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

Although SV40 oncoproteins have been detected in malignant pleural mesotheliomas (MPMs), their role in the pathogenesis and clinical behavior of these neoplasms remains controversial. In the present study, we sought to define the relevance of SV40 T/t antigen expression in established human mesothelioma cell lines deficient for p16INK4a as well as ARF expression. SV40 early region sequences were readily detected in genomic DNA isolated from pleural mesothelioma lines; however, levels of SV40 T/t antigen expression were highly variable in these cells. An adenoviral vector expressing an antisense transcript to SV40 early region inhibited T antigen expression and mediated significant growth inhibition and apoptosis in T-antigen-positive mesothelioma cells and SV40-transformed COS-7 cells. Abrogation of T/t antigen expression coincided with enhanced p21/WAF-1 expression, suggesting that restoration of p53-mediated pathways may have contributed to the growth inhibition and apoptosis induced by the antisense construct. These effects were not observed after similar treatment of mesothelioma or lung cancer cells containing no SV40 DNA sequences. Collectively, these data suggest that SV40 oncoproteins contribute to the malignant phenotype of pleural mesotheliomas and indicate that interventions designed to abrogate their expression may be efficacious in the treatment of individuals with these neoplasms.
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PMID:Antisense to SV40 early gene region induces growth arrest and apoptosis in T-antigen-positive human pleural mesothelioma cells. 1062 92

We report on the case of a 42-year-old man suffering from an irresectable adenocarcinoma of the liver. The patient was treated with 5-fluorouracil for 6 months when the disease progressed and second line therapy with gemcitabine was started. After 4 months diastolic blood pressure increased and edema of the legs as well as vomiting occurred. Laboratory tests revealed anemia and thrombopenia accompanied by an elevation of plasma D-dimer, lactatdehydrogenase, creatinine, and urea levels in the serum. In addition, a pronounced proteinuria as well as renal hematuria were detected and subsequently a hemolytic uremic syndrome was diagnosed. After treatment with high-dose glucocorticoids, anticoagulants and transfusions of packed RBC the course of disease improved. Since Gemcitabine is now widely used for treatment of solid organ cancer (e.g. pancreatic adenocarcinoma, biliary tract cancer, lung cancer etc.), it is necessary to be aware of Gemcitabine-induced hemolytic uremic syndrome as a rare but potentially fatal side effect.
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PMID:[A 42-year-old patient with the hemolytic-uremic syndrome under gemcitabine therapy for an adenocarcinoma of the liver. The hemolytic-uremic syndrome and gemcitabine]. 1096 57

The cyclin-dependent kinase inhibitor p16INK4a encoded by the INK4A/CDKN2A/MTS1 gene is a frequent target of 9p21 inactivation in human lung cancers. The p14ARF transcript, which is an alternative spliced form of this locus, is also altered or deleted in a proportion of human lung cancers and has been shown to inhibit cell cycle progression as an endogenous cellular regulator of the p53 protein, raising the possibility that it might constitute an additional lung tumor suppressor gene at the 9p21 locus. To test the candidacy of p14ARF as a lung cancer suppressor and assess the role it plays in radiosensitivity, we transfected the wild-type p14ARF gene into four cell lines which had various endogenous gene backgrounds of INK4A-/p53+/RB+ (A549 and H460), INK4A+/p53+/RB- (H446) as well as p14ARF+/p53-/RB+ (Calu-1). We found that transfection of p14ARF is related to an obvious growth inhibition in all wtp53 cell lines, regardless of INK4A/ARF and RB status. Although it has been shown that p53-induced G1 checkpoint in response to DNA damage by ionizing radiation is p14ARF-independent, we found the radiosensitivity of two p14ARF-deficient cell lines was increased after p14ARF gene transfer. The results indicated that cell cycle redistribution after acquiring the exogenous gene might be the main explanation for the enhanced sensitization. An increased radiation-induced apoptotic proportion in one cell line also suggested a fortified p53 function that might be triggered by the restored p14ARF protein.
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PMID:The exogenous wild-type p14ARF gene induces growth arrest and promotes radiosensitivity in human lung cancer cell lines. 1141 96

Chromosome band 9p21 is a frequent target of homozygous deletion in many tumor types. Putative tumor suppressor genes, CDKN2A (p16), p14(ARF) and CDKN2B (p15), were localized to 9p21. However, there have been reports that suggest that there may be other genes targeted for inactivation in the region. We have developed a method to search for transcribed sequences within large genomic regions. We tested our approach in a 100-kilobase region on 9p21, which is 40 kilobases telomeric to CDKN2A. The method, termed expressed sequence selection (ESS), resulted in the isolation of genomic fragments known to be from 9q21 that are homologous to transcribed sequences. One fragment was used to obtain a 1.2 kilobase cDNA. The sequence of the 5' half of the cDNA was almost identical to exons 3-5 of the MTAP gene, which maps to chromosome band 9p21. The 3' portion of the cDNA had sequence homology to the ALA gene, which maps to chromosome arm 9q. Using Northern blot analysis, the 1.2 Kb cDNA identified several widely expressed transcripts ranging from 1 Kb to 8.5 Kb and displayed a complex pattern of alternative splicing in which certain exons of the 1.2 Kb cDNA are excluded from some of the splice products. Using cancer tissue Northern blots, we could show that all of the transcripts are absent from a leukemia cell line and a lung cancer cell line (K562, A549) with homozygous, genomic deletions within chromosome band 9p21. In addition, the 7 Kb transcript is also absent from two additional tumor cell lines (Molt4, a leukemia derived cell line, and in G361, a melanoma derived cell line) with homozygous deletions. Further investigation will determine whether the difference in the expression pattern between the 7 Kb transcript compared with the other sized transcripts could be due to specific targeting for alteration in certain tumor types.
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PMID:Identification of a 1.2 Kb cDNA fragment from a region on 9p21 commonly deleted in multiple tumor types. 1156 37

