Possible involvement of tyrosine kinase inhibitors on the expression of CXCR4 in chronic myeloid leukemia

Purpose: Chronic myeloid leukemia (CML) treatment has improved significantly in the last decade with the introduction of tyrosine kinase inhibitors (TKIs), which target BCR/ABL oncoprotein. However, a large proportion of patients develop resistance to this treatment protocol, with frequent relapse cases. CXCR4 up-regulation in leukemic cells induced by TKIs has been reported as a mechanism of chemoresistance by promoting migration of these cells to bone marrow, where they receive pro-survival signals and persist as quiescent cells. In the present study, we investigated the possible influence of treatment on the expression of CXCR4 and CXCL12 in peripheral blood cells of CML patients. Methods: Relative expressions (RE) were calculated from mRNA obtained from leukocytes of 21 patients in chronic phase, under treatment, and 54 healthy individuals, used as controls.Results: CXCR4 expression was increased in CML patients compared to controls (RE: 1.931; p = 0.006). In CML patients, CXCR4 and CXCL12 expressions were correlated (r = 0.631; p = 0.002), and no differences in the expression of these genes were observed among different treatment protocols. However, CXCR4 expression was positively correlated with imatinib treatment period duration of treatment (r = 0.56; p = 0.02). Conclusion: This data has pointed peripheral blood CXCR4 expression as a possible marker for treatment monitoring, which may be useful to predict which patients would be benefit from newly developed treatments targeting CXCR4 and BCR/ABL concomitantly

BRAZILIAN ARCHIVES OF BIOLOGY AND TECHNOLOGY A N I N T E R N A T I O N A L J O U R N A L Detection of Lsr2 Gene of Mycobacterium leprae in Nasal Mucus

ABSTRACT In the present study, nasal mucus from patients with leprosy were analyzed by PCR using specific primers for Lsr2 gene of Mycobacterium leprae

Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

The aim of the present study was to investigate the rs1800468 (G-800A), rs1800469 (C-509T), rs1800470 (C29T), and rs1800471 (G74C) TGFB1 genetic polymorphisms and their haplotype structures in patients with Wilms Tumor (WT) and neoplasia-free controls. The genomic DNA was extracted from 35 WT patients and 160 neoplasia-free children, and the TGFB1 polymorphisms were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism. The haplotype structures were inferred, and permutation and logistic regression tests were performed to check for differences in haplotype distribution between the control and WT individuals. Positive associations were found in the recessive model for rs1800469 T allele (OR: 8.417; 95% CI: 3.177 to 22.297; P < 0.001) and for the rs1800470 C allele (OR: 3.000; 95% CI: 1.296 to 6.944; P = 0.01). Haplotype analysis revealed a significant negative association between GCTG and WT (OR: 0.236, 95% CI: 0.105 to 0.534; P = 0.0002); by contrast, the GTTG haplotype was associated with increased risk for WT (OR: 12.0; 95% CI: 4.202 to 34.270; P < 0.001). Furthermore, rs1800469 was negatively correlated with tumor size and a trend toward a positive correlation for capsular invasion was observed in the dominant model (Tau-b: −0.43, P = 0.02 and tau-b: 0.5, P = 0.06, respectively). This is the first study with rs1800468, rs1800469, rs1800470, and rs1800471 TGFB1 polymorphisms in WT, and our results suggest that the TGFB1 promoter and signal peptide region polymorphisms may be associated with WT susceptibility and clinical presentation

Cytotoxic constituents of propolis inducing anticancer effects: a review

Objectives Propolis is a honeybee product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. In this review, the antitumour effects of propolis extracts and its constituents (e. g. flavonoids, terpenes and caffeic acid phenethyl ester) are discussed.Key findings The effect of propolis on experimental carcinogenesis is discussed, as well as its possible mechanisms of action against tumours, involving apoptosis, cell cycle arrest and interference on metabolic pathways. Propolis seems to be efficient against different tumour cells both in vitro and in vivo, which suggests its potential in the development of new anticancer drugs.Summary Propolis extracts may be important economically and would allow a relatively inexpensive cancer treatment. Preclinical investigations are needed to further elucidate the benefits of propolis and its antitumour properties

Possible involvement of tyrosine kinase inhibitors on the expression of CXCR4 in chronic myeloid leukemia

