A decline in the function of the microvasculature occurs with ageing. An impairment of endothelial properties represents a main aspect of age-related microvascular alterations. Endothelial dysfunction manifests itself through a reduced angiogenic capacity, an aberrant expression of adhesion molecules and an impaired vasodilatory function. Increased expression of adhesion molecules amplifies the interaction with circulating factors and inflammatory cells. The latter occurs in both conduit arteries and resistance arterioles. Age-related impaired function also associates with phenotypic alterations of microvascular cells, such as endothelial cells, smooth muscle cells and pericytes. Age-related morphological changes are in most of cases organ-specific and include microvascular wall thickening and collagen deposition that affect the basement membrane, with the consequent perivascular fibrosis. Data from experimental models indicate that decreased nitric oxide (NO) bioavailability, caused by impaired eNOS activity and NO inactivation, is one of the causes responsible for age-related microvascular endothelial dysfunction. Consequently, vasodilatory responses decline with age in coronary, skeletal, cerebral and vascular beds. Several therapeutic attempts have been suggested to improve microvascular function in age-related end-organ failure, and include the classic anti-atherosclerotic and anti-ischemic treatments, and also new innovative strategies. Change of life style, antioxidant regimens and anti-inflammatory treatments gave the most promising results. Research efforts should persist to fully elucidate the biomolecular basis of age-related microvascular dysfunction in order to better support new therapeutic strategies aimed to improve quality of life and to reduce morbidity and mortality among the elderly patients.

Primary cardiac sarcomas are malignant neoplasms deriving from mesenchymal cells and confined to the heart at the time of diagnosis. Most cardiac sarcomas have the same histologic appearance similar to their soft tissue counterpart. Consequently, an extremely rare metastasis from a preexisting noncardiac sarcoma should be excluded. Nevertheless, primary heart sarcomas are exceptionally rare. In a large study by the American Medical Association, prevalence of primary cardiac sarcomas at autopsy was 0.0017%,¹ x 1 Straus, R and Merliss, R. Primary tumor of the heart. Arch Pathol. 1945; 39: 74–78 Google Scholar See all References with an incidence from 0.001 to 0.030%² x 2 McAllister, H and Fenoglio, J. Tumors of the Cardiovascular System Fascicle 15, 2nd Series. Armed Forces Institute of Pathology, Washington, D.C.; 1978 Google Scholar See all References and a general incidence of 0.07%.³ x 3 Chomette, G, Auriol, M, Cabrol, C et al. [Primary malignant tumors of the heart. Anatomo-clinical study of 12 cases]. Ann Med Interne (Paris). 1985; 136: 301–305 PubMed | Google Scholar See all References Cardiac metastases at autopsy occur 20 to 40 times more frequently than primary neoplasms⁴ x 4 Lymbumer, R. Tumours of the heart: histopathological and clinical study. Can Med Assoc J. 1934; 30: 368–373 PubMed | Google Scholar See all References and originate mainly from cutaneous melanoma, lung, and breast carcinomas. Sarcomas represent approximately 10 to 20% of total primary cardiac tumors⁵ x 5 Burke, AP and Virmani, R. Tumors of Heart and Great Vessels, Vol. 16, 3rd series. AFIP, Washington, D.C.; 1996 Google Scholar See all References ^{, 6} x 6 Shapiro, LM. Cardiac tumours: diagnosis and management. Heart. 2001; 85: 218–222 Crossref | PubMed | Google Scholar See all References and occur without any gender predilection. Cardiac sarcomas may arise in any area of the heart, although angiosarcoma is typically found in the right atrium,⁷ x 7 Janigan, DT, Husain, A, and Robinson, NA. Cardiac angiosarcomas. A review and a case report. Cancer. 1986; 57: 852–859 Crossref | PubMed | Scopus (156) | Google Scholar See all References whereas fibrosarcoma and undifferentiated sarcoma in the left atrium.⁵ x 5 Burke, AP and Virmani, R. Tumors of Heart and Great Vessels, Vol. 16, 3rd series. AFIP, Washington, D.C.; 1996 Google Scholar See all References ^{, 8} x 8 Burke, AP, Cowan, D, and Virmani, R. Primary sarcomas of the heart. Cancer. 1992; 69: 387–395 Crossref | PubMed | Scopus (402) | Google Scholar See all References Transthoracic echocardiography is the most common method of instrumental investigation.⁹ x 9 Edwards, LC III and Louie, EK. Transthoracic and transesophageal echocardiography for the evaluation of cardiac tumors, thrombi, and valvular vegetations. Am J Card Imaging. 1994; 8: 45–58 PubMed | Google Scholar See all References Elective therapy includes complete surgical excision when possible, followed by radio- and chemotherapy. Despite these therapeutic strategies, prognosis of cardiac sarcomas is very poor, with median survival of less than 1 year.¹⁰ x 10 Grebenc, ML, Rosado de Christenson, ML, Burke, AP et al. Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation. Radiographics. 2000; 20: 1073–1103 Crossref | PubMed | Scopus (303) | Google Scholar See all References

Retinol and vitamin A derivatives influence cell differentiation, proliferation, and apoptosis and play an important physiologic role in a wide range of biological processes. Retinol is obtained from foods of animal origin. Retinol derivatives are fundamental for vision, while retinoic acid is essential for skin and bone growth. Intracellular retinoid bioavailability is regulated by the presence of specific cytoplasmic retinol and retinoic acid binding proteins (CRBPs and CRABPs). CRBP-1, the most diffuse CRBP isoform, is a small 15 KDa cytosolic protein widely expressed and evolutionarily conserved in many tissues. CRBP-1 acts as chaperone and regulates the uptake, subsequent esterification, and bioavailability of retinol. CRBP-1 plays a major role in wound healing and arterial tissue remodelling processes. In the last years, the role of CRBP-1-related retinoid signalling during cancer progression became object of several studies. CRBP-1 downregulation associates with a more malignant phenotype in breast, ovarian, and nasopharyngeal cancers. Reexpression of CRBP-1 increased retinol sensitivity and reduced viability of ovarian cancer cellsin vitro. Further studies are needed to explore new therapeutic strategies aimed at restoring CRBP-1-mediated intracellular retinol trafficking and the meaning of CRBP-1 expression in cancer patients’ screening for a more personalized and efficacy retinoid therapy.

The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC) tumors, its association with the clinical course of the disease, and the underlying mechanism(s). Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFNγ) induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1β (IL-1β) production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1β production by monocytes.