single-Arm Phase 3B Study.
No full textThe aim of this study was to assess the safety and efficacy of extending bevacizumab therapy beyond 15 months in nonprogressive ovarian cancer.
PATIENTS AND METHODS: In this multinational prospective single-arm study (ClinicalTrials.gov NCT01239732), eligible patients had International Federation of Gynecology and Obstetrics stage IIB to IV or grade 3 stage I to IIA ovarian cancer without clinical signs or symptoms of gastrointestinal obstruction or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the preceding 6 months. Prior neoadjuvant chemotherapy was permitted. After debulking surgery, patients received bevacizumab 15 (or 7.5) mg/kg every 3 weeks (q3w) with 4 to 8 cycles of paclitaxel (investigator's choice of 175 mg/m q3w or 80 mg/m weekly) plus carboplatin AUC 5 to 6 q3w. Single-agent bevacizumab was continued until progression or for up to 24 months. The primary end point was safety.
RESULTS: Between December 2010 and May 2012, 1021 patients from 35 countries began study treatment. Bevacizumab was administered at 15 mg/kg in 89% of patients and for more than 15 months in 53%. Median follow-up duration was 32 months (range, 1-50 months). The most common all-grade adverse events were hypertension (55% of patients), neutropenia (49%), and alopecia (43%). The most common grade 3 or higher-grade adverse events were neutropenia (27%) and hypertension (25%). Bevacizumab was discontinued because of proteinuria in 5% of patients and hypertension in 3%. Median progression-free survival (PFS) was 25.5 months (95% confidence interval, 23.7-27.6 months).
CONCLUSION: Extended bevacizumab demonstrated increased incidences of proteinuria and hypertension compared with 12 or 15 months of bevacizumab in previous trials, but these rarely led to bevacizumab discontinuation. Median PFS is the longest reported for frontline bevacizumab-containing therapy. The longer bevacizumab duration beyond 15 months in this study may improve PFS without substantially compromising safet
Physiologic uptake of 18F-FDG in transposed ovaries may mimic metastasis on 18F-FDG PET/CT imaging
No full textUterine Leiomyosarcoma: Does the Primary Surgical Procedure Matter?
No full textBackground:Uterine leiomyosarcoma (LMS) has a poor prognosis even after early-stage diagnosis. Because there are no accurate diagnostic tools for preoperatively distinguishing LMS from uterine leiomyoma, surgeons might opt for partial surgical procedures such as myomectomy or subtotal hysterectomy. We sought to determine whether a surgical procedure that cuts through the tumor influences prognosis.Materials and Methods:Demographic and clinical data of consecutive patients with stage I LMS treated between 1969 and 2005 were reviewed. The study population was divided into group A: patients whose first surgical intervention was total hysterectomy (n = 21); and group B: patients who underwent procedures involving tumor injury, for example, myomectomy, laparoscopic hysterectomy with a morcellator knife, or hysteroscopic myomectomy (n = 16). Survival rates were analyzed and compared. A Cox proportional hazards model was used to assess the association between variables of interest and prognosis.Results:The median age at diagnosis was 50 years (range, 30-74 years). Median follow-up duration was 44 months. The 2 groups did not differ significantly in age at diagnosis, menopausal status, gravidity, parity, postoperative radiotherapy, or time to last follow-up. Kaplan-Meier curves showed significantly better survival rates (P = 0.04) and a significant advantage in recurrence rate (P = 0.03) for group A compared with group B. Survival in group A was 2.8-fold better than that in group B (95% confidence interval, 1.02-7.67). These estimates remained stable after adjustment for age, menopausal status, and radiotherapy.Conclusions:In patients with stage I LMS, primary surgery involving tumor injury seems to be associated with a worse prognosis than total hysterectomy as a primary intervention.</jats:sec
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