Search results for "complex"
showing 10 items of 5889 documents
Naturally processed and HLA-B8-presented HPV16 E7 epitope recognized by T cells from patients with cervical cancer.
2004
Several major histocompatibility complex (MHC) alleles have been reported to present peptides derived from the HPV16 E7 oncoprotein to T cells. We describe an overrepresentation of the HLA-B8 allele (28.44%) in cervical cancer patients as compared to the MHC class I allele frequency in a local healthy control population (18.80%) and the identification of an HLA-B8-binding peptide TLHEYMLDL (HPV16 E77–15), which is able to drive HPV16 E7-specific and MHC class I-restricted T-cell responses in peripheral blood lymphocytes from healthy individuals. TLHEYMLDLspecific T cells recognize the naturally processed and presented peptide on HPV16 cervical cancer cells transfected with the HLA-B8 gene d…
Desferrioxamine as an appropriate chelator for 90Nb: Comparison of its complexation properties for M-Df-Octreotide (M=Nb, Fe, Ga, Zr)
2014
The niobium-90 radioisotope ((90)Nb) holds considerable promise for use in immuno-PET, due to its decay parameters (t½ = 14.6h, positron yield=53%, Eß(+)(mean) = 0.35 MeV and Eß(+)(max) = 1.5 MeV). In particular, (90)Nb appears well suited to detect in vivo the pharmacokinetics of large targeting vectors (50-150 kDa). In order to be useful for immuno-PET chelators are required to both stabilize the radionuclide in terms of coordination chemistry and to facilitate the covalent attachment to the targeting vector. Different chelators were evaluated for this purpose in terms of radiolabelling efficiency and stability of the radiolabelled Nb(V) complex and in order to determine the most suitable…
T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
2021
Abstract Purpose: Gliomas are intrinsic brain tumors with a high degree of constitutive and acquired resistance to standard therapeutic modalities such as radiotherapy and alkylating chemotherapy. Glioma subtypes are recognized by characteristic mutations. Some of these characteristic mutations have shown to generate immunogenic neoepitopes suitable for targeted immunotherapy. Experimental Design: Using peptide-based ELISpot assays, we screened for potential recurrent glioma neoepitopes in MHC-humanized mice. Following vaccination, droplet-based single-cell T-cell receptor (TCR) sequencing from established T-cell lines was applied for neoepitope-specific TCR discovery. Efficacy of intravent…
Long-term freedom from recurrence in 2 stage IV melanoma patients following vaccination with tyrosinase peptides.
2002
We report here on 2 patients who received adjuvant vaccination with an HLA-A2- or HLA-A24-restricted tyrosinase peptide, respectively, and GM-CSF for frequently relapsing stage IV melanoma. Following resection of metastases and irradiation of brain metastases in 1 patient, both patients were without evidence of disease when receiving the first vaccination. While the patients had had 9 and 12, respectively, mostly s.c., relapses during the 3 years before vaccination, they experienced freedom from relapse for more than 2 years after vaccination. We found a T-cell response to the vaccine peptide in both patients in the peripheral blood by ex vivo IFN-gamma ELISPOT assay. The T-cell population …
Bmi1 and Cell of Origin Determinants of Brain Tumor Phenotype
2007
Glioblastomas frequently express oncogenic EGFR and loss of the Ink4a/Arf locus. Bmi1, a positive regulator of stem cell self renewal, may be critical to drive brain tumor growth. In this issue of Cancer Cell, Bruggeman and colleagues suggest that brain tumors with these molecular alterations can be initiated in both neural precursor and differentiated cell compartments in the absence of Bmi1; however, tumorigenicity is reduced, and tumors contain fewer precursor cells. Surprisingly, tumors appear less malignant when initiated in precursor cells. Bmi1-deficient tumors also had fewer neuronal lineage cells, suggesting a role for Bmi1 in determination of cell lineage and tumor phenotype.
Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasi…
2013
Triple-negative breast cancers (TNBCs) are clinically aggressive forms associated with a poor prognosis. We evaluated the cytotoxic effect exerted on triple-negative MDA-MB231 breast cancer cells both by parthenolide and its soluble analogue dimethylamino parthenolide (DMAPT) and explored the underlying molecular mechanism. The drugs induced a dose- and time-dependent decrement in cell viability, which was not prevented by the caspase inhibitor z-VAD-fmk. In particular in the first hours of treatment (1–3 h), parthenolide and DMAPT strongly stimulated reactive oxygen species (ROS) generation. The drugs induced production of superoxide anion by activating NADPH oxidase. ROS generation caused…
Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases
2013
Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious tha…
A Review of Mathematical and Computational Methods in Cancer Dynamics.
2022
Cancers are complex adaptive diseases regulated by the nonlinear feedback systems between genetic instabilities, environmental signals, cellular protein flows, and gene regulatory networks. Understanding the cybernetics of cancer requires the integration of information dynamics across multidimensional spatiotemporal scales, including genetic, transcriptional, metabolic, proteomic, epigenetic, and multi-cellular networks. However, the time-series analysis of these complex networks remains vastly absent in cancer research. With longitudinal screening and time-series analysis of cellular dynamics, universally observed causal patterns pertaining to dynamical systems, may self-organize in the si…
Gp80 (clusterin; TRPM-2) mRNA level is enhanced in human renal clear cell carcinomas
1994
The gp80 glycoprotein complex (clusterin, apolipoprotein J, TRPM-2) is a widely expressed protein that has been attributed functions in tissue remodelling, immune defense and transport of lipids and biologically active peptides. The expression of the protein appears to be elevated in several neurodegenerative, apoptotic and malignant processes. We show here that in patients with renal clear cell carcinoma gp80 mRNA is 3-fold overexpressed in tissue of the tumors compared with adjacent non-tumor tissue.
Genome-Wide Haplotype Analysis of Cis Expression Quantitative Trait Loci in Monocytes
2013
In order to assess whether gene expression variability could be influenced by several SNPs acting in cis, either through additive or more complex haplotype effects, a systematic genome-wide search for cis haplotype expression quantitative trait loci (eQTL) was conducted in a sample of 758 individuals, part of the Cardiogenics Transcriptomic Study, for which genome-wide monocyte expression and GWAS data were available. 19,805 RNA probes were assessed for cis haplotypic regulation through investigation of ∼2,1×109 haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >104-fold smaller than the best single SNP p-value. Replication of significant haplotype effects were tested f…