Estado actual del valor pronóstico de los marcadores moleculares en pacientes con cáncer colorrectal y la predicción de respuesta al tratamiento adyuvante

Colorectal cancer is one of the best studied of all malignant diseases interms of genetics and/or molecular prognostic factors. These factors, and relationships with prognosis, may have important implications especially in the design of surgical and adjuvant chemo-radiotherapy options. However, the true prognostic significance of all known factors has yet to be realised. We have reviewed the literature with specific focus on the role of molecular markers involved in prognosis and the prediction of response to adjuvant treatment.     

Bradykinin-induced vasoconstriction of rat mesenteric arteries precontracted with noradrenaline.

1. Administration of bradykinin caused dose-dependent vasoconstriction in rat isolated perfused mesenteric arteries precontracted with noradrenaline. 2. The vasoconstrictor response was not mediated by BK1-bradykinin receptors. 3. Inhibition of cyclo-oxygenase with indomethacin, aspirin or meclofenamate abolished the vasoconstrictor effect of bradykinin, showing that a member of the arachidonic acid cascade may be involved. 4. Inhibitors of thromboxane synthesis (imidazole and UK 38485) did not affect or only reduced the bradykinin-induced vasoconstriction. 5. The endoperoxide H2/thromboxane A2 receptor antagonist SQ 29548 significantly reduced the vasoconstrictor effect of bradykinin, but did not affect the vasoconstrictor response to noradrenaline, adrenaline, vasopressin, 5-hydroxytryptamine or prostaglandins. 6. The eicosanoid(s) that mediate bradykinin-induced vasoconstriction appear to be synthesized outside the arterial endothelium. 7. The data suggest that the vasoconstrictor effect of bradykinin in the rat isolated mesenteric artery is mediated by vasoconstrictor arachidonic acid metabolites including the cyclic endoperoxides and/or the thromboxanes.     

Gonadotrophin dynamics during reproductive life.

OBJECTIVE: To evaluate the follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in early follicular phase throughout the reproductive years. METHOD: FSH and LH concentrations were determined by radioimmunoassay (RIA). Linear and polynomial regressions were carried out considering basal FSH as the dependent and age as the independent variable. RESULTS: FSH levels increased throughout the reproductive years (P<0.025). A positive correlation between age and basal FSH levels was detected (P<0.05). The Pearson squared coefficient of r(2)=0.889 was obtained. Using polynomial regression, the inclination of the parabole (Y=7.97-0.009x+0.057x(2)) was 0.359 and the generalized correlation coefficient was r=0.795. The goodness of fit analysis showed that the parabole may better represent the phenomenon (F=4.7; P<0.05). The LH levels remained constant, increasing only beyond 40 years of age. CONCLUSION: The FSH levels rose in a nonlinear way during the reproductive life and the LH concentrations increased discreetly only in patients over 40 years of age.     

Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells

Sulfasalazine (SSZ) is a drug used in inflammatory bowel disease, whose precise mechanism of action remains to be clarified. Here, we report that incubation of Raw 264.7 cells with SSZ but not salicylates [acetylsalicylic acid (ASA), 4-aminosalicylic acid (4-ASA), and 5-ASA] causes a mixed apoptotic and necrotic form of cell death. In contrast to its metabolites, sulfapyridine and 5-ASA, SSZ exposure in Raw 264.7 cells resulted in a threefold increase in ceramide generation, as well as a robust production of reactive oxygen species (ROS). However, inhibition of ceramide production by fumonisin B1 failed to attenuate cell death. Preincubation with catalase, cyclosporin A (CsA), and bongkrekic acid attenuated ROS production. When dead cells were quantified for apoptotic versus necrotic cell death, catalase and N-acetylcysteine reproducibly attenuated apoptosis, whereas CsA, in addition to reducing apoptosis, was observed to dramatically enhance necrosis. In conclusion, the cell-death response induced by SSZ in Raw 264.7 cells involves ROS in the apoptotic limb but is independent of ceramide formation.     

Allergy, asthma and markers of infections among Albanian migrants to Southern Italy

BACKGROUND: Studies of immigrants represent an useful tool to determine the relative relevance of environmental vs genetic factors in causing the reported rapid increase of the prevalence of sensitization and allergic diseases. METHODS: A total of 152 Albanian migrants to Southern Italy responded to a questionnaire based on the European Community Respiratory Health Survey (ECRHS) and 139 of them underwent skin prick test, and 61 serological assays for total IgE and IgG antibodies against Toxoplasma gondii (TG), herpes simplex virus 1 (HSV-1), hepatitis A virus (HAV) and Helicobacter pylori (HP). RESULTS: Reported asthma was rare (2/152; 1.3%) and reported nasal allergies rather frequent (24/152; 15.8%). Sensitization to common inhalant allergens occurred in 27/139 (19.4%) subjects. The frequency of skin sensitization to pollen (P = 0.003) and that of hay fever (P = 0.004) increased with the time spent in Apulia. All the 61 sera had antibodies against HAV, 59/61 (96.7%) against HSV-1, 48/61 (78.7%) against HP and 34/61 (55.7%) against TG. The prevalence of skin sensitization and hay fever symptoms were correlated to the duration of residence in Southern Italy. CONCLUSIONS: Data presented indicate that Albanian migrants to Italy, in spite of the low prevalence of allergic diseases and sensitization in their country of origin, manifest with time an increasing prevalence of sensitization to local allergens and nasal symptoms after immigration to Italy. This would suggest a permanent role of allergen exposure and lifestyle factors in influencing the appearance of sensitization and symptoms of allergic diseases.     

Breast fat necrosis secondary to warfarin-induced calciphylaxis,a rare mimicker of breast cancer: A case report and a review of literature

Breast fat necrosis (BFN) is usually a benign inflammatory response to breast trauma. However, an extremely rare cause of fat necrosis is calciphylaxis, a calcification of small- and medium-sized arteries causing thrombosis and ischemia. It is classified into (A) uremic (B) nonuremic-induced calciphylaxis. Calciphylaxis has been reported to be encountered in different parts of the body. However, to the best of our knowledge there is only one case in the English literature of BFN 2ry to warfarin-induced calciphylaxis. We report a 65-year-old female, known case of atrial fibrillation on warfarin, presented with a left breast mass of 4-month duration. The mass was painful and progressively enlarging. Examination of the left breast showed 7 × 4 cm mass, spanning from 10-2 o'clock, free from surrounding structures, with preserved overlying skin. However, the mass was not visualized on mammogram. Ultrasound showed a left breast lobulated hypoechoic mass containing a hyperechoic component. Biopsy showed fat necrosis. After 1 month, she presented with ulceration of the overlying skin. After wide local excision, histopathology demonstrated a calciphylaxis-induced fat necrosis. Considering the patient's background, the diagnosis was BFN secondary to warfarin-induced calciphylaxis. Hence, the warfarin was shifted to Rivaroxaban, 6 months follow-up showed no evidence of recurrence. In conclusion, the rarity of nonuremic calciphylaxis is reflected on the delay of diagnosis in some of the reported cases and the lack of grading system used to guide the management of such difficult wounds. However, keeping a high index of suspicion is important whenever such wounds are encountered with presence of risk factors other than end-stage kidney disease.     

Pure yolk sac tumors in genital and extragenital sites: study on three pedriatic cases, with cytological findings on two

Cytopathological findings on three pedriatic gonadic-extragonadic pure yolk sac tumor are reported: the highly variable histological patterns (reticular, solid, festooning or pseudopapillary, polyvesicular vitelline), reflecting differentiation towards extraembryonic yolk sac structures, are not appreciated in cytologic samples. Since the tumor's cytologic spectrum is very broad, the most diagnostic differential difficulty with yolk sac tumor is adenocarcinoma. The presence of intracellular and extracellular hyaline globules, that are periodic acid-Schiff stain (PAS) positive and diastase resistant and correspond to alpha-fetoprotein production, alpha-fetoprotein positivity of the neoplastic cells; showing nuclear pleomorphism and vacuolated "bubbly" cytoplasm are the most consistent cytologic hallmarks of this neoplasm, which diagnosis would be confirmed by histologic, immunocytochemical and clinical findings.