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Anupama Kohli MD Stephen P. Baker MCS MPH Nilima A. Patwardhan MD Ashraf Khan MD MRCPATH 《Endocrine pathology》1998,9(2):117-123
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. 相似文献
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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. 相似文献
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Martin Gnoni Renato Beas Anupama Raghuram Celeste D az-Pardav Adrian Riva-Moscoso Fortunato S Pr ncipe-Meneses Ra l V squez-Garagatti 《World Journal of Experimental Medicine》2021,11(5):66-78
Cardiovascular disease (CVD) has become one of the commonest causes of comor bidity 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. 相似文献
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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. 相似文献
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RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. 总被引:21,自引:0,他引:21
Gerold Bepler Swati Sharma Alan Cantor Ashish Gautam Eric Haura George Simon Anupama Sharma Eric Sommers Lary Robinson 《Journal of clinical oncology》2004,22(10):1878-1885
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. 相似文献
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The clinical relevance of steroid hormone receptor corepressors. 总被引:2,自引:0,他引:2
Rakesh Kumar Anupama E Gururaj Ratna K Vadlamudi Suresh K Rayala 《Clinical cancer research》2005,11(8):2822-2831
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The beneficial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate. Moreover, the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated. These include particle size, shape and surface charge/chemistry. Restricting the particle size of nanocarriers below 200 nm contributes to internalization via clathrin and caveolae mediated pathways. Similarly, a moderate negative surface potential confers endolysosomal escape and targeting towards mitochondria, endoplasmic reticulum (ER) and Golgi. This review aims to provide an insight into these physicochemical attributes of nanocarriers fabricated using amphiphilic graft copolymers affecting cellular internalization. Fundamental principles understood from experimental studies have been extrapolated to draw a general conclusion for the designing of optimized nanoparticulate drug delivery systems and enhanced intracellular uptake via specific endocytic pathway.KEY WORDS: Amphiphilic, Copolymer, Nanoparticles, Internalization, Intracellular fate 相似文献