Expression of BCL-2 and p53 in oncocytic (Hürthle cell) tumors of the thyroid: An immunohistochemical study

Previous studies have established that thyroid follicular neoplasms of higher malignant potential show a high p53 and low bc1-2 expression. This however has not been well studied in Oncocytic (Hürthle cell) neoplasms, the management of which remains controversial. We therefore studied the expression of p53 and bc1-2 in 18 Hürthle cell adenomas (HCA) and 8 Hürthle cell carcinomas (HCC) and compared them with their benign and malignant counterparts, respectively, including 16 follicular adenomas (FA) and 68 papillary carcinomas (PC). All 16 FA were bc1-2 positive, 4 were 2+, and 12 were 3+. On the other hand, 14/18 (78%) HCA showed bc1-2 expression, 5 were 1+, 6 were 2+, and only 3 were 3_. Similarly, HCC showed a weaker bc1-2 staining pattern compared to PC. Only 1 FA showed grade 1, p53 staining, the remaining 15 were negative, and 15/18 HCA showed p53 expression of varying grades. This difference in p53 staining was statistically significant (p=0.005). A significant p53 overexpression was also seen in HCC compared to PC (p=0.005). In conclusion, there appears to be an inverse relationship between p53 and bc1-2 expression in thyroid follicular neoplasms. A higher expression of p53 and lower levels bc1-2 in Hürthle cell neoplasms may have biological and clinical implications. This may support a more aggressive surgical treatment for HCA compared to FA.     

Estimation of the minimum number of test specimens for fatigue testing of acrylic bone cement

In the literature on fatigue testing of acrylic bone cements, data sets of various sizes have been used in different test series for the same cement formulation. There are two important consequences of this situation. First, it means that some test series last much longer than others, with all the implications for the cost of testing. Second, it makes drawing conclusions about the fatigue performance of a cement, based on the results of different literature series, a problematic issue. Clearly then, a recommendation as to what should be the minimum number of test specimens to use that would allow for confidence in the results of the statistical treatment of the test results (Gmin) would be desirable. In the present work, a method that could be used to culminate in such a recommendation is described. This method involves (i) obtaining experimental fatigue test results and (ii) analyzing those results using the Weibull probability distribution function and other statistical methods. This methodology is illustrated using fatigue life results obtained from uniaxial tension-compression fatigue tests on specimens fabricated from the polymerizing dough of one commercially available acrylic bone cement. For a tolerable error of 5%, we estimated Gmin to be either 7 (if the fatigue life results are treated using the two-parameter Weibull distribution function) or 11 (if the fatigue life results are treated using the three-parameter Weibull distribution function). To be on the conservative side, we therefore recommend that Gmin be 11. Three key limitations of the methodology presented here are discussed.     

Potential role of intermittent fasting on decreasing cardiovascular disease in human immunodeficiency virus patients receiving antiretroviral therapy

Cardiovascular disease (CVD) has become one of the commonest causes of comorbidity and mortality among People living with human immunodeficiency virus (HIV) (PLWH) on antiretroviral therapy (ART). Nearly 50% of PLWH are likely to have an increased risk of developing CVD, including coronary heart disease, cerebrovascular disease, peripheral artery disease and aortic atherosclerosis. Aside from the common risk factors, HIV infection itself and side effects of antiretroviral therapy contribute to the pathophysiology of this entity. Potential non-pharmacological therapies are currently being tested worldwide for this purpose, including eating patterns such as Intermittent fasting (IF). IF is a widespread practice gaining high level of interest in the scientific community due to its potential benefits such as improvement in serum lipids and lipoproteins, blood pressure (BP), platelet-derived growth factor AB, systemic inflammation, and carotid artery intima-media thickness among others cardiovascular benefits. This review will focus on exploring the potential role of intermittent fasting as a non-pharmacological and cost-effective strategy in decreasing the burden of cardiovascular diseases among HIV patients on ART due to its intrinsic properties improving the main cardiovascular risk factors and modulating inflammatory pathways related to endothelial dysfunction, lipid peroxidation and aging. Intermittent fasting regimens need to be tested in clinical trials as an important, cost-effective, and revolutionary coadjutant of ART in the fight against the increased prevalence of cardiovascular disease in PLWH.     

