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)

Hepatocytes are an important physiological model for evaluation of metabolic and biological effects of xenobiotics. They do not proliferate in culture and are extremely sensitive to damage during freezing and thawing, even after the addition of classical cryoprotectants. Thus improved cryopreservation techniques are needed to reduce cell injury and functional impairment. Here, we describe a new and efficient cryopreservation method, which permits long-term storage and recovery of large quantities of healthy cells that maintain high hepatospecific functions. In culture, the morphology of hepatocytes cryopreserved with wheat protein extracts (WPE) was similar to that of fresh cells. Furthermore, hepatospecific functions such as albumin secretion and biotransformation of ammonium to urea were well maintained during 4 days in culture. Inductions of CYP1A1 and CYP2B in hepatocytes cryopreserved with WPEs were similar to those in fresh hepatocytes. These findings clearly show that WPEs are an excellent cryopreservant for primary hepatocytes. The extract was also found to cryopreserve other human and animal cell types such as lung carcinoma, colorectal adenocarcinoma, Chinese hamster ovary transfected with TGF-b1 cDNA, cervical cancer taken from Henrietta Lacks, intestinal epithelium, and T cell leukemia. WPEs have potential as a universal cryopreservant agent of mammalian cells. It is an economic, efficient and non-toxic agent.
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PMID:Wheat extracts as an efficient cryoprotective agent for primary cultures of rat hepatocytes. 1692 46

Single nucleotide polymorphism (SNP) mapping arrays were used to perform DNA copy number analysis of five human cancer cell lines (four malignant mesotheliomas; one non-small cell lung carcinoma) to identify and map the end-points of deletions of 9p. All five cell lines exhibited homozygous deletions encompassing the CDKN2A (alias INK4A/ARF) and CDKN2B loci. The DNA analysis profiles demarcated precisely two different, but overlapping, deletions in each mesothelioma cell line, but the lung cancer cells showed two copies of a single deletion. In the latter cell line, allele analysis revealed that virtually all SNPs for chromosome 9 were homozygous, suggestive of uniparental disomy. These findings demonstrate the utility of SNP-based mapping arrays for high-resolution analysis of genomic imbalances in cancer cells.
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PMID:High-resolution analysis of 9p loss in human cancer cells using single nucleotide polymorphism-based mapping arrays. 1696 58

A 56-year-old woman, with dysgeusia in which nearly all food was felt as sweet, was admitted to our hospital seeking for treatment. Serum sodium concentration was 113 mmol/L, but serum creatinine, zinc, urea nitrogen, and potassium, as well as blood glucose, were all within normal ranges. Dysgeusia disappeared when serum sodium level was normalized, but recurred when hyponatremia relapsed. She was diagnosed as having large cell lung carcinoma. We considered that the cause of hyponatremia was inappropriate secretion of antidiuretic hormone (SIADH) due to lung carcinoma. Miraculin is one of taste-modifying substances which fits the sweet receptor site and induces a strong sweet taste. We considered that taste-modifying substances same as miraclin are involved in the pathophysiology of this disease.
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PMID:[Sweetness dysgeusia in a case of SIADH caused by lung carcinoma]. 1698 5

To continue exploration of structure activity relationship of novel 1-(indoline-5-sulfonyl)-4-phenylimidazolidinones (1) reported as anticancer agent with broad spectrum, three 1-(arylsulfonyl)-4-vinylimidazolidinones (2) were synthesized from methyl serinate (3) in 8 steps. Reaction of intermediate 2-phenoxycarbonylaminobut-3-enyl p-toluenesulfonate (10) with arylsulfonamide in the presence of potassium carbonate produced corresponding 2 and N-(4-vinyloxazolidin-2-yl)arylsulfonamide 11 in approximately equal ratio. This reaction is believed to undergo through urea intermediate 16 as shown in scheme 3. 1-Arylsufonyl-4-vinylimidazolidinones 2 show much reduced activity against human colon carcinoma (Colo205), human chronic myelogenous leukemia (K562), and human ovarian adenocarcinoma (SK-OV-3) and compatible activity against human lung carcinoma (A549) compared to 1. Therefore phenyl at 4-position should be the optimum planar motif for the activity of 1.
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PMID:Evaluation of anticancer activity of 4-vinyl-1-arylsulfonylimidazolidinones. 1702 43

A problem in proteomic analysis of lung cancer tissue is the presence of complex components of different histological backgrounds (squamous cell carcinoma, small cell lung carcinoma, and adenocarcinoma). The efficient solubilization of protein components before two-dimensional electrophoresis (2-DE) is a very critical. Poor solubilization has been associated with a failure to detect proteins and diffuse, streaked and/or trailing protein spots. Here, we have optimized the solubilization of human lung cancer tissue to increase protein resolution. Isoelectric focusing (IEF) rehydration buffer containing a thiourea-urea mixture provided superior resolution, whereas a buffer without thiourea yielded consistently poor results. In addition, IEF rehydration buffers containing CHAPS and DTT gave superior resolution, whereas buffers containing Nonidet P-40 (NP-40) and/or Triton X-100 did not. A tributylphosphine-containing buffer gave consistently poor results. Using optimized conditions, we used 2-D gel analysis of human lung cancer tissue to identify 11 differentially-expressed protein spots by MALDI-mass spectrometry. This study provides a methodological tool to study the complex mammalian proteomes.
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PMID:Buffer optimization for high resolution of human lung cancer tissue proteins by two-dimensional gel electrophoresis. 1880 Jan 91

Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related death worldwide, with an overall 5-year survival rate of only 10-15%. Deregulation of the Ras pathway is a frequent hallmark of NSCLC, often through mutations that directly activate Kras. p53 is also frequently inactivated in NSCLC and, because oncogenic Ras can be a potent trigger of p53 (ref. 3), it seems likely that oncogenic Ras signalling has a major and persistent role in driving the selection against p53. Hence, pharmacological restoration of p53 is an appealing therapeutic strategy for treating this disease. Here we model the probable therapeutic impact of p53 restoration in a spontaneously evolving mouse model of NSCLC initiated by sporadic oncogenic activation of endogenous Kras. Surprisingly, p53 restoration failed to induce significant regression of established tumours, although it did result in a significant decrease in the relative proportion of high-grade tumours. This is due to selective activation of p53 only in the more aggressive tumour cells within each tumour. Such selective activation of p53 correlates with marked upregulation in Ras signal intensity and induction of the oncogenic signalling sensor p19(ARF)( )(ref. 6). Our data indicate that p53-mediated tumour suppression is triggered only when oncogenic Ras signal flux exceeds a critical threshold. Importantly, the failure of low-level oncogenic Kras to engage p53 reveals inherent limits in the capacity of p53 to restrain early tumour evolution and in the efficacy of therapeutic p53 restoration to eradicate cancers.
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PMID:Selective activation of p53-mediated tumour suppression in high-grade tumours. 2121 53

The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 dysregulation is thought to contribute to the development of cancer. We reported that (bis)guanidines, (bis)biguanides, and their urea- and thiourea isosteres are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of small molecule amidoximes that are moderate inhibitors of recombinant LSD1 but that produce dramatic changes in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2, H-cadherin (HCAD), and the transcription factor GATA4. These compounds represent leads for an important new series of drug-like epigenetic modulators with the potential for use as antitumor agents.
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PMID:Low molecular weight amidoximes that act as potent inhibitors of lysine-specific demethylase 1. 2287 79

BACKGROUND.: Lung cancer is the leading cause of cancer deaths. Angiogenesis is crucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. PATIENTS AND METHODS.: Clinical data, blood samples and broncho-alveolar lavage (BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. RESULTS.: We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affected side of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage of disease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. CONCLUSION.: Angiogenin and VEGF concentrations in systemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF.
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PMID:Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patients. 2341 43

Non-small-cell lung carcinoma (NSCLC) is among the deadliest of human cancers. The CDKN2A locus, which houses the INK4a and ARF tumor suppressor genes, is frequently altered in NSCLC. However, the specific role of ARF in pulmonary tumorigenesis remains unclear. KRAS and other oncogenes induce the expression of ARF, thus stabilizing p53 activity and arresting cell proliferation. To address the role of ARF in Kras-driven NSCLC, we compared the susceptibility of NIH/Ola strain wild-type and Arf-knockout mice to urethane-induced lung carcinogenesis. Lung tumor size, malignancy and associated morbidity were significantly increased in Arf(-/-) compared with Arf(+/+) animals at 25 weeks after induction. Pulmonary tumors from Arf-knockout mice exhibited increased cell proliferation and DNA damage compared with wild-type mice. A subgroup of tumors in Arf(-/-) animals presented as dedifferentiated and metastatic, with many characteristics of pulmonary sarcomatoid carcinoma, a neoplasm previously undocumented in mouse models. Our finding of a role for ARF in NSCLC is consistent with the observation that benign adenomas from Arf(+/+) mice robustly expressed ARF, while ARF expression was markedly reduced in malignant adenocarcinomas. ARF expression also frequently colocalized with the expression of p21(CIP1), a transcriptional target of p53, arguing that ARF induces the p53 checkpoint to arrest cell proliferation in vivo. Taken together, these findings demonstrate that induction of ARF is an early response in lung tumorigenesis that mounts a strong barrier against tumor growth and malignant progression.
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PMID:ARF inhibits the growth and malignant progression of non-small-cell lung carcinoma. 2375 94

Vitamin C (vit C) has been shown to diminish cisplatin (CP)-induced nephrotoxicity and oxidative damage in healthy rats and mice. However, little is known whether vit C has similar actions and enhances the anticancer effect of CP in tumor-bearing mice. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before intraperitoneal administration with CP (5 mg/kg) in the presence or absence of low- (200 mg/kg) and high- (1000 mg/kg) dose vit C twice a week for an additional 28 days. Results reveal that vit C or CP treatment alone significantly inhibited tumor growth, although vit C in combination with CP did not further inhibit tumor growth, as compared to CP treatment alone. In addition, CP significantly induced nephrotoxicity and oxidative damage, as evidenced by increased plasma levels of blood urea nitrogen and creatinine as well as levels of lipid peroxidation and carbonyls, decreased ratios of GSH/GSSG in liver and kidney. Vit C significantly reversed these undesirable side effects induced by CP, and most of these actions of vit C were dose-dependent. Overall, we conclude that vit C can protect against CP-induced nephrotoxicity and damage without reducing CP's effectiveness in LLC-bearing mice.
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PMID:Vitamin C protects against cisplatin-induced nephrotoxicity and damage without reducing its effectiveness in C57BL/6 mice xenografted with Lewis lung carcinoma. 2515 54


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