Caloric restriction reinforces the stem cell pool in the aged brain without affecting overall proliferation status.

Overfeeding (OF) and obesity increase the risk for brain aging and neurodegenerative diseases due to increased oxidative stress and neuroinflammation, which likely contribute to cellular dysfunction. In contrast, caloric restriction (CR) is an intervention known for its effects on extending both life- and health-span. In the current study, the effects on the aging brain of two short-term feeding regimens, OF and CR, were investigated. We applied these diets for 12 weeks to both young and aged zebrafish. We performed protein and mRNA level analysis to examine diet-mediated effects on any potential age-related alterations in the brain. Markers implicated in the regulation of brain aging, cell cycle, proliferation, inflammation, and cytoskeleton were analyzed. The most prominent result observed was a downregulation in the expression levels of the stem cell marker, Sox2, in CR-fed animals as compared to OF-fed fish. Furthermore, our data highlighted significant age-related downregulations in Tp53, Myca, and L-plastin levels. The multivariate analyses of all datasets suggested that as opposed to OF, the adaptive mechanisms increasing lifespan via CR are likely exerting their effects by reinforcing the stem cell pool and downregulating inflammation. The data reveal important therapeutic targets with respect to the state of nutrient uptake for the slowing down of the detrimental effects of aging, resulting in a healthy and extended lifespan, as well as lowering the risk for neurodegenerative disease.

Effectiveness and safety of cabazitaxel chemotherapy for metastatic castration-resistant prostatic carcinoma on Turkish patients (The Anatolian Society of Medical Oncology).

OBJECTIVE: Prostate cancer is among the most common cancers in males. Prostate cancer is androgen dependent in the beginning, but as time progresses, it becomes refractory to androgen deprivation treatment. At this stage, docetaxel has been used as standard treatment for years. Cabazitaxel has become the first chemotherapeutic agent which has been shown to increase survival for patients with metastatic Castrate Resistant Prostate Cancer (mCRPC) that progresses after docetaxel. Phase 3 TROPIC study demonstrated that cabazitaxel prolongs survival. PATIENTS AND METHODS: In this study, we evaluated a total of 103 patients who took cabazitaxel chemotherapy for mCRPC diagnosis in 21 centers of Turkey, retrospectively. This study included patients who progressed despite docetaxel treatments, had ECOG performance score between 0-2, and used cabazitaxel treatment. Patients received cabazitaxel 25 mg/m2 at every 3 weeks, and prednisolone 5 mg twice a day. RESULTS: Median number of cabazitaxel cures was 5.03 (range: 1-17). Cabazitaxel response evaluation detected that 34% of the patients had a partial response, 22.3% had stable disease and 32% had a progressive disease. Grade 3-4 hematological toxicities were neutropenia (28.2%), neutropenic fever (14.5%), anemia (6.7%), and thrombocytopenia (3.8%). In our study, median progression-free survival (PFS) was 7.7 months and overall survival (OS) was 10.6 months. CONCLUSIONS: This study reflects toxicity profile of Turkish patients as a Caucasian race. We suggest that cabazitaxel is a safe and effective treatment option for mCRPC patients who progress after docetaxel. Moreover, ethnicity may play important roles both in treatment response and in toxicity profile.

The inmunohistochemical expression of c-Met is an independent predictor of survival in patients with lioblastoma multiforme

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care (AU)

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The immunohistochemical expression of c-Met is an independent predictor of survival in patients with glioblastoma multiforme.

BACKGROUND AND AIMS: Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols. METHODS: Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 ± 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 ± 2.3 vs. 22.6 ± 2.5 months, respectively, p < 0.01) and PFS (12.3 ± 2.1 vs. 19.1 ± 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05). CONCLUSIONS: Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.

Prognostic significance of estrogen receptor, progesterone receptor, HER2/neu, Ki-67, and nm23 expression in patients with invasive breast cancer.

PURPOSE: To determine the prognostic significance of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, Ki-67, and nm23 immunohistochemical expression with respect to progression free survival (PFS) and overall survival (OS) in Turkish patients with invasive breast cancer (IBC). METHODS: Patients with IBC (n = 81; mean age = 51.9 ± 11.1 years) were prospectively enrolled at the Department of Oncology, Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin- fixed, paraffin-embedded tissue sections. RESULTS: We did not find any significant association between immunohistochemical expression of ER, PR, HER2/ neu, Ki-67, and nm23 and the baseline characteristics of IBC patients. The median patient PFS was 30 months (range 22-45), and the median OS was 32 months (range 23-46). Stratification of the patient population according to nm23 immunohistochemical expression revealed a statistically significant difference in terms of both OS (p < 0.05) and DFS (p < 0.05). Multivariate Cox regression analysis indicated that tumor grade, axillary lymph node status, and nm23 immunohistochemical expression were the 3 main independent prognostic factors for PFS and OS in IBC patients. CONCLUSION: Reduced nm23 immunohistochemical expression is an independent negative prognostic factor for OS and PFS. Patients with negative nm23 expression may require a more intensive follow-up.

A multi-institutional evaluation of carboplatin plus docetaxel regimen in elderly patients with advanced gastric cancer.

