Clonación y transcripción del gen EBER-1 del virus Epstein-Barr: estudio de su expresión genética por hibridación in situ / Cloning and transcription of gene EBER-1 of Epstein-Barr virus: study of its genetic expression by hybridization in situ

La capacidad de virus de Eptein Barr (VEB) de inducir transformación e inmortalización de linfocitos y su alta prevalencia en algunas neoplásias linfoides ha motivado intensa investigación de su biología y comportamiento. Describimos la hibridación in situ (HIS), para la identidicación de transcriptos del virus de Epstein-Barr, desarrollado en la Unidad de Biología Molecular del Centro de Investigación en Cáncer Maes Heller, en biopsias de linfoma incluidas en parafina.El gen EBER-1 (Epstein Barr-encoded RNA) fue clonado y transcrito, el ARN transcrito fue evaluado con óptimos resultados en las líneas celulares Raji y Daudi que expresan EBER. Este transcrito marcado fue usado como sonda para determinar la expresión genética del virus en 159 especimenes biológicos en estudio y en controles positivos y negativos conocidos empleando la HIS.La actividad transcripcional del virus fue observada en 44 de los casos estudiados. Concluimos que la HIS en tejido incluido en parafina es una buena alternativa para detectar actividad del VEB y la presencia o ausencia de EBER puede ser considerada como marcador biológico en la etiopatología de estos linfomas

Oncogenes E6-E7 de los papilomavirus humanos de alto riesgo detectados por PCR en biopsias de pene incluidas en parafina / Oncogenes E6-E7 of the human papillomavirus of high risk detected by PCR in penile biopsia included in paraffin

La alta prevalencia del papilomavirus humano (PVH), referida a nivel mundial, en lesiones genitales de ambos sexos, el rol del varón como reservorio pasivo del virus, y el incremento de la mortalidad por cáncer genital en la mujer en nuestro país, motiva la determinación y correlación de los oncogenes de los PVH de alto riesgo con la neoplasia de pene. Informamos de diez casos de biopsias de carcinoma escamoso de pene, incluidos en parafina, los cuales fueron investigados para la presencia de los oncogenes E6-E7 de PVH de alto riesgo, utilizando cebadores tipo específico para los PVH-16 y 18, mediante la reacción en cadena de polimerasa (PCR). El 40 de los casos mostró un producto de amplificación ADN E6-E7 de los PVH estudiados, correspondiendo el 75 de ellos a detección simple por PVH-18 y el 25 presentó mixta ADN E6-E7 del PVH-16 y 18 simultáneamente. El producto de amplificación fue sometido a comprobación por análisis de restricción específico. La prevalencia obtenida de los oncogenes E6-E7 de los PVH de alto riesgo, usando un método tan sensible como la PCR, apoya el rol de estos virus en el proceso de carcinogénesis de la neoplasia de pene

Epstein-Barr virus in nasal lymphomas contains multiple ongoing mutations in the EBNA-1 gene.

We have described 5 major subtypes of Epstein-Barr virus (EBV) based on variations in EBNA-1 sequences. These include P-ala (identical to the prototype B95.8 virus), P-thr, V-pro, V-leu, and V-val. Normal individuals often carry multiple EBV subtypes, the most common being P-ala, whereas EBV-associated tumors examined to date always contain a single subtype, which only on rare occasion is P-ala. The primary hypotheses that these observations generate are as follows: (1) Each of these EBV subtypes are naturally occurring, and in normal individuals the multiplicity of subtypes results from multiple infections. (2) EBV subtypes in normal individuals are generated in vivo from a single infecting virus subtype by mutations in EBNA-1. The second hypothesis essentially excludes the possibilities that the nonrandom association of certain subtypes with lymphomas is secondary to the geographic distribution of EBV subtypes and, if proven correct, could provide strong support for a direct role of EBV in tumorigenesis. In this report, we provide evidence for the latter hypothesis. We show that the P-ala EBV subtype present in most nasal lymphomas undergoes and accumulates multiple mutations consistent with the generation of variant species of EBNA-1 in vivo. This phenomenon is similar to the generation of quasispecies in RNA viruses and is the first description of in vivo generation of subtypes in DNA viruses. In RNA-based viruses, including human immunodeficiency virus and hepatitis C virus, the emergence of quasispecies is linked to replication infidelity and significantly influences disease processes through its effect on viral tropism, the emergence of viruses resistant to the host defenses or to therapy, and pathogenicity. The present data thus raise important questions relating to the mechanisms whereby these mutations are generated in EBV and their relevance to the pathogenicity of EBV-associated lymphomas.

[Lymphomas of the gastrointestinal tract: a neoplastic disease of underdevelopment]. / Linfomas del tracto gastrointestinal: una enfermedad neoplásica del subdesarrollo.

458/3,495 malignant lymphomas seen at the Instituto de Enfermedades Neoplásicas between 1965-1992, had primary extranodal disease in the GI tract. This is one of the largest institutional series reported, which would suggest that this is a relatively frequent malignancy in Peruvian population. Fifty per cent of cases had a primary in the small bowel and 38.9 per cent in the stomach. The age at presentation, the clinical picture and the location at the intestine show similarities with the so called Mediterranean lymphoma. Cases were classified according to the TNM system, and patients in stages I-II were surgically resected; 80 per cent of them were alive and free of disease at 5 years. Gastric lymphomas with inoperable disease were treated with chemotherapy with a 5-year survival of 50 per cent.

Percutaneous intrathoracic aspiration biopsy.

An analysis of 617 percutaneous intrathoracic aspiration biopsies (PIAB) performed on 587 patients with pulmonary and mediastinal lesions between 1954 and 1985 are presented. The effectiveness of the procedure between 1954 and 1980 and between 1981 and 1985 with a positivity of 71.6% and 84.9%, respectively, was compared. These results are statistically significant and reflect improvement in the technique employed. A greater positivity was found where the lesion measured 2 to 3 cm in diameter. Complications for this series were 7.8%. In diffuse infiltrating lesions, the positivity is less than that obtained for the whole series, and the risk of developing a pneumothorax is greater. The false-negative cases include those in which an inadequate sample was obtained for diagnosis (13.9% of the total series) and samples containing elements of the chest wall or blood (5.2%).

Local control of osteogenic sarcoma by radiation and chemotherapy.

Sixteen patients with osteogenic sarcoma of limbs were treated with high dose methotrexate followed by leucovorin rescue, adriamycin and radiotherapy to the primary tumor. A post-treatment surgical biopsy was performed in 15 of the 16 patients. In 12 of 15 patients (80%), the follow-up biopsy was negative for active tumor. Complications of treatment were myelosuppression (16 cases), moist desquamation (13 cases), soft tissue necrosis (2 cases) local infection (2 cases), fibrosis (9 cases) and bone fracture (4 cases). The mean survival time in this group of patients was 712 days.