Detection of Epstein-Barr virus (EBV) in human lymphoma tissue by a novel microbial detection array.

Background: Infectious agents are estimated to play a causative role in approximately 20% of cancers worldwide. Viruses, notably the Epstein-Barr virus (EBV), are associated with 10-15% of B-cell lymphomas and are found at a higher frequency in immunosuppressed patients. In this study, we screened human lymphoma tissues using a novel Lawrence Livermore Microbial Detection Array (LLMDA), a comprehensive detection system that contains probes for all sequenced viruses and bacteria.

Therapeutic benefit of bortezomib on acute graft-versus-host disease is tissue specific and is associated with interleukin-6 levels.

Bortezomib, a proteasome inhibitor capable of direct antitumor effects, has been shown to prevent acute graft-versus-host disease (GVHD) when administered in a short course immediately after bone marrow transplantation (BMT) in mice. However, when bortezomib is given continuously, CD4(+) T cell-mediated gastrointestinal tract damage increases GVHD mortality. To investigate the protective effects of bortezomib on other organs, we used a CD8-dependent acute GVHD (aGVHD) model of C3H.

Treatment of chronic graft-versus-host disease with bortezomib.

Chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT) has emerged as a predominant complication following HSCT and has a distinct etiology. We and others have previously demonstrated that bortezomib, a proteasome inhibitor, can prevent but not treat acute GVHD in mice. To assess the effects of bortezomib on cGVHD, a mouse minor histocompatibility antigen-mismatched strain combination was used to mimic clinical cGVHD sclerodermatous pathogenesis and phenotype.

Characterization of naturally-occurring humoral immunity to AAV in sheep.

AAV vectors have shown great promise for clinical gene therapy (GT), but pre-existing human immunity against the AAV capsid often limits transduction. Thus, testing promising AAV-based GT approaches in an animal model with similar pre-existing immunity could better predict clinical outcome. Sheep have long been used for basic biological and preclinical studies.

Expression levels of the PiT-2 receptor explain, in part, the gestational age-dependent alterations in transduction efficiency after in utero retroviral-mediated gene transfer.

Background: A fundamental obstacle to using retroviral-mediated gene transfer (GT) to treat human diseases is the relatively low transduction levels that have been achieved in clinically relevant human cells. We previously showed that performing GT in utero overcomes this obstacle and results in significant levels of transduction within multiple fetal organs, with different tissues exhibiting optimal transduction at different developmental stages. We undertook the present study aiming to elucidate the mechanism for this age-dependent transduction, testing the two factors that we hypothesized could be responsible: (i) the proliferative status of the tissue at the time of GT and (ii) the expression level of the amphotropic PiT-2 receptor.

Breast carcinomatous tumoral emboli can result from encircling lymphovasculogenesis rather than lymphovascular invasion.

The canonical view of the origin of tumor lymphovascular emboli is that they usually originate from lymphovascular invasion as part of a multistep metastatic process. Recent experimental evidence has suggested that metastasis can occur earlier than previously thought and we found evidence that tumor emboli formation can result from the short-circuiting step of encircling lymphovasculogenesis. Experimentally, we used a xenograft of human inflammatory breast cancer (MARY-X), a model that exhibited florid tumor emboli, to generate tumoral spheroids in vitro.

E-cadherin accumulation within the lymphovascular embolus of inflammatory breast cancer is due to altered trafficking.

E-Cadherin functions as a tumor suppressor in some invasive breast carcinomas and metastasis is promoted when its expression is lost. It has been observed, however, that in one of the most aggressive human breast cancers, inflammatory breast cancer (IBC), E-cadherin is overexpressed and this accounts for the formation of the lymphovascular embolus, a structure efficient at metastasis and resistant to chemotherapy through unknown cytoprotective mechanisms. Studies using a human xenograft model of IBC, MARY-X, indicate that the mechanism of E-cadherin overexpression is not transcriptional but related to altered protein trafficking.