Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This phase III study was conducted to evaluate the usefulness of lenograstim as support for ACE (doxorubicin, cyclophosphamide, and etoposide) chemotherapy in previously untreated patients with small-cell lung cancer. Patients were randomized to receive up to six 3-week cycles of either ACE alone (n = 139) or ACE with lenograstim support (150 microg/m2/day subcutaneously, days 4-13, n = 141). Compared with the chemotherapy-alone group, the lenograstim support group was more likely to achieve neutrophil recovery (absolute neutrophil count, > or =1.5 x 10(9) cells/l) by day 14 (95.8-100% vs. 14.3-24.1% across the cycles) and less likely to experience at least one infectious episode (36.7 vs. 54.0%; p = 0.004), chemotherapy delay (51.8 vs. 56.2%; NS), or dose reduction (17.3 vs. 27.7%; p = 0.037). Objective response and event-free and overall survival rates were similar. Lenograstim was well tolerated. Lenograstim may allow the interval between cycles of ACE to be reduced to 2 weeks; such dose intensification may lead to more favorable objective response and survival rates.
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PMID:Lenograstim as support for ACE chemotherapy of small-cell lung cancer: a phase III, multicenter, randomized study. 1095 71

The randomized clinical trial, LU19, conducted by the Medical Research Council Lung Cancer Working Party, was designed to compare ACE (doxorubicin, cyclophosphamide and etoposide) chemotherapy plus G-CSF (granulocyte colony-stimulating factor) at 2-week intervals versus ACE chemotherapy alone at standard 3-week intervals in patients with small-cell lung cancer. This trial investigated whether more intensive administration of ACE would improve overall survival and affect the quality of life of patients. The report on overall survival and other outcome measures will be published in the Journal of Clinical Oncology. In this paper we focus on methods of analysing aspects of data reflecting quality of life. Twelve symptoms of lung cancer and its treatment - cough, haemoptysis, pain, nausea, vomiting, hoarse voice, sore mouth, rash, lethargy, lack of appetite, alopecia, and dysphagia - were scheduled to be assessed on seven occasions for the ACE arm and on eight occasions for the ACE+G-CSF arm by clinicians during the first 18 weeks of the treatment period. However, in practice the number of assessment forms completed per patient ranged from 1 to 9, and assessment time-points were very different from those planned. These 'messy' longitudinal data are explored by both a summary measure approach, in which experience of a symptom is summarized by a single value, and an extensive model-based statistical approach, which explicitly takes into account correlation within repeated measures. These analyses provide a clear picture of symptom comparisons between the two treatments. The application of various methods offers not only an approach to assessing the robustness of the results but also a basis for investigating reasons for inconsistency of results across methods. We conclude that except lethargy, which is worse in the ACE+G-CSF arm, all symptoms are similar across the two arms during the treatment period.
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PMID:Analysis of messy longitudinal data from a randomized clinical trial. MRC Lung Cancer Working Party. 1098 40

Although radiotherapy improves locoregional control and survival in patients with non-small-cell lung cancer, radiation pneumonitis is a common treatment-related toxicity. Many pulmonary function tests are not significantly altered by pulmonary toxicity of irradiation, but reductions in D(L(CO)), the diffusing capacity of carbon monoxide, are more commonly associated with pneumonitis. Several patient-specific factors (e.g. age, smoking history, tumor location, performance score, gender) and treatment-specific factors (e.g. chemotherapy regimen and dose) have been proposed as potential predictors of the risk of radiation pneumonitis, but these have not been consistently demonstrated across different studies. The risk of radiation pneumonitis also seems to increase as the cumulative dose of radiation to normal lung tissue increases, as measured by dose-volume histograms. However, controversy persists about which dosimetric parameter optimally predicts the risk of radiation pneumonitis, and whether the volume of lung or the dose of radiation is more important. Radiation oncologists ought to consider these dosimetric factors when designing radiation treatment plans for all patients who receive thoracic radiotherapy. Newer radiotherapy techniques and technologies may reduce the exposure of normal lung to irradiation. Several medications have also been evaluated for their ability to reduce radiation pneumonitis in animals and humans, including corticosteroids, amifostine, ACE inhibitors or angiotensin II type 1 receptor blockers, pentoxifylline, melatonin, carvedilol, and manganese superoxide dismutase-plasmid/liposome. Additional research is warranted to determine the efficacy of these medications and identify nonpharmacologic strategies to predict and prevent radiation pneumonitis.
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PMID:Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer: pulmonary function, prediction, and prevention. 1596 60

