1,721,175 research outputs found
Effect of Ramipril and Vitamin E on Atherosclerosis.
No full textTo the Editor:
In their study, Lonn et al1 report on the results of the SECURE
study, which evaluated the effect of ramipril and vitamin E on
atherosclerosis. The authors conclude that long-term treatment
with ramipril has a beneficial effect on atherosclerosis progression
whereas vitamin E has no effect
Myxoid dermatofibrosarcoma protuberans: morphological, ultrastructural and immunohistochemical features
No full textTwo uncommon cases of dermatofibrosarcoma protuberans with prominent myxoid changes are presented. The tumors appeared as large multinodular cutaneous plaques that arose at the sites of excision of previous tumors some years earlier. In addition to limited fibrous storiform features, focally observed in deep and peripheral portions of the tumors, a diffuse myxoid pattern could be observed. The latter consisted of homogeneous areas of rare, stellate or spindle-shaped cells, haphazardly scattered in abundant myxoid matrix. Cells of myxoid neoplastic tissue showed mainly a positive immunoreaction for fibrohistocytic markers and the absence either of muscular, neural or human progenitor cell antigens. Mitotic figures were fewer and cell proliferation rates were lower in myxoid as compared to those of typical dermatofibrosarcoma protuberans used as a control. The ultrastructural examination of myxoid areas revealed a prevalent fibroblast-like cell population showing dilated cytoplasmic vesicles, sometimes containing glycosaminoglycans-like substances. The extent of myxoid changes together with the characteristic morphological, ultrastructural and immunohistochemical features confirm that myxoid dermatofibrosarcoma protuberans is a distinct variant of this fibrohistiocytic tumor to be considered in the differential diagnosis among myxoid tumors of the skin
Simultaneous vulvar intraepithelial neoplasia and Paget's disease: Report of two cases
No full textWe describe a very rare association between intraepithelial, extramammary Paget's disease and human papillomavirus- (HPV) negative, keratinized type of VIN III observed in two elderly women. In both cases, morphological and immunohistochemical investigation showed two heterogeneous but intimately admired neoplastic populations of vulvar epithelium. Atypical keratinocytes stained markedly and diffusely positive for high molecular weight cytokeratins, and moderately for p53 protein and c-erbB-2 immunostainings. Paget cells were diffusely positive for CEA, EMA, and low molecular weight cytokeratins, moderately and focally for c-erbB-2 and (in one case) for S-100. Morphological and immunohistochemical phenotypic differences between Paget cells and atypical keratinocytes suggest a simultaneous and incidental association of two distinct neoplastic disorders more than a mixed carcinoma in situ of vulvar epithelium
Symptomatic laryngeal nodular chondrometaplasia: A clinicopathological study
No full textA 41 year old man with a history of politrauma presented with a nodular mass of the left false vocal cord, associated with progressive dysphonia, dyspnoea, and dysphagia. A computed tomography scan of the neck region showed a rounded and circumscribed mass without infiltration of the surrounding tissues. Histological investigation of the nodule revealed the presence of fibroelastic cartilaginous tissue, surrounded by a thin rim of fibrous tissue, with rare hypercellular areas, occasional binucleated cells, slight hyperchromasia, and an irregular nuclear profile. Mitotic activity was absent. The patient's history of laryngeal trauma, with the subsequent progressive onset of clinical symptoms, helps to distinguish the chondrometaplastic nature of this nodule from true laryngeal cartilaginous tumours, such as chondroma and low grade chondrosarcoma
From normal to malignant phenotype: survival and cell death escaping mechanisms
No full textGenetic damage acquisition, apoptosis inhibition, metabolic pathways shifting and growth signals self-sufficiency are the first steps in “survival mechanism” of the tumoral cell clone. Hence, the second important step is constituted by the proliferative advantage that leads to cooperation among tumor cells by an adaptative evolution of DNA repair and metabolic pathways to survival. Moreover, tumor progression implies immune escaping mimetism and trigger several processes that synergistically induce a cooperation among transformed cells that compete for space and resources such as oxygen and nutrients. Therefore in tumorigenesis the extra cellular milieu and tissue microenviroment heterotypic interactions cooperate to promote tumor growth, angiogenesis and cancer cell motility through elevated secretion of pleiotropic chemokines. In this view proteins involved in DNA repair , cell death induction and metabolism are inhibited or shifted towards other pathways by soluble mediators that orchestrate such change redirected towards the survival of malignant phenotype. In particular we focus our attention on defined pathways that underlie the promotion, initiation and progression of the tumor conferring resistance and aggressiveness to the neoplastic cells. We report the behaviour and the non conventional function of DNA repair proteins Ku70 and 80 and clusterin isoforms in tumorigenesis and the overexpression and non physiological distribution of the metabolic tumor suppressor FAS.
In tumorigenesis Ku70 and Ku80, proteins involved in DNA repair and apoptosis induction, paradoxically translocate from the nucleus to the cytoplasm where they sterically inhibit cell death induction binding Bax by the cooperative interaction with the overproduced s-clusterin.
