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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Majority of cancer cells upregulate co-inhibitory molecule B7-H1 which confers resistance to anti-tumor immunity, allowing cancers to escape from host immune surveillance. We addressed the molecular mechanism underlying the regulation of cancer-associated B7-H1 expression in response to interferon-gamma (IFN-gamma). Using promoter constructs in luciferase assay, the region between 202 and 320 bp from the translational start site is responsible for B7-H1 expression. Electrophoretic mobility shift assay, site-directed mutagenesis and knockdown experiment using siRNA revealed that interferon regulatory factor-1 (IRF-1) is primarily responsible for the constitutive B7-H1 expression as well as for the IFN-gamma-mediated B7-H1 upregulation in a human lung cancer cell line A549. Additionally, AG490, a Janus activated kinase/signal transducer and activator of transcription inhibitor, greatly abolished the responsiveness of A549 cells to IFN-gamma by reducing the IRF-1 transcription. Our findings support a critical role of IRF-1 in the regulation of constitutive and IFN-gamma-induced expression of B7-H1 in cancer cells.
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PMID:Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). 1641 38

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy (specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine.
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PMID:Immunotherapy of lung cancer: an update. 1651 54

Cardiac computed tomographic angiography (CTA) allows for simultaneous evaluation of the lung fields and associated structures. There is a debate as to the benefit of or need for routine overread of the lung fields for incidental findings. The possible improvement in cancer diagnosis with routine overreads is balanced against the major limitations of CT lung screening. Current limitations include (a) a high rate of nodule detection given that >50% of participants may have at least one noncalcified nodule; (b) the increased costs and radiation exposure associated with the resulting follow-up CT scans; (c) the cost and the morbidity of follow-up, including further testing, as well as biopsy or resection of benign noncalcified nodule (at least 25% of such procedures in several trials); (d) a small but difficult to quantify potential risk of cancer associated with multiple follow-up CT scans; and (e) a potential for increased anxiety of both the patient and the physician about nonsignificant pathology. All of these limitations are balanced against a possibility that this could lead to an earlier detection of lung cancer with the consequent improvement in the chances of the patients' survival. Extensive studies of screening CT in older smokers have revealed the prevalence of cancer to be between 0.3 and 1%. However, when applied to an ambulatory population of patients presenting for an evaluation of angina, the prevalence of lung cancer or significant non-cardiac findings may be significantly lower. We have reviewed all the relevant literature and sought to determine the potential benefits and harms of specifically overreading CTA for non-cardiac pathology. The weight of the evidence suggests that it is most prudent to not specifically reconstruct and re-read CTA scans for lung nodules. If a non-cardiac abnormality is visualized by the primary interpreter of the cardiac CT, appropriate referral or follow-up is prudent.
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PMID:Incidental findings with cardiac CT evaluation: should we read beyond the heart? 1763 Jun 79

The CHEK2 1100delC protein-truncating mutation has a carrier frequency of approximately 0.7% in Northern and Western European populations and confers an approximately 2-fold increased risk of breast cancer. It has also been suggested to increase risks of colorectal and prostate cancer, but its involvement with these or other types of cancer has not been confirmed. The incidence of cancer other than breast cancer in 11,116 individuals from 734 non-BRCA1/2 breast cancer families from the United Kingdom, Germany, Netherlands, and the United States was compared with that predicted by population rates. Relative risks (RR) to carriers and noncarriers were estimated by maximum likelihood, via the expectation-maximization algorithm to allow for unknown genotypes. Sixty-seven families contained at least one tested CHEK2 1100delC mutation carrier. There was evidence of underreporting of cancers in male relatives (422 cancers observed, 860 expected) but not in females (322 observed, 335 expected); hence, we focused on cancer risks in female carriers. The risk of cancers other than breast cancer in female carriers was not significantly elevated, although a modest increase in risk could not be excluded (RR, 1.18; 95% confidence interval, 0.64-2.17). The carrier risk was not significantly raised for any individual cancer site, including colorectal cancer (RR, 1.60; 95% confidence interval, 0.54-4.71). However, between ages 20 to 50 years, the risks of colorectal and lung cancer were both higher in female carriers than noncarriers (P = 0.041 and 0.0001, respectively). There was no evidence of a higher prostate cancer risk in carriers than noncarriers (P = 0.26), although underreporting of male cancers limited our power to detect such a difference. Our results suggest that the risk of cancer associated with CHEK2 1100delC mutations is restricted to breast cancer, although we cannot rule out a small increase in overall cancer risk.
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PMID:A multicenter study of cancer incidence in CHEK2 1100delC mutation carriers. 1716 83

