Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 6 (IL-6) and leukaemia inhibitory factor (LIF) can have pleiotropic effects on different cell types. M1 myeloid leukaemic cells respond to IL-6 with activation of a terminal differentiation programme which includes activation of genes for certain haemopoietic regulatory proteins (IL-6, IL-1 alpha, IL-1 beta, granulocyte-macrophage colony-stimulating factor [GM-CSF], M-CSF, tumour necrosis factor and transforming growth factor [TGF] beta 1) and for receptors for some of these proteins, thus establishing a network of positive and negative regulatory cytokines. IL-6 and some other cytokines also induce during differentiation sustained levels of transcription factors that can regulate and maintain gene expression in the differentiation programme. M1 leukaemic cells induced to differentiate with IL-6 undergo programmed cell death (apoptosis) on withdrawal of IL-6, and can be rescued from apoptosis by IL-6, IL-3, M-CSF, G-CSF or IL-1, but not by GM-CSF. These differentiating leukaemic cells can also be rescued from apoptosis by the tumour promoter TPA (12-O-tetradecanoylphorbol-13-acetate) but not by the non-tumour-promoting isomer 4-alpha-TPA, and rescue from apoptosis can be achieved by different pathways. Apoptosis can also be induced in undifferentiated M1 leukaemic cells by expression of the wild-type form of the tumour suppressor p53 protein and IL-6 can rescue the cells from this wild-type p53-mediated apoptosis. There are clones of M1 cells that differentiate with IL-6 but not with LIF and another M1 clone that differentiates with either IL-6 or LIF. Differentiation induced by IL-6 or LIF is inhibited by TGF-beta 1. The pleiotropic effects of LIF, like those of IL-6, are presumably also in a network of interacting regulatory proteins.
 ...
PMID:Regulation of leukaemic cells by interleukin 6 and leukaemia inhibitory factor. 142 20

Prostate cancer is one of the leading causes of cancer deaths in the Western world and current therapies are of limited efficacy in advanced disease. Both ex vivo and in vivo gene therapy strategies offer exciting new possible approaches to the management of this disease. Ex vivo gene therapy involving interleukin-2 or granulocyte-macrophage colony-stimulating factor transduced whole tumour cell vaccines has shown great promise in animal models. The feasibility of in vivo corrective gene therapy involving the replacement of mutant tumour suppressor genes, antisense strategies and the insertion of suicide genes has been demonstrated in preclinical models. Several of these therapies are now entering phase I/II studies in patients with prostate cancer.
 ...
PMID:Gene therapy for prostate cancer. 890 97

Retinoblastoma binding protein 1 (RBP-1) is a 143-kDa nuclear phosphoprotein that promotes cell growth by inhibiting the product of retinoblastoma tumour suppressor gene (pRB). We recently found that RBP-1 contains KASIFLK, a heptameric peptide (250-256) recognized by human antibodies and overexpressed by breast cancer cells. In the present study, we demonstrate that human T-cells stimulated with RBP-1 decameric peptides containing KASIFLK can kill human breast cancer cells. These decamers, GLQKASIFLK (247-256) and KASIFLKTRV (250-259), have anchor motifs for both HLA-A2 and HLA-A3. Peripheral blood lymphocytes from 41 normal donors were stimulated by these peptides in culture media containing 15 IU ml(-1) interleukin-2, 25 IU ml(-1) interleukin-7 and 500 IU ml(-1) granulocyte-macrophage colony-stimulating factor. Cytotoxic activity of the T-cells was assessed against autologous B lymphoblastoid cells pulsed with each peptide. Stimulation by GLQKASIFLK generated specific cytotoxic T lymphocyte (CTL) lines from HLA-A2, A3 donors, HLA-A2 donors and HLA-A3 donors. Stimulation with KASIFLKTRV generated specific CTL lines from HLA-A2 donors. No HLA-A2-, A3 CTL line showed specific cytotoxicity against these target cells. These CTL lines were also cytotoxic against HLA-A2 and HLA-A3 breast cancer cells but not against normal fibroblastoid cell lines, normal epidermal cell lines, or a melanoma cell line. RBP-1 peptide antigens may be of clinical significance as a potential peptide vaccine against human breast cancer.
 ...
PMID:Cytotoxic T lymphocytes that recognize decameric peptide sequences of retinoblastoma binding protein 1 (RBP-1) associated with human breast cancer. 1049 63

Gene therapy encompasses deliberate alteration of the genetic material of cancer cells. Somatic-cell therapy involves the administration to cancer patients of living cells that have been genetically manipulated or processed to change their biological characteristics. Gene therapy of cancer, although much hyped, is still in its very early infancy. Current approaches to delivering genes into cells include physico-chemical methods, viral vectors and direct DNA injection. None of these strategies is in any way perfect and their efficacy leaves much to be desired. Based on the somatic mutation theory of carcinogenesis, it would be attractive to repair genetic alterations responsible for neoplastic transformation and clonal evolution of cancer cells. Attempts have been made to replace inactivated tumour suppressor genes in cancer cells through intact wild type gene copies, or to suppress the leukaemogenic effects of chromosomal fusion genes in leukaemia through antisense oligonucleotides. One of the snags of these concepts is that cancer cells harbour several if not myriads of mutated genes, and clonal tumour heterogeneity seems to be the rule rather than the exception. It is at present impossible to repair all gene mutations in cancer lesions of a given patient if such were to be the aim of therapy. Nevertheless, some interesting clinical data have been reported. These include the local injection via bronchoscopy of p53 wild type gene copies into p53-deficient lung cancer lesions and other tumours. Somatic-cell therapy includes a considerable spectrum of interventions. Tumour cells may be transduced with genes which upon their expression will render the tumour cells more immunogenic. Tumour-infiltrating lymphocytes may be harvested, transduced with a gene of interest and re-injected. Since they recognise tumours specifically, they will serve as vehicles to carry therapeutic genes into cancer lesions where the gene product can exert an anti-cancer effect. Such attempts might increase the immunogenicity of tumours considerably. Examples are the transduction of tumour-infiltrating lymphocytes with a gene for tumour necrosis factor alpha or the transduction of tumour cells with the gene for granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with metastatic renal cell carcinoma. Protocols on gene therapy and somatic-cell therapy seem to be a worthy goal of cancer research. However, it seems unlikely that gene therapy will provide magic anti-cancer bullets in the near future or the definitive cancer cure, although this is often promised in the media. Careful clinical and laboratory research will pave the way towards stepwise improvement of cancer patient care.
 ...
PMID:[Molecular therapy in malignant tumors]. 1060 49