Targeting gallbladder carcinoma: bone marrow-derived stem cells as therapeutic delivery vehicles of myxoma virus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gallbladder carcinoma (GBC) has a high mortality rate, requiring synergistic anti-tumor management for effective treatment. The myxoma virus (MYXV) exhibits a modest clinical value through its oncolytic potential and narrow host tropism.</p><p><b>METHODS</b>We performed viral replication assays, cell viability assays, migration assays, and xenograft tumor models to demonstrate that bone marrow-derived stem cells (BMSCs) may enhance efficiency of intravenous MYXV delivery.</p><p><b>RESULTS</b>We examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication, leading to an oncolytic effect. Furthermore, we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system. BMSCs failed to affect the growth of GBC cells, in terms of tumor volume and survival time. Finally, we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone, almost to the same extent as intratumoral injection of MYXV.</p><p><b>CONCLUSION</b>This study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors.</p>

Study in the killing effect of Myxoma virus to C6 glioma cell in vitro / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To evaluate the susceptibility of C6 glioma cells to Myxoma virus and the killing effect of Myxoma virus to the C6 glioma cells in vitro.</p><p><b>METHODS</b>C6 glioma cells were infected with myxoma virus, used death virus as the negative control, 5-FU as the positive control, DEMD as blank control. The number of living cells were counted every 24 h, and Western-Blot method, inverted microscope and MTT assay were applicated to observe the cell morphology and survival rate in each group.</p><p><b>RESULTS</b>The cell number were decreased rapidly in virus effected group and 5-FU group, with significant differences to the negative and blank control groups. And cells in virus effected group appeared cytopathic effect.</p><p><b>CONCLUSIONS</b>C6 glioma cells were susceptible to myxoma virus and myxoma virus had killing effect to C6 glioma cells in vitro.</p>

Effects of myxoma virus on gliomas of rats models in vivo / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To explore the in vivo effects of myxoma virus (MV) on gliomas of rat model. Methods C6 glioma cells were implanted into the frontal lobe of SD rats using stereotactic methods to establish animal models of glioma.</p><p><b>METHODS</b>C6 glioma cells were implanted into the frontal lobe of SD rats using stereotactic methods to establish animal models of glioma. Models were divided into 4 groups randomly after tumor growth was affirmed, and MV, 5-FU, MV + 5-FU, and denatured myxoma virus (DV) were implanted into the tumors using stereotactic methods, bodyweight, tumor size, expression of glial fibrillary acidic protein (GFAP), Akt of each model were observed.</p><p><b>RESULTS</b>The gliomas in all SD rats were established successfully. And tumor growth in MV, 5-FU, MV + 5-FU were significantly decreased as compared with DV group after injection, sizes of some tumors were lessened, and GFAP expression decreased in MV, 5-FU and MV +5-FU groups. The expression of PI3k, Akt and mTOR were decreased in MV and MV +5-FU groups.</p><p><b>CONCLUSION</b>C6 glioma SD rat models could be established successfully using stereotactic methods. MV may enhance biological activity of chemotherapeutic drugs on tumor cells of animal models in vivo by regulating some genes of PI3K-Akt-mTOR signal pathway.</p>

Ultrastructural study of poxvirus causing myxomatosis in rabbits, in São Paulo and Santa Catarina, Brazil / Estudio ultraestructural del poxvirus causal de mixomatosis en conejos, en São Paulo y Santa Catarina, Brasil

The myxomatosis is a contagious worldwide disease caused by poxvirus which infects domestic and wild rabbits. In the present study we present two distinct outbreaks of myxomatosis when raising rabbits, one for commercial purpose of production of meat and skins and, another one for the commercialization of ornamental rabbits. The observed signs were ocular, auricular, nasal, testis lesions and many times scattered throughout the body of the animals. The lesions were characterized by formation of nodules that by palpation disclosed gummy or gelatinous aspect. At the transmission electron microscopy, all the skin and crust samples were analyzed by negative staining technique. A great number of particles with morphology similar to the poxvirus, some enveloped in a brick-shaped and irregular disposition of tubules on the external membrane, measuring 300x240 nm on the average were visualized. Ultra thin sections revealed the presence of intracytoplasmic inclusion bodies surrounded by membrane containing oval particles, measuring 270 x 130 nm, containing nucleus or an internal biconcave (dumbbell-shaped) core. Immature particles (empty), surrounded by membrane were also observed. In addition, intracytoplasmic electron dense inclusion bodies containing viral particles budding of dense amorphous material and intranuclear fibrillar or "digital" inclusions showing a regular striation and arranged in groups were found in the middle of granular material. The nuclei were deformed with densely condensed chromatin forming amorphous and electron dense inclusion bodies. In the immunocytochemistry technique, the antigen-antibody reaction was strongly marked by the particles of colloidal gold, emphasizing the viral particles. The techniques used in this study were important in the diagnosis of the affected animals.