Immunohistochemical evaluation of lung carcinomas for key enzymes involved in cellular metabolism (lactate dehydrogenase LDH 1 and 5, pyruvate dehydrogenase PDH, pyruvate dehydrogenase kinase PDHK-1, monocarboxylate transporters MCT 1, 2 and 4, glucose transporter GLUT1, hypoxia inducible factors HIF1alpha and 2alpha) show a complementary metabolic profile between cancer cells and tumor-associated stroma. Cancer cells share enzyme/transporter activities suggestive of an anaerobic metabolism with high affinity for glucose absorption, anaerobic glycolysis and lactate extrusion. On the other hand, the tumour-associated fibroblasts express patterns involved in aerobic pathways and lactate oxidation. These findings bring forward the hypothesis that tumor associated stroma is an accomplice in tumor growth and survival sustaining an independent cellular and metabolic tumor domain. The development of agents exploiting such cancer specific metabolic pathways may prove of importance in the treatment of lung cancer.
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PMID:Lung cancer: a comparative study of metabolism related protein expression in cancer cells and tumor associated stroma. 1788 95

This randomised trial compared platinum-based to anthracycline-based chemotherapy in patients with small-cell lung cancer (limited or extensive stage) and <or=2 adverse prognostic factors. Patients were randomised to receive six cycles of either ACE (doxorubicin 50 mg/m(2) i.v., cyclophosphamide 1 g/m(2) i.v. and etoposide 120 mg/m(2) i.v. on day 1, then etoposide 240 mg/m(2) orally for 2 days) or PE (cisplatin 80 mg/m(2) and etoposide 120 mg/m(2) i.v. on day 1, then etoposide 240 mg/m(2) orally for 2 days) given for every 3 weeks. For patients where cisplatin was not suitable, carboplatin (AUC6) was substituted. A total of 280 patients were included (139 ACE, 141 PE). The response rates were 72% for ACE and 77% for PE. One-year survival rates were 34 and 38% (P=0.497), respectively and 2-year survival was the same (12%) for both arms. For LD patients, the median survival was 10.9 months for ACE and 12.6 months for PE (P=0.51); for ED patients median survival was 8.3 months and 7.5 months, respectively. More grades 3 and 4 neutropenia (90 vs 57%, P<0.005) and grades 3 and 4 infections (73 vs 29%, P<0.005) occurred with ACE, resulting in more days of hospitalisation and greater i.v. antibiotic use. ACE was associated with a higher risk of neutropenic sepsis than PE and with a trend towards worse outcome in patients with LD, and should not be studied further in this group of patients.
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PMID:Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. 1866 90

Lung cancer is the most common form of cancer in the world, and 90% of patients die from their disease. The angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents, and it has been suggested that they decrease the risk of some cancers, although available data are conflicting. Accordingly, we investigated the anticancer activity of the ACE inhibitor, captopril, in athymic mice injected with highly tumorigenic LNM35 human lung cells as xenografts. Using this model, we demonstrated that daily IP administration of captopril (2.8 mg/mouse) for 3 weeks resulted in a remarkable reduction of tumor growth (58%, P < 0.01) and lymph node metastasis (50%, P= 0.088). There were no undesirable effects of captopril treatment on animal behavior and body weight. In order to determine the mechanism by which captopril inhibited tumor growth, we investigated the impact of this drug on cell proliferation, apoptosis, and angiogenesis. Immunohistochemical analysis demonstrated that captopril treatment significantly reduced the number of proliferating cells (Ki-67) in the tumor samples but was not associated with inhibition of tumor angiogenesis (CD31). Using cell viability and fluorescent activated cell sorting analysis tests, we demonstrated that captopril inhibited the viability of LNM35 cells by inducing apoptosis, providing insight about the mechanisms underlying its antitumorigenic activities. In view of these experimental findings, we conclude that captopril could be a promising option for the treatment of lung cancer.
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PMID:Captopril as a potential inhibitor of lung tumor growth and metastasis. 1883 85

