Science News, Information and Educational Resources


Science Feed Image

    		•    

    Expression and regulation of B7-H3 immunoregulatory receptor, in human mesothelial and mesothelioma cells: Immunotherapeutic implications.

    J Cell Physiol. 2011 Oct;226(10):2595-600

    Authors: Calabrò L, Sigalotti L, Fonsatti E, Bertocci E, Di Giacomo AM, Danielli R, Cutaia O, Colizzi F, Covre A, Mutti L, Natali PG, Maio M

    No treatment prolongs the survival of malignant mesothelioma (MM) patients. Since MM elicits anti-tumor host's immune responses, immunotherapy represents a promising strategy for its control. Immunomodulatory antibodies against components of the B7 family of immunomodulatory molecules that regulate T cell activation are being investigated in human malignancies including MM. The expression of B7-H3, a new component of the B7 family was investigated in primary cultures of human mesothelial cells (HMC) and in MM cell lines by flow cytometry and molecular analyses, and in MM tissues by immunohistochemistry. The role of DNA hypomethylating agents in modulating levels of B7-H3 expression in MM cells was also studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that B7-H3 mRNA was consistently detectable in mesothelial and MM cells investigated; however, real-time quantitative RT-PCR analyses showed highly heterogeneous levels of B7-H3 mRNA among investigated MM cells. The analysis of B7-H3 protein expression indicated that comparable levels of B7-H3 were expressed on both cell types. Treatment with the DNA hypomethylating agent 5-aza-2'-deoxycytidine did not significantly affect the expression of B7-H3 mRNA in MM cells. In vivo, while B7-H3 was expressed in all 13 tumor biopsies of the epithelial variant, with high levels in 54% of cases, it was rarely detectable in spindle type MM in which 1/5 biopsies weakly expressed B7-H3. These findings suggest that B7-H3 is a promising target for new immunotherapeutic strategies in MM, with particular emphasis in the epithelial variant. J. Cell. Physiol. 226: 2595-2600, 2011. © 2010 Wiley-Liss, Inc.

    PMID: 21792917 [PubMed - in process]

    www.ncbi.nlm.nih.gov


      ...Read On

    Autologous peripheral blood progenitor cell (PBPC) transplantation is the treatment of choice for selected myeloma patients. However, tumor cells contaminating the apheresis product are a potential source of relapse. Here we report a sequential purging strategy targeting mature and immature clonogenic myeloma cell populations in the autograft. Thawed PBPC products of myeloma patients were treated with rituximab to kill CD138?20+ B cells (highly clonogenic immature cells), and bortezomib to target CD138+ cells (normal and differentiated myeloma plasma cells), followed by coculture with allogeneic mesenchymal stem cells (MSC) from normal donors. After 7 days of coculture, nonadherent cells were removed and cultured in the absence of MSC for an additional 7 days. Then, efficacy of purging (removal of CD138?20+ and CD138+ cells) was assessed by flow cytometry and PCR. We used our ex vivo purging strategy to treat frozen aphereses from 16 patients. CD138+ and CD138?20+(19+) cells present in the initial products were depleted more than 3 and 4 logs, respectively based on 106 flow-acquisition events, and to levels below the limit of detection by PCR. In contrast, total nucleated cell (TNC), CD34+ cell, and colony-forming cell numbers were increased by approximately 12 to 20, 8-, and 23-fold, respectively. Overall, ex vivo treatment of apheresis products with rituximab, bortezomib, and coculture with normal donor MSC depleted mature and immature myeloma cells from clinical aphereses while expanding the normal hematopoietic progenitor cell compartment. Cancer Res; 71(14); 5040–9. ©2011 AACR. cancerres.aacrjournals.org


