Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our expanding knowledge of the immune system has provided a basis of rationality for immunotherapy. Some non-specific immunotherapy has achieved the status of standard treatment: interferon in hairy cell leukemia and chronic myelogenous leukemia, BCG in bladder cancer, and levamisole in colon cancer adjuvant therapy. Tumor infiltrating lymphocytes, moreover, offer a level of specificity heretofore unknown. Combined with the newly available synthetic cytokines that regulate the normal immune system there is the potential for a major breakthrough in biotherapeutics. Problems remain. We have yet to identify tumor antigens with the precision necessary for effective immunotherapy. Indeed, we have no assurance that tumors will regularly synthesize new antigens. In the broad spectrum of immune deficiency syndromes, we have yet to see an increase in the common epithelial tumors that account for the great bulk of human cancer. This suggests that we still have a great deal more to learn.
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PMID:Immunotherapy of cancer with lymphokines and lymphokine-activated killer cells. 192 49

Plasmapheresis is being used with considerable frequency in the management of malignant and non-malignant disorders. More recently, staphylococcal Protein A immunoadsorption has been employed in similar clinical situations. In patients with malignancy, plasmapheresis has been shown to produce alterations in plasma proteins, decrease circulating immune complexes, remove "specific" and "non-specific" blocking factors, change immune reactivity, and affect monocyte function. Partial responses have been reported in a small number of patients with carcinoma of lung, colon, and breast following plasmapheresis. In addition, there are reports of favorable responses in patients with melanoma, head and neck tumors, lymphomas, leukemias, and Kaposi's sarcoma in acquired immune deficiency. All these responses were partial and brief, and the treatment did not alter the course of the disease. Plasmapheresis has been useful in the management of hyperviscosity and occasionally of paraneoplastic syndromes. It may also have a role in the treatment of thrombotic thrombocytopenic purpura associated with mitomycin-C therapy. Protein A immunoadsorption, by which circulating immune complexes are selectively removed, can activate the complement system, increase blastogenic responses, and increase the natural killer cell activity. It has been shown to produce partial responses in breast and colon cancer, as well as Kaposi's sarcoma in acquired immune deficiency. It may have a useful role to play in the management of mitomycin-C-associated thrombotic thrombocytopenic purpura. Both plasmapheresis and Protein A immunoadsorption should be considered investigational interventions at this time. Toxicity of plasmapheresis, though uncommon, can be serious and may rarely be fatal. Toxicity of Protein A immunoadsorption is mild, consisting mainly of influenza-like symptoms and rash.
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PMID:Therapeutic plasmapheresis and protein A immunoadsorption in malignancy: a brief review. 222 1

Two cancer cell lines were established in vitro from a single patient with colon cancer; AKT-CC-K-LM cells from liver metastatic nodules and AKT-CC-K-PC cells from peritoneal dissemination nodules. The two cell lines were similar in doubling time, number of chromosomes, and chromosomal abnormalities. However, they differed in morphology in vitro, in the expression level of cell surface adhesion molecules (carcinoembryonic antigen; CEA, E-cadherin, sialyl Le(a), sialyl Le(x), and CD44v6), and in their metastatic properties. AKT-CC-K-LM cells grew in vitro as adherent clusters and AKT-CC-K-PC cells as adherent single cells. The expression levels of CEA, E-cadherin, sialyl Le(a), and sialyl Le(x) was significantly higher in AKT-CC-K-LM cells. The expression of CD44v6 was significantly higher in AKT-CC-K-PC cells. After the injection of AKT-CC-K-LM cells to the spleen or peritoneal cavity of severe combined immune deficiency mice, metastatic nodules were observed only in the liver. In contrast, the injection of AKT-CC-K-PC cells to the spleen or peritoneal cavity yielded metastatic nodules only in the peritoneal cavity. These cell lines may contribute to elucidating the relationship between cell surface adhesion molecules and the metastatic properties of cancer cells.
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PMID:Characteristics of two cancer cell lines derived from metastatic foci in liver and peritoneum of a patient with colon cancer. 985 57

