Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An important goal of cancer immunology is the identification of antigens associated with tumor destruction. Vaccination with irradiated tumor cells engineered to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) generates potent, specific, and long-lasting antitumor immunity in multiple murine tumor models. A phase I clinical trial of this vaccination strategy in patients with advanced melanoma demonstrated the consistent induction of dense CD4(+) and CD8(+) T lymphocyte and plasma cell infiltrates in distant metastases, resulting in extensive tumor destruction, fibrosis, and edema. Antimelanoma antibody and cytotoxic T cell responses were associated with tumor cell death. To characterize the targets of these responses, we screened an autologous cDNA expression library prepared from a densely infiltrated metastasis with postvaccination sera from a long-term responding patient. High-titer IgG antibodies detected ATP6S1, a putative accessory unit of the vacuolar H(+)-ATPase complex. A longitudinal analysis of this patient revealed an association between the vaccine-induced increase in antibodies to ATP6S1 and tumor destruction. Three additional vaccinated melanoma patients and three metastatic non-small cell lung carcinoma patients vaccinated with autologous GM-CSF-secreting tumor cells similarly showed a correlation between humoral responses to ATP6S1 and tumor destruction. Moreover, a chronic myelogenous leukemia patient who experienced a complete remission after CD4(+) donor lymphocyte infusions also developed high-titer antibodies to ATP6S1. Lastly, vaccination with GM-CSF-secreting B16 melanoma cells stimulated high-titer antibodies to ATPS1 in a murine model. Taken together, these findings demonstrate that potent humoral responses to ATP6S1 are associated with immune-mediated destruction of diverse tumors.
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PMID:ATP6S1 elicits potent humoral responses associated with immune-mediated tumor destruction. 1198 66

Involvement of granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) in non-lymphohematopoietic malignant tumors accompanied by leukocytosis was clinicopathologically investigated. Among 1,778 autopsy cases in the last 20 years, 485 lesions of 439 cases with non-lymphohematopoietic malignant tumors accompanied by leukocytosis with a white blood cell count of 10,000/mm3 or greater during the course were immunohistologically examined for G-CSF and GM-CSF. Three (0.7%) and two cases (0.5%) were G-CSF- and GM-CSF-positive, respectively. GM-CSF mRNA was confirmed by using non-fixed cryopreserved tumor tissues in one case positive for GM-CSF. G-CSF-positive cases were large cell carcinoma of the lung, adenocarcinoma of the colon, and adenocarcinoma of the stomach, and GM-CSF-positive cases were spindle cell carcinoma of the lung and malignant thymoma. In the case with stomach carcinoma, the primary lesion showing moderately differentiated adenocarcinoma was negative, but the lung metastatic lesion showing less differentiated adenocarcinoma was G-CSF-positive. The survival period was six months or less in four out of five positive cases. The highest white blood cell count in five CSF-positive cases was markedly elevated: 29,400-103,500/mm3 (mean: 59,700/mm3). In four cases, excluding one case which may have been markedly affected by chemotherapy, the bone marrow showed hyperplasia, and the number of the granulocyte series cells significantly increased. There were three cases (0.7%) negative for both G-CSF and GM-CSF, although they showed marked leukocytosis (60,000/mm3 or higher) which were higher than the mean count of CSF-positive cases and was not observed in autopsy cases with non-tumorous diseases. Other stimulating factors may be involved in the development of leukocytosis in such cases.
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PMID:Clinicopathological study of involvement of granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor in non-lymphohematopoietic malignant tumors accompanied by leukocytosis. 1237 Nov 27

Chemotherapy-associated myelosuppression is a major limitation of anticancer therapy in both local advanced and metastatic NSCLC. In the past, primary prophylactic use of hematopoietic growth factors was administered in these patients to reduce the incidence of febrile neutropenia, to avoid dose reduction and dose delay, and to improve patient quality of life. However, so far, for myeloid growth factors significance is missing that response to treatment can be improved in terms of better outcome. Therefore, the routine use of primary for secondary prophylactic CSF in patients with stage III or IV NSCLC is discouraged. This is due to the fact that there is no evidence that intensified chemotherapy schedules improve patients' prognosis. The application of CSF may be considered (but not given routinely) in patients with pre-existing neutropenia due to diseases or (extensive) prior chemotherapy, poor performance status, previous radiotherapy of areas with large amounts of bone marrow reserve or a history of recurrent febrile neutropenia while receiving earlier therapy. However, none of these indications has ever been proven in randomised clinical trial. In contrast, locally advanced NSCLC is a potentially curable disease. Future schedules may combine increased dose intensity of chemotherapy with sequential or simultaneous radiotherapy, where the primary or secondary use of myeloid growth factors may be justified. Chemotherapy-associated thrombopenia: So far, no thrombopoietic factors are available for clinical use.
Lung Cancer 2002 Dec
PMID:Role of supportive care in the treatment of NSCLC: supportive care for myelotoxicity. 1246 53

