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

Any operation for lung cancer that is planned as curative includes dissection of the lymph nodes in the mediastinum in order to allow correct staging of the disease. It is well known that ipsilateral lymph node metastases (N2) mean a poor prognosis. Since most patients with this finding die from metastatic tumor progression within 3 years after the operation, it can be assumed that positive findings in the mediastinal lymph nodes represent generalization of the cancer. Therefore, the probability of a therapeutic effect from more radical removal of lymph nodes in the mediastinum is rather low. On the other hand, it is justified to apply and evaluate additional systemic treatment in these tumor stages.
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PMID:[Technique and rationale of lymph node dissection in bronchial carcinoma]. 961 23

Transitions from small cell (SCLC) to non-small cell lung cancer (NSCLC) cells have been documented both in vitro and in vivo and are thought to be an important step during tumor progression of human small cell lung cancer towards a treatment-resistant tumor state. We have screened NSCLC and SCLC cell lines for differences in the composition of nuclear transcription factors using consensus oligonucleotide sequences (SRE, Ets, TRE, CRE, B-motif, GAS, E-box). We found NSCLC cells to exhibit significantly higher AP-1 binding activity than SCLC cells consistent with the increased expression of CD44, an AP-1 target gene. To gain more insight into the molecular mechanisms underlying these differences, we analysed SCLC cell lines (NCI-N592 and NCI-H69) which were phenotypically transformed into NSCLC-type cells by transfection with activated H-ras and c-myc oncogenes. In these cells, ras-induced transition is accompanied by a strong induction of AP-1-binding activity along with increased expression of CD44 mRNA and protein. When analysing the composition of the AP-1 complex in more detail and comparing ras-induced versus phorbol ester-induced changes, we found Fra-1 to be the major component induced in ras-transfected but not in phorbol-ester treated or non-treated parental SCLC cells. This finding is paralleled by the observation that among the various members of the Fos and Jun family analysed (c-Fos, FosB, Fra-1, Fra-2, c-Jun, JunD, JunB) fra-1 is the only gene to be exclusively expressed in NSCLC cells but not in cells of SCLC origin. Our data, thus, point to a histiotype-related mechanism of recruitment among AP-1 proteins which may have bearings on the fate of lung cancer development.
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PMID:Transition from SCLC to NSCLC phenotype is accompanied by an increased TRE-binding activity and recruitment of specific AP-1 proteins. 966 39

Lung cancer is the end result of a multistep process in which genetic and molecular changes accompany, in an unknown temporal sequence, histological precursor (preinvasive) bronchial lesions. Biomarkers allowing prediction of the rate of progression of precursor lesions at different locations in the anatomical field may be clinically useful. Toward this aim, we analyzed, using immunohistochemistry, the expression of the p53 gene and of its transcriptional target genes bax, bcl2, and waf1 in preinvasive bronchial lesions from 69 patients with lung cancer and in similar lesions from 20 patients with no cancer progression. p53 accumulation occurred with increasing frequency, from 19% in mild dysplasia to 36% in moderate dysplasia and 59% in carcinoma in situ, and was exclusively observed in patients with p53-positive carcinoma. The higher frequency of the p53-positive immunophenotype in lesions adjacent to the p53-positive carcinoma, as compared to lesions distant from it, suggests that p53 mutant preneoplastic lesions had a higher rate of progression to invasion than did p53-negative lesions. Similar lesions in patients with no progression to lung cancer were all p53 negative. Bcl2 overexpression and Bax down-regulation, as shown by immunostaining, occurred in preinvasive lesions and were mainly maintained during invasion. The expressions of bax, bcl2, and waf1 did not correlate with p53 status. We conclude that p53 stabilization in preinvasive lesions has high predictive value for progression to invasion and that Bax/Bcl2 imbalance contributes to the clonal expansion during premalignant states.
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PMID:p53 mutant immunophenotype and deregulation of p53 transcription pathway (Bcl2, Bax, and Waf1) in precursor bronchial lesions of lung cancer. 967 34

Vascular endothelial growth factor (VEGF) expression and mutations of cancer-related genes increase with cancer progression. This correlation suggests the hypothesis that oncogenes and tumour suppressors regulate VEGF, and a significant correlation between p53 alteration and increased VEGF expression in human lung cancer was reported recently. To further examine this hypothesis, we analysed VEGF protein expression and mutations in p53 and K-ras in 27 non-small-cell lung cancers (NSCLC): 16 squamous cell, six adenocarcinomas, one large cell, two carcinoids and two undifferentiated tumours. VEGF was expressed in 50% of the squamous cell carcinomas (SCC) and carcinoids but none of the others. p53 mutations occurred in 14 tumours (52%), and K-ras mutations were found in two adenocarcinomas and one SCC; there was no correlation between the mutations and VEGF expression. As nitric oxide also regulates angiogenesis, we examined NOS expression in NSCLC. The Ca2+-dependent NOS activity, which indicates NOS1 and NOS3 expression, was significantly reduced in lung carcinomas compared with adjacent non-tumour tissue (P < 0.004). Although the Ca2+-independent NOS activity, which indicates NOS2 expression, was low or undetectable in non-tumour tissues and most carcinomas, significant activity occurred in three SCC. In summary, our data do not show a direct regulation of VEGF by p53 in NSCLC. Finally, we did not find the up-regulation of NOS isoforms during NSCLC progression that has been suggested for gynaecological and breast cancers.
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PMID:Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53. 968 99

