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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxicity, response, and long-term results of a definitive chemotherapy/radiation therapy (RT) protocol in patients with unresectable stage III non-small-cell lung cancer (NSCLC) were evaluated. Two cycles of cisplatin-based chemotherapy were delivered before RT, and another 2 cycles were added for patients who responded to the first 2 cycles of chemotherapy. The first course of radiation covered the primary lesion and elective nodal regions, given in 2 Gy per fraction, 5 days a week for a dose of 40 Gy. Late-course hyperfractionated accelerated RT was delivered to the gross tumor twice a day for an additional 27 Gy within 2 weeks, using 1.5 Gy per fraction. Fifty-three patients with unresectable stage IIIA (N2) and IIIB NSCLC were eligible for analysis. Twelve patients developed grade 3 neutropenia, and 3 patients developed grade 4 neutropenia. Grade 2 or 3 esophagitis was observed in 14 and 2 patients, respectively, and grade 2 or 3 pneumonitis was observed in 9 and 1 patient, respectively. Six patients developed grade 2 and 1 patient developed grade 3 late lung toxicity. The median survival time was 15.5 months. Twenty-six of 53 patients (49%) have died of locoregional progression inside the thorax. The distant metastasis rate was 59.5% (22 of 37 patients) for those who did not respond to chemotherapy and 18.8% (3 of 16 patients) for those who responded to chemotherapy (P = 0.006). Late-course hyperfractionated accelerated RT combined with induction chemotherapy was well tolerated and yielded long-term results that compare favorably with those of studies using 2 cycles of induction chemotherapy and conventional fractionated RT. However, local control was still discouraging.
Clin Lung Cancer 2005 Mar
PMID:Neoadjuvant chemotherapy followed by late-course accelerated hyperfractionated radiation therapy for locally advanced non-small-cell lung cancer: long-term results of a phase I/II clinical trial. 1584 82

Standardized uptake value (SUV) has been linked to tumor aggressiveness and long-term prognosis. Based on the hypothesis that positron emission tomography (PET) SUV serves as a surrogate for biologic aggression, we investigated whether