The Endoplasmic Reticulum Chaperone GRP170: From Immunobiology to Cancer Therapeutics.

Glucose-regulated protein 170 (GRP170) is the largest member of glucose-regulated protein family that resides in the endoplasmic reticulum (ER). As a component of the ER chaperone network, GRP170 assists in protein folding, assembly, and transportation of secretory or transmembrane proteins. The well documented cytoprotective activity of intracellular GRP170 due to its intrinsic chaperoning property has been shown to provide a survival benefit in cancer cells during tumor progression or metastasis.

HLA-DO increases bacterial superantigen binding to human MHC molecules by inhibiting dissociation of class II-associated invariant chain peptides.

HLA-DO (H2-O in mice) is an intracellular non-classical MHC class II molecule (MHCII). It forms a stable complex with HLA-DM (H2-M in mice) and shapes the MHC class II-associated peptide repertoire. Here, we tested the impact of HLA-DO and H2-O on the binding of superantigens (SAgs), which has been shown previously to be sensitive to the structural nature of the class II-bound peptides.

Tollip-induced down-regulation of MARCH1.

In addition to their classical antigen presenting functions, MHC class II molecules potentiate the TLR-triggered production of pro-inflammatory cytokines. Here, we have addressed the effect of Tollip and MARCH1 on the regulation of MHC II trafficking and TLR signaling. Our results show that MARCH1-deficient mice splenocytes are impaired in their capacity to produce pro-inflammatory cytokines in response to poly(I:C) and that TLR3 and MHC II molecules interact in the endocytic pathway.

Forced expression of HLA-DM at the surface of dendritic cells increases loading of synthetic peptides on MHC class II molecules and modulates T cell responses.

Adoptive transfer of autologous dendritic cells (DCs) loaded with tumor-associated CD4 and CD8 T cell epitopes represents a promising avenue for the immunotherapy of cancer. In an effort to increase the loading of therapeutic synthetic peptides on MHC II molecules, we used a mutant of HLA-DM (DMY) devoid of its lysosomal sorting motif and that accumulates at the cell surface. Transfection of DMY into HLA-DR(+) cells resulted in increased loading of the exogenously supplied HA(307-318) peptide, as well as increased stimulation of HA-specific T cells.

CD1a and CD1d genes polymorphisms in breast, colorectal and lung cancers.

CD1 molecules might contribute to anti-tumor immune response by presentation of tumor-derived lipid and glycolipid antigens to T cells and NKT cells. Polymorphisms in CD1 genes have been suggested to modify ligand binding of CD1 molecules and thereby change the antigen presenting ability of these molecules. The aim of this study was to investigate the exon 2 polymorphisms of CD1a and CD1d in several high incident cancers in Iran.

Evidence for a human leucocyte antigen-DM-induced structural change in human leucocyte antigen-DObeta.

Human leucocyte antigen (HLA)-DO is a non-classical major histocompatibility complex class II molecule which modulates the function of HLA-DM and the loading of antigenic peptides on molecules such as HLA-DR. The bulk of HLA-DO associates with HLA-DM and this interaction is critical for HLA-DO egress from the endoplasmic reticulum. HLA-DM assists the early steps of HLA-DO maturation presumably through the stabilization of the interactions between the N-terminal regions of the alpha and beta chains.

Frequency of cystathionine beta-synthase 844INS68 polymorphism in Southern Iran.

Iranian population with an Indo-European origin is one of the oldest populations in the world. Historical evidence suggests the close similarity in the origin of Iranian, European and north Indian population. However, there are few anthropological and genetic evidences on this subject.

Establishment and characterization of a human large cell lung cancer cell line with neuroendocrine differentiation.

Characterization of a human lung cancer cell line is reported. This cell line was established from a patient referred to Nemazi Hospital of Shiraz University of Medical Sciences with a diagnosis of poorly differentiated carcinoma. Sterile sample from peritoneal effusion was taken and immediately cultured in RPMI-1640 medium containing 20% FBS, at 37 degrees C with 5% CO2.

The frequency of CCR5Delta32 and CCR2-64I in southern Iranian normal population.

Host genetic control of HIV infection involves certain polymorphisms of some chemokine receptor genes that are associated with susceptibility and progression of HIV-1 infection. Recent data suggest that two important polymorphisms in CCR2 and CCR5 chemokine receptors, CCR5Delta32 and CCR2-64I, prevent HIV transmission and delay disease progression. In this study allele and haplotype frequencies of the CCR5Delta32 and CCR2-64I mutations were determined in southern Iranian normal population using PCR and PCR restriction fragment length polymorphism (PCR-RFLP) assays.

The promoter region (-800, -509) polymorphisms of transforming growth factor-beta1 (TGF-beta1) gene and recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is regarded as a common pregnancy complication in southern Iran. The exact causes of RSA are not yet known. Transforming growth factor-beta1 (TGF-beta1) is produced by T regulatory lymphocytes (Treg), which play an important role in the physiology of pregnancy.

Cytotoxic T lymphocyte antigen-4 gene in breast cancer.

The exon 1 polymorphism (49A/G) of ctla-4 gene corresponds to an amino acid exchange (threonine to alanine) in the leader peptide of the expressed protein. There are reports concerning the higher level of G allele in subjects with various autoimmune diseases, which has resulted in the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders. This study was undertaken to investigate the correlation of exon 1 (49A/G) polymorphism in the ctla-4 gene and breast cancer.

The expression of p53, c-erbB-1 and c-erbB-2 molecules and their correlation with prognostic markers in patients with head and neck tumors.

Molecular prognostic and predictive factors have extensively been studied in different cancers during the past decades, some of which were found to be useful in diagnosis, follow up or even treatment of some malignant tumors. To assess the significance of c-erbB-1, c-erbB-2 and p53 expression in head and neck tumors among Iranian patients and their correlation with known prognostic factors, samples from 53 patients with squamous cell carcinomas of larynx and tongue were studied immunohistochemically. Strong immunoreactivity of c-erbB-1, c-erbB-2 and p53 was observed in 37 (70%), 40 (76%) and 37 (70%) of cases, respectively.