Cancer Induces Cardiomyocyte Remodeling and Hypoinnervation in the Left Ventricle of the Mouse Heart

Cancer is often associated with cachexia, cardiovascular symptoms and autonomic dysregulation. We tested whether extracardiac cancer directly affects the innervation of left ventricular myocardium. Mice injected with Lewis lung carcinoma cells (tumor group, TG) or PBS (control group, CG) were analyzed after 21 days. Cardiac function (echocardiography), serum levels of TNF-α and Il-6 (ELISA), structural alterations of cardiomyocytes and their innervation (design-based stereology) and levels of innervation-related mRNA (quantitative RT-PCR) were analysed. The groups did not differ in various functional parameters. Serum levels of TNF-α and Il-6 were elevated in TG. The total length of axons in the left ventricle was reduced. The number of dense core vesicles per axon profile was reduced. Decreased myofibrillar volume, increased sarcoplasmic volume and increased volume of lipid droplets were indicative of metabolic alterations of TG cardiomyocytes. In the heart, the mRNA level of nerve growth factor was reduced whereas that of β1-adrenergic receptor was unchanged in TG. In the stellate ganglion of TG, mRNA levels of nerve growth factor and neuropeptide Y were decreased and that of tyrosine hydroxylase was increased. In summary, cancer induces a systemic pro-inflammatory state, a significant reduction in myocardial innervation and a catabolic phenotype of cardiomyocytes in the mouse. Reduced expression of nerve growth factor may account for the reduced myocardial innervation

In vitro effect of trimetazine on K-Cl cotransport and superoxide dismutase activity in Hemoglobin SS erythrocytes

Background and Purpose: Trimetazidine (TMZ) (1-2,3,4 trimethoxybenzyl piperazine dihydrochloride) is a cyto-productive agent which is used as an anti-anginal drug. Sickle Cell Anemia (SCA) is characterized by increased K-Cl cotransport (KCC) activity and self-generated free radicals. The aim of study was to investigate the effect of TMZ on KCC activity and free radicals in SCA patients. Material and Method: The blood samples were drawn by 20 patients with SCA. After the washing procedure the samples were encubated with TMZ for 20 min. Superoxide dismutase (SOD) and KCC activity were measured before and after incubation. Results and Conclusion: It was observed that treatment with TMZ for 20 min has a negative effect on SOD activity in linear relation with the doses used as 50, 100, 150, 200 mM, in vitro (respectively 2494.95±102.73, 2253±99.51, 1497.25±111.14 U/g Hb). However; TMZ had no effect on neither volume dependent nor chloride dependent KCC activity. In conclusion further in vivo studies with TMZ should be conducted

The role of azacitidine in the treatment of elderly patients with aml - results of a retrospective multicenter study

20th Congress of European-Hematology-Association -- JUN 11-14, 2015 -- Vienna, AUSTRIAWOS: 00036120490243

Myeloid Leukemia: Results of a Retrospective Multicenter Study

Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts.Materials and Methods: In this retrospective multicenter study, 130 patients of >= 60 years old who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included.Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of = 5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact.Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA

The role of azacitidine in the treatment of elderly patients with acute myeloid leukemia: Results of a retrospective multicenter study [Akut miyeloid lösemili yaşlı hastaların tedavisinde azasitidinin rolü: Retrospektif çok merkezli bir çalışmanın sonuçları]

PubMed ID: 27095141Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. Materials and Methods: In this retrospective multicenter study, 130 patients of ?60 years old who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (?5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA. © 2016, Turkish Society of Hematology. All rights reserved