FLT3 and NPM-1 mutations in a cohort of acute promyelocytic leukemia patients from India.

Background: Acute promyelocytic leukemia (APL) with t (15;17) is a distinct category of acute myeloid leukemia (AML) and is reported to show better response to anthracyclin based chemotherapy. A favorable overall prognosis over other subtypes of AML has been reported for APL patients but still about 15% patients relapse. Methods: This study evaluated the presence of Famus like tyrosine kinase‑3 (FLT3) and nucleophosmin‑1 (NPM1) gene mutations in a cohort of 40 APL patients. Bone marrow/peripheral blood samples from patients at the time of diagnosis and follow‑up were processed for immunophenotyping, cytogenetic markers and isolation of DNA and RNA. Samples were screened for the presence of mutations in FLT3 and NPM1 genes using polymerase chain reaction followed by sequencing. Results: Frequency of FLT3/internal tandem duplication and FLT3/tyrosine kinase domain was found to be 25% and 7% respectively. We observed a high frequency of NPM1 mutation (45%) in the present population of APL patients.

Radiation up-regulates the expression of VEGF in a canine oral melanoma cell line

To evaluate radiosensitivity and the effects of radiation on the expression of vascular endothelial growth factor (VEGF) and VEGF receptors in the canine oral melanoma cell line, TLM 1, cells were irradiated with doses of 0, 2, 4, 6, 8 and 10 Gray (Gy). Survival rates were then determined by a MTT assay, while vascular endothelial growth factor receptor (VEGFR)-1 and -2 expression was measured by flow cytometry and apoptotic cell death rates were investigated using an Annexin assay. Additionally, a commercially available canine VEGF ELISA kit was used to measure VEGF. Radiosensitivity was detected in TLM 1 cells, and mitotic and apoptotic cell death was found to occur in a radiation dose dependent manner. VEGF was secreted constitutively and significant up-regulation was observed in the 8 and 10 Gy irradiated cells. In addition, a minor portion of TLM 1 cells expressed vascular endothelial growth factor receptor (VEGFR)-1 intracellularly. VEGFR-2 was detected in the cytoplasm and was down-regulated following radiation with increasing dosages. In TLM 1 cells, apoptosis plays an important role in radiation induced cell death. It has also been suggested that the significantly higher VEGF production in the 8 and 10 Gy group could lead to tumour resistance.

Papel do fator de crescimento vascular endotelial na angiogênese e na retinopatia diabética / The role of vascular endothelial growth factor in angiogenesis and diabetic retinopathy

A retinopatia diabética (RD) é uma complicação microvascular do diabetes melito, sendo importante causa de cegueira adquirida. Fatores angiogênicos, como o vascular endothelial growth factor (VEGF), estão envolvidos na patogênese da RD. O VEGF-A é uma citocina potente e multifuncional que atua por meio dos receptores VEGFR-1 e VEGFR-2 expressos no endotélio vascular causando aumento da permeabilidade vascular e estímulo à neovascularização em processos fisiológicos e patológicos. O VEGFR-2 é o principal mediador mitogênico, angiogênico e do aumento da permeabilidade vascular. Alguns polimorfismos do VEGF têm sido estudados na suscetibilidade e risco de progressão da RD. Importante associação entre o polimorfismo 634C/G e a presença de RD é relatada principalmente em relação ao alelo C. A homozigose CC estaria relacionada à RD proliferativa (RDP) e a níveis sérico e vítreo aumentados de VEGF, sugerindo que a presença do alelo C seja um fator de risco independente para RD. Os conhecimentos sobre o VEGF levaram ao desenvolvimento de agentes antiVEGF com o objetivo de inibir a neovascularização patológica e são uma realidade na prática médica do tratamento da RD.

Diabetic retinopathy (DR), a DM microvascular complication, is the leading cause of blindness. Angiogenic factors such as vascular endothelial growth factor (VEGF) are involved in the pathogenesis of DR. VEGF-A is a potent, multifunctional cytokine that acts through the receptors VEGFR-1 and VEGFR-2 expressed in the vascular endothelium and causing increased vascular permeability and neovascularization stimulation in both physiological and pathological processes. The expression of VEGFR-1 is upregulated by hypoxia and is less responsive to VEGF compared to VEGFR-2 which is the main mediator mitogenic, angiogenic, and increased vascular permeability. VEGF polymorphisms have been studied in DR susceptibility and progression. Significant association between the polymorphism 634C / G and the presence of RD is reported mainly in relation to allele C. The homozygous CC is associated to proliferative RD and to increased vitreous and serum levels of VEGF suggesting that the presence of the C allele is an independent risk factor for RD. The knowledgement of VEGF lead to the development of anti-VEGF drugs (pegaptanib, ranibizumab and bevacizumab) aiming to prevent pathological neovascularization. The anti-VEGF therapy is a reality in practice medical treatment of DR.

Differential Expression of Placenta Growth Factors and Their Receptors In the Normal and Pregnancy-Induced Hypertensive Human Placentas

Placental development requires extensive angiogenesis and the invasion of the maternal decidua by the trophoblasts. Adequate and organized interaction of vascular endothelial growth factors (VEGF), placenta growth factors (PlGF), and their receptors are essential for a normal development and function of the placenta. In this study, we evaluated the expressions of PlGFs and their receptors, mRNAs by Northern blotting, in situ hybridization and RT-PCR in the normal and pregnancy-induced hypertensive (PIH) placentas. The expression level of PlGF-2 mRNA was lower in the PIH placentas compared to control as assessed by Northern blotting and in situ hybridization. PlGF mRNA was mainly localized to the vasculosyncytial membrane of placental villi and villous stroma. The expression of PlGF receptor-1 (PlGFR-1) was significantly increased in the PIH placentas compared to the normal ones. These results suggest that the alteration of PlGF-2 and PlGFR-1 mRNA expressions in the placenta are related to the pathogenesis of PIH.