Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ex vivo genetically engineered cytokine-secreting tumor cell vaccines have been shown to prevent metastatic disease in animal models of lung and breast cancer. Because of the inefficiency of existing modes of gene delivery in transducing primary human tumor cells, it has been difficult to clinically apply this strategy. In this study, liposome-mediated delivery of an adeno-associated virus (AAV)-based plasmid containing the sequence for murine gamma-interferon (gamma-IFN) (pMP6A-mIFN-gamma) was used to generate cytokine-secreting murine tumor cell vaccines. High levels of gamma-IFN and elevated class I major histocompatibility complex expression after transfer of pMP6A-mIFN-gamma into the murine lung cancer cell line, D122, was demonstrated. The efficiency of gene transfer was determined by two different methods and was estimated to be 10-15%. Irradiated gamma-IFN D122 cells generated by this novel gene delivery system (D122/pMP6A-mIFN-gamma) and also by standard retroviral methods (DIF2) were administered as weekly vaccinations by intraperitoneal injection to animals bearing 7-day-old intrafootpad D122 tumors. Hindlimb amputation was performed when footpad diameters reached 7 mm, and lungs were harvested 28 days later. Animals vaccinated with gamma-IFN-secreting D122 cells produced by AAV-based plasmids delivery demonstrated a significant delay in footpad tumor growth when compared with controls and DIF2 cells. Fifty-seven percent of animals vaccinated with D122/pMP6A-mIFN-gamma were free of pulmonary metastases 28 days after amputation, significantly improved from the 0, 7, and 15% observed in animals vaccinated with irradiated parental D122 cells, irradiated D122 cells lipofected with an empty-cassette vector (pMP6A), or DIF2 cells, respectively. These results and the ability to transfer genes with this delivery system to a broad range of tumor types support its use in the generation of cytokine-secreting tumor cell vaccinations for use in clinical trials.
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PMID:Active immunization with tumor cells transduced by a novel AAV plasmid-based gene delivery system. 910 11

An adenovirus/DNA complex was constructed by chemically linking poly-L-lysine to the capsid of the replication-defective adenovirus dl312, allowing for coupling with plasmid DNA by an ionic interaction. We have previously demonstrated that this adenovirus/DNA complex can efficiently transduce malignant cells with a plasmid expressing the beta-galactosidase gene both in vitro and in vivo. In this report, we show that this system can deliver a therapeutic gene that encodes for the tumor suppressor protein p53 to lung cancer cells, both in vitro and in vivo, leading to significant biological effects. Transfection of the p53-negative human lung cancer cell line H1299 with the adenovirus/DNA complex carrying a plasmid expressing the p53 gene resulted in high levels of p53 protein and induction of apoptosis. Injection of the complex carrying the p53 gene to subcutaneous tumor sites 5 days after tumor cell implantation resulted in a significant inhibition of tumorigenicity as measured by the number and size of tumors that developed 21 days after treatment. Three and six injections of the complex carrying the p53 gene into H1299 subcutaneous tumor nodules led to significant dose-related tumor growth suppression 18 days after the first injection compared with control-treated tumors. This adenovirus/DNA complex, therefore, is capable of efficiently delivering the p53 gene into malignant cells in vitro and in vivo and now provides a general gene delivery vector that is simple to construct and capable of testing therapeutic genes in malignant cells.
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PMID:Delivery of the p53 tumor suppressor gene into lung cancer cells by an adenovirus/DNA complex. 917 38

Rhizoxin is an antineoplastic drug that inhibits tubulin polymerization. In this study, we demonstrated that rhizoxin was approximately twice as active in vitro against a human small-cell lung cancer cell line with non-P-glycoprotein-mediated resistance to vindesine, H69/VDS, as against its parental line, H69. Tubulin polymerization in H69/VDS, demonstrated by Western blot analysis, was inhibited markedly by rhizoxin compared with that in H69, in a concentration-dependent manner. A drug-accumulation study showed that the intracellular rhizoxin level in H69/VDS was 15% lower than that in H69, whereas efflux from H69/VDS was enhanced slightly. These results indicate that enhanced inhibition of tubulin polymerization rather than increased intracellular drug concentration accounted for the higher sensitivity of H69/VDS to rhizoxin. In an experiment using mice with severe combined immunodeficiency and inoculated subcutaneously with H69/VDS, in vivo tumor growth was reduced markedly by three intermittent intraperitoneal doses of rhizoxin compared with that in mice inoculated with H69. Three weeks after the last rhizoxin dose, the relative treated/untreated tumor volumes were 0.29 for H69, but only 0.06 for H69/VDS, indicating that H69/VDS regrowth was minimal even after a 3-week treatment-free period. In conclusion, rhizoxin conquers vindesine resistance of a human small-cell lung cancer cell line in vitro and in vivo.
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PMID:In vitro and in vivo modulation by rhizoxin of non-P-glycoprotein-mediated vindesine resistance. 917 91