Purpose: Chronic myeloid leukemia (CML) treatment has improved significantly in the last decade with the introduction of tyrosine kinase inhibitors (TKIs), which target BCR/ABL oncoprotein. However, a large proportion of patients develop resistance to this treatment protocol, with frequent relapse cases. CXCR4 up-regulation in leukemic cells induced by TKIs has been reported as a mechanism of chemoresistance by promoting migration of these cells to bone marrow, where they receive pro-survival signals and persist as quiescent cells. In the present study, we investigated the possible influence of treatment on the expression of CXCR4 and CXCL12 in peripheral blood cells of CML patients. Methods: Relative expressions (RE) were calculated from mRNA obtained from leukocytes of 21 patients in chronic phase, under treatment, and 54 healthy individuals, used as controls.Results: CXCR4 expression was increased in CML patients compared to controls (RE: 1.931; p = 0.006). In CML patients, CXCR4 and CXCL12 expressions were correlated (r = 0.631; p = 0.002), and no differences in the expression of these genes were observed among different treatment protocols. However, CXCR4 expression was positively correlated with imatinib treatment period duration of treatment (r = 0.56; p = 0.02). Conclusion: This data has pointed peripheral blood CXCR4 expression as a possible marker for treatment monitoring, which may be useful to predict which patients would be benefit from newly developed treatments targeting CXCR4 and BCR/ABL concomitantly.</p

<b>Determination of lactate dehydrogenase (LDH) and <em>Bcr-Abl</em> transcript in the follow-up of patients with chronic myeloid leukemia</b> - doi: 10.4025/actascihealthsci.v32i2.6408 <b>Determination of lactate dehydrogenase (LDH) and <em>Bcr-Abl</em> transcript in the follow-up of patients with chronic myeloid leukemia</b> - doi: 10.4025/actascihealthsci.v32i2.6408

Chronic myeloid leukemia (CML) is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present <em>Bcr-Abl</em> transcripts. Lactate dehydrogenase (LDH) is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the <em>Bcr-Abl</em> transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the <em>Bcr-Abl</em> (b3a2) transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L^-1 and 589 U L^-1). Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease.<br>Chronic myeloid leukemia (CML) is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present <em>Bcr-Abl</em> transcripts. Lactate dehydrogenase (LDH) is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the <em>Bcr-Abl</em> transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the <em>Bcr-Abl</em> (b3a2) transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L^-1 and 589 U L^-1). Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease

Determination of lactate dehydrogenase (LDH) and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia = Determinação da lactate desidrogenase (LDH) e do transcrito Bcr-Abl em pacientes com leucemia mielóide crônica

Chronic myeloid leukemia (CML) is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH) is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2) transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1). Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease. <br><br>Leucemia mieloide crônica (LMC) é uma desordem mieloproliferativa maligna que é originada de célula-tronco pluripotente caracterizada por expansão anormal, maligna de clones de células tronco da medula óssea na circulação. A grande maioria dos pacientes com LMC apresentam transcritos Bcr-Abl. Lactato desidrogenase (LDH),considerado um marcador bioquímico para crescimento tumoral, glicólise anaeróbica, e tem sido considerado um fator de pior prognóstico da LMC. Portanto, este estudo visa avaliar a concentraçãode LDH no plasma e a detecção do transcrito Bcr-Abl em 22 pacientes com LMC e 56 indivíduos saudáveis. Foram avaliados 22 pacientes com LMC e 56 doadores saudáveis. A concentração de LDH no plasma foi maior nos pacientes com LMC. Todos pacientes com LMC neste estudoestavam em tratamento, mesmo assim quatro pacientes apresentavam o transcrito Bcr-Abl (b3a2) no sangue periférico. Dois dos quatro pacientes com o transcrito b3a2 apresentavam LDH elevado (486 U L-1 e 589 U L-1). Embora o estudo tenha sido realizado com um pequeno número de amostras, é possível sugerir alteração de terapia para os dois pacientes que apresentam o transcrito b3a2 na amostra de sangue periférico com concentração de LDH elevada

Changes in gene expression in PBMCs profiles of PPAR alpha target genes in obese and non-obese individuals during fasting

Background: The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. Aim: This study aimed to evaluate the differences in the expression of PPAR alpha target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARa target genes in PBMCs under fasting conditions. Methods: Q-PCR was utilized to assess the mRNA expression levels of target genes. Results: In both groups, the FFA concentrations in. creased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. Conclusion: However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in beta-oxidation and glucose level maintenance are affected by these factors.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES