Assessment of vaccine-induced CD4 T cell responses to the 119-143 immunodominant region of the tumor-specific antigen NY-ESO-1 using DRB1*0101 tetramers.

Abstract: Purpose: NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group, is presently viewed as an important model antigen for the development of generic anticancer vaccines. The ESO119-143 region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we generated DRB1*0101/ESO119-143 tetramers and used them to assess CD4 T-cell responses in vaccinated patients expressing DRB1*0101 (DR1). Experimental Design: We generated tetramers of DRB1*0101 incorporating peptide ESO119-143 using a previously described strategy. We assessed ESO119-143-specific CD4 T cells in peptide-stimulated post-vaccine cultures using the tetramers. We isolated DR1/ESO119-143 tetramer(+) cells by cell sorting and characterized them functionally. We assessed vaccine-induced CD4(+) DR1/ESO119-143 tetramer(+) T cells ex vivo and characterized them phenotypically. Results: Staining of cultures from vaccinated patients with DR1/ESO119-143 tetramers identified vaccine-induced CD4 T cells. Tetramer(+) cells isolated by cell sorting were of T(H)1 type and efficiently recognized full-length ESO. We identified ESO123-137 as the minimal optimal epitope recognized by DR1-restricted ESO-specific CD4 T cells. By assessing DR1/ESO119-143 tetramer(+) cells using T cell receptor (TCR) beta chain variable region (V beta)-specific antibodies, we identified several frequently used V beta. Finally, direct ex vivo staining of patients' CD4 T cells with tetramers allowed the direct quantification and phenotyping of vaccine-induced ESO-specific CD4 T cells. Conclusions: The development of DR1/ESO119-143 tetramers, allowing the direct visualization, isolation, and characterization of ESO-specific CD4 T cells, will be instrumental for the evaluation of spontaneous and vaccine-induced immune responses to this important tumor antigen in DR1-expressing patients

Iowa Insurance Division Report to the Governor for Year End 2001

Iowa Insurance Division Report to the Governor for Year End 2001

Iowa Insurance Division Report to the Governor for Year End 2002

Iowa Insurance Division Report to the Governor for Year End 2003

Iowa Insurance Division Report to the Governor for Year End 2003

Iowa Insurance Division Report to the Governor for Year End 2003

Iowa Insurance Division Report to the Governor for Year End 2004

Iowa Insurance Division Report to the Governor for Year End 2004

Iowa Insurance Division Report to the Governor for Year End 2005

Iowa Insurance Division Report to the Governor for Year End 2005

Iowa Insurance Division Report to the Governor for Year End 2006

Iowa Insurance Division Report to the Governor for Year End 2006

Iowa Insurance Division Report to the Governor for Year End 2007

Iowa Insurance Division Report to the Governor for Year End 2007

Iowa Insurance Division Report to the Governor for Year End 2008

Iowa Insurance Division Report to the Governor for Year End 2008

The ATP-binding cassette transporter-encoding gene CgSNQ2 is contributing to the CgPDR1-dependent azole resistance of Candida glabrata.

Our previous investigation on Candida glabrata azole-resistant isolates identified two isolates with unaltered expression of CgCDR1/CgCDR2, but with upregulation of another ATP-binding cassette transporter, CgSNQ2, which is a gene highly similar to ScSNQ2 from Saccharomyces cerevisiae. One of the two isolates (BPY55) was used here to elucidate this phenomenon. Disruption of CgSNQ2 in BPY55 decreased azole resistance, whereas reintroduction of the gene in a CgSNQ2 deletion mutant fully reversed this effect. Expression of CgSNQ2 in a S. cerevisiae strain lacking PDR5 mediated not only resistance to azoles but also to 4-nitroquinoline N-oxide, which is a ScSNQ2-specific substrate. A putative gain-of-function mutation, P822L, was identified in CgPDR1 from BPY55. Disruption of CgPDR1 in BPY55 conferred enhanced azole susceptibility and eliminated CgSNQ2 expression, whereas introduction of the mutated allele in a susceptible strain where CgPDR1 had been disrupted conferred azole resistance and CgSNQ2 upregulation, indicating that CgSNQ2 was controlled by CgPDR1. Finally, CgSNQ2 was shown to be involved in the in vivo response to fluconazole. Together, our data first demonstrate that CgSNQ2 contributes to the development of CgPDR1-dependent azole resistance in C. glabrata. The overlapping in function and regulation between CgSNQ2 and ScSNQ2 further highlight the relationship between S. cerevisiae and C. glabrata.

A Preclinical Model for ERα-Positive Breast Cancer Points to the Epithelial Microenvironment as Determinant of Luminal Phenotype and Hormone Response.

Seventy-five percent of breast cancers are estrogen receptor α positive (ER(+)). Research on these tumors is hampered by lack of adequate in vivo models; cell line xenografts require non-physiological hormone supplements, and patient-derived xenografts (PDXs) are hard to establish. We show that the traditional grafting of ER(+) tumor cells into mammary fat pads induces TGFβ/SLUG signaling and basal differentiation when they require low SLUG levels to grow in vivo. Grafting into the milk ducts suppresses SLUG; ER(+) tumor cells develop, like their clinical counterparts, in the presence of physiological hormone levels. Intraductal ER(+) PDXs are retransplantable, predictive, and appear genomically stable. The model provides opportunities for translational research and the study of physiologically relevant hormone action in breast carcinogenesis.

Carotenoids are related to the colour and lipid content of the pequi (Caryocar brasiliense Camb.) pulp from the Brazilian Savanna

This study investigated the colour, proximate composition, bioactive compounds (phenolic and carotenoid contents), and antioxidant activity of the pulp of pequi from different regions of the Brazilian Savanna. The colour parameters and the lipid and carotenoid contents of the pulp were significantly different between the samples. The lipid content ranged from 135.4 to 322.5 g/kg. The pequi pulp showed high total phenolic content (1.8 to 3.3 mg GAE/g). The carotenoid amount ranged from 37 to 187 µg/g. The carotenoid content was significantly correlated with the colour and lipid content of the pequi pulp. The antioxidant activity showed a mean IC50 value of 197.9 µg/mL. The pequi pulp is rich in phenolic compounds and carotenoids and has a good antioxidant activity. Its colour is influenced by the carotenoid content, which can be predicted by regression models using routine colour parameters.

An appeal to the people ; being a review of the late correspondence and documents, relating to the rejection of the British Minister : including an examination of the "arrangement" of April last /

Introduction "To the people of the United States" signed Wm. Coleman.