Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson's disease.

Abstract: Dysfunction of mitochondrial complex I is associated with a wide spectrum of neurodegenerative disorders, including Parkinson's disease (PD). In rodents, inhibition of complex I leads to degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNpc), as seen in PD, through activation of mitochondria-dependent apoptotic molecular pathways. In this scenario, complex I blockade increases the soluble pool of cytochrome c in the mitochondrial intermembrane space through oxidative mechanisms, whereas activation of pro-cell death protein Bax is actually necessary to trigger neuronal death by permeabilizing the outer mitochondrial membrane and releasing cytochrome c into the cytosol. Activation of Bax after complex I inhibition relies on its transcriptional induction and translocation to the mitochondria. How complex I deficiency leads to Bax activation is currently unknown. Using gene-targeted mice, we show that the tumor suppressor p53 mediates Bax transcriptional induction after PD-related complex I blockade in vivo, but it does not participate in Bax mitochondrial translocation in this model, either by a transcription-independent mechanism or through the induction of BH3-only proteins Puma or Noxa. Instead, Bax mitochondrial translocation in this model relies mainly on the JNK-dependent activation of the BH3-only protein Bim. Targeting either Bax transcriptional induction or Bax mitochondrial translocation results in a marked attenuation of SNpc dopaminergic cell death caused by complex I inhibition. These results provide further insight into the pathogenesis of PD neurodegeneration and identify molecular targets of potential therapeutic significance for this disabling neurological illness.

Neutrophil to lymphocyte ratio (NLR) as an indicator of poor prognosis in stage IV non-small cell lung cancer

Abstract: Neutrophil to lymphocyte ratio (NLR), an index of systemic inflammation, has been associated with worse survival for many types of cancer. The aim of this study is to investigate the clinical significance of the blood NLR as a prognostic factor in non-small cell lung cancer (NSCLC) patients. Stage IV NSCLC patients diagnosed in our institution between April 2004 and March 2009 were retrospectively reviewed. Potential prognostic factors such as histology, gender, performance status, response to chemotherapy and NLR were analyzed. NLR was assessed baseline and during chemotherapy treatment. Overall survival (OS) and progression free survival (PFS) were calculated by the Kaplan–Meier method. A total of 171 patients were included in the study and 60 patients (35.1 %) presented a NLR ≥5. Median survival for the entire cohort was 9.3 months. We found that patients with undifferentiated carcinoma and patients with NLR ≥5 had a worse survival. Median PFS of patients with NLR <5 was 5.62 months and in patients with NLR ≥5 was 3.25 months (p = 0.098), and OS was 11.1 versus 5.6 months for patients with NLR<5 and NLR ≥5, respectively (p = 0.017). During the chemotherapy treatment, patients who normalized NLR after one cycle presented better outcomes (OS 8.7 vs. 4.3 months, p = 0.001, for patients who normalized NLR and for patients who remained persistently elevated). After multivariate analysis, histology and NLR remained independent predictors of survival (p < 0.05). In our analysis, elevated NLR is a predictor of shorter survival in patients with advanced NSCLC and the variation of NLR during the first cycle of treatment predicts survival. NLR is an easily measured, reproducible test that could be considered to be incorporated in the routine practice in NSCLC patients.

Adjuvant Trastuzumab: A Milestone in the Treatment of HER-2-Positive Early Breast Cancer

Abstract: Up to one fourth of women diagnosed with early breast cancer (EBC) have tumors that are human epidermal growth factor receptor 2 (HER-2) positive. This is associated with a high risk of relapse and death from meta-static disease. Trastuzumab, a monoclonal antibody directed against the extracellular domain of HER-2, improves survival and quality of life in women with HER-2-positive metastatic breast cancer receiving chemotherapy. Four major adjuvant trials-Herceptin Adjuvant (HERA), National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group (NCCTG) N9831, and Breast Cancer International Research Group (BCIRG) 006-including between them >13,000 women with HER-2-positive EBC, have investigated different adjuvant treatment approaches with trastuzumab. These trials have shown that trastuzumab reduces the 3-year risk of recurrence by about half in this population. The benefit was similar across the trials despite differences in patient populations, chemotherapy regimens, and sequencing of treatment. At a 2-year follow-up, interim results from the combined analysis of the NSABP B-31 and NCCTG N9831 trials showed a one third lower mortality for trastuzumab, and there was a trend toward an overall survival benefit in the HERA and BCIRG trials. A small Finnish trial, FinHer, investigating another regimen of trastuzumab, has also shown similarly positive results. Further follow-up of the major adjuvant trials will clarify the survival benefit for women receiving trastuzumab, as well as the optimal treatment duration (1 or 2 years). Notably, cardiac events in the trastuzumab-containing arms of these trials have remained within acceptable levels, with a slightly higher (0.6%-3.3%) incidence of congestive heart failure that mostly responded to treatment. Further follow-up will provide information on long-term cardiac safety. Overall, results from clinical trials are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk:benefit ratio demonstrated in these studies.

Investigations in GABAA receptor antibody-associated encephalitis

Abstract: Objective: To report the clinical features, comorbidities, receptor subunit targets, and outcome in patients with anti-GABA A receptor (GABA A R) encephalitis. Methods: Clinical study of 26 patients, including 17 new (April 2013–January 2016) and 9 previously reported patients. Antibodies to α1, β3, and γ2 subunits of the GABA A R were determined using reported techniques. Results: Patients9 median age was 40.5 years (interquartile range 48.5 [13.75–62.35] years; the youngest 2.5 months old; 13 female). Symptoms included seizures (88%), alteration of cognition (67%), behavior (46%), consciousness (42%), or abnormal movements (35%). Comorbidities were identified in 11 (42%) patients, including 7 tumors (mostly thymomas), 2 herpesvirus encephalitis (herpes simplex virus 1, human herpesvirus 6; coexisting with NMDAR antibodies), and 2 myasthenia without thymoma. Brain MRI was abnormal in 23 (88%) patients, showing in 20 (77%) multifocal, asynchronous, cortical-subcortical T2/fluid-attenuated inversion recovery abnormalities predominantly involving temporal (95%) and frontal (65%) lobes, but also basal ganglia and other regions. Immunologic or tumor therapy resulted in substantial improvement in 18/21 (86%) assessable patients; the other 3 (14%) died (2 status epilepticus, 1 sepsis). Compared with adults, children were more likely to have generalized seizures ( p = 0.007) and movement disorders ( p = 0.01) and less likely to have a tumor ( p = 0.01). The main epitope targets were in the α1/β3 subunits of the GABA A R. Conclusions: Anti-GABA A R encephalitis is characterized by frequent seizures and distinctive multifocal cortical-subcortical MRI abnormalities that provide an important clue to the diagnosis. The frequency of symptoms and comorbidities differ between children (more viral-related) and adults (more tumor-related). The disorder is severe but most patients respond to treatment.