Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

The value of an acute octreotide suppression test in predicting response to long-term somatostatin analogue therapy in patients with acromegaly

Context: The usefulness of the acute octreotide test in the selection of patients with acromegaly for chronic somatostatin depot analogues treatment is controversial. Aims: To determine the efficacy of acute octreotide suppression test (OST) in predicting response to long-term somatostatin analogue (Octreotide-long-acting repeatable, OCT-LAR) therapy in patients with acromegaly. Settings and Design: Prospective study (2006-2007) conducted at a tertiary healthcare centre in western India. Materials and Methods: Sixteen drug-naive patients with active acromegaly (postoperative±post radiotherapy) underwent 50 µg subcutaneous OST. Ten patients were treated with OCT-LAR for one year. Remission was defined as a nadir growth hormone (GH) < 1 ng/ml during 75 g oral glucose tolerance test (OGTT) (0, 10, 30, 60, 120, 180 min) and normal age, sex-matched insulin-like growth factor 1 (IGF1) levels. Statistical Analysis: SPSS Software Version 11 was used for data analysis. Results: Using GH cutoff < 1 ng/ml, four patients (40%) achieved control at 12 months, while five patients (50%) achieved normal IGF1 values. The mean basal GH levels in 10 responsive, four controlled and six uncontrolled patients were 34.7±61.14, 4.5±1.3 and 54.8±74.2 ng/ml respectively which suppressed to mean nadir GH of 3.75±4.03, 0.66±0.15 and 5.8±4 ng/ml respectively. Sensitivity, specificity, negative and positive predictive value for nadir GH < 1 ng/ml reached after an OST was 100% each in predicting remission in our cohort. Odds for control increased if the baseline GH was low (< 5 ng/ml in our cases). Conclusions: Nadir GH < 1 ng/ml following an OST is a useful predictive marker of achieving disease remission with long-term OCT-LAR therapy

Study of bone mineral density in resident doctors working at a teaching hospital

Context : The erratic lifestyle of resident doctors may affect their serum 25-hydroxy vitamin D [25-(OH)D] levels and bone mineral density (BMD). Aim : To study BMD and the effect of environmental factors on it in resident doctors. Settings and Design : Prospective, cross-sectional study conducted in a tertiary healthcare centre. Materials and Methods : BMD was obtained by dual-energy X-ray absorptiometry and was correlated with various factors including weight, height, body mass index (BMI), sun exposure, physical activity, parathyroid hormone, 25-(OH)D, dietary factors. Statistical Analysis : SPSS software Version 10 (Unpaired t test was used to compare BMD of different groups and Pearson′s correlation coefficient was used to calculate correlation). Results : Two hundred and fourteen apparently healthy resident doctors were enrolled in the study. Based on Caucasian normative data, osteopenia was noted in 104 (59.7%) males and 27 (67.5%) females. Thirty-two (18.39%) males and five (12.5%) females had osteoporosis. The BMD values of males were 0.947±0.086, 0.911±0.129 and 1.016±0.133 at lumbar spine, femur neck and total hip while those in females were 0.981±0.092, 0.850±0.101 and 0.957±0.103 respectively. BMD of our cohort was lesser by 12.5-18.2% and 4.2-14.5% than the Caucasian and available Indian figures, respectively. BMD had significant positive correlation with weight, height, BMI, physical activity, and dietary calcium phosphorus ratio. 25-(OH)D levels were insufficient in 175 (87.5%) subjects but had no correlation with BMD. Conclusions : Young healthy resident doctors had significantly lower BMD, contributors being lower BMI, lower height, reduced bioavailability of dietary calcium and inadequate physical activity. Deficiency of vitamin D did not contribute to low BMD

A clinicopathologic study of 11 rosette-forming meningiomas: a rare and potentially confusing pattern

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Bone mineral density and disorders of mineral metabolism in chronic liver disease

AIM: To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis