Распространенность инфекции HPV/p16+ среди пациентов с орофарингеальной плоскоклеточной карциномой в центре высокоспециализированной медицинской помощи в Южной Индии

Introduction. Oropharyngeal squamous cell carcinomas are often found to be associated with human papilloma virus (HPV) infection. The prevalence of HPV infection among oropharyngeal squamous cell carcinomas patients in India is comparatively lower to that of the same worldwide. Aim. To find out the prevalence of HPV infection among oropharyngeal squamous cell carcinomas patients who presented in our hospital.Settings and design. Retrospective cross-sectional study.Materials and methods. Tissue block of 60 patients with biopsy-proven oropharyngeal squamous cell carcinomas were subjected to immunohistochemistry for evaluating p16 expression. The p16 expression pattern was correlated with the demographic details. Data was entered in Microsoft Excel and Statistical Analysis was done with the help of SPSS version 22 (IBM Corp. Released, 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp.).Results. Prevalence of HPV infection in our study was found to be 11.7 %. 85.8 % of all p16-positive patients had moderate-well differentiated disease. 6 out of 7 p16-positive patients had higher T stage (T3–4). All the patients who were p16+ were found to have a higher Nodal stage (N2–3). 100 % of all p16+ patients were found to have stage IV disease.Conclusion. Prevalence of HPV infection was found to be similar to that of previous studies conducted in India. These patients also presented with advanced nodal disease at presentation and thereby, an advanced overall stage.Введение. Орофарингеальная плоскоклеточная карцинома часто связана с заражением вирусом папилломы человека (ВпЧ). Распространенность инфекции ВпЧ среди пациентов с данной патологией в Индии сравнительно ниже, чем в других странах.Цель исследования – определить распространенность инфекции ВпЧ среди пациентов с орофарингеальной плоскоклеточной карциномой, получавших лечение в нашей больнице.Дизайн исследования. Ретроспективное одномоментное исследование.Материалы и методы. Образцы тканей 60 пациентов с подтвержденным биопсией диагнозом «орофарингеальная плоскоклеточная карцинома» были исследованы иммуногистохимически на экспрессию p16. Было проведено сравнение профиля экспрессии p16 с демографическими данными. полученные результаты оценены с помощью программы Microsoft Excel. Статистический анализ выполнен с использованием программного обеспечения SPSS version 22 (IBM Corp. Released, 2013. IBM SPSS Statistics для Windows, версия 22.0, Армонк, Нью-Йорк: IBM Corp.).Результаты. Частота встречаемости ВпЧ в нашем исследовании составила 11,7 %. Среднеи высокодифференцированное заболевание наблюдалось у 85,8 % пациентов с положительной экспрессией p16. Шесть из 7 больных с такой экспрессией p16 имели более высокую T-стадию (T3–4), а все больные с таким показателем – высокую N-стадию (N2–3). У всех пациентов с положительной экспрессией p16 наблюдалось заболевание стадии IV.Заключение. Распространенность инфекции ВпЧ была близкой к значениям, полученным в других исследованиях в Индии. Для пациентов с этой инфекцией также были характерны вовлеченность лимфатических узлов (N-стадия) в патологический процесс и более высокая общая стадия заболевания

2′-AMP and 3′-AMP Inhibit Proliferation of Preglomerular Vascular Smooth Muscle Cells and Glomerular Mesangial Cells via A2B Receptors