      ...Read On

    Cell Biologist, Temporary. We are currently looking for a scientist to join this Biopharma Unit in Cambridge. In this role you will assist with characterisation of the binding properties and biological activity of domain antibodies and recombinant proteins to support early stage drug discovery programmes. Essential for this role is your practical experience in cell culture, assay development and optimisation of fluorescence based techniques such as Flow Cytometry, confocal microscopy and FRET. Ability to implement and run siRNA knockdown protocols is essential. You should be highly motivated and have a proven ability to handle multiple projects working both within a team and independently. Your experience of biological assay techniqueswill be complemented with a desire to develop, trouble shoot and validate protocols. For this role you must have a life science degree, PhD (or equivalent) and research experience in the field of cell biology and an understanding of molecular biology would be advantageous. This is a temporary position until December 2011. CK Science is an Equal Opportunities employer and welcomes applications from all who meet our selection criteria. If you do not hear back from us within 5 working^days of your application for this role, it means that on this occasion you have not been shortlisted for the next stage of the recruitment campaign. Entitlement to work in the EEA is essential. Please quote reference ST22426 in all correspondence. Key words: Cell Biology, Molecular Biology, Assay Development, Biotechnology, Pharmaceutical jobs.
    ckscience.co.uk   ...Read On

    Cell Based Assay Scientist - Based along the M4 Corridor, our client is a leading global provider of contract dosage form development and manufacturing services to the pharmaceutical and biotechnology industries. They are currently looking for aCell Based Assay Scientist with experience in mammalian cell culture techniques, including cell growth, the production, storage and maintenance of master and working cell banks. Experience in cell based assays, such as those measuring inhibition of cell proliferation, cell death, changes in cell morphology is essential Experience of the validation of cell based assays is strongly preferred and experience of ELISAs, flow cytometry, fluorescence and luminescence assays are also essential. Experience in performing other bio-analytical techniques for example SDS-PAGE, IEX would be advantages as would any experience of working in a tissue culture laboratory in a GMP environment. CK Science is an Equal Opportunities employer and welcomes applications from all who meet our selection criteria. If you do not hear back from us within 5 working days of your application for this role, it means that on this occasion you have not been shortlisted for the next stage of the recruitment campaign. Entitlement to work in the EEA is essential. Please quote reference ST22382 in all correspondence. Keywords: Cell, Assay, ELISA, SDS, flow cytometry, Mammalian, cell culture
    ckscience.co.uk   ...Read On

    Autologous peripheral blood progenitor cell (PBPC) transplantation is the treatment of choice for selected myeloma patients. However, tumor cells contaminating the apheresis product are a potential source of relapse. Here we report a sequential purging strategy targeting mature and immature clonogenic myeloma cell populations in the autograft. Thawed PBPC products of myeloma patients were treated with rituximab to kill CD138?20+ B cells (highly clonogenic immature cells), and bortezomib to target CD138+ cells (normal and differentiated myeloma plasma cells), followed by coculture with allogeneic mesenchymal stem cells (MSC) from normal donors. After 7 days of coculture, nonadherent cells were removed and cultured in the absence of MSC for an additional 7 days. Then, efficacy of purging (removal of CD138?20+ and CD138+ cells) was assessed by flow cytometry and PCR. We used our ex vivo purging strategy to treat frozen aphereses from 16 patients. CD138+ and CD138?20+(19+) cells present in the initial products were depleted more than 3 and 4 logs, respectively based on 106 flow-acquisition events, and to levels below the limit of detection by PCR. In contrast, total nucleated cell (TNC), CD34+ cell, and colony-forming cell numbers were increased by approximately 12 to 20, 8-, and 23-fold, respectively. Overall, ex vivo treatment of apheresis products with rituximab, bortezomib, and coculture with normal donor MSC depleted mature and immature myeloma cells from clinical aphereses while expanding the normal hematopoietic progenitor cell compartment. Cancer Res; 71(14); 5040–9. ©2011 AACR.
    cancerres.aacrjournals.org   ...Read On


    		   
    You can link to this article on your web site using following code:

    Website Code:

    Forum Code:  




     
    		 
    Comments

    We're looking for comments that are interesting, substantial or highly amusing. If your comments are excessively self-promotional (use your real name, no keywords please), obnoxious, or even worse, boring, you will be banned from commenting. Your comment must be related to the post. Please do not comment on how great or wonderful the post is. All comments are moderated and, if approved, will display in less than 24 hours.


    blog comments powered by Disqus