De novo methylation of CpG islands is a common phenomenon in human cancer, but the mechanisms of cancer-associated DNA methylation are not known. We have used tiling arrays in combination with the methylated CpG island recovery assay to investigate methylation of CpG islands genome-wide and at high resolution. We find that all four HOX gene clusters on chromosomes 2, 7, 12, and 17 are preferential targets for DNA methylation in cancer cell lines and in early-stage lung cancer. CpG islands associated with many other homeobox genes, such as SIX, LHX, PAX, DLX, and Engrailed, were highly methylated as well. Altogether, more than half (104 of 192) of all CpG island-associated homeobox genes in the lung cancer cell line A549 were methylated. Analysis of paralogous HOX genes showed that not all paralogues undergo cancer-associated methylation simultaneously. The HOXA cluster was analyzed in greater detail. Comparison with ENCODE-derived data shows that lack of methylation at CpG-rich sequences correlates with presence of the active chromatin mark, histone H3 lysine-4 methylation in the HOXA region. Methylation analysis of HOXA genes in primary squamous cell carcinomas of the lung led to the identification of the HOXA7- and HOXA9-associated CpG islands as frequent methylation targets in stage 1 tumors. Homeobox genes are potentially useful as DNA methylation markers for early diagnosis of the disease. The finding of widespread methylation of homeobox genes lends support to the hypothesis that a substantial fraction of genes methylated in human cancer are targets of the Polycomb complex.
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PMID:Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay. 1736 52

We analysed the biologic properties of a small cell lung carcinoma cell line (designated KK0206) established from a patient with SCLC who had cancer-associated retinopathy (CAR). Morphological and immunohistochemical studies showed that KK0206 cells have features of the classic type of SCLC. KK0206 cells grew in suspension, forming relatively small clumps of cells with a doubling time of 72 h. On light microscopy, the cells were relatively small with little cytoplasm. On immunohistochemistry using anti-bovine recoverin rabbit antibody, the cells were intensely positive for recoverin. In addition, they were positive for NSE, Ki-67, and TP53. They also expressed human recoverin, a photoreceptor protein, whose presence was confirmed by RT-PCR analysis with cDNA sequencing and Western blot analysis. The point mutation of their TP53 gene (exon 156) was detected as well. The present study demonstrates that human recoverin is expressed in SCLC cells cultured from an anti-recoverin antibody-negative patient with CAR. KK0206 might be important for further research on SCLC related retinopathy.
Lung Cancer 2007 Jun
PMID:Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy. 1737 19

Abundant evidence suggests that a unifying principle governing the molecular pathology of cancer is the co-dependent aberrant regulation of core machinery driving proliferation and suppressing apoptosis. Anomalous proteins engaged in support of this tumorigenic regulatory environment most probably represent optimal intervention targets in a heterogeneous population of cancer cells. The advent of RNA-mediated interference (RNAi)-based functional genomics provides the opportunity to derive unbiased comprehensive collections of validated gene targets supporting critical biological systems outside the framework of preconceived notions of mechanistic relationships. We have combined a high-throughput cell-based one-well/one-gene screening platform with a genome-wide synthetic library of chemically synthesized small interfering RNAs for systematic interrogation of the molecular underpinnings of cancer cell chemoresponsiveness. NCI-H1155, a human non-small-cell lung cancer line, was employed in a paclitaxel-dependent synthetic lethal screen designed to identify gene targets that specifically reduce cell viability in the presence of otherwise sublethal concentrations of paclitaxel. Using a stringent objective statistical algorithm to reduce false discovery rates below 5%, we isolated a panel of 87 genes that represent major focal points of the autonomous response of cancer cells to the abrogation of microtubule dynamics. Here we show that several of these targets sensitize lung cancer cells to paclitaxel concentrations 1,000-fold lower than otherwise required for a significant response, and we identify mechanistic relationships between cancer-associated aberrant gene expression programmes and the basic cellular machinery required for robust mitotic progression.
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PMID:Synthetic lethal screen identification of chemosensitizer loci in cancer cells. 1742 1