In fact in tumor progression the pattern shift of the production of the two isoforms of clusterin that display different functions one antagonist of the other is observed. The nuclear pro-apoptotic form is inhibited during tumorigenesis and the over-production of cytoplasmic and secreted form is closely linked to metastasis invasion. Therefore the dynamic interaction among Ku70, Bax and Clusterin seems to have an import role in tumor insurgence as in its progression. Focusing on the regulating role of one member with respect to the activity of the others, the observation of their expression and relationship in tumor progression models could provide important information on their contribution to tumor behavior.
Moreover biochemical studies have demonstrated that one of the multiple differences between tumoral cells and healthy counterparts resides in the metabolic pathway, the uptake of glucose and the glycolitic process. The altered metabolism of neoplasia would favor an increased cell survival, promoting tumor size increase and cancer aggressiveness.
To prevent an accumulation of fatty acids, special alterations take place during tumor formation.
One metabolic cause is the loss of cytosolic glycerol 3-P dehydrogenase. Glycerol 3-P is the backbone of triglycerides. In tumor cells, the strong reduction of glycerol 3-P dehydrogenase leads to an increase in fatty acid release. The accumulation of dihydroxyacetone-P leads to an increased ether-linked glycerolipid synthesis. The release of fatty acids, the over expression of FAS and the accumulation of ether-linked lipids may protect tumor cells from immune attack.
Cooperation through the sharing of diffusible products and the redirection of some specific guardian pathways raises new questions about tumorigenesis and has implication on designing new therapeutic approaches
Aging influences development and progression of early aortic atherosclerotic lesions in cholesterol-fed rabbits
No full textThe arterial wall in aged animals shows an increased susceptibility to develop atherosclerotic lesions, although the mechanisms by which aging acts are still unclear. We investigated early aortic lesions in aged rabbits (5 to 6 years old, AH group) and young rabbits (2 months old,YH group) after 2 months of 0.2% cholesterol feeding. Fatty streaks or spots mainly in the proximal segments occupied a relative surface area that was greater in AH than in YH rabbits, although plasma cholesterol and lipoprotein levels did not differ. YH lesions showed an irregular endothelial profile mainly from accumulations of large, rounded, RAM 11-positive macrophagic foam cells. There was a higher percentage of myocytic, CD-5-positive, proliferating, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and larger accumulation of glycosaminoglycans in AH fatty streaks than in YH lesions. Ligation-mediated polymerase chain reaction confirmed differences in apoptosis. Early fibromuscular coats and subendothelial plasma-like insudate were also observed in AH lesions. Aged-matched normocholesterolemic rabbits showed a diffuse aortic intimal thickening composed of myocytic cells with a synthetic phenotype and extracellular matrix rich in glycosaminoglycans. In addition, in aged rabbits, we observed a spontaneous increase of monocytes adhering to the endothelial surface and a reduced expression of endothelial: nitric oxide synthase in areas distant from the branches. These plasma cholesterol-independent spontaneous changes in the aortic wall of aged rabbits seem to act as a multiple atherogenic risk factor. Moreover, age-related differences in the distribution, composition, and proliferative and apoptotic rates represent crucial events during the progression of early fatty streaks to advanced plaques
Solid alveolar rhabdomyosarcoma of the hand in adolescence: A clinical, histologic, immunologic, and ultrastructural study
No full textRhabdomyosarcoma (RMS), a high-grade, malignant, skeletal muscle tumor, represents approximately 5% of neoplasms in children. The poorly differentiated forms of RMS are often not easily diagnosed and classified, Among the four histologic variants, alveolar RMS is the least frequently reported subtype. A poorly differentiated solid variant of alveolar RMS occurred on the right hand of a 16-year-old girl. Because of the tumor size, local invasiveness, and occurence of cutaneous and breast metastases at presentation, the clinical staging was group IV (T2/N0/M1). Surgical excisions of the primary and metastatic locations were performed and chemotherapy with vincristine, dactinomycin, cyclophosphamide, and doxorubicin was administered. Light and electron microscopy studies revealed a solid proliferation with a focal alveolar pattern of monomorphous, small, round neoplastic cells without easily detectable muscular morphologic features. The skeletal muscle origin was revealed by the positive immunostaining for desmin, alpha-sarcomeric actin, muscle-specific actins, and enolase, and confirmed by immunoblotting for desmin. Despite the age of our patient, which is considered by some authors an independent predictor of outcome, all prognostic variables were unfavorable. However, a disease-free interval during three years of follow-up underlines the importance of multidisciplinary regimens for the treatment of this rare solid tumor of childhood and adolescence
Familial occurrence of pseudoxanthoma-elasticum-like papillary dermal elastolysis
No full textWe report the morphological, immunohistochemical and ultrastructural cutaneous findings of two sisters, aged 72-74, with pseudoxanthoma-elasticum- like papillary dermal elastolysis (PDE), recently defined as an age-related condition. To our knowledge, these are the first familial cases of PDE reported in the literature. The lesions appeared as small, asymptomatic, soft papules around the neck and axillary regions. The affected skin revealed a marked decrease of normal elastic network of papillary dermis without alterations in either the relevant collagen or reticular dermis. Ultrastructural and immunohistochemical examinations showed activated dermal fibroblasts with abundant elongated dendritic cytoplasmic processes and the absence of myofibroblasts. The well documented avoidance of sun exposure (the patients are both nuns), the rare incidence of the disorder (only six cases reported), and the familial occurrence suggest that genetic or inherited predisposition should also be considered in the pathogenesis of PDE
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