La mixomatosis es una enfermedad contagiosa de distribución mundial, causada por poxvirus que infecta conejos domésticos y salvajes. En este estudio presentamos dos distintos surtos por mixomatosis que ocurrieron en producciones de conejos, una para fines comerciales de producción de carne y pieles y otra para el comercio de conejos domésticos. Las señales observadas fueron afecciones oculares, nasales, testiculares y, a veces, también distribuida por todo el cuerpo de los animales. Estas se caracterizaban por formación de nódulos que a la palpación tenían un aspecto gelatinoso o gomoso. En la microscopía electrónica de transmisión, por la técnica de contrastación negativa, se pudo observar en todas las muestras examinadas de piel y de costras, un gran número de partículas típicas de poxvirus, con envoltura y forma de ladrillo, mostrando disposición irregular de los túbulos sobre la membrana externa, midiendo 300 x 240 nm en el promedio. Cortes ultrafinos de fragmentos de piel y de costras revelaron la presencia de cuerpos de inclusión intracitoplasmáticas, envueltos por membrana y conteniendo partículas ovales, midiendo 270 x 130 nm, conteniendo núcleo o centro interno bicóncavo (forma de mancuernas). Partículas inmaduras (vacías) envueltas por membrana fueron observadas. También fueron analizados cuerpos de inclusión intracitoplasmáticos, electrodensos, conteniendo partículas virales brotando del material denso y amorfo. Fueron observadas inclusiones intranucleares fibrilares o "digitales" mostrando una estriación periódica y disposición en grupos en medio del material granular. Los núcleos estaban deformados con cromatina densamente condensada formando cuerpos de inclusiones electrodensas y amorfas. En la técnica de imunocitoquímica la reacción antígeno-anticuerpo fue intensamente marcada por las partículas de oro coloidal realzando fuertemente las partículas virales.

Achados clínicos e anatomopatológicos em um surto de mixomatose no Rio de Janeiro (relato de caso) / Clinical and anatomopatological findings in a mixomatosis outbreak in Rio de Janeiro (case report)

Relata-se, um surto de Mixomatose atingindo um criatório de coelhos (Oryctolagus cuniculus) no município de Maricá, RJ – Brasil, no ano de 2002, onde foram examinados e necropsiados seis animais. Clinicamente foram observados edema de face, orelhas, pálpebras e genitália externa; blefaro-conjuntivite purulenta, além de deformação naso-labial e presença de nódulos cutâneos principalmente no pavilhão auricular. À necropsia observou-se, além das alterações já encontradas no exame clínico, aumento dos linfonodos retrofaríngeos e submandibulares em dois animais e alterações pneumônicas e esplenomegalia em outros dois. Microscopicamente foram observadas alterações epididérmicas e, na derme, aspecto mixomatoso. Ainda foram observadas pneumonia intersticial com edema, e degeneração testicular.

Lessons in détente or know thy host: the immunomodulatory gene products of myxoma virus.

The poxvirus, myxoma virus, encodes within its genome at least eleven different proteins that compromise, skew, or disable the innate and adaptive responses of its hosts. In the laboratory rabbit, Oryctolagus cuniculus, these effects result in myxomatosis, a fatal condition characterized by skin lesions and systemic immunosuppression. Interestingly, while myxoma infection also causes skin lesions in its natural host and in natural populations of O. cuniculus in Australia where this novel host and the virus have co-evolved, the condition of myxomatosis does not ensue and infection is not fatal. In this review I discuss the biochemical properties of the characterized immunomodulatory proteins of myxoma virus, and their pathogenic effects in laboratory rabbits. Disruption of any one myxoma immunomodulatory gene diminishes the severity of the infection without compromising infectivity. Thus, the characterized immunomodulatory genes appear not to be required for a productive infection in vivo. The differences in the severity of their effects in laboratory-bred versus wild O. cuniculus suggest that the outcome of myxoma infection is a consequence of the interplay between the viral immunomodulatory gene products and the cells and molecules of the host immune system.

Infecciones virales en huéspedes comprometidos: II Parte. Virus ARN / Viral infections in compromissed host: II Part. ARN viruses

En este artículo: 1) se presenta al virus de la inmunodeficiencia humana causante del síndrome de inmunodeficiencia adquirida, SIDA, y las drogas antivirales e inmunomoduladoras que están en estudio o aprobadas para su tratamiento y el de las infecciones virales oportunistas que afectan a este tipo de pacientes; y 2) se revisan otros virus cuyo genoma es ARN y que infectan a huéspedes comprometidos, señalándose las medidas preventivas y terapéuticas susceptibles de ser aplicadas en ellos