Addressing the puzzling role of amidated gastrin(17) (G17) and the gastrin/CCKB/CCK2 receptor in colorectal carcinogenesis, we analysed potential candidate genes involved in G17-dependent NF-kappaB inhibition and apoptosis. The colorectal carcinoma cell line Colo320 overexpressing the wild-type CCK2 receptor (Colo320wt) underwent G17-induced apoptosis along with suppressed NF-kappaB activation and decreased expression of the antiapoptotic NF-kappaB target genes cIAP1 and cIAP2, whereas G17 was without effect on Colo320 cells expressing a CCK2 receptor bearing a loss of function mutation (Colo320mut). Gene microarray analysis revealed an elevated expression of the stress response gene IEX-1 in G17-treated Colo320wt but not Colo320mut cells. Quantitative real-time PCR and conventional RT-PCR confirmed this G17-dependent increase of IEX-1 expression in Colo320wt cells. If these cells were subjected to IEX-1 knockdown by small interfering RNA transfection, the apoptosis-inducing effect of G17 was abolished. Moreover, tumor necrosis factor alpha (TNFalpha)- or 5-FU-induced apoptosis that is greatly enhanced by G17 treatment in Colo320wt cells was prevented if IEX-1 expression was repressed. Under these conditions of blocked IEX-1 expression, the NF-kappaB activity remained unaffected by G17, in particular in Colo320wt cells co-treated with TNFalpha and also the suppressive effect of G17 on cIAP1 and cIAP2 expression was not observed anymore if IEX-1 expression was blocked. Conversely, IEX-1 overexpression in Colo320mut cells caused an increase of basal and TNFalpha- or 5-FU-induced apoptosis, an effect not further triggered by G17 treatment. Using a xenograft tumor model in severe combined immune deficiency mice, we could show that experimental systemic hypergastrinemia induced by the administration of omeprazole led to enhanced apoptosis as well as to a marked increase of IEX-1 expression in Colo320wt tumors, but not in Colo320mut tumors. These observations indicate that the proapoptotic effect of G17 on human colon cancer cells expressing the wild-type CCK2 receptor is mediated by IEX-1, which modulates NF-kappaB-dependent antiapoptotic protection and thereby exerts tumor-suppressive potential.
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PMID:The apoptosis-inducing effect of gastrin on colorectal cancer cells relates to an increased IEX-1 expression mediating NF-kappa B inhibition. 1770 4

The JC virus (JCV) may infect human oligodendrocytes and consequently cause progressive multifocal leukoencephalopathy (PML) in patients with immune deficiency. In addition, the virus has also been detected in other human tissues, including kidney, B lymphocytes, and gastrointestinal tissue. The recombinant major structural protein, VP1, of JCV is able to self-assemble to form a virus-like particle (VLP). It has been shown that the VLP is capable of packaging and delivering exogenous DNA into human cells for gene expression. However, gene transfer is not efficient when using in vitro DNA packaging methods with VLPs. In this study, a novel in vivo DNA packaging method using the JCV VLP was used to obtain high efficiency gene transfer. A reporter gene, the green fluorescence protein, and a suicide gene, the herpes simplex virus thymidine kinase (tk), were encapsidated into VLPs in Escherichia coli. The VLP was used to specifically target human colon carcinoma (COLO-320 HSR) cells in a nude mouse model. Intraperitoneal administration of ganciclovir in the tk-VLP-treated mice greatly reduced tumor volume. These findings suggest that it will be possible to develop the JCV VLP as a gene delivery vector for human colon cancer therapy in the future.
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PMID:Efficient gene transfer using the human JC virus-like particle that inhibits human colon adenocarcinoma growth in a nude mouse model. 2041 Sep 28

Pleiotrophin (PTN) is a secreted cytokine that is expressed in various cancer cell lines and human tumor such as colon cancer, lung cancer, gastric cancer and melanoma. It plays significant roles in angiogenesis, metastasis, differentiation and cell growth. The expression of PTN in the adult is limited to the hippocampus in an activity-dependent manner, making it a very attractive target for cancer therapy. RNA interference (RNAi) offers great potential as a new powerful therapeutic strategy based on its highly specific and efficient silencing of a target gene. However, efficient delivery of small interfering RNA (siRNA) in vivo remains a significant hurdle for its successful therapeutic application. In this study, we first identified, on a cell-based experiment, applying a 1:1 mixture of two PTN specific siRNA engenders a higher silencing efficiency on both mRNA and protein level than using any of them discretely at the same dose. As a consequence, slower melanoma cells growth was also observed for using two specific siRNA combinatorially. To establish a robust way for siRNA delivery in vivo and further investigate how silence of PTN affects tumor growth, we tested three different methods to deliver siRNA in vivo: first non-targeted in-vivo delivery of siRNA via jetPEI; second lung targeted delivery of siRNA via microbubble coated jetPEI; third tumor cell targeted delivery of siRNA via transferrin-polyethylenimine (Tf-PEI). As a result, we found that all three in-vivo siRNAs delivery methods led to an evident inhibition of melanoma growth in non-immune deficiency C57BL/6 mice without a measureable change of ALT and AST activities. Both targeted delivery methods showed more significant curative effect than jetPEI. The lung targeted delivery by microbubble coated jetPEI revealed a comparable therapeutic effect with Tf-PEI, indicating its potential application for target delivery of siRNA in vivo.
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PMID:Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis. 2856 67