The genetic mechanisms underlying the progression to the metastatic phenotype of lung cancer are poorly understood. We recently showed that small cell lung cancer (SCLC) and metastasizing squamous cell carcinomas are characterized by an increased incidence of allelic loss on chromosome 10q. In the present study we performed a deletion mapping using 24 polymorphic markers on chromosome 10q22-q26 in 39 squamous cell carcinomas (SCC) of the lung identifying 14 metastatic carcinomas (74%) and three non-metastatic SCC (15%) with allelic imbalance. The allelotype analysis indicated three regions of allelic loss that were clustered at the loci Afm086/D10S541, D10S185 and D10S1782/D10S169. A localized microsatellite instability was observed in two carcinomas for the markers D10S1686 and D10S1782. In addition the PTEN/MMAC1 gene was analysed by direct DNA sequencing and Southern blot analysis in 25 and 28 carcinomas, respectively, without detecting any genomic alterations. Similarly, no altered transcript was detected in 15 tumor cell lines and 20 primary tumors by Northern blot analysis or RT-PCR. In summary, three distinct regions of allelic imbalance were identified suggesting that multiple tumor suppressor genes on chromosome 10q contribute to tumor progression and metastases formation of lung cancer.
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PMID:Distinct regions of allelic imbalance on chromosome 10q22-q26 in squamous cell carcinomas of the lung. 969 38

Lymphocytopenia is a prognostic factor for shorter survival in advanced lung cancer and it is likely related to an interleukin-2 (IL-2) deficiency occurring during cancer progression. Major surgery itself for cancer is known to induce lymphocytopenia in the postoperative period. Postoperative lymphocyte decrease in colorectal cancer can be prevented by preoperative administration of recombinant human (rhIL-2), indicating that it is possible to drive appropriately important host defence agents during critical events, such as major surgery. The aim of this study is to verify if recombinant human interleukin-2 (rhIL-2) administered preoperatively is able to prevent the lymphocyte decrease occurring after radical surgery in operable lung cancer. This phase II study included 40 patients with operable NSCLC screened as stage II or IIIA, randomized to receive rhIL-2, 9000000 IU subcutaneously twice daily for 3 days before surgery (treated group, 20 patients) or not (control group, 20 patients). At baseline, there were no significant differences in total lymphocyte number and lymphocyte subsets (T-cell, T-helper, CD8+, natural killer, CD4/CD8 ratio) between groups. Postoperatively the control group showed a decrease in total lymphocyte count, T-lymphocyte count, T-helper cell number and CD4/CD8 ratio, significant at the 14th postoperative day relative to baseline values. In contrast, in the rhIL-2 treated group, at the 3rd and at the 14th postoperative days, a significant increase was observed over both baseline and control group values of total lymphocyte count, T-cells and T-helper cells. NK cell number increased significantly only over the control group. CD4/CD8 ratio was increased at the 14th postoperative day significantly over both baseline and control values. At pathological staging after surgery, four patients in the rhIL-2 group and four in the control group resulted in stage pIIIB; one patient in the rhIL-2 group resulted in stage IV (contralateral metastasis). Indeed, 15/20 rhIL-2 treated patients and 16/20 control patients were radically operated. After a 24-month follow-up, 12/20 rhIL-2 treated patients were alive and 8/15 radically operated were disease-free; 8/20 control patients were alive and 4/16 radically operated were disease-free. Toxicity was mild to moderate and easy manageable; treatment was suspended in one patient due to skin rash with hypotension grade II. The preoperative administration of rhIL-2 is feasible and prevents lymphocyte decrease occurring postoperatively after surgery for lung cancer. Further studies are required to assess the impact on survival.
Lung Cancer 1998 Jun
PMID:Phase-II randomized study of pre-operative IL-2 administration in operable NSCLC. 973 54