Autoimmune diseases have been extensively studied in man and experimental animal models and salient points are reviewed, as a clear understanding of the immune mechanisms involved is essential if one is to understand the potential of immune interactions with established cancer cells or in the premalignant period of hyperplasia. Such reactions may be of benefit to the host, with down regulation of tumor growth, or unfavourable, with facilitation of oncogenesis and cancer growth. In particular, evidence is cited that supports a beneficial effect of the host response to non-small-cell lung cancer and the association of a poor prognosis in established breast cancer caused by a heightened immune response to the tumor. Histologic evidence supports these conclusions, as do studies of specific and nonspecific immune reactivity in breast cancer patients. The potential for cytokines to stimulate breast cancer growth, increase angiogenesis and decrease cell adhesion is reviewed, also recent evidence for autologous lymphocyte stimulation of breast cancer. Parallels between immune promotion of breast cancer in mice, caused by the mouse mammary tumor virus, and the development of breast cancer in women are also reviewed. If the mouse model has relevance for human breast cancer, one could predict that there would be a reduced incidence of breast cancer in a population of chronically immunosuppressed women following organ transplantation. Such is the case. This finding, plus the fact that all treatments that have shown efficacy in breast cancer have one thing in common, they are immunosuppressive, strongly support the role of immune facilitation of breast cancer growth and immune promotion of oncogenesis in breast cancer in a substantial number of growth.
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PMID:Evidence for immune facilitation of breast cancer growth and for the immune promotion of oncogenesis in breast cancer. 922 71

The use of high-resolution computed tomography and magnetic resonance imaging have allowed the detailed description of morphologic findings associated with lung cancer. In particular, the desmoplastic response of lung tissue to tumor growth has not been adequately described. This article reviews roentgenologic and pathologic correlations of primary lung carcinomas. An irregular or indistinct tumor margin may be caused by tumor infiltration, an irregular desmoplastic response to the tumor growth, or irregular contraction in the central portion of the tumor. Solid tumor growth, on the other hand, may be associated with a well-defined tumor margin, with or without displacement of adjacent anatomical structures.
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PMID:Factors affecting the radiologic appearance of peripheral bronchogenic carcinomas. 924 73

We examined the expression of gelsolin in a murine ras tumor and a number of human stomach, colon, bladder, and lung cancer cell lines and tissues. In most of the cell lines and tumor tissues, gelsolin expression was undetectable or extremely low in comparison with its expression in normal epithelial cells. Upon the introduction of the exogenous human wild-type gelsolin cDNA into human cancer cell lines, the gelsolin transfectants had greatly reduced colony-forming ability and tumorigenicity in vivo. After UVC irradiation, the gelsolin-overexpressing bladder cancer cells demonstrated increased accumulation and/or protracted delay in G2 phase as compared to neotransfected cells. UVC-induced production of diacylglycerol was reduced in gelsolin-overexpressed UMUC-2 cells as compared to neo-transfected UMUC-2 cells. Levels of cyclin B in the synchronized and gelsolin-overexpressing UMUC-2 cells remained low during the G2 delay. To investigate the in vivo efficacy of gene therapy with the gelsolin tumor suppressor, we treated human urinary bladder cancers (UMUC-2 and DAB-1), inoculated in nude mice, with recombinant retrovirus packaging cells containing the human gelsolin cDNA. This gene therapy resulted in remarkable tumor growth inhibition, and prolonged survival time in the majority of animals. These observations suggest that gelsolin plays a key role as a tumor suppressor by regulating a G2 checkpoint function of cancer cells through phosphoinositol lipid metabolism, and demonstrate the potential of using the gelsolin tumor suppressor in human urinary bladder carcinoma.
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PMID:[Tumor suppressive function of gelsolin]. 930 38

