RESUMEN
Objectives: To find the frequency of complete remission rate after standard 3+7 induction therapy in patients with Acute Myeloid Leukemia (AML) among different clinicopathological groups. Methods: Non-probability purposive sampling technique was used to collect data from July 2016 to Jan 2017, conducted at Department of Oncology, Jinnah Hospital Lahore. Sample size of 50 cases was calculated with 95% confidence level, 14% margin of error and taking expected percentage of complete remission (CR) 57% in AML patients after 3+7 induction therapy. Results: Out of 46 patients, majority had AML-M2. AML- Not Otherwise Specified (NOS) disease. Most common pathological presentation was Total Leucocyte Count (TLC) of <50,000/mm3 (60%) as compared to patients with hyperleukocytosis i.e., TLC >50,000/mm3 (40%). Twenty-two percent had low Lactate Dehydrogenase (LDH) level involvement and 78% had high LDH level involvement. As compared to target of 57 %, complete response was observed in 54% patients, (p<0.02) with better results in younger age group, male patients with low LDH and TLC level. Conclusion: It was concluded that 3+7 induction chemotherapy has 54% CR rates in patients with AML. Whereas, in AML-M5, AML-M6, AML-NOS patients especially, with high LDH and TLC and patients with advanced age, CR rate is low and needs more aggressive treatment.
RESUMEN
Connexin 43 (Cx43) is the most important protein in the gap junction channel between cardiomyocytes. Abnormalities of Cx43 change the conduction velocity and direction of cardiomyocytes, leading to reentry and conduction block of the myocardium, thereby causing arrhythmia. It has been shown that IL-1ß reduces the expression of Cx43 in astrocytes and cardiomyocytes in vitro. However, whether caspase-1 and IL-1ß affect connexin 43 after myocardial infarction (MI) is uncertain. In this study we investigated the effects of VX765, a caspase-1 inhibitor, on the expression of Cx43 and cell-to-cell communication after MI. Rats were treated with VX765 (16 mg/kg, i.v.) 1 h before the left anterior descending artery (LAD) ligation, and then once daily for 7 days. The ischemic heart was collected for histochemical analysis and Western blot analysis. We showed that VX765 treatment significantly decreased the infarct area, and alleviated cardiac dysfunction and remodeling by suppressing the NLRP3 inflammasome/caspase-1/IL-1ß expression in the heart after MI. In addition, VX765 treatment markedly raised Cx43 levels in the heart after MI. In vitro experiments were conducted in rat cardiac myocytes (RCMs) stimulated with the supernatant from LPS/ATP-treated rat cardiac fibroblasts (RCFs). Pretreatment of the RCFs with VX765 (25 µM) reversed the downregulation of Cx43 expression in RCMs and significantly improved intercellular communication detected using a scrape-loading/dye transfer assay. We revealed that VX765 suppressed the activation of p38 MAPK signaling in the heart tissue after MI as well as in RCMs stimulated with the supernatant from LPS/ATP-treated RCFs. Taken together, these data show that the caspase-1 inhibitor VX765 upregulates Cx43 expression and improves cell-to-cell communication in rat heart after MI via suppressing the IL-1ß/p38 MAPK pathway.