The role of hydrogen sulfide in homocysteine-induced cardiodynamic effects and oxidative stress markers in the isolated rat heart

This study aimed to assess the role of H2S in homocysteine-induced cardiodynamic effects in the isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique. The maximum and minimum rates of pressure in the left ventricle (dp/dt max, dp/dt min), systolic and diastolic left ventricular pressures (SLVP, DLVP), heart rate (HR), and coronary flow (CF) were measured. A spectrophotometrical method was used to measure the following oxidative stress markers: index of lipid peroxidation (thiobarbituric acid reactive substances, TBARS), nitrite level (NO2−), superoxide anion radicals (O2•−), and hydrogen peroxide (H2O2) concentrations. The administration of 10 µmol/l DL-homocysteine (DL-Hcy) alone decreased dp/dt max, SLVP, and CF but did not change any oxidative stress parameters. The administration of 10 µmol/l DL-propargylglycine (DL-PAG) decreased all cardiodynamic parameters and increased the concentration of O2•−. The co-administration of DL-Hcy and DL-PAG induced a significant decrease in all estimated cardiodynamic parameters and decreased the concentration of NO2− and O2•− but increased the levels of TBARS and H2O2. Homocysteine shows a lower pro-oxidative effect in the presence of hydrogen sulfide (H2S), which indicates a potential anti-oxidative capacity of H2S

Dose-escalation study of weekly irinotecan and daily carboplatin with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer

Dose-escalation study was performed to evaluate the maximum tolerated dose, recommended dose and toxicity profile of weekly irinotecan with daily carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. Thirty-one previously untreated patients with unresectable stage III non-small-cell lung cancer were enrolled in this study. Patients received weekly irinotecan plus carboplatin (20 mg m−2 daily for 5 days a week) for 4 weeks and thoracic radiotherapy (60 Gy in 30 fractions). The irinotecan dose was escalated from 30 mg m−2 in increments of 10 mg m−2. Four irinotecan dose levels were given and 30 patients were assessable. Their median age was 62 years (range: 52–72 years), 28 had a performance status of 0–1 and two had a performance status of 2, 12 had stage IIIA disease and 18 had IIIB disease. There were 19 squamous cell carcinomas, 10 adenocarcinomas, and one large cell carcinoma. The dose-limiting toxicities were pneumonitis, esophagitis, thrombocytopenia and neutropenia. The maximum tolerated dose of irinotecan was 60 mg m−2, with two patients developing grade 4 pulmonary toxicity and one patient died of pneumonitis (grade 5). The recommended dose of irinotecan was 50 mg m−2. Other grade 3 or 4 toxicities were nausea and vomiting. Three patients achieved complete remission and 15 had partial remission, for an objective response rate of 60.0%. The median survival time was 14.9 months, and the 1- and 2-year survival rates were 51.6% and 34.2%, respectively. The study concluded that the major toxicity of this regimen was pneumonitis. This therapy may be active against unresectable non-small-cell lung cancer and a phase II study is warranted

Redox Parameters in Blood of Thyroid Cancer Patients After the Radioiodine Ablation

The radioactive iodine (I-131) ablation is a well-accepted treatment modality for differentiated thyroid cancer patients. Unfortunately, the radiation induces the oxidative stress and damages cells and tissues, simultaneously activating the mechanisms of antioxidative defense. Since the mechanisms of those processes are not completely known, we wanted to examine the changes in the most important reactive oxygen species and antioxidative components, as well as their correlation and significance for lipid peroxidation. Our results showed that the level of thiobarbituric acid reactive substances was increased during the first 30 days after the radiotherapy. Among antioxidant components, superoxide dismutase was increased in the 3rd and 30th day; catalase in 7th and reduced glutathione in 3rd and 7th day after the radiotherapy. As regards the prooxidants, the reduction of hydrogen peroxide (H2O2) was recorded in 7th and 30th day, and superoxide anion radical (O-2(center dot-)) was unchanged after the exposure to I-131. These results indicate that differentiated thyroid cancer patients are under constant oxidative stress despite the observed increase in antioxidative and reduction in prooxidative parameters. The understanding of these early processes is important since their progress determines the latter effects of I-131 therapy

Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that <it>VEGF </it>polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients.</p> <p>Methods</p> <p>We genotyped three potentially functional <it>VEGF </it>variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between <it>VEGF </it>variants and overall survival (OS).</p> <p>Results</p> <p>Gender, Karnofsky's performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, <it>P </it>= 0.022), compared with the <it>VEGF </it>-460 TT genotype.</p> <p>Conclusions</p> <p>Our study suggests that <it>VEGF </it>-460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings.</p

Distant metastases of a squamous cell carcinoma of the tongue in peripheral skeletal muscles and adjacent soft tissues

A 66-year-old female patient was admitted to our department with a large tumor of the tongue measuring 10 cm in diameter. The tumor occupied nearly the entire oral cavity and showed exophytic and ulcerative areas. Histological analysis revealed a low grade squamous cell carcinoma (SCC) of the tongue. Bilateral enlarged cervical lymphatic masses were also present. The extent of the tumor infiltration was assessed by fluoro-2-deoxy-glucose-positron emission tomography (PET) scans showing an elevated activity of the tracer corresponding to the assumed cervical metastases. Additionally, pulmonary metastases were identified. Contrast enhanced computed tomography (CT) scans showed metastases in the soft tissues of the abdomen, legs and arms. Foci of distant metastases were found in the left upper anterior thoracal wall, near the intraabdominal portion of the aorta, near the right iliac crest and in both the right vastus medialis- and adductor magnus muscles. The final diagnosis was a T4N3M1(G3)(C3) SCC of the tongue with multiple distant thoracal, abdominal and intramuscular metastases. The survival expectancy was five weeks, and the patient finally deceased by cardiopulmonary complications