KRN 5500 is a new semi-synthetic antitumor compound derived from spicamycin and has a unique structure. The compound showed a broad spectrum of antitumor activity against human colon, stomach, esophageal, breast and lung cancer xenografts in nude mice. Therapeutic efficacy of KRN 5500 against liver metastasis of COL-1 human colon cancer scid mice was examined. The treatment with KRN 5500 inhibited tumor growth in the liver and reduced the serum TPA concentration to a normal level. KRN 5500 inhibits protein synthesis in rabbit reticulocyte lysates. Among several metabolites of KRN 5500, only SAN-Gly showed a potent inhibitory activity against protein synthesis in reticulocyte lysates. TLC analysis of KRN 5500 metabolites using 7 human colon cancer cell lines and 3 normal cell lines demonstrated a correlation between the cytotoxicity of KRN 5500 and converting activity from KRN 5500 to SAN-Gly. These results indicate that SAN-Gly is the intracellular active metabolite and that converting activity from KRN 5500 to SAN-Gly is the major determinant of KRN 5500 cytotoxicity.
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PMID:[Protein synthesis inhibitor--antitumor activity and mode of action of KRN 5500]. 930 56

Aberrant angiogenesis-the new vessels formation is a mandatory event in the process of tumor growth and expansion. Studies on mechanisms involved in tumor-induced angiogenesis (TIA) and on its possible inhibitors are needed in order to introduce in future new methods of tumor treatment. The aim of our study was to determine the usefulness of the modified cutaneous TIA (mice without immunosuppression) test for screening in vivo of the angiogenesis modifiers. In both models (classical and modified TIA) we demonstrated comparable angiogenesis activity following human lung cells inoculation and similar degree of neovascularization response inhibition caused by theobromine. We reported that in modified TIA model preincubation with theobromine significantly suppressed angiogenic potential of human lung cancer cells as well as the ability of those cells to produce proangiogenic cytokine-bFGF.
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PMID:Screening of angiogenesis inhibitors by modified tumor-induced angiogenesis (TIA) test in lung cancer. 933 46

Halichondrin B and homohalichondrin B are novel tubulin-interacting agents isolated from marine sponges. The in vivo antitumor activities of these compounds were examined in human tumor models in immunodeficient mice and rats. In nude mice, regression or pronounced delay of subcutaneous tumor growth was obtained with both halichondrins, at a maximum tolerable dose of 20 micrograms/kg Q2Dx5, in three of four vinblastine-sensitive tumors, including two melanomas and one osteosarcoma; one small-cell lung cancer line was resistant. The halichondrins as well as vinblastine showed only marginal activity against KM20L colon carcinoma xenografts. In a LOX melanoma lung colony formation assay in groups of six nude mice, all control animals were sacrificed because of respiratory symptoms 38 days after cell injection, and likewise one vinblastine-treated mouse after 53 days. All halichondrin-treated mice in the lung colony assay appeared healthy throughout an observation period of 112 days (p = 0.002). Upon necropsy all vinblastine-treated animals, and two of six mice in the halichondrin group, had macroscopic lung tumor colonies. In a nude rat model for LOX bone marrow metastases, the mean lifespan of untreated control animals was 15 days. Whereas vinblastine had only a marginal effect (17 days) in this model, halichondrin B prolonged the lifespan of the animals to 32 days, representing a significant (p = 0.0016) difference between the two compounds. In conclusion, the halichondrins, which comprise a subtype of tubulin-interactive anti-mitotic agents, showed distinct antitumor activity profiles in human tumor models, thereby encouraging their further preclinical development and possible clinical evaluation.
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PMID:Comparative antitumor activities of halichondrins and vinblastine against human tumor xenografts. 941 95

For localized, non-small cell carcinomas (stages I and II) surgery is the treatment of choice because these lesions usually can be excised completely. The choice of the surgical procedure--lobectomy, pneumonectomy, segmental or sleeve resection--depends on the extent of malignant disease and the patients functional status. The procedure of choice is usually that which will encompass all existing disease and provide maximum conservation of normal lung tissue. On occasion, stage III disease may present borderline cases for surgery. Indications are based on existing or imminent complications in advanced locoregional tumor growth. Localized chest-wall or pericardium invasion, superior sulcus tumors, limited mediastinal nodal involvement, and phrenic involvement are not absolute surgical contraindications. Each case must carefully be evaluated and individualised. This kind of tumor management requires sophisticated techniques. The primary aim is to achieve complete tumor resection and to avoid an exploratory thoracotomy or an incomplete surgical resection. The hilar and mediastinal lymph nodes have to be completely resected to ensure a real R0-resection. The presence of distant or extrathoracic metastasis is indicative of inoperability and a surgical procedure is an absolute contraindication. There is no proven place to date for debulking surgical procedures in lung cancer.
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PMID:[Surgical therapeutic strategy in non-small-cell bronchial carcinoma]. 943 84


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