Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-3 (IL-3) is a multipotent hematopoietic growth factor produced by activated T-cells, monocytes/macrophages and stroma cells. Human IL-3 gene is located on chromosome 5 near segment 5q31. The high affinity receptor for human IL-3 is composed of alpha and beta subunits. IL-3 shares common beta subunit with GM-CSF and IL-5 which has been mapped to chromosome 22q13.1. The biological effects of IL-3 have been studied in human and murine hematopoietic cell lines and normal human bone marrow cells. Addition of IL-3 to the culture medium induces proliferation, maturation and probably self renewal of pluripotent hematopoietic stem cells and cells of myeloid, erythroid and megakaryocytic lineages. Various clinical trials have assessed the in vivo potential of recombinant human interleukin 3 (rhIL-3). Initial results of phase I/II studies of IL-3 at a dose of 5-10 ug/kg subcutaneous (s/c) daily for 5-10 days in patients with relapsed lymphomas, small cell lung cancer, breast cancer and ovarian cancer have shown that post-chemotherapy application of IL-3 reduces chemotherapy delays and induces faster regeneration of granulocytes and platelets. However, these results were not confirmed in phase III studies. The role of IL-3 alone in the treatment of myelodysplastic syndromes (MDS), aplastic anemia (AA) and other bone marrow failure disorders have also been disappointing. However, preliminary studies of IL-3 in combination with chemotherapeutic agents and immunosuppression have demonstrated encouraging results in patients with MDS and aplastic anemia respectively. The therapeutic potential of IL-3 in peripheral blood stem cell harvesting and priming of stem cells before harvest is beginning to be identified. Initial results of IL-3 in combination with granulocyte macrophage colony stimulating factor (GM-CSF) or later acting growth factor like granulocyte colony stimulating factor (G-CSF) have yielded larger amounts of peripheral blood stem cells during PBSC harvesting. This approach and application of IL-3 with cocktail of other cytokines for ex-vivo expansion of stem cells, dendritic cell development and gene transfer requires further evaluation. The role of IL-3 in murine models of antiphospholipid syndrome (APLS) for prevention of recurrent abortion remains experimental and warrants careful assessment of adverse effects of IL-3 therapy on pregnant woman and fetus. The exact therapeutic role of IL-3 in oncology and nononcology patients is beginning to be identified. It appears that future application of IL-3 in combination with other cytokines is an attractive way forward in the prevention of treatment related mortality and morbidity in oncology patients. It also holds prospects for development of new therapeutic strategies for dose escalation and immune modulation for relapsed cancer patients.
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PMID:Interleukin-3: Promises and Perspectives. 2741 83

Background. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chemotherapy with or without ipilimumab and to correlate them with survival. Patients and methods. Two cohorts of SCLC patients were studied: patients treated with chemotherapy (n = 47), and patients treated with chemotherapy plus ipilimumab (n = 37). Baseline, on-treatment and after-treatment serum samples were evaluated for the presence of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, GM-CSF, and Mip-1alpha using a Luminex assay. Differential changes in cytokines between cohorts were analyzed. Associations between cytokine levels and their changes with overall survival were evaluated. Results. Patients treated with ipilimumab showed a global increase of all cytokines after treatment initiation. A high level of IL-8 at baseline was associated with worse prognosis regardless of treatment. Baseline increased IL-2 levels predicted sensitivity to ipilimumab, while high IL-6 and TNF-alpha predicted resistance. An on-treatment increase in IL-4 levels in patients treated with immune-chemotherapy was associated with a better overall survival. Conclusions. The addition of ipilimumab to standard chemotherapy in SCLC modulates the serum levels of cytokines. Baseline levels and their change over time relate to overall survival. Blood-based biomarkers are convenient for patients, and our results support prospective validation of cytokines as predictive biomarkers for ipilimumab in SCLC.
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PMID:Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer. 3106 60

Introduction: Lung cancer is a devastating disease with poor overall survival. Despite significant advances in the treatment of lung cancers using radiochemotherapy, targeted therapies and/or immune therapies prognosis remains poor. The capacity of natural killer (NK) cells to provide a first line of defense that can bridge and orchestrate innate and 'downstream' adaptive immune responses renders them to be an ideal platform on which to base new cancer therapeutics.Areas covered: We provide an overview of the mechanisms controlling the effector functions of NK cells, tumor-directed immune escape, the impact and influence of NK cells on the development of effective, protective anti-tumor immunity and the therapeutic potential of combined cytokine-, complement-dependent- and antibody-dependent cellular cytotoxicity (CDC/ADCC), NK-92-, KIR mismatch- and CAR-NK cell-based therapies.Expert opinion: Despite promising results of immuno-oncological approaches, a relevant proportion of patients do not profit from these therapies, partly due to an ineffective NK cell activation, a lack of tumor-specific NK cells, an upregulated expression of checkpoint pathways, and a low mutational burden, which hinders the development of long-term adaptive immunity. Strategies that re-activate NK cells in combination with other therapies are therefore likely to be beneficial for the clinical outcome of patients with lung cancer.Abbreviations: ADCC: antibody-dependent cell-mediated cytotoxicity; ALK: anaplastic lymphoma kinase; CAR: chimeric antigen receptor; CDC: complement-dependent cytotoxicity; CEACAM-1: carcinoembryonic antigen-related cell adhesion molecule 1; DC: dendritic cell; DNAM: activating, maturation receptor; EGFR, epidermal growth factor receptor; EMT: epithelial-to-mesenchymal transition; EpCAM: epithelial cell adhesion molecule; GM-CSF: granulocyte monocyte colony stimulating factor; HIF: hypoxia inducible factor; IDO, indoleamine 2,3-dioxygenase; IFN: interferon; IL: interleukin; ITIM/ITAM: immune tyrosine-based inhibitory/activatory motif; KIR: killer cell immunoglobulin-like receptor; LAG-3: lymphocyte activation gene 3; MDSC: myeloid derived suppressor cells; MICA/B: MHC class I-related proteins A/B; MHC: major histocompatibility complex; mTOR: mechanistic target of rapamycin; NCAM: neuronal adhesion molecule; NCR: natural cytotoxicity receptor; NK: natural killer; NSCLC: non-small cell lung cancer; PD-1: programmed cell death 1; PS: phosphatidylserine; SCLC: small cell lung cancer; STAT: signal transducer and activator of transcription; TAM: tumor-associated M2 macrophages; TCR: T cell receptor; TIGIT: T cell immunoglobulin and ITIM domain; Tim-3: T cell immunoglobulin- and mucin domain-containing 3; TNF: tumor necrosis factor; ULBP: UL16-binding protein.
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PMID:NK cell-based therapeutics for lung cancer. 3171 56

An 84-year-old man was admitted to our hospital with new-onset refractory status epilepticus of unclear etiology. On the third day, diffusion-weighted brain MRI demonstrated lesions in the right medial temporal and parietal lobes. As a CSF sample showed pleocytosis, paraneoplastic limbic encephalitis (PLE) associated with small cell lung cancer (SCLC) was suspected. The patient was also positive for anti-gamma aminobutyric acid (GABA)B receptor antibody in the CSF, which has recently been reported in elderly patients with SCLC-related PLE. Methylprednisolone pulse therapy ameliorated the symptoms. It is noteworthy that immune therapy often improves the symptoms of PLE with anti-GABAB receptor antibody, even though radical therapy for the lung cancer may be difficult.
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PMID:[Paraneoplastic anti-gamma aminobutyric acid (GABA)B receptor antibody limbic encephalitis associated with small cell lung cancer presenting as new-onset status epilepticus: a case report]. 3322 37


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