PURPOSE: Albeit the majority of gastric cancers occur at advanced age, little is known regarding the optimal systemic treatment of elderly patients with advanced gastric cancer (AGC). METHODS: Patients with AGC who were ≥ 65 years old and were treated with carboplatin (area under the curve/AUC 5,on day 1, every 3 weeks) plus docetaxel (75 mg/m(2), on day 1, every 3 weeks) at 3 institutions were included in this retrospective analysis. The efficacy and the safety data of the regimen were analyzed. RESULTS: A total of 30 patients were enrolled. They received 128 cycles of chemotherapy, with a median of 4 cycles (range 2-8). Complete response (CR) and partial response (PR) were observed in 2 (6.7%) and 10 patients (33.3%), respectively, amounting to an overall objective response rate (ORR) of 40%. Seven patients (23.3%) had disease stabilization (SD), and 11 (36.7%) showed disease progression (PD). The most common grade 3-4 toxicity was neutropenia occurring in 19 patients (63.3%). The mean progression-free survival (PFS) was 6.0 ± 0.5 months (95% CI: 5.0-7.4), and the mean overall survival (OS) 12.0 ± 1.0 months (95% CI: 9.2-12.1). CONCLUSION: Carboplatin plus docetaxel seems to be an active and well-tolerated regimen, representing a valuable alternative to cisplatin- and/or fluoropyrimidine-containing regimens for the treatment of elderly patients with AGC.

Identification of prognostic factors in patients with metastatic gastrointestinal stromal tumors.

PURPOSE: Gastrointestinal stromal tumors (GISTs) have a complex biology which is reflected by a marked clinical heterogeneity. Thus, there has been great interest in identifying prognostic factors influencing tumor recurrence and survival. The aim of this study was to identify potential clinical and immunohistochemical prognostic factors that may affect survival and treatment outcomes in patients with metastatic GISTs. METHODS: Between 2000 and September 2011, a total of 41 patients with metastatic GISTs (29 males and 12 females; mean age: 57.4±11.8 years; range 29-74) were referred to the Department of Oncology, Uludag University Medical School. Survival analysis for a number of potential prognostic factors was made with the main outcome results of progression-free survival (PFS) and overall survival (OS7rpar;. RESULTS: The most common sites of isolated metastases comprised the liver (n=18), followed by lymph nodes (n=5), the omentum (n=1), and the mesothelium (n=1). The remaining patients had metastases at multiple sites. Cox regression analysis identified ileal location as the only significant predictor of poor PFS both after first-line (p=0.023) and second-line therapy (p=0.016). Tumor location in the ileum (p=0.025) and S100 immunoreactivity (p=0.041) were both independent predictors of OS. CONCLUSION: Tumor site and S100 positivity were the main significant independent predictors of clinical outcomes in patients with metastatic GISTs treated by standard of care.

Structure and photoluminescence of (Ca,Eu)(2)SiS(4) powders.

The photoluminescence of Ca(2)SiS(4):Eu powders was investigated in detail as a function of europium concentration (from 0.1% Ca substitution to the fully substituted Eu(2)SiS(4)). At low europium dopant concentration (<10%) the powders crystallize in an orthorhombic structure and the emission spectrum is dominated by two broad emission bands, at 564 and 660 nm. The emission can be tuned from yellow (CIE x = 0.46,y = 0.53) to red (CIE x = 0.65,y = 0.35) by variation of the Eu concentration. An energetic coupling exists between both bands, leading to a broad excitation wavelength range. Powders with high europium concentration (>40%) crystallize in a monoclinic structure, details of which were determined by Rietveld refinement of x-ray diffraction data. For the composition CaEuSiS(4) (i.e. 50% substitution), the luminescence peaks at 614 nm, shifting to shorter wavelengths upon further substitution of Ca by Eu. Although considerable thermal quenching is present at room temperature in the fully Eu-substituted compound, Eu(2)SiS(4) is still photoluminescent, with a peak emission wavelength of 577 nm. A strong correlation is found between the crystallographic and luminescent properties of the (Ca,Eu)(2)SiS(4) powders. The broad emission and excitation bands make this phosphor a good candidate for use in phosphor-converted light-emitting diodes (pcLEDs).

Serum levels of vitamin E in relation to cardiovascular diseases.

Serum vitamin E levels in healthy people (n = 71) and patients with cardiovascular diseases (n = 62) were determined. The cases of cardiovascular disease comprised patients with acute myocardial infarction (AMI) (n = 31), atherosclerosis (AT) (n = 23) and myocardial ischaemia (MI) (n = 8). The mean (+/- SD) serum vitamin E levels of the control group and the group with cardiovascular disease were 1.12 +/- 0.27 mg% and 0.98 +/- 0.41 mg%, respectively. Patients with AMI, AT and MI had corresponding levels of 0.97 +/- 0.48 mg%, 1.00 +/- 0.39 mg% and 1.01 +/- 0.44 mg%, respectively. Overall serum vitamin E levels were lower in the group with cardiovascular disease than in the control group. Patients and the control group are also discussed with respect to a number of potentially confounding parameters such as age, sex, smoking status, quetelet index (kg/m2), alcohol consumption, dietary intake and serum lipids.