To carry out safe anticancer chemotherapy one should consider the kidney function. Insufficiency of that main organ responsible for drugs excretion, caused either by neoplastic disease or by chemotherapy, can diminish the possibility or even make impossible of carrying out a complete treatment cycle. The aim of our work was to evaluate the kidney function in patients with lung cancer during anticancer chemotherapy containing cisplatin. The tubular function was studied by estimation the activity of N-acetyl-beta-D-glucosaminidase in urine and glomerular function was studied by estimation the concentration of creatinine in urine, urea, uric acid and electrolytes in plasma. The observations have recorded that neoplastic process, as well as chemotherapy impaired the tubular function. It has showed that it does exist a necessity of detailed estimation of kidney excretory function before, during and after the end of anticancer therapy. Determination of NAG activity in urine may be helpful for the recognition of the patients at high nephrotoxicity risk, who need special care.
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PMID:[Anticancer chemotherapy containing cisplatin in patients with lung cancer and kidney function]. 1210 68

p14(ARF), a product of the INK4A/ARF locus, induces p53 upregulation by neutralizing the effects of MDM2, a transcriptional target of p53 that antagonizes its function. Here we report that adenovirus-mediated p14(ARF) gene transfer leads to the accumulation of ectopically transduced p53 and to apoptosis in human cancer cells. We constructed an adenoviral vector expressing p14(ARF) (Ad-ARF) and examined its synergistic effect with p53-expressing adenovirus (Ad5CMV-p53 or Ad-p53) in human lung and esophageal cancer cells. Simultaneous Ad-ARF and Ad-p53 infection increased p53 protein levels not only in a wild-type p53-expressing cell line, but also in cell lines with deleted p53. This resulted in a significant in vitro cytotoxicity compared with Ad-p53 infection alone. Coinfection of Ad-ARF and Ad-p53 also resulted in an increase in expression of p53-inducible genes, including p21(WAF-1/Cip1), p53R2, and Noxa. In addition, the growth of human lung cancer tumors subcutaneously implanted into nu/nu mice was inhibited significantly by intratumoral injection with Ad-ARF and Ad-p53. Our data demonstrate that overexpression of ectopic p14(ARF) may render cells more sensitive to p53-mediated apoptosis, an outcome that has important implications for the treatment of human cancers.
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PMID:Adenovirus-mediated p14ARF gene transfer cooperates with Ad5CMV-p53 to induce apoptosis in human cancer cells. 1216 19

Lung cancer is the leading cause of cancer death among both men and women, accounting for more than 28% of all cancer deaths. In fact, more people die of lung cancer than of colon, breast, and prostate cancers combined. Although lung cancer is largely induced by smoking, there is strong evidence for genetic susceptibility and gene-environment interactions in the development of lung cancer. Inbred mouse models offer an effective means of identifying candidate lung cancer susceptibility loci since genetic heterogeneity and enormous variation in exposure levels to environmental agents make it difficult to identify lung cancer susceptibility loci in humans. Papg-1 (pulmonary adenoma progression 1) was previously mapped to a region on mouse chromosome 4. This locus contains a candidate gene, Cdkn2a also referred to as Ink4a/Arf, which dually encodes two established tumor suppressors p16(INK4a) and ARF. Cdkn2a became a primary candidate for Papg-1 for two reasons: (1) two haplotypes of mouse Cdkn2a were found to segregate with differential genetic susceptibility to lung tumor progression in mice; and (2) in vitro studies showed that the p16(INK4a) allele from the BALB/cJ mouse had a significantly decreased ability to bind and inhibit CDK6 and to suppress cell growth when compared with the p16(INK4a) allele from the A/J mouse. Here, we report that mice with a heterozygous deficiency for the A/J Cdkn2a allele were significantly more susceptible to lung tumor progression than mice with a heterozygous deficiency for a BALB/cJ Cdkn2a allele, when compared to their respective wild type mice. These results offer strong evidence that naturally occurring variation of p16(INK4a) influences susceptibility to enhance lung tumor progression making it a strong candidate for the lung tumor progression locus, Papg-1.
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PMID:A strong candidate gene for the Papg1 locus on mouse chromosome 4 affecting lung tumor progression. 1218 99