Biochemical, histological and echocardiographic changes during experimental cardiomyopathy in STZ-induced diabetic rats.

Diabetes mellitus is associated with an increased susceptibility to cardiovascular disease and it has been suggested that alterations in myocardial function may contribute to the development of diabetic cardiovascular complications. The objective of the present study is to examine the left ventricular (LV) function in streptozotocin (STZ)-induced diabetic rats in a definite course of time by non-invasive methods, i.e. M-mode and Doppler echocardiography. From the results, it was found that treatment of animals with STZ resulted in increase in blood glucose, triglycerides, cholesterol, low density lipoproteins (LDL) and decrease in serum total protein levels.Echocardiographic studies revealed that LV internal dimension (mm) during systole was significantly increased after 12 weeks of diabetes when compared to base line data of the same animals and with control animals 6.50+/-0.13 versus 4.25+/-0.17, versus 4.34+/-0.25 (P<0.05), however there was no significant change after 4-8 weeks of diabetes. Also LV internal dimension (mm) during end diastole increased significantly only after 12 weeks of diabetes than to base line data of the same animals and with control animals 7.71+/-0.34 versus 6.18+/-0.25, versus 6.25+/-0.18 (P<0.05). Fractional shortening (%), 15.69+/-5.1 versus 31.22+/-1.7, versus 30.56+/-2.1 (P<0.05), and ejection fraction (%) 37+/-2.31 versus 68.18+/-2.8, versus 60.32+/-3.5 (P<0.05), differ significantly after 12 weeks of diabetes when compared to base line data of the same animals and with control animals. E-wave (cm/s) was significantly decreased after 12 weeks of diabetes 21.11+/-1.5 versus 35.19+/-4.5, versus 32.75+/-3.0 (P<0.05), and A-wave (cm/s) was significantly increased after 12 weeks of diabetes 34.88+/-4.2 versus 19.21+/-2.8, versus 20.59+/-2.1 (P<0.05); thus, diabetic animals after 12 weeks had an inversed E/A ratio. Histological studies revealed that after 8 weeks of diabetes, necrosis was minimal, but after 12 weeks of diabetes extensive focal endomyocardial necrosis was observed. From this study, we conclude that overt LV systolic and diastolic dysfunction was fully visible at 12 weeks of diabetes on echocardiography and this non-invasive technique of echocardiography is useful in diagnosing LV dysfunction in diabetic rats without the need of invasive histopathological procedures.     

p21-activated kinase signaling in breast cancer

The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials.     

RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer.

PURPOSE: RRM1 has important functions in the determination of the malignant phenotype. It controls cell proliferation through deoxynucleotide production and metastatic propensity through PTEN induction. It is located in a region of loss of heterozygosity in non-small-cell lung cancer (NSCLC), which is a predictor of poor survival. We hypothesized that RRM1 expression would be a significant predictor of outcome in NSCLC. PATIENTS AND METHODS: A retrospective data set of 49 patients and a prospective data set of 77 patients with resectable NSCLC were studied. RNA was extracted from tumor and normal lung tissue, and expression of the genes RRM1, PTEN, and RRM2 was determined by real-time quantitative polymerase chain reaction. RESULTS: RRM1 expression was significantly correlated with PTEN and RRM2 expression in tumor tissue. RRM1 and PTEN expression in tumor tissue was highly predictive of overall (P =.011 and.018, respectively) and disease-free survival (P =.002 and.026, respectively). Patients with high levels of expression lived longer and had disease recurrence later than patients with low levels of RRM1 and PTEN. In a multivariate analysis, high RRM1 expression was predictive of long survival independent of tumor stage, performance status, and weight loss. CONCLUSION: RRM1 is a biologically and clinically important determinant of malignant behavior in NSCLC. Knowing the level of expression of this gene adds significant information to management decisions independent of the currently used outcome predictors of tumor stage, performance status, and weight loss. Future clinical trials should stratify patients based on expression of this gene to avoid unwanted biases.