The Effects of Chronomodulated Therapy with 5-Fluorouracil (5-Fu) and Folinic Acid (Fa) on the Toxicity and Quality of Life in Patients with Advanced Gastric Cancer

This study was designed to assess the tolerability of chronomodulated infusion chemotherapy, individualized by the rhythm of peripheral blood cells. Twenty patients with metastatic gastric cancer were randomized to chronotherapy or day-time arms of 5-fluorouracil (FU) (600 mg/m², 8 h inf.d1-5) and folinic acid (FA) (20 mg/m², iv, d1-5) in the first cycle and crossed-over to the other arm in the following cycles. Ten of 18 evaluable patients were assigned to chronotherapy arm and eight to day-time in the first cycle. Although there was no significant difference between two arms on enrollment, chronotherapy arm yielded an improvement of 45% of QLQ-C30 scores (p = 0.021) and the day-time arm had 11% improvement (p = 0.575). After the crossing-over, chronotherapy arm, again, had a significant improvement in QLQ-C30 scores, compared to the day-time arm (14% vs. -18%, p = 0.001, respectively). Mucositis/diarrhea was significantly higher in the day-time arm compared to chronotherapy arm (p = 0.015). In conclusion, chronomodulated infusion of 5-FU might improve the quality of life.     

Predictive diagnostic and/or prognostic biomarkers obtained from routine blood biochemistry in patients with solitary intracranial tumor

BackgroundRadiological and/or laboratory tests may be sometimes inadequate distinguishing glioblastoma from metastatic brain tumors. The aim of this study was to find possible predictive biomarkers produced from routine blood biochemistry analysis results evaluated preoperatively in each patient with solitary brain tumor in distinguishing glioblastoma from metastatic brain tumors as well as revealing short-term prognosis.MethodsPatients admitted to neurosurgery clinic between January 2015 and September 2018 were included in this study and they were divided into GLIOMA (n=12) and METASTASIS (n=17) groups. Patients'' data consisted of age, gender, Glasgow Coma Scale scores, duration of stay in hospital, Glasgow Outcome Scale (GOS) scores and histopathological examination reports, hemoglobin level, leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet count results, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio values, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were evaluated preoperatively.ResultsThe CRP levels of METASTASIS group (143.10 mg/L) were higher than those of GLIOMA group (23.90 mg/L); and it was 82% sensitive and 75% specific in distinguishing metastatic brain tumor from glioblastoma if CRP value was >55.00 mg/L. A positive correlation was determined between GOS score and hemoglobin level and between ESR and CRP values. However, GOS scores were negatively correlated with the ESR level and duration of stay in hospital.ConclusionsStudy results demonstrated that CRP values could be predictive biomarker in distinguishing metastatic brain tumor from glioblastoma. In addition, ESR, CRP, hemoglobin levels and duration of stay in hospital could be prognostic biomarkers in predicting short-term prognosis of patients with solitary brain tumor.     

Examination of antimicrobial effect of fluoxetine in experimental sepsis model: An in vivo study

Since most infectious diseases can develop into sepsis, it is still a major medical problem. Some in-vivo studies showed promising properties of fluoxetine in the treatment of infections. This study aims the antimicrobial effect of fluoxetine on the inflammatory process used in the treatment of sepsis-modeled rats. Besides, to investigate the efficacy of fluoxetine on modifying the antibiotic effect of imipenem in the inflammatory response. An experimental sepsis model was divided into negative control, positive control, fluoxetine 5 mg/kg, imipenem 60 mg/kg, and combined (fluoxetine; imipenem). Procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), lactate, myeloperoxidase activity (MPO), the inflammation markers interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alfa (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels were measured by enzyme-linked immunosorbent assay method. Oxidative stress markers, total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), and native thiol (NT) were measured using photometric methods. Oxidative stress index (OSI) was calculated according to TAS and TOS levels. The statistical analysis was performed by Statistical Package for Social Sciences version 22.0. After treatment with fluoxetine, imipenem, and combined groups, IL-1β, IL-6, TNF-α, MPO activity, MCP-1, hs-CRP, PCT, lactate, and the oxidative stress markers OSI, and disulfide levels were decreased (p < 0.05). The TT, NT, and TAS levels significantly statistically increased (p < 0.05). This research demonstrates that fluoxetine has effects as anti-inflammatory and antioxidant, and the combined treatment with antibioticum imipenem indicates positive synergistic effects in the experimental sepsis model.     

Detection of p16 promotor hypermethylation in “Maras powder” and tobacco users

Background: A plant powder called “Maras powder” is widely used instead of cigarette smoking in the South-Eastern region of Turkey. It has been confirmed that this powder comprises tobacco Nicotiana rustica L. Methods: The aim of this study was to assess the effect of Maras powder and cigarette smoking on the P16 promotor hypermethylation. Twenty-two Maras powder users (Group I), 12 cigarette smokers (Group II), and 16 healthy controls who neither smoked nor used Maras powder (Group III) were included in the study. Hypermethylation of the P16 gene was examined using methylation-specific PCR (MSP) method in the blood of the three groups. Results: Aberrant P16 methylation was found in 7 of the 22 (31.8%) in Group I, in 3 of 12 (25%) in Group II, and in 1 of 16 (6.25%) in Group III. Conclusion: Maras powder may be as harmful as cigarette smoking, leading to hypermethylation in P16 and warrants detailed studies on this subject.     

Overcoming drug resistance in hormone- and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination

Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose- and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array^® (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated ≥3-fold change by the combination treatment. These results may be important in devising mechanism-based and targeted therapeutic strategies for prostate cancer, especially in devising combination therapy for drug resistant prostate cancers.     

PI3K/AKT/mTOR pathway and autophagy regulator genes in paranasal squamous cell carcinoma metastasis

Molecular Biology Reports - Although there are many studies on the role of PI3K/AKT/mTOR pathway and autophagy genes in the mechanism of head and neck cancer formation and prognostic significance,...