We reported a 62-year-old woman had sensorimotor neuropathy with small cell lung carcinoma (SCLC) and anti-GM1 antibody. She was admitted with several months history of progressive numbness, walking disturbance and anorexia. Neurologic examination revealed severe numbness and deep sensory disturbance of extremities and body, and mild weakness of distal extremities. Deep tendon reflexes were absent. Her limbs were ataxic. Nerve conduction studies showed no sensory evoked responses. CSF protein was elevated. Sural nerve biopsy revealed severe loss of myelinated fibers and perivascular mononuclear cells surrounding the perineurial vessel. Vasculitic neuropathy was diagnosed, and prednisolone was started, with no benefit. In the clinical course, she developed cough attacks and was found the lymphnode swelling in the mediastinum and supraclavicular fossa, which was diagnosed SCLC. Although anti-Hu antibody were not detected, anti-GM1 antibody was positive. She was treated with intravenous immunoglobulin, with transient improvement. The rare case of the paraneoplastic peripheral neuropathy with SCLC and anti-GM1 antibody was reported.
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PMID:[A patient of sensorimotor neuropathy with small cell lung carcinoma and anti-GM1 antibody]. 1271 89

A number of cancer vaccine and gene therapy approaches are being evaluated in patients with lung cancer. Cancer vaccine strategies include GM-CSF gene-modified cancer cells, liposomal MUC1 peptide, anti-idiotype antibody targeting GD3, Mage-3 peptide, and mutant p53 pulsed dendritic cells among others. Preliminary human trials have demonstrated immune responses as well as tumor regression in late stage disease. The largest human gene therapy experience in lung cancer is with intratumoral gene replacement therapy, predominantly with p53, but such approaches are limited to locoregional disease control. Earlier stage gene therapy programs targeting the immune system or tumor vasculature hold promise as systemic therapies for treatment of advanced, disseminated disease.
Lung Cancer 2003 Aug
PMID:Lung cancer vaccines and gene therapy. 1286 69

Paraneoplastic neurological syndromes are rare remote effects of different types of cancer. Paraneoplastic limbic encephalitis is a specific syndrome, most often associated with small cell lung carcinoma. This report describes the case of a pure limbic encephalitis in association with breast cancer. An anti-neuronal antibody was found in the serum and CSF of the patient which has not been reported so far.
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PMID:A new anti-neuronal antibody in a case of paraneoplastic limbic encephalitis associated with breast cancer. 1474 25

We report two cases of paraneoplastic limbic encephalitis (PLE) that differed in their clinical patterns, the underlying tumours, and the associated paraneoplastic antibodies. The first patient was a young adult male, with anti-MA-2 antibodies and testicular tumour. The clinical picture was restricted to limbic involvement. The second patient was a 56-year old, female heavy smoker; with seizures and depression, but also vertigo and diplopia. A low level of serum anti-Hu antibodies led to the detection of a small cell lung carcinoma by total body PET-scanning. In both cases, intrathecal synthesis of CSF oligoclonal IgG bands and of the corresponding paraneoplastic antibodies was demonstrated.
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PMID:Paraneoplastic limbic encephalitis: diagnostic relevance of CSF analysis and total body PET scanning. 1550 68

