Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CTLs specific for tumor antigens play a major role in immunity against cancer. Improved binding affinity of putative TAA peptides could enhance the in vivo immunogenicity of these self-altered self- tumor antigens. We examined here the efficacy of tumor vaccines composed of an altered peptide ligand of MUT-1, designated MUT-D, which exhibited significantly higher class-I allele K(b) binding affinity than its native counterpart MUT-1. The peptide was loaded on antigen presenting cells composed of the C57BL/6-syngeneic fibroblast cell line BLK.CL4. These cells were treated with proteasome inhibitor in order to shut off the degradation of proteins and the subsequent loading of endogenous peptides onto MHC class-I molecules, thus allowing for the pulsing of these cells with the modified peptide MUT-D. Proteasome-inhibited and modified peptide-loaded fibroblasts induced a peptide-specific CTL that significantly delayed primary tumor progression and protected the pre-immunized mice against the development of lung metastasis following the surgical removal of the primary tumor. Genetic modification of the fibroblasts to express the immunostimulatory cytokine IL-2 did not improve the APC function of the modified cells, nor did it result in augmentation of the potency of the vaccine. Our results suggest that the proteasome-inhibited fibroblasts pulsed with modified, high binder tumor-associated antigen peptide are good antigen-presenting cells and represent an effective form of tumor vaccine.
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PMID:Induction of antitumor immunity by proteasome-inhibited syngeneic fibroblasts pulsed with a modified TAA peptide. 1062 83

The expression of B7-1/2 molecules in addition to TAA in APC significantly improves the generation of specific CTL in vitro. Moreover, human fibroblasts, usually devoid of APC capacity, can be engineered into effective APC upon infection with recVV encoding costimulatory molecules together with specific epitopes. The generation of artificial APC by infection of non professional APC with appropriately engineered recVV is a new concept that may be useful in the implementation of immunotherapy strategies.
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PMID:[B7 costimulation molecules improve induction of tumor specific cytotoxic T-cells against MART-1(27-35)]. 1451 26

A 25-year-old female with familial adenomatous polyposis (FAP) presented with an abdominal tumor just below the scar due to a colectomy performed 15 months previously. This tumor (tumor A) measured 7 cm in diameter, was diagnosed as a desmoid tumor of the abdominal wall, and was excised. Despite the subsequent administration of sulindac (300 mg daily for 1 year), a desmoid tumor recurred at the same site. Excision was performed again when the tumor was 8 cm in diameter, and examination revealed it to consist of a large tumor (B) and a small tumor (C) that bulged out from tumor B. Germ-line APC analysis showed a C deletion at codon 1460 resulting in a stop codon. Two somatic mutations were observed in tumor A: a TCAA deletion at codon 1068 and a deletion of a codon at bp 1192-2097. In tumor B, a somatic mutation was found at codon 1041 changing CAA to TAA. We could not detect any somatic mutations in tumor C. We conclude that somatic mutation analysis of the APC gene can be used to identify whether a recurrent desmoid tumor in a patient with FAP is a new primary tumor or a recurrence from microscopic remnants of the original tumor.
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PMID:Identification of somatic APC mutations in recurrent desmoid tumors in a patient with familial adenomatous polyposis to determine actual recurrence of the original tumor or de novo occurrence. 1870 58

Cytokine gene therapy has recently become a new prospective modality in the treatment of cancer. Active immunization with gene-modified tumour cells in experimental systems employs either live Vaccines at subthreshold, non-tumorigenic doses, or irradiated cytokine-producing vaccines. The effects exerted on tumour cells by the vaccine-produced cytokines are usually pleiomorphic, either direct (cytolysis, upregulation of MHC, TAA, or adhesion molecule expression, terminal differentiation) or indirect (recruitment, amplification and activation of APC, helper and defence effector cells, damage of the blood supply) or both. The aim of this article is to review and summarize recent results of the cytokine gene therapy in experimental tumour systems, as well as to discuss the prospects and limitations of this novel approach in the management of cancer patients. The review is primarily focused on the therapeutic vaccination; however, when relevant, the results obtained with preventive vaccination are also briefly discussed.
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PMID:Cytokine gene-modified vaccines for immunotherapy of cancer (review). 2155 99

Targeting the mitotic machinery using anti-mitotic drugs for elimination of cancer cells is a century-old concept, which continues to be routinely used as a first line of treatment in the clinic. However, patient response remains unpredictable and drug resistance limits effectiveness of these drugs. Cancer cells exit from drug-induced mitotic arrest (mitotic slippage) to avoid subsequent cell death which is thought to be a major mechanism contributing to this resistance. The tumor cells that acquire resistance to anti-mitotic drugs have chromosomal instability (CIN) and are often aneuploid. In this review, we outline the key mechanisms involved in dictating the cell fate during perturbed mitosis and how these processes impede the efficacy of anti-mitotic therapies. Further, we emphasize the recent work from our laboratory, which highlights the functional role of CEP55 in protecting aneuploid cells from death. We also discuss the rationale of targeting CEP55 in vivo, which could prove to be a novel and effective therapeutic strategy for sensitizing cells to microtubule inhibitors and might offer significantly improved patient outcome. Abbreviations: APC/C: Anaphase-Promoting Complex/Cyclosome; BAD: BCL2-Associated agonist of cell Death; BAK1: BCL2 Antagonist Kinase1; BAX: BCL2-Associated X; BCL2: B-cell Chronic Lymphocytic Leukaemia (CLL)/Lymphoma 2; BH: BCL2 Homology Domain; BID: BH3-Interacting domain Death agonist; BIM: BCL2-Interacting Mediator of cell death; BUB: Budding Uninhibited by Benzimidazoles; CDC: Cell Division Cycle; CDH1: Cadherin-1; CDK1: Cyclin-Dependent Kinase 1; CEP55: Centrosomal Protein (55 KDa): CIN: Chromosomal Instability; CTA: Cancer Testis Antigen; EGR1: Early Growth Response protein 1; ERK: Extracellular Signal-Regulated Kinase; ESCRT: Endosomal Sorting Complexes Required for Transport; GIN: Genomic Instability; MAD2: Mitotic Arrest Deficient 2; MCL1: Myeloid Cell Leukemia sequence 1; MPS1: Monopolar Spindle 1 Kinase; MYT1: MYelin Transcription factor 1; PLK1: Polo Like Kinase 1; PUMA: p53-Upregulated Mediator of Apoptosis; SAC: Spindle Assembly Checkpoint; TAA: Tumor-Associated Antigen.
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PMID:Mitotic slippage: an old tale with a new twist. 3060 Oct 84