This phase II study was designed to assess the response rate and toxicity of paclitaxel and cisplatin chemotherapy in Chinese patients with untreated advanced non-small-cell lung cancer (NSCLC). Eligibility requirements included histologically confirmed stage IIIb-IV NSCLC, Eastern Cooperative Oncology Group performance status less than 2, no previous chemotherapy, and adequate bone marrow, renal, and hepatic function. From April 1996 through March 1997, 32 patients were treated. The dose of paclitaxel was 135 mg/m2 as a 3-hour infusion on day 1 and cisplatin 75 mg/m2 on day 2. The regimen was repeated every 3 to 4 weeks for up to 6 to 8 cycles unless there was evidence of tumor progression. The median age was 57 years (range, 31-77 years). Sixty-five percent were men. Sixty-nine percent had adenocarcinoma, and 75% had stage IV disease. One hundred seventy-two cycles were administrated; 18 patients (56%) completed all six cycles. Peripheral neuropathy and myelosuppression were the principle toxicities. Neurotoxicity appeared to be dose limiting and manifested primarily as paresthesia. Grade 2 neurotoxicity was observed in 5% of courses, which was slowly reversible. However, the severity of myelosuppression was generally mild to moderate. No episode of neutropenic fever was noted. Thrombocytopenia remained infrequent throughout the study. Other nonhematologic toxicities were also generally mild. The objective response rate was 50%. In conclusion, this combination of paclitaxel and cisplatin is active in Chinese patients with advanced NSCLC. It merits further investigation in phase III trials.
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PMID:Preliminary result of phase II study of paclitaxel and cisplatin chemotherapy for advanced non-small-cell lung cancer in Chinese patients. 978 6

Vinorelbine, docetaxel and cisplatin have documented single-agent activity in non-small-cell lung cancer (NSCLC); a multicenter phase II trial was initiated in order to evaluate the tolerance and efficacy of their combination. A total of 24 chemotherapy-naive patients with measurable stage IIIB or IV NSCLC and performance status (PS; WHO) 0-2 entered the study. Vinorelbine (20 mg/m2 i.v.) was given on days 1 and 15, cisplatin (60 mg/m2) on day 1, and docetaxel (100 mg/m2) on day 16, in cycles of 28 days. Recombinant human granulocyte colony-stimulating factor (150 microg/m2 s.c.) was administered prophylactically from day 17 to day 27. One pathological complete (4%) and six partial responses (25%) were documented (overall response 29%; 95% CI 11.6-49.2%). A total of five patients (21%) had stable and 12 (50%) progressive disease. The median duration of response was 28 weeks and the median time to tumor progression 36 weeks; the median survival was 20 weeks. Grade 3-4 neutropenia occurred in 16 patients (67%) while 13 of them (54%) developed febrile neutropenia. Grade 4 mucositis occurred in two patients (8%) and one of them also presented grade 4 diarrhea. There were four treatment-related deaths: two from sepsis, one from massive hemoptysis due to a pulmonary abscess and one from acute myocardial ischemia 7 days post-chemotherapy. In conclusion, the high incidence of neutropenic episodes and treatment-related deaths led to an early discontinuation of patient enrollment. This combination, in the schedule and the doses used, could not be recommended for off protocol treatment of patients with advanced NSCLC.
Lung Cancer 1998 Sep
PMID:Combination chemotherapy with docetaxel, vinorelbine and cisplatin as first-line treatment of advanced non-small-cell lung cancer: a multicenter phase II study of the Greek Cooperative Group for Lung Cancer. 985 99

Synchronous primary lung cancer (SPLC) occurs in up to 0.5% of patients with lung cancer. Among SPLC cases, coexistence of small cell carcinoma (SCLC) and non-small cell carcinoma has been reported in a very small fraction. Futhermore, there have been no reports discussing treatment and prognosis of SPLC presenting with SCLC and NSCLC. We report on two cases of SPLC presenting SCLC in limited stage and operable NSCLC. One patient developed synchronously SCLC and adenocarcinoma of the lung, while the other SCLC and squamous cell carcinoma of the lung. The clonal origin of these synchronous lung cancers was evaluated using immunohistochemical and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses. Both of the patients were diagnosed based on transbronchial lung biopsy (TBLB) and mediastinoscopic biopsy. They were successfully treated with chemoradiotherapy and adjuvant surgery, and are now doing well without any signs of tumor progression for about one year. In both cases, a response of mediastinal lymph node for concurrent chemoradiotherapy was quite different from that of the mass in the lung field. In case 2, p53 mutation was observed in the SCLC tissue, but not in the NSCLC tissue by PCR-SSCP. In both cases, carcinoembryonic antigen was documented in the NSCLC tissue, but not in the SCLC tissue by immunohistochemical staining. This report indicates the importance of the accurate diagnosis of SPLC by employing TBLB and/or media-stinoscopy for the optimal treatment of patients having SPLC presenting with SCLC and NSCLC. Diagnostic criteria and standard treatment of this disease should be established.
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PMID:Synchronous primary lung cancer presenting with small cell carcinoma and non-small cell carcinoma: diagnosis and treatment. 986 5

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.
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PMID:Immunohistopathological characterizatin of spontaneous metastases in a human lung mucoepidermoid adenocarcinoma (HLMC) xenograft. 988 55


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