We previously demonstrated increased numbers of CD34(+) progenitor cells in the peripheral blood of tumor bearers. Also demonstrated was the feasibility of chemoattracting these cells by sponge implants containing VEGF. The present study used a murine Lewis lung carcinoma (LLC) model to test if CD34(+) cells that are chemoattracted to a tumor excision site can be differentiated in situ into dendritic cells and whether this leads to increased local immune reactivity. After surgically excising established LLC tumors, mice received at the excision site gelatin sponge implants containing VEGF to chemoattract CD34(+) cells, and/or GM-CSF plus SCF to induce CD34(+) cell differentiation into dendritic cells. In some studies, lysates of GFP-transfected LLC cells (LLC(GFP)) were also included in the implants as a source of tumor antigen. After 2 weeks, implants and local lymph nodes were removed and analyzed. Implants containing VEGF, GM-CSF/SCF or VEGF/GM-CSF/SCF had a higher proportion of CD34(+) cells compared to control implants. However, the number of dendritic cells was higher in implants containing GM-CSF/SCF or VEGF/GM-CSF/SCF than those containing either VEGF or diluent. Regional lymph node from mice containing GM-CSF/SCF or VEGF/GM-CSF/SCF implants showed increased dendritic cell levels. However, when lysates from LLC(GFP) were added to the implants, the highest proportion of dendritic cells associated with GFP was in lymph nodes of mice containing GM-CSF/SCF implants. Lymph node cells from mice with GM-CSF/SCF or VEGF/GM-CSF/SCF had a higher level of proliferation and IFN-gamma secretion in response to in vitro LLC lysate challenge, with the greatest response being from lymph node cells of mice with GM-CSF/SCF implants. These results suggest the feasibility of using GM-CSF/SCF-containing implants to increase dendritic cell levels, uptake of tumor antigens, trafficking to lymph nodes and stimulation of immune reactivity at tumor excision sites with residual tumor.
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PMID:Cytokine-containing gelfoam implants at a postsurgical tumor excision site to stimulate local immune reactivity. 1645 Mar 95

ABT-869 is a structurally novel, receptor tyrosine kinase (RTK) inhibitor that is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor families (e.g., KDR IC50 = 4 nmol/L) but has much less activity (IC50s > 1 micromol/L) against unrelated RTKs, soluble tyrosine kinases, or serine/threonine kinases. The inhibition profile of ABT-869 is evident in cellular assays of RTK phosphorylation (IC50 = 2, 4, and 7 nmol/L for PDGFR-beta, KDR, and CSF-1R, respectively) and VEGF-stimulated proliferation (IC50 = 0.2 nmol/L for human endothelial cells). ABT-869 is not a general antiproliferative agent because, in most cancer cells, >1,000-fold higher concentrations of ABT-869 are required for inhibition of proliferation. However, ABT-869 exhibits potent antiproliferative and apoptotic effects on cancer cells whose proliferation is dependent on mutant kinases, such as FLT3. In vivo ABT-869 is effective orally in the mechanism-based murine models of VEGF-induced uterine edema (ED50 = 0.5 mg/kg) and corneal angiogenesis (>50% inhibition, 15 mg/kg). In tumor growth studies, ABT-869 exhibits efficacy in human fibrosarcoma and breast, colon, and small cell lung carcinoma xenograft models (ED50 = 1.5-5 mg/kg, twice daily) and is also effective (>50% inhibition) in orthotopic breast and glioma models. Reduction in tumor size and tumor regression was observed in epidermoid carcinoma and leukemia xenograft models, respectively. In combination, ABT-869 produced at least additive effects when given with cytotoxic therapies. Based on pharmacokinetic analysis from tumor growth studies, efficacy correlated more strongly with time over a threshold value (cellular KDR IC50 corrected for plasma protein binding = 0.08 microg/mL, >or=7 hours) than with plasma area under the curve or Cmax. These results support clinical assessment of ABT-869 as a therapeutic agent for cancer.
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PMID:Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. 1664 71

Paraneoplastic neurodegenerative diseases are defined as damage to central and peripheral nervous tissue related to a malignancy, in the absence of metastases. If they represent first disease manifestation, the diagnosis can pose a real problem. A case of 59-year-old woman is described, who suffered during her last nine months of life from meningoencephalitis, with cranial nerves pareses and progressive quadruparalysis. The CSF exhibited a temporary inflammatory response with slow improvement, whereas the clinical status progressed continually toward terminal bronchopneumonia. An extensive infectious agent search was negative. Though the result of the autoantibody panel available (anti Yo, Hu, Ri) was negative, the paraneoplastic degeneration remained a part of the differential diagnosis. Post-mortem examination revealed residual brain stem meningoencephalitis and advanced cerebellar loss of Purkinje cells, in the presence of a neuroendocrine small cell lung carcinoma in the right lower lobe. The carcinoma only manifested intravitally, with paratracheal lymphadenomegaly on imaging. Rapid progress in the diagnostics of autoimmune neurodegeneration with the increasing spectrum of autoantibody detection tools has recently increased the possibilities of revealing clinically silent, primary manifesting neurodegeneration. In the future, it may also represent a target for therapeutic intervention.
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PMID:[Paraneoplastic encephalitis]. 1683 4


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