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)

Computed tomography (CT) guided fine needle aspiration biopsy (CT-guided FNAB) represents the procedure of choice for diagnosing peripheral primary lung cancer before surgery. The aim of the present study was to assess the reliability of the immunocytochemical evaluation of biological parameters and DNA flow cytometry on cellular material obtained from non-small cell lung cancer (NSCLC) patients by CT-guided FNAB. Thirty consecutive CT-guided FNABs obtained from NSCLC patients were submitted both to the immunocytochemical evaluation of p53, Ki67, bcl-2 and to flow cytometric DNA analysis. p53, Ki67 and bcl-2 were assessable in 60% (18/30), 53% (16/30) and 48% (10/21) of the cases, respectively. Flow cytometric DNA analysis was performed in 19 out of the 30 cases and 74% (14/19) of the histograms were evaluable. Cytofluorimetric S-phase fraction (SPF), was obtained in 57% (8/14) of the cases. The results of the current study suggest that CT-guided FNAB from primary NSCLC patients may represent an effective practice for the evaluation of biologic parameters and could be useful as a preoperative procedure. The role of neoadjuvant chemotherapy in operable NSCLC is still under debate. We suppose that in the future the presurgical characterization of NSCLC could suggest the opportunity of a neoadjuvant systemic treatment aimed to improve the clinical outcome. Moreover, in locally advanced or metastatic NSCLC immunocytochemistry could help to predict the response to chemotherapy and/or radiotherapy, avoiding ineffective treatments and supporting the development of more rational therapies.
Lung Cancer 2002 Mar
PMID:Biological parameters on computed tomography guided fine needle aspiration biopsy from peripheral primary non-small cell lung cancer. 1184 97

Surgical material (removed lungs or their parts) from 58 patients operated in 1993-1998 was investigated. Lung adenocarcinomas (LAC) are characterized by low proliferative activity of tumor cells. With a decrease of LAC differentiation, tumor cell death by terminal differentiation also diminished which was accompanied by low bcl-2 expression and enhancement of spontaneous apoptosis with active accumulation of protein products of p53 expression in tumor cells nuclei. Expression of c-myc and bax remained unchanged. On the whole, the picture reminds that in lung squamous cell carcinoma. Bronchioloalveolar carcinoma is characterized by low proliferative activity combined with higher apoptosis compared to LAC. Large cell lung carcinoma and adenomatous-squamous lung carcinoma demonstrated the highest proliferation and spontaneous apoptosis of tumor cells with accumulation in these cells of p53, bcl-2 and bax comparing to non-small cell lung carcinoma (NSLC) with adenomatous differentiation. Progression of NCLC with adenomatous differentiation largely depends not only on proliferative activity of tumor cells but on tumor cell death due to terminal differentiation, apoptosis and necrosis as well.
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PMID:[Correlation between proliferative processes and cell death in non-small cell lung cancer with glandular differentiation at different stages of tumor progression]. 1188 98

Non-small cell lung cancer (NSCLC) is a malignant tumor with poor prognosis. Although the prognostic variables determining short-term survival have been well described, relatively little attention has been paid to factors associated with long-term survival. In search of these factors we studied the expression of several molecular markers in NSCLC. Only tumor samples of patients with squamous cell carcinomas and stage III tumors with a postoperative survival of at least 5 years and those of patients who died within 2 years after resection were selected for this study. The expression of several parameters including oncogene and suppressor gene products, proliferative, apoptotic, angiogenic and resistance-related factors were investigated and the differences in these two extreme populations were determined by the Wilcoxon rank sum test. Factors involved in proliferation (ras, fos, erbB-1, jun, cyclin A) were downregulated whereas factors involved in apoptosis (p53, bcl-2, CD95) were upregulated in the long survival group. Direct measurement of parameters of proliferation (cell cycle analysis by flow cytometry, PCNA index) revealed a lower proliferative activity in tumors of the long survivors compared to short survivors. In conclusion, tumors of the long survival group are characterized by a downregulation of factors involved in proliferation and an upregulation of factors involved in apoptosis. These tumors may grow more slowly and this may influence long-term survival of patients with NSCLC.
Lung Cancer 2002 Jun
PMID:Characteristics of long-term survivors of untreated lung cancer. 1200 38