The superior vena cava (SVC) syndrome occurs when obstruction of this vessel interrupts venous return of blood from the head, upper extremities and thorax to the right atrium. Most cases of SVC syndrome result from neoplasia, especially from lung cancer, but other non-cancer-associated causes may include fibrosis caused by radiotherapy, collagen-vascular diseases, arteriovenous shunts or thrombosis as a complication of use of central venous catheters or devices. We report here the case of a 60-year-old woman with non-small cell lung cancer who was treated, after three lines of chemotherapy, with the epidermal growth factor receptor inhibitor erlotinib and subsequently presented to the hospital with abrupt onset of syncope, shortness of breath and cyanosis (face, neck and trunk). A CT scan of the chest demonstrated a massive thrombosis of both brachiocephalic veins and the SVC. The patient was treated with the systemic thrombolytic agent urokinase, with resolution of the clinical picture and no bleeding complications. The possible pathogenetic causes of thrombosis of the brachiocephalic veins and SVC syndrome in this case are discussed. It is possible that acute thrombosis may be associated with erlotinib use, even if it is likely that cancer may be the main cause of the thrombotic complication.
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PMID:Massive thrombosis of brachiocephalic veins and superior vena cava syndrome in a patient with non-small cell lung cancer treated with the epidermal growth factor receptor inhibitor erlotinib. 1756 30

Patients with malignant mesothelioma (MM), an aggressive cancer associated with asbestos exposure, usually present clinically with advanced disease and this greatly reduces the likelihood of curative treatment. MM is difficult to diagnose without invasive techniques; the development of non-invasively detectable molecular markers would therefore be highly beneficial. DNA methylation changes in cancer cells provide powerful markers that are potentially detectable non-invasively in DNA shed into bodily fluids. Here we examined the methylation status of 28 loci in 52 MM tumors to investigate their potential as molecular markers for MM. To exclude candidate MM markers that might be positive in biopsies/pleural fluid due to contaminating surrounding non-tumor lung tissue/DNA, we also examined the methylation of these markers in lung samples (age- or environmentally induced hypermethylation is frequently observed in non-cancerous lung). Statistically significantly increased methylation in MM versus non-tumor lung samples was found for estrogen receptor 1 (ESR1; p = 0.0002), solute carrier family 6 member 20 (SLC6A20; p = 0.0022) and spleen tyrosine kinase (SYK; p=0.0003). Examination of associations between methylation levels of the 28 loci and clinical parameters suggest associations of the methylation status of metallothionein genes with gender, histology, asbestos exposure, and lymph node involvement, and the methylation status of leucine zipper tumor suppressor 1 (LZTS1) and SLC6A20 with survival.
Lung Cancer 2007 Nov
PMID:DNA methylation profile of 28 potential marker loci in malignant mesothelioma. 1765 10

p14ARF (ARF) and topoisomerase I play central roles in cancer and have recently been shown to interact. The interaction activates topoisomerase I, an important target for camptothecin-like chemotherapeutic drugs, but the regulation of the interaction is poorly understood. We have used the H358 and H23 lung cancer cell lines and purified recombinant human topoisomerase I to demonstrate that the ARF/topoisomerase I interaction is regulated by topoisomerase I serine phosphorylation, a modification that regulates topoisomerase I activity. Both cell lines express wild-type ARF and topoisomerase I proteins at equivalent levels, but H23 topoisomerase I, unlike that of H358 cells, is largely devoid of serine phosphorylation, has low activity, and complexes poorly with ARF. The ability of H23 topoisomerase I to complex with ARF can be restored by treatment with the serine kinase, casein kinase II. Consistent with these observations, we show that the response of H23 cells to camptothecin treatment is unaffected by changes in intracellular levels of ARF. However, in H358 and PC-3 cells, which express a serine phosphorylated topoisomerase I that complexes with ARF, ectopic overexpression of ARF causes sensitization to camptothecin, and siRNA-mediated down-regulation of endogenous ARF causes desensitization to camptothecin. These biological responses correlate with increased and decreased levels, respectively, of ARF/topoisomerase I complex and DNA-bound topoisomerase I. Thus, ARF is a serine phosphorylation-dependent coregulator of topoisomerase I in vivo, and it regulates cellular sensitivity to camptothecin by interacting with topoisomerase I. Certain cancer associated defects affecting ARF/topoisomerase I complex formation could contribute to cellular resistance to camptothecin.
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PMID:Serine phosphorylation-dependent coregulation of topoisomerase I by the p14ARF tumor suppressor. 1800 78


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