Studies show that kidneys produce 2′,3′-cAMP, 2′,3′-cAMP is exported and metabolized to 2′-AMP and 3′-AMP, 2′-AMP and 3′-AMP are metabolized to adenosine, 2′,3′-cAMP inhibits proliferation of preglomerular vascular smooth muscle cells (PGVSMCs) and glomerular mesangial cells (GMCs), and A2B (not A1, A2A, or A3) adenosine receptors mediate part of the antiproliferative effects of 2′,3′-cAMP. These findings suggest that extracellular 2′,3′-cAMP attenuates proliferation of PGVSMCs and GMCs partly via conversion to corresponding AMPs, which are metabolized to adenosine that activates A2B receptors. This hypothesis predicts that extracellular 2′-AMP and 3′-AMP should exert A2B receptor-mediated antiproliferative effects. Therefore, we examined the antiproliferative effects (cell counts) of 2′-AMP and 3′-AMP. In PGVSMCs and GMCs, 2′-AMP and 3′-AMP exerted concentration-dependent antiproliferative effects. 3′-AMP was equipotent with and 2′-AMP was 3-fold less potent than 5′-AMP (prototypical adenosine precursor). In PGVSMCs, the effects of 2′-AMP and 3′-AMP were mimicked by adenosine, and 8-[4-[((4-cyanophenyl)carbamoylmethyl)oxy]phenyl]-1,3-di(n-propyl)xanthine (MRS-1754) (A2B receptor antagonist) equally blocked the antiproliferative effects of 2′-AMP, 3′-AMP, and adenosine but less effectively blocked the effects of 2′,3′-cAMP. Similar results were obtained in GMCs except that MRS-1754 also incompletely blocked the effects of 3′-AMP. We conclude that in PGVSMCs, 2′-AMP and 3′-AMP are antiproliferative, the antiproliferative effects of 2′-AMP and 3′-AMP are mediated nearly entirely by adenosine/A2B receptors, and some of the antiproliferative effects of 2′,3′-cAMP are independent of adenosine/A2B receptors. Similar conclusions apply to GMCs except that 3′-AMP also has actions independent of adenosine/A2B receptors. Because A2B receptors are renoprotective, 2′-AMP and 3′-AMP may provide renoprotection by generating adenosine that activates A2B receptors

Modulation by angiotensin II of isoproterenol-induced cAMP production in preglomerular microvascular smooth muscle cells from normotensive and genetically hypertensive rats

ABSTRACT The objectives of the present study were to determine whether angiotensin II (Ang II) modifies beta-adrenoceptor-induced cAMP production in preglomerular microvascular smooth muscle cells (PMVSMCs), to determine whether the Ang II/betaadrenoceptor interaction on cAMP production differs in PMVSMCs from normotensive Wistar-Kyoto (WKY) rats vs. PMVSMCs from spontaneously hypertensive rats (SHR), and to elucidate the mechanism of Ang II/beta-adrenoceptor interactions on cAMP production in PMVSMCs. In cultured PMVSMCs, isoproterenol increased cAMP levels and this effect was markedly enhanced by Ang II. The Ang II enhancement of isoproterenol-induced cAMP was significantly greater in SHR PMVSMCs compared with WKY PMVSMCs. Neither inhibition of calcineurin with FK506, inhibition of calcium-calmodulin with W-7 and calmidazolium, nor inhibition of G i proteins with pertussis toxin attenuated Ang II enhancement of isoproterenolinduced cAMP in PMVSMCs from either SHR or WKY rats. Moreover, the effect of Ang II on isoproterenol-induced cAMP was not mimicked by alpha-2 adrenoceptor stimulation. In contrast, chelation of intracellular calcium with BAPTA-AM attenuated, increasing intracellular calcium with A23187 augmented, and inhibition of protein kinase C with either calphostin C or chelerythrine chloride abolished Ang II enhancement of isoproterenol-induced cAMP. We conclude that in cultured PMVSMCs Ang II enhances the cAMP response to beta-adrenoceptor agonists via a mechanism that involves coincident activation of adenylyl cyclase by stimulatory G proteins and protein kinase C. Thus, protein kinase C-mediated activation of adenylyl cyclase may attenuate Ang II-induced vasoconstriction in the renal microcirculation by raising the intracellular levels of cAMP, and this mechanism may be augmented in genetic hypertension. Several studies demonstrate that Ang II enhances the formation of cAMP in response to a variety of agonists. Ang II potentiation of cAMP formation has also been observed in other cell types. Although Ang II enhances agonist-stimulated cAMP formation in smooth muscle cells from large conduit arteries, whether this occurs in smooth muscle cells from resistance vessels is unknown. In this regard, in the perfused rat kidney, Ang II inhibits rather than stimulates isoproterenol-induced cAMP forma