Surgical and biopsy material was used from 57 patients with lung carcinoma (LC): 17 patients (group I) lived close to testing area from the childhood to 1993 and were exposed to radiation at the year dose 0.1 ber. For comparison surgical and biopsy material from 40 patients (group 2) was taken who lived in the territories of Kazakhstan (10 patients) and Moscow (30 patients) with normal radiation background. The following features of LC were found in the groups in question: constant observation of dust particles and interstitial and focal fibrosis in tumours of various localization and histological type; prevailing small cell carcinoma as compared to other histological types; high frequency of nonsmall cell lung carcinoma; higher expression of IGFII, IGFBP1,2 and rare expression of IGFB3; proliferative activity followed by an increased expression of c-myc, bcl-2.
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PMID:[Morphological, cytogenetic and molecular biological characteristics of lung cancer in persons exposed for a long time to radionuclide radiation pollution in the Semipalatinsk region of Kazakhstan]. 1257 34

Surgical series of non-small cell lung cancer (NSCLC) pathologic samples have shown that the expression of the proteins bcl-2 and bax, which regulate cell death, may have prognostic implications. Laboratory data also suggests that these proteins may impact chemotherapy response. In order to determine the rate of bcl-2 and bax expression in advanced NSCLC and assess the impact on chemotherapy response and patient survival, we performed immunohistochemistry on biopsy samples from patients enrolled in a phase I/II trial of vinorelbine plus docetaxel. We chose to study the pathology of patients in this specific trial because both docetaxel and vinorelbine phosphorylate bcl-2 and we hypothesized that this mechanism may affect clinical outcome. The goal of this study was to determine the feasibility of this analysis, and to observe any differences in response rate or survival based on bcl-2 or bax staining results. Unstained slides from paraffin blocks were obtained for 31 patients (55%) on the phase I/II trial. The patient characteristics for this subgroup did not differ significantly from the entire cohort of patients on the trials. Bcl-2 staining was positive in 5/31 samples (16%, 95% CI 3-29%) and bax was positive in 19/28 samples (68%, 95% CI 51-85%). Bcl-2 and bax staining did not correlate with response (p = 0.65 and 1.00 respectively, Fisher's exact test), or survival (by Kaplan-Meier curves). In conclusion, bcl-2 and bax expression was similar in this population with advanced NSCLC to previously reported results for early stage disease, but did not predict response to vinorelbine plus docetaxel in this series.
Lung Cancer 2003 Feb
PMID:Bcl-2 and bax expression in advanced non-small cell lung cancer: lack of correlation with chemotherapy response or survival in patients treated with docetaxel plus vinorelbine. 1258 65

Both intrinsic and acquired resistance to chemotherapeutic drugs are major obstacles in the treatment of non-small-cell lung cancer. Apart from classical drug resistance mechanisms, the failure of tumor cells to undergo apoptosis also plays an important role in drug resistance. Mutations and defects in the apoptotic pathway are, therefore, additional factors that determine drug resistance. The tumor suppressor gene p53, the retinoblastoma gene, and the bcl-2 family members are important factors in this pathway. Recently much attention has been drawn to different apoptotic pathways induced by naturally occurring death receptor ligands (such as tumor necrosis factor, Fas ligand, and tumor necrosis factor-related apoptosis-inducing ligand) or induced by drugs that affect the downstream pathway from the epidermal growth factor receptor. Insight regarding the proteins that determine sensitivity for chemotherapeutic drugs could provide new targets for cancer treatment, which may help to at least partly overcome drug resistance in non-small-cell lung cancer
Clin Lung Cancer 2002 Nov
PMID:The role of apoptosis-related genes in non-small-cell lung cancer. 1470 67

Antisense oligonucleotides (ASONs) are one of the new classes of molecularly targeted agents that have transitioned from the laboratory into clinical trials. Rational drug design has resulted in agents directed against a number of important cellular targets, including the mRNA of bcl-2, protein kinase (PK) C-alpha, PKA-I, H-ras, c-raf, R1 and R2 subunit of ribonucleotide reductase, and transforming growth factor beta2. These drugs are well tolerated with favorable toxicity profiles, and preliminary studies have demonstrated that they can be feasibly combined with chemotherapy. Plasma half-life is short, generally necessitating continuous prolonged intravenous infusion. Shorter administration schedules are being investigated. Efficacy has been demonstrated in early-phase studies in non-small-cell lung cancer (NSCLC), non-Hodgkin's lymphoma, ovarian cancer, melanoma, and prostate cancer. Molecular correlative studies with peripheral blood mononuclear cells and tumor tissue have demonstrated suppression of target proteins, suggesting that these drugs are indeed reaching the target. Here we discuss the current status of development of ASONs, focusing on LY900003 (formerly ISIS 3521), an agent directed against PKC-alpha currently under study in NSCLC. Phase III studies will determine the ultimate role these agents will play in the treatment of cancer. Future areas of study include combination with radiation and other molecularly targeted agents, alternative dosing schedules, liposomal administration, and the development of new antisense agents directed against additional molecular targets.
Clin Lung Cancer 2003 Jan
PMID:Antisense oligonucleotides in the treatment of non-small-cell lung cancer. 1472 Mar 40

