Inactivation of CREBBP expands the germinal center B cell compartment, down-regulates MHCII expression and promotes DLBCL growth.

The genes encoding the histone acetyl-transferases (HATs) CREB binding protein (CREBBP) and EP300 are recurrently mutated in the activated B cell-like and germinal center (GC) B cell-like subtypes of diffuse large B cell lymphoma (DLBCL). Here, we introduced a patient mutation into a human DLBCL cell line using CRISPR and deleted and in the GC B cell compartment of mice. CREBBP-mutant DLBCL clones exhibited reduced histone H3 acetylation, expressed significantly less MHCII, and grew faster than wild-type clones in s.

The hematopoietic oncoprotein FOXP1 promotes tumor cell survival in diffuse large B-cell lymphoma by repressing S1PR2 signaling.

Aberrant expression of the oncogenic transcription factor forkhead box protein 1 (FOXP1) is a common feature of diffuse large B-cell lymphoma (DLBCL). We have combined chromatin immunoprecipitation and gene expression profiling after FOXP1 depletion with functional screening to identify targets of FOXP1 contributing to tumor cell survival. We find that the sphingosine-1-phosphate receptor 2 (S1PR2) is repressed by FOXP1 in activated B-cell (ABC) and germinal center B-cell (GCB) DLBCL cell lines with aberrantly high FOXP1 levels; S1PR2 expression is further inversely correlated with FOXP1 expression in 3 patient cohorts.

DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and tumor cell survival in diffuse large B cell lymphoma.

The epigenetic dysregulation of tumor suppressor genes is an important driver of human carcinogenesis. We have combined genome-wide DNA methylation analyses and gene expression profiling after pharmacological DNA demethylation with functional screening to identify novel tumor suppressors in diffuse large B cell lymphoma (DLBCL). We find that a CpG island in the promoter of the dual-specificity phosphatase DUSP4 is aberrantly methylated in nodal and extranodal DLBCL, irrespective of ABC or GCB subtype, resulting in loss of DUSP4 expression in 75% of >200 examined cases.

Surgical management of pelvic organ prolapse in women.

Background: Pelvic organ prolapse may occur in up to 50% of parous women. A variety of urinary, bowel and sexual symptoms may be associated with the prolapse.

Objectives: To determine the effects of the many different surgeries used in the management of pelvic organ prolapse.

MPN patients harbor recurrent truncating mutations in transcription factor NF-E2.

The molecular etiology of myeloproliferative neoplasms (MPNs) remains incompletely understood, despite recent advances incurred through the discovery of several different mutations in MPN patients. We have recently described overexpression of the transcription factor NF-E2 in MPN patients and shown that elevated NF-E2 levels in vivo cause an MPN phenotype and predispose to leukemic transformation in transgenic mice. We report the presence of acquired insertion and deletion mutations in the NF-E2 gene in MPN patients.

The role of microRNAs in the pathogenesis and treatment of hematopoietic malignancies.

microRNAs (miRNAs) comprise a recently discovered class of non-coding RNAs with regulatory functions in post-transcriptional gene expression control. Many miRNAs are located in genomic regions that are frequently deleted in cancer, or are subject to epigenetic and transcriptional deregulation in cancer cells. The miRNA transcriptome of cancer cells is very different from that of their normal cell counterparts.

Laparoscopic sacrocolpopexy for recurrent pelvic organ prolapse after failed transvaginal polypropylene mesh surgery.

Introduction And Hypothesis: A prospective case series to assess the safety and efficacy of laparoscopic sacrocolpopexy for the surgical management of recurrent pelvic organ prolapse (POP) after transvaginal polypropylene mesh prolapse surgery.

Methods: Between January and December 2010, women with post-hysterectomy recurrent prolapse (≥ stage 2 POP-Q) after transvaginal polypropylene mesh prolapse surgery were included. Perioperative morbidity and short-term complications were recorded and evaluated.

Vaginal invagination: definition, clinical presentation and surgical management.

Introduction And Hypothesis: The objective of this observational study is to define vaginal invagination identified at vaginal prolapse surgery and to report the prevalence and risk factors for its development.

Methods: All women undergoing vaginal prolapse surgery between January and December 2010 were prospectively evaluated intraoperatively for invagination of the vagina. The preoperative details and characteristics of the invagination were recorded and the area of vaginal mucosa released was quantified in square centimetres.

Off-label use of misoprostol for labor induction: a nation-wide survey in Switzerland.

Objective: Off-label use of drugs is frequent in obstetrical practice. No data however are available about nation-wide off-label use in obstetrics regarding frequency and patient information. The objective of our study was to assess the clinical practice of off-label use of misoprostol for labor induction.

Painful bladder syndrome: management and effect on sexual function and quality of life.

Objectives: Primary aim of this study was to evaluate the effect of our therapeutical management in patients with painful bladder syndrome (PBS)/interstitial cystitis (IC) on sexual function, quality of life and bladder symptoms using validated tools prospectively

Material And Methods: A prospective case controlled study The setting is a tertial referral centre. We included 69 patients with PBS/IC according to the National Institute of Diabetes and Kidney Disease (NIDDK) into this study All patients were managed applying determined therapeutical steps including tetracycline, bladder instillation consisting of heparine, local anaesthetic and natrium-bicarbonate, prednisolon and antihistaminics or instillation with DMSO. Sexual function, quality of life and symptoms were evaluated with validated tools FSFI, King's Health Questionnaire and visual analogue scale (VAS).

Sexual function after sacrocolpopexy.

Introduction: Pelvic organ prolapse affects approximately 50% of parous women over 50 years of age and has a lifetime risk of 30-50%. Vault descent or prolapse occurs in about 20% after hysterectomy and can have a negative effect on sexual function. Sacrocolpopexy is the gold standard of surgical treatment for apical prolapse in fit, sexually active patients.

An adjustable sling in the management of recurrent urodynamic stress incontinence after previous failed midurethral tape.

Objective: The aim of this prospective study was to evaluate the feasibility and outcome of an adjustable sling system AMI in patients with recurrent urinary stress incontinence after failed suburethral sling insertion.

Patients And Methods: Twenty-five patients with recurrent urinary stress incontinence treated with an adjustable sling system AMI were analyzed for feasibility and outcome. Patients' incontinence bother was quantified using the Visual Analogue Scale (VAS) from 0 to 10.