The sensitivity of human tissues and tumors to infection with type C adenoviruses correlates with the expression of the human coxsackie B-and adenovirus receptor, hCAR. HCAR is heterogeneously expressed in various tissues and types of human cancer cells, which has implications for the use of adenoviruses as vectors in cancer gene therapy. Using immunoblotting, real-time PCR, FACS-analysis and sensitivity to infection with adenovirus-lacZ, we analyzed the expression level of hCAR in glioma Grade IV cell lines. With realtime PCR, we also analyzed hCAR expression in primary human astrocytomas of different malignancy grades, as well as in their xenograft derivatives. Analysis of a set of 10 cell lines showed great variation in hCAR expression. Susceptibility to Ad5lacZ correlated well with hCAR expression, whereas no correlation was observed with the expression of ␣v3/␣v5 integrins, proposed to function as co-receptors for adenoviruses. A great variation of CAR expression was also observed in primary astrocytomas of different malignancy grades. The mean value of CAR expression was significantly lower in 22 Grade IV tumors as compared to the values for 6 Grade II (p ؍ 0.01) and 6 Grade III (p ؍ 0.01) tumors. When the hCAR expression in 11 xenografts derived from Grade IV gliomas were compared to the levels detected in the original parental tumors, a mean 12-fold higher expression was seen in the xenografts (P ؍ 0.01). Two xenografts with low hCAR expression grew considerably faster than the hCAR-expressing cells. Our results have relevance for the use of adenoviruses in gene therapy against astrocytomas.
Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains a puzzling clinical entity that is characterized by clinical evidence of myocardial infarction (MI) with normal or near-normal coronary arteries on angiography (stenosis < 50%). Major advances in understanding this condition have been made in recent years. The precise pathogenesis is poorly understood and is being studied and examined further. Guidelines indicate that MINOCA is a group of heterogeneous diseases with different mechanisms of pathology. Since there are multiple possible pathological mechanisms, it is not certain that the classical secondary prevention and treatment strategy for MI with obstructive coronary artery disease (MI-CAD) is optimal for MINOCA patients. The prognosis and predictors for MINOCA patients remain unclear. Although the prognosis is slightly better for MINO-CA patients than for MI-CAD patients, MINOCA isn't always benign. The aim of this paper was to review the literature and evaluate MINOCA epidemiology, clinical features, etiology, diagnosis, treatment, and prognosis.
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