CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer.

Cancer-associated fibroblasts (CAFs) are abundantly present in the microenvironment of virtually all tumors and strongly impact tumor progression. Despite increasing insight into their function and heterogeneity, little is known regarding the origin of CAFs. Understanding the origin of CAF heterogeneity is needed to develop successful CAF-based targeted therapies.

A gain and dynamic range independent index to quantify spillover spread to aid panel design in flow cytometry.

In conventional flowcytometry one detector (primary) is dedicated for one fluorochrome. However, photons usually end up in other detectors too (fluorescence spillover). 'Compensation' is a process that corrects the spillover signal from all detectors except the primary detector.

Tumor-initiating cells are not enriched in cisplatin-surviving BRCA1;p53-deficient mammary tumor cells in vivo.

Although many breast cancers respond to chemotherapy or hormonal therapy, lack of tumor eradication is a central clinical problem preceding the development of drug resistant tumors. Using the K14cre;Brca1(F5-13/F5-13);p53(F2-10/F2-10) mouse model for hereditary breast cancer, we have previously studied responses of mammary tumors to clinically relevant anti-cancer drugs, including cisplatin. The BRCA1- and p53-deficient tumors generated in this model are hypersensitive to cisplatin and never become resistant to this agent due to the large, irreversible deletion in Brca1.

Systemic treatment with either cyclosporin A or methotrexate does not influence the T helper 1/T helper 2 balance in psoriatic patients.

Cyclosporin A and methotrexate are highly effective drugs in the treatment of psoriasis. It was hypothesized that these therapies might modulate T helper cell cytokine secretion patterns or T cell migration patterns. Flow cytometric determination of interferon-gamma (IFNgamma) and interleukin 4 (IL4) producing T helper cell frequencies, as well as of cutaneous lymphocyte associated antigen (CLA) expressing T cell frequencies was performed in patients suffering from severe psoriasis, before, during, and after a scheduled immunosuppressive regimen with either cyclosporin A or methotrexate.

Immune responsiveness in renal transplant recipients: mycophenolic acid severely depresses humoral immunity in vivo.

Background: Current immunosuppressive drug treatments for renal transplant recipients result in high one-year graft survival rates. Despite adequate suppression of the immune response directed to the allograft, the immune system remains able to cope with many infectious agents.

Methods: To define the influence of distinct immunosuppressive treatment protocols, primary and secondary cellular and humoral immune responses in groups of renal transplant recipients were studied: patient treated with prednisolone and cyclosporine A (P/CsA); with IgA CD3 monoclonal antibody as a rejection treatment superimposed on prednisolone and cyclosporine A (IgA CD3 mAb+P/CsA); and with prednisolone, cyclosporine A and mycophenolate mofetil (P/CsA/MMF).

Differentiation of human alloreactive CD8(+) T cells in vitro.

Expansion and differentiation of alloantigen-reactive CD8(+) T cells in mixed lymphocyte cultures was followed by measurement of the loss of carboxyfluorescein diacetate succinimidyl ester (CFSE) fluorescence of responder cells. Proliferation of CD8(+) T cells became detectable on day 4 of culture and, 2 days later, > 60% of the CD8(+) T cells in culture were dividing alloreactive lymphocytes. In parallel with expansion, CD8(+) T-cell differentiation was initiated, as evidenced by an increase in the number of CD45RA(-) and CD27(-) T cells and acquisition of the ability to produce interferon-gamma after restimulation with the specific alloantigen.