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Beersheba, Israel

Collins M.A.,Loyola University | Neafsey E.J.,Loyola University | Wang K.,University of Chicago | Achille N.J.,Oncology Institute | And 2 more authors.
Molecular Neurobiology

There is no question that chronic alcohol (ethanol) abuse, a leading worldwide problem, causes neuronal dysfunction and brain damage. However, various epidemiologic studies in recent years have indicated that in comparisons with abstainers or neverdrinkers, light/moderate alcohol consumers have lower risks of age-dependent cognitive decline and/or dementia, including Alzheimer̄s disease (AD). Such reduced risks have been variously attributed to favorable circulatory and/or cerebrovascular effects of moderate ethanol intake, but they could also involve ethanol preconditioning phenomena in brain glia and neurons. Here we summarize our experimental studies showing that moderate ethanol preconditioning (MEP; 20̈C30 mM ethanol) of rat brain cultures prevents neurodegeneration due to β-amyloid, an important protein implicated in AD, and to other neuroinflammatory proteins such as gp120, the human immunodeficiency virus 1 envelope protein linked to AIDS dementia. The MEP neuroprotection is associated with suppression of neurotoxic proteinevoked initial increases in [Ca+2]i and proinflammatory mediators¡-e. g., superoxide anion, arachidonic acid, and glutamate. Applying a sensor → transducer → effector model to MEP, we find that onset of neuroprotection correlates temporally with elevations in effector heat shock proteins (HSP70, HSP27, and phospho-HSP27). The effector status of HSPs is supported by the fact that inhibiting HSP elevations due to MEP largely restores gp120-induced superoxide potentiation and subsequent neurotoxicity. As upstream mediators, synaptic N-methyld-aspartate receptors may be initial prosurvival sensors of ethanol, and protein kinase C epsilon and focal adhesion kinase are likely transducers during MEP that are essential for protective HSP elevations. Regarding human consumption, we speculate that moderate ethanol intake might counter incipient cognitive deterioration during advanced aging or AD by exerting preconditioning-like suppression of ongoing neuroinflammation related to amyloidogenic protein accumulation. © 2010 Springer Science+Business Media, LLC. Source

Kushnir I.,Oncology Institute | Tzuk-Shina T.,Rambam Health Care Campus
Israel Medical Association Journal

Background: Glioblastoma multiforme (GBM) is an ultimately fatal disease that affects patients of all ages. Elderly patients (65 years and older) constitute a special subgroup of patients characterized by a worse prognosis and frequent comorbidities. Objectives: To assess the efficacy of different treatment modalities in terms of survival in elderly patients with GBM. Methods: Using retrospective analysis, we extracted, anonymized and analyzed the files of 74 deceased patients (aged 65 or older) treated for GBM in a single institution. Results: Mean survival time was 8.97 months and median survival time 7.68 months. Patients who underwent tumor resection had a mean survival of 11.83 months, as compared to patients who underwent no surgical intervention or only biopsy and had a mean survival of 5.22 months (P < 0.0001). Patients who underwent full radiation treatment had a mean survival of 11.31 months, compared to patients who received only partial radiotherapy or none at all and had a mean survival of 4.09 months (P < 0.0001). Patients who underwent chemotherapy had a mean survival of 12.4 months, compared to patients who did not receive any chemotherapy and had a mean survival of 5.89 months (P < 0.001). Conclusions: Age alone should not be a factor in the decision on which treatment should be given. Treatment should be individualized to match the patient's overall condition and his or her wishes, while taking into consideration the better overall prognosis expected with aggressive treatment. Source

Cohen M.,Haifa University | Baziliansky S.,Rambam Health Care Campus | Beny A.,Oncology Institute
Journal of Geriatric Oncology

Background: Studies generally report lower emotional distress in older patients with cancer than in younger patients with cancer. The personality construct of resilience was previously found to be higher with age, but has not been assessed in relation to emotional distress in older patients with cancer. Objective: To assess the mediating effect of resilience on the associations between age and emotional distress in patients with colorectal cancer (CRC). Patients and Methods: An exploratory cross-sectional study of 92 individuals, aged 27-87. years, diagnosed with CRC stage II-III, 1-5. years prior to enrollment in the study. They completed the Wagnild and Young's resilience scale and Brief Symptoms Inventory-18, cancer-related problem list, and demographic and disease-related details. Results: Older age, male gender, and less cancer-related problems were associated with higher resilience and lower emotional distress. A Structural Equation Modeling (SEM) analysis and mediation tests showed that, while controlling for cancer-related problems, resilience mediated the effects of age and gender on emotional distress. Conclusions: The study enlarges the explanation for the consistent previous findings on the better adjustment of older patients with cancer. Increased professional support should be provided for patients with low resilience levels. © 2013 Elsevier Inc. Source

Zhu R.,Soochow University of China | Zou S.-T.,Oncology Institute | Wan J.-M.,Soochow University of China | Li W.,Soochow University of China | And 2 more authors.
Oncology Reports

BTG1, which belongs to the BTG/Tob family, regulates cell cycle progression in a variety of cell types and appears to play roles in inhibiting proliferation, promoting apoptosis and stimulating cellular differentiation in multiple cell types. However, it remains unclear whether BTG1 is a breast cancer suppressor gene, and the role of BTG1 in breast cancer cell growth has not yet been determined. In the present study, we observed that BTG1 was weakly expressed in human breast tumors and in breast cancer cells (MCF-7 and MDA-MB-231). In addition, we investigated the potential effects of BTG1 on breast cancer cell proliferation, cell cycle distribution and apoptosis after stable transfection with the BTG1 expression vector. We found that overexpression of BTG1 inhibited cell proliferation, induced G0/G1 cell cycle arrest and promoted apoptosis. Further investigation indicated that overexpression of BTG1 was involved in the inhibition of the expression of cell cycle-related proteins, cyclin B1 and cyclin D1, and pro-apoptotic factors, Bax and caspase-3, and was also involved in the promotion of anti-apoptotic factor Bcl-2. In vivo, animal experiments showed that tumors overexpressing BTG1 displayed a slower growth rate than the control xenografts. TUNEL end staining assay revealed that BTG1 induced tumor necrosis and apoptosis. Taken together, our data revealed that, in breast cancer cells, BTG1 inhibits cell growth through induction of cell cycle arrest and apoptosis. These results indicate that BTG1 may be used as a novel therapeutic target for human breast cancer treatment. Source

Harel R.,Stereotactic Radiosurgery Unit | Harel R.,Spine Surgery Unit | Zach L.,Oncology Institute
Neurological Research

Early diagnosis, better imaging, and advanced treatment of cancer patients extend survival and increase the incidence of symptomatic spine metastases. The treatment algorithm for spine metastases has shifted to a more aggressive approach in recent years. Spine stereotactic radiosurgery (SRS) is a relatively new tool utilizing advanced imaging systems, planning software, image-guided localization, and intensitymodulated dose delivery. Radiosurgery of spine metastases yields high rates of pain-and tumor control, and offers both the patients and the treating physicians an effective noninvasive alternative. This review presents the indications and outcomes for SRS and describes current techniques. © W. S. Maney & Son Ltd 2014. Source

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