The purpose of this study was to evaluate the feasibility and activity of radiotherapy (RT) treatment in elderly patients with locally advanced lung cancer. From January 2002 to December 2007, 51 consecutive patients (43 men and 8 women) aged > or = 65 received RT for locally advanced lung cancer, 22 with radical intent and 16 in adjuvant setting. Thirty-six patients received chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery vs. no surgery, radiation dose and chemotherapy. The median age was 74.7 years (range 65-91). Of the patients, 15.7% had no co-morbidity, 41.2% mild, 25.5% moderate, and 17.6% had severe co-morbidities. Sixteen subjects (31.4%) underwent surgery. All patients completed the planned radiation schedule, while chemotherapy was reduced in 16 patients. At a median follow-up of 22 months, the 2- and 3-year overall survival rates were 46.5% and 35.4%, respectively. Patients with no or mild co-morbidities (p < 0.0001) and a good performance status (p < 0.0001) had a better survival. The actuarial progression-free survival at 2 and 3 years was 41.4% and 38.2%, respectively. Acute lung toxicity rates were different between patients with different ACE-27 indexes, whereas late toxicity was not influenced. In conclusion, in elderly patients, the compliance with RT is good and the rate of toxicity is acceptable. Patients with no or mild co-morbidities have a significantly better survival. The increasing severity of co-morbidities may sufficiently shorten the remaining life expectancy, cancel the gains obtained by RT and increase the acute lung toxicity. Further prospective trials are needed to confirm these results.
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PMID:Safety and feasibility of radiotherapy treatment in elderly non-small-cell lung cancer (NSCLC) patients. 1941 Mar 5

Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.
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PMID:Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity. 1971 47

Angiotensin II (AngII) is a multifunctional bioactive peptide and previous studies have shown that the renin-angiotensin system (RAS) of both host and tumor are important in tumor growth and angiogenesis in lung cancer. Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS, with 42% amino acid homology to ACE. However, the expression and function of ACE2 in non-small cell lung cancer (NSCLC) are still unclear. In the present study, we analyzed ACE2 expression in NSCLC tissue by Western blot analysis and immunohistochemistry. AngII concentrations in the tissue homogenate were also detected using radio-immunoassay. We also examined the function of ACE2 by transducing A549 cells with MSCV-ACE2. We have shown for the first time that ACE2 expression decreased in NSCLC tissue in which AngII was higher than the matching non-malignant tissues. A concentration of 10(-6) mol/l of AngII significantly increased expression of vascular endothelial growth factor a (VEGFa) and AT1-R and decreased ACE2 expression. We also found that overexpression of ACE2 may have a protective effect by inhibiting cell growth and VEGFa production in vitro. ACE2 may become a target of novel strategies to treat NSCLC.
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PMID:The angiotensin-converting enzyme 2 in tumor growth and tumor-associated angiogenesis in non-small cell lung cancer. 2020 77

Non-inflammatory swelling in the head and neck area are usually caused by allergic angioedema. However, other differential diagnoses must always be considered. Superior vena cava syndrome is a rare differential diagnosis of angioedema. Since we treated two such patients within only a few weeks of one another with the initial supposition of an ACE inhibitor-induced angioedema, but who ultimately proved to have lung cancer, we would like to draw attention to this disease pattern.
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PMID:[Facial swelling caused by small cell lung cancer: a rare differential diagnosis of angioedema]. 2060 1


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