The monoclonal antibody nBT062 conjugated to maytansinoids has potent and selective cytotoxicity against CD138 positive multiple myeloma cells _in vitro_ and _in vivo_

CD138 (Syndecan1) is highly expressed on multiple myeloma (MM) cells. In this study, we examined the anti-MM effect of murine/human chimeric CD138-specific monoclonal antibody (mAb) nBT062 conjugated with highly cytotoxic maytansinoid derivatives _in vitro_ and _in vivo_. These agents significantly inhibited growth of CD138-positive MM cell lines and primary tumor cells from MM patients, without cytotoxicity against peripheral blood mononuclear cells from healthy volunteers. In MM cells, they induced G2/M cell cycle arrest followed by apoptosis associated with cleavage of PARP and caspase-3, -8 and -9. Non-conjugated nBT062 completely blocked cytotoxicity induced by nBT062-maytansinoid conjugate, confirming that binding is required for inducing cytotoxicity. Moreover, nBT062-maytansinoid conjugates blocked adhesion of MM cells to bone marrow stromal cells (BMSCs). Co-culture of MM cells with BMSCs, which protects against dexamethasone-induced death, had no impact on the cytotoxicity of the immunoconjugates. Importantly, nBT062-SPDB-DM4 and nBT062-SPP-DM1 significantly inhibited MM tumor growth _in vivo_ in both human multiple myeloma xenograft mouse models and in SCID-human bone grafts (SCID-hu mouse model). These studies provide the preclinical framework supporting evaluation of nBT062-maytansinoid derivatives in clinical trials to improve patient outcome in MM

Effective generation of transgenic pigs and mice by linker based sperm-mediated gene transfer.

BACKGROUND: Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves the production efficiency of large transgenic animals. RESULTS: The linker protein, a monoclonal antibody (mAb C), is reactive to a surface antigen on sperm of all tested species including pig, mouse, chicken, cow, goat, sheep, and human. mAb C is a basic protein that binds to DNA through ionic interaction allowing exogenous DNA to be linked specifically to sperm. After fertilization of the egg, the DNA is shown to be successfully integrated into the genome of viable pig and mouse offspring with germ-line transfer to the F1 generation at a highly efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated again by FISH analysis and F2 transmission in pigs. Furthermore, expression of the transgene is demonstrated in 61% (35/57) of transgenic pigs (F0 generation). CONCLUSIONS: Our data suggests that LB-SMGT could be used to generate transgenic animals efficiently in many different species

NK cells and cancer: you can teach innate cells new tricks

Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide host defence against microbial infection and tumours. Here, we review evidence for the role of NK cells in immune surveillance against cancer and highlight new therapeutic approaches for targeting NK cells in the treatment of cancer

Critical Anthropologies in / of Central Europe

Cargo is a peer-reviewed journal published by the Czech Association for Social Anthropology (CASA). Cargo focuses on theory-and-practice of ethnographic research, critical discussion of anthropological theory, and on ethical issues of producing anthropological knowledge. Th e journal publishes academic articles, interviews with key scholars in anthropology, and texts debating methods of teaching anthropology. Cargo seeks to present materials that are innovative, challenging, and sometimes experimental. As a journal publishing texts in Czech, Slovak, and English, Cargo aims to reach scholars whose fi eldwork and topics are close to geographical area of Central and East Europ

Critical Anthropologies in / of Central Europe

Cargo is a peer-reviewed journal published by the Czech Association for Social Anthropology (CASA). Cargo focuses on theory-and-practice of ethnographic research, critical discussion of anthropological theory, and on ethical issues of producing anthropological knowledge. Th e journal publishes academic articles, interviews with key scholars in anthropology, and texts debating methods of teaching anthropology. Cargo seeks to present materials that are innovative, challenging, and sometimes experimental. As a journal publishing texts in Czech, Slovak, and English, Cargo aims to reach scholars whose fi eldwork and topics are close to geographical area of Central and East Europ

Critical Anthropologies in / of Central Europe

Cargo is a peer-reviewed journal published by the Czech Association for Social Anthropology (CASA). Cargo focuses on theory-and-practice of ethnographic research, critical discussion of anthropological theory, and on ethical issues of producing anthropological knowledge. Th e journal publishes academic articles, interviews with key scholars in anthropology, and texts debating methods of teaching anthropology. Cargo seeks to present materials that are innovative, challenging, and sometimes experimental. As a journal publishing texts in Czech, Slovak, and English, Cargo aims to reach scholars whose fi eldwork and topics are close to geographical area of Central and East Europ

Epidemiología de la difilobotriasis en la cuenca del río Valdivia, Chile

Entre los meses de marzo y octubre de 1987 fueron examinados 1295 personas de seis distritos ribereños de la cuenca del río Valdivia, determinándose un 1,2% de prevalencia de infección por Diphyllobothrium en los distritos de Riñihue y Las Huellas. Además, se comprobó un 5,3% y un 9,8% de prevalencia en perros de los distritos de Riñihue y Malihue, respectivamente, pero no se observó infección en gatos y cerdos. Los parásitos recuperados después del tratamiento fueron identificados como Diphyllobothrium latum. La infección humana por D. latum en los distritos afectados se favorece por el consumo de peces ahumados o sometidos a cocción insuficiente. La investigación de 1450 peces (4 especies introducidas y 11 autóctonas) capturados entre 1986-1987 en la cuenca del río Valdivia, demostró la existencia de plerocercoides de D. latum y/o Diphyllobothrium dendriticum en Salmo gairdneri y Salmo trutta, entre los peces introducidos, y en algunas especies autóctonas. La prevalencia e intensidad media en las infecciones de los peces así como el grado de agregación de las infrapoblaciones varía en los distintos sectores. Algunas especies de peces actuarían como huésped intermediario y otras como huéspedes paraténicos de Diphyllobothrium spp. en la cuenca del río Valdivia. Como medidas de control para la difilobotriasis en los distritos afectados se propone un mejoramiento de las condiciones de saneamiento básico, educación sanitaria y tratamiento de las personas infectadas