We performed a retrospective analysis of potential prognostic markers in 260 patients with surgically resected stage I and II non small-cell lung cancer (NSCLC) with a minimum 5-year follow-up. Cox proportional hazard models and Wilcoxon tests were employed to analyze the effect of patient characteristics on survival and disease-free survival (DFS). In the univariate analysis, the following were significant predictors of shorter overall survival: N-stage (N1 vs N0) (p<0.001); T-stage (T2 vs T1) (p<0.001); antigen A (loss vs presence) (p<0.01); cough (present vs absent) (p=0.01); bcl-2 expression (positive vs negative) (p=0.03); age (>63.5 vs <63.5) (p=0.03); mucin (positive vs negative) (p<0.03). The following were significant predictors of shorter DFS: N-stage (p<0.001); T-stage (p=0.001); loss of antigen A (p=0.01); mucin expression (p<0.01); cough (p=0.02); Ki-67 expression (p=0.02) and negative bcl-2 expression (p=0.03). Analysis of survival difference for histologic subtype, degree of differentiation, aneuploidy, %S-phase, codon 12 K-ras mutation, and immunohistochemistry staining for Lewisy, p53, Rb, microvessel count, HER2, E-cadherin and neuroendocrine markers did not reach statistical significance. In multivariate analysis, the following predicted for shorter overall survival: N-stage (p<0.01), antigen A (p=0.01), age (p<0.01), and bcl-2 (p=0.05); and for DFS, N-stage (p<0.01), antigen A (p<0.01), Ki-67 (p=0.03), mucin (p=0.04) and T-stage (p=0.05). Of all the clinical-pathological, proliferative, and biological markers studied, only a few carried independent prognostic significance.
Clin Lung Cancer 1999 Aug
PMID:Prognostic markers in resected stage I and II non small-cell lung cancer: an analysis of 260 patients with 5 year follow-up. 1472 52

Lung carcinoma is a leading cause of death. However, there are few indicators that can aid in prediction and prognosis. Many tumour markers are available, but their reliability is questionable. For example, Ki-67 expression has been associated with increased as well as decreased survival or with no clinical significance. The varying results have been attributed to the methodology, relative intensity of staining, variety of marking and statistical methods. To determine whether differential expression of markers within tumours may be a contributory factor to this lack of agreement, we used two marking methods to evaluate the level of expression of Ki-67, p53 and bcl-2, in addition to the apoptotic index, in serial sections of non-small cell carcinoma. All stains exhibited a degree of heterogeneity. This small study highlights the importance of standardisation of marking methods and interpretation of results if tumour markers are to be used as predictive or prognostic factors.
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PMID:Heterogeneity of immunostaining for tumour markers in non-small cell lung carcinoma. 1474 66

Despite novel therapies in lung cancer treatment the 5-year survival rate still remains poor. Furthermore, screening concepts for early diagnosis, based on conventional sputum cytology and chest radiography, have so far not demonstrated an impact on decreasing lung-cancer mortality. More specific molecular markers allow new insights in the process of lung carcinogenesis. Furthermore they raise the hope that they provide new tools for early diagnosis and screening of high-risk individuals, determination of prognosis, and identification of innovative treatments. In this review, these perspectives of molecular targets in lung cancer will be discussed and summarised. Angiogenesis-stimulating factors (VEGF, FGF, MMP, etc.), parameters concerning tumour cell proliferation and apoptosis (EGFR, p53, K-ras, rb, bcl-2, etc.) are well known. Several of these genetic factors have already been investigated, but no single parameter has yet gained a sufficient selectivity regarding prognostic significance or therapeutic efficacy. New aspects in the complex tumour-stroma interaction and the interactive, cross-talking signal transduction pathways and recently developed functional genomic approaches, such as DNA microarrays and proteomics might lead to further progress in biological staging models and treatment concepts.
Lung Cancer 2004 Aug
PMID:Molecular oncology--perspectives in lung cancer. 1555 1


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