Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma.

Malignant gliomas exhibit extensive heterogeneity and poor prognosis. Here we identify mitotic Olig2-expressing cells as tumor-propagating cells in proneural gliomas, elimination of which blocks tumor initiation and progression. Intriguingly, deletion of Olig2 resulted in tumors that grow, albeit at a decelerated rate.

Management of multiple sclerosis during pregnancy and the reproductive years: a systematic review.

Objective: To examine the evidence guiding management of multiple sclerosis (MS) in reproductive-aged women.

Data Sources: We conducted an electronic literature search using PubMed, ClinicalTrials.gov, and other available resources.

Birth outcomes in newborns fathered by men with multiple sclerosis exposed to disease-modifying drugs.

Objective: The aim of this study was to determine the incidence of births fathered by men with multiple sclerosis (MS) exposed to a disease-modifying drug (DMD) around the time of conception, and investigate the association between DMD exposure and birth outcomes in newborns of exposed and unexposed MS fathers.

Methods: Population-based databases in British Columbia (BC), Canada, (the BCMS database, Vital Statistics Birth Registry, Population Data BC Consolidation File/Census GeoData, BC PharmaNet and the BC Perinatal Database Registry) were linked in this retrospective cohort study (1996 to 2010). Multivariate models were used to examine the association between interferon-beta (IFNβ) or glatiramer acetate (GA) exposure (within 64 days prior to or at conception; i.

A review of safety-related pregnancy data surrounding the oral disease-modifying drugs for multiple sclerosis.

The recent approval of several oral disease-modifying drugs (DMDs) for multiple sclerosis (MS) brings promise of improved clinical effectiveness as well as greater drug compliance compared to the existing non-oral DMDs, and substantially increases patient choice and therapeutic options in the effective management of MS. However, for men and women with MS of childbearing age, concerns about the effect of oral DMDs on pregnancy and the fetus may arise. Some limited data from animal reproductive studies of oral DMDs suggest a potential increased risk of early pregnancy loss, impaired growth and birth defects.

Obstetrical epidural and spinal anesthesia in multiple sclerosis.

To examine obstetrical epidural and spinal anesthesia use in women with multiple sclerosis (MS) and the relationship with MS clinical factors. This was a retrospective cohort study, linking clinical data from women with MS in the British Columbia (BC) MS database to obstetrical data (1998-2009) from the BC Perinatal Database Registry. We compared epidural use in 431 deliveries to women with MS and 2,959 deliveries from the general population, as well as spinal use in cesarean deliveries (128 to women with MS and 846 in the general population), considering parity and using multivariate models.

Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review.

Based on fair quality Level 3 evidence, Lu et al.(1) note that glatiramer acetate (GA) exposure was not associated with lower mean birthweight, lower mean gestational age, preterm birth (37 weeks), congenital anomaly, or spontaneous abortion. However, GA was given an indeterminate recommendation because further research is needed.

Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance.

When contemplating a pregnancy, women treated for multiple sclerosis (MS) with a disease-modifying drug must decide to discontinue their medication before conception or risk exposing their unborn child to potential drug toxicity. Few studies exist as reference for patients and physicians, and of those available, the majority are less than ideal due to real-world constraints, ethical issues and methodological shortcomings. The authors provide a brief summary of existing animal and human data with current recommendations regarding the safety of IFN-β, glatiramer acetate, natalizumab, mitoxantrone, fingolimod and teriflunomide during pregnancy and lactation in women with MS.

Birth hospitalization in mothers with multiple sclerosis and their newborns.

Objective: To compare the duration of birth hospitalization in mothers with multiple sclerosis (MS) and their newborns relative to the general population and to investigate the impact of MS-related clinical factors on the length of birth hospitalization stays.

Methods: Data from the British Columbia Perinatal Database Registry and the British Columbia MS database were linked in this retrospective cohort study. The duration of birth hospitalization in mothers with MS and their newborns (n = 432) were compared with a frequency-matched sample of the general population (n = 2,975) from 1998 to 2009.

Disease-modifying drugs for multiple sclerosis in pregnancy: a systematic review.

Objective: To systematically review the literature regarding safety of disease-modifying drug (DMD) use during pregnancy on perinatal and developmental outcomes in offspring of patients with multiple sclerosis (MS).

Methods: A PubMed and EMBASE search up to February 2012 was conducted with a manual search of references from relevant articles. Selected studies were evaluated using internationally accepted criteria.

CTLA-4 is important in maintaining long-term survival of cardiac allografts.

Introduction: CTLA-4 is a negative regulatory molecule upregulated on activated T cells; however, its role in induction and maintenance of transplant tolerance is not well understood.

Methods: The characteristics and effects of a novel mouse anti-rat CTLA-4 antibody (Ab) (242B58) were examined using fluorescence-activated cell sorter, mixed lymphocyte reaction, enzyme-linked immunospot, signaling studies, and a rat model of cardiac transplant tolerance induced by administration of anti-CD28 Ab and cyclosporine.

Results: The anti-CTLA4 Ab was shown to bind to CTLA-4 but not prevent subsequent binding of B7 to CTLA-4.