miR-9 inhibits the metastatic ability of hepatocellular carcinoma via targeting beta galactoside alpha-2.6-sialyltransferase 1

Glycosylation of cell surface proteins regulates critical cellular functions, including invasion and metastasis in cancer cells. Emerging evidence has shown that microRNAs (miRNAs) are involved in regulating both the glycosylation modifications on cell surface and the progression of cancer. In this study, we investigated the role of miR-9 in alfa -2,6-linked sialylation and the metastasis of mouse hepatocellular carcinoma (HCC). According to array-based miRNA expression profiling data of HCC cell lines Hepa1-6, Hca-P, and Hca-F with different lymphatic metastatic capacities, reverse correlation was found between miR-9 expression levels and the metastatic potential in these HCC cells. Additionally, Beta-galactoside alfa -2,6-sialyltransferase 1 (St6gal1) expression level is associated negatively with miR-9 and positively with metastatic potential. Bioinformatics analysis indicated that miR-9 could target St6gal1, which was verified by luciferase reporter assays. miR-9 overexpression reduced expression of St6gal1, which subsequently suppressed HCC cells metastatic potential. Moreover, upregulation of miR-9 could inhibit integrin-Beta1/FAK-mediated cell motility and migration signaling in mouse HCC cells. Together, our results suggest that miR-9 could act as a tumor suppressor and regulate mouse HCC cells migration and invasion by inhibiting the alfa-2,6-linked sialylation. This finding may provide insight into the relationship between abnormal miRNA expression and aberrant cell surface glycosylation during tumor lymphatic metastasis

Hepatic preneoplasia induction in male Wistar rats: histological studies up to five months post treatment

Background: Liver preneoplasia development in rats can be mimicked by an initiation-promotion model that induces the ppearance of altered hepatocyte foci (FAH). Aims: We compare two initiation-promotion models to evaluate the presence of FAH or additional hepatic pathologies in which other organs were affected up to five month post treatment. Material and methods: FAH were induced in male adult Wistar rats with two doses of dietylnitrosamine (DEN, 150 mg/kg bw) followed by 4 doses per week (3 weeks) of 2-acetylaminofluorene (2-AAF, 20 mg/kg bw) or with one dose of DEN (200 mg/kg bw) followed by 2 doses per week (3 weeks) of 2-AAF. DEN 150, DEN 200 and control rats (received the vehicle of the drugs) groups were compared. Rats were euthanized immediately after the last dose of 2-AAF, at 3, 4 and 5 months (n = 3 for euthanasia times per group). Samples of livers, lungs, idneys, pancreatic tissue and small bowel were processed for histological and immunohistochemical analysis. Results: FAH persisted for 5 months in all livers of the DEN groups. Three months after withdrawal of 2-AAF, one rat from DEN 150 group developed fibrosis and 5 months after 2-AAF removal another rat from the same group presented a microscopic hyperplastic nodule. Only the lungs had damages compatible with lesions induced by gavage-related reflux in DEN groups. Conclusion: We concluded that up to five month post treatments, FAH persisted in all the livers from DEN groups; livers from DEN 200 group showed no other hepatic lesions besides FAH, and only the lungs suffered pathological alterations in both treated groups (AU)

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Eficacia de los programas de cribado de hepatocarcinoma: ¿mejoran las opciones terapéuticas de estos pacientes? / Are hepatocellular carcinoma surveillance programs effective at improving the therapeutic options?

Objetivo: determinar si la utilización en nuestro medio delprograma de cribado de HCC establecido –alfa-fetoproteína (AFP)y ecografia semestral– en pacientes con hepatopatía crónica permitedetectar pacientes en estadios precoces de la enfermedad.Material y métodos: Diseño experimental: estudio retrospectivo.Criterios diagnósticos de HCC: 2 o más técnicas de imagencon lesión hipervascular mayor de 2 cm o 1 técnica de imagencon lesión hipervascular mayor de 2 cm asociado a AFPmayor de 400 ng/ml. Pacientes: 85 pacientes diagnosticados deHCC en el Hospital Donostia entre los años 2003 y 2005. Datosanalizados: información demográfica (sexo, edad), factores deriesgo (alcohol, virus de hepatitis, hemocromatosis, otras enfermedadesasociadas), e información clínica (etiología de la hepatopatía,estadio de Child-Pugh, determinación de AFP, hallazgos radiológicos,criterios de resecabilidad, tratamiento recibido,evolución). Se divide la muestra en dos grupos según hubieran seguidoo no un programa de cribado.Resultados: el 70% de los pacientes del grupo de cribado sediagnostican en estadio precoz frente al 26,7% del grupo de nocribado (p < 0,05). Trece pacientes no pueden recibir tratamientocurativo a pesar del diagnóstico en fase precoz (9 en el grupo decribado y 4 en el de no cribado). La sensibilidad global del cribadoen nuestra serie es del 95%.Conclusiones: en nuestro medio, el programa de cribado dehepatocarcinoma es eficaz en términos de aplicación de tratamientoscurativos(AU9

Aim: to evaluate whether the current surveillance programs(ultrasonography and alpha-fetoprotein testing every six months)are successful in detecting patients in the early stages.Material and methods: the health records of all patientsdiagnosed with hepatocellular carcinoma in Donostia Hospitalbetween 2003 and 2005 were reviewed retrospectively. Eightyfivepatients (11 women and 74 men) were included in the studyand demographic data, risk factors and clinical data were obtained.Patients were split into two groups according to whether ornot they had been included in a surveillance program.Results: seventy per cent of patients of the surveillance groupis diagnosed in early stage opposite to 26.7% of patients in nosurveillance group (p < 0.05). Thirteen patients cannot receivecurative treatment in spite of the diagnosis in early stage (9 in thesurveillance group and 4 in the no surveillance group. The globalsensibility of the surveillance program in our series is 95%.Conclusions: current hepatocellular carcinoma surveillanceprograms, which comprise six-monthly ultrasonography and alpha-fetoprotein tests, are highly sensitive and effective. These programsresult in the detection of hepatocellular carcinoma in itsearly-stages, when potentially curative treatment may be offered(AU)

Gonadectomía vía laparoscópica en una paciente con síndrome de Morris / Laparoscopic gonadectomy in a woman with Morris syndrome

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