We describe two patients who developed acute renal failure secondary to severe pericardial effusion. In one patient, the pericardial effusion was due to coxsackievirus infection, and in the other patient, it was due to lung cancer. One patient was in cardiac tamponade, and the other was not yet in tamponade, as per echocardiographic criteria. Kidney function was relatively normal in both patients before the pericarditis episodes. In both patients, pericardiocentesis caused immediate massive diuresis with quick recovery of renal function back to baseline. In the first patient, blood urea nitrogen and serum creatinine decreased from 82 mg/dL and 7.6 mg/dL to 71 mg/dL and 4.6 mg/dL in the next 48 hours, then to 23 mg/dL and 1.3 mg/dL 5 days after the pericardiocentesis. In the second patient, blood urea nitrogen and serum creatinine decreased from 109 mg/dL and 2.9 mg/dL to 40 mg/dL and 0.9 mg/dL in the next 48 hours and 17 mg/dL and 0.7 mg/dL 3 days after release of tamponade. Pericardial effusion can affect renal hemodynamics in many different ways, including increased atrial natriuretic peptide secretion, increased renal efferent nerve activity, and increased secretion of renin and vasopressin. Although pericardial effusion is a complication of uremia, acute renal failure per se can occur in nonuremic cases of pericardial effusion. Two cases of acute renal failure resulting from pericardial effusion were reported in the literature in the past. Pericardial effusion should be included in the broad list of prerenal causes of acute renal failure.
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PMID:Pericardial effusion leading to acute renal failure: two case reports and discussion of pathophysiology. 1232 21

Hypermethylation of cytosines in CpG-rich islands of the promoter regions of regulatory genes has been discovered as a common mechanism of gene silencing during carcinogenesis. We analysed 64 primary lung carcinomas for promoter methylation of the tumour suppressor genes (TSGs) p16 (p16(INK4a)/CDKN2A) and p14 (p14(ARF)) by methylation-specific PCR, in order to evaluate aberrant methylation as a potential biomarker for epigenetic alterations in tobacco-related lung cancer. Methylation of p16 was observed in 34% (22/64) of the lung tumours examined. In particular, p16 methylation occurred in nonsmall cell lung cancer (NSCLC) only, with 41 % (22/54) of the tumours being positive. The highest frequency was found in large cell carcinoma (5/7, 71%), followed by adenocarcinoma (9/25, 36%) and squamous cell carcinoma (7/21, 33%). Methylation of the p14 gene was less frequent in lung cancer (4/52, 8%). When association with tobacco smoking was analysed, 42% (21/50) of NSCLC from ever smokers exhibited p16 methylation. Interestingly, the analysis revealed a significantly higher risk of p16 methylation in former smokers as compared to current smokers [odds ratio (OR) 5.1; 95% confidence interval (CI) 1.3-22]. The difference was retained after adjustment for age (OR 3.7; 95% CI 0.9-17). The promoter methylation results were then combined with data on genetic alterations determined previously in the same set of tumours. This data similarly showed that p16 methylation in parallel with p53 gene mutation or p14 methylation occurred more frequently in former smokers than in current smokers (44% vs. 14%; P = 0.035). Taken together, our data suggest that analysis of promoter methylation in TSGs may provide a valuable biomarker for identification of groups with an elevated risk of cancer, such as smokers and ex-smokers.
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PMID:Aberrant p16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer. 1291 69

Current hemodialysis treatment is insufficient because of intermittent treatment and loss of tubular function. In order to overcome the loss of tubular function, a bioartificial kidney has been developed consisting of continuous hemofiltration (CHF) with 10 L/day of filtrate and a bioartificial tubule device using proximal tubular epithelial cells and hollow fiber membranes. Ten L/day of CHF enabled plasma levels of urea, creatinine, uric acid and, beta2-microglobulin in eight renal failure patients to be maintained at remarkably low levels. The concept was tested with 6 L (4 mL/min) of 10 L/day (7 mL/min) filtrate regenerated by a bioartificial tubule device and 4 L/day (3 mL/min) replaced by food and drinks. Lewis lung cancer-porcine kidney 1 (LLC-PK1) cells with a cell density of 107 cells/mL were seeded inside polysulfone hollow fiber modules four times at 1 h intervals while rotating the module 90 degrees each time, and were cultured for 48 h to form confluent monolayers. The leak rates of urea and creatinine across LLC-PK1 cell-attached polysulfone membrane modules (membrane areas: 56 cm2 and 4000 cm2) were investigated. Via conversion from 56 m2 to 1 m2 hollow fiber modules with LLC-PK1 cells for 24 h, the transport rates of H2O, glucose and Na+ were, respectively, 40, 65 and 35% of the target transported amounts from 6 L/day of filtrate. The rates are expected to approach 100% when 4-5 g/dL of albumin is added to the basal portion of the medium since the results were obtained without the addition of albumin for colloidal osmotic pressure.
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PMID:Research into the development of a wearable bioartificial kidney with a continuous hemofilter and a bioartificial tubule device using tubular epithelial cells. 1472 Feb 90


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