Correction: Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.

[This corrects the article DOI: 10.1371/journal.pntd.0005370.].

Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.

Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy.

[Oncogenic osteomalacia. Report of two cases]. / Osteomalacia oncogénica. Presentación de dos casos.

Oncogenic osteomalacia is a rare disease. It is caused by a tumor that produces fibroblast growth factor 23, a hormone that decreases the tubular phosphate reabsorption and impairs renal hydroxylation of vitamin D. This leads to hyperphosphaturia with hypophosphatemia and low calcitriol levels. About 337 cases have been reported and we studied two cases; 44 and 70 year-old men who sought medical attention complaining of suffering diffuse bone pain over a period of approximately one year. In both cases, a laboratory test showed biochemical alterations compatible with a hypophosphatemic osteomalacia. In the first case, a soft tissue tumor of the right foot was removed, one year after the diagnosis. The patient was allowed to diminish the phosphate intake, but symptoms reappeared at this time. Eight years later, a local recurrence of the tumor was noted. A complete excision was now performed. The patient was able to finally interrupt the phosphate intake. In the second case, an F-18 fluorodeoxyglucose positron emission tomography, with computed tomography revealed a 2.26 cm diameter hypermetabolic nodule in the soft tissue of the right forefoot. After its removal, the patient discontinued the phosphate intake. Both patients are asymptomatic and show a regular phosphocalcic laboratory evaluation. The histopathological diagnosis was, in both cases, a phosphaturic mesenchymal tumor, a mixed connective tissue variant. This is the prototypical variant of these tumors.

Correlation of immunocytochemical and immunohistochemical determination of estrogen and progesterone receptors in breast cancer.

OBJECTIVE: To evaluate prospectively the degree of correlation between immunocytochemical (ICC) and immunohistochemical (IHC) determination of estrogen (ER) and progesterone receptors (PR) in breast cancer. STUDY DESIGN: Fine needle aspiration cytology (FNAC) of 101 primary breast cancers were immunostained for ER and PR. They were compared with similar determinations in formalin-fixed paraffin sections of biopsies from the same patients. In cases of discrepancy, the histologic result was considered the gold standard. RESULTS: For ER a cytohistologic correlation of 94%, with a sensitivity of 96.1% and specificity of 86.9%, was found. For PR the cytohistologic correlation was 71.2%, with a sensitivity of 65.7% and specificity of 83.8%. CONCLUSION: ICC determination of hormone receptors in routinely fixed smears obtained by FNAC is a simple method that correlates adequately with the results of IHC determinations, especially for ER.

Expresion de p53 y de bcl-2 en adenomas y carcinomas colorrectales / Expression of p53 and bcl-2 in colorectal adenomas and carcinomas

Trabajos recientes han asociado a los genes p53 y bcl-2 en el proceso de la transformación neoplásica. Dado que la secuencia adenoma-carcinoma en el colon y recto es un buen modelo natural de carcinogénesis, consideramos de interes analizar la expresión de bcl-2 y de p53 en estas neoplasias. Se estudiaron 73 pólipos adenomatosos (adenomas) y 60 adenocarcinomas de colon y recto. De los adenomas 16 tenían displasia leve, 27 moderada, 15 severa y en 15 había carcinoma focal. Todos los adenocarcinomas sobrepasaban la muscular propia y eran moderadamente diferenciados. La expresión de los genes se analizó por inmunohistoquímica utilizando al anticuerpo bcl-2 de Dako y el anticuerpo p53 de Novocastra. Los resultados mostraron que hubo acumulación de proteína p53 en 34/73 (46 por ciento)del total de los adenomas y en 47/60 (78 por ciento) de los adenocarcinomas ( p= 0,0001). El conjunto de adenomas con displasia mostró una reactividad de 26/58 (45 por ciento), similar a 8/15 (53 por ciento, p = 0,4) de los adenomas con carcinoma focal, aunque diferente a la de los adenocarcinomas, 47/60 (78 por ciento, p = 0,0001). Con referencia al bcl-2, 53/73 (73 por ciento) del total de los adenomas lo expresaban mientras que en los adenocarciomas la expresión se observó en 14/60 (23 por ciento, p = 0,0000). En los adenomas sin carcinoma se encontró una expresión de 47/58 (81 por ciento) que comparada con la observada en los adenomas con carcinoma focal, 6/15 (40 por ciento), y con adenocarcinoma, 14/60 (23 por ciento), mostraron diferencias estadísticamente significativas (p = 0,001 y p + 0,0000 respectivamente). Cuando se analizó la frecuencia de expresión de los dos genes estudiados en las diferentes neoplasias se observó entre ellos una relación inversa. Este trabajo permite concluir que la expresión de bcl-2 es un evento temprano en la carcinogénesis y que es reemplazado por la mutación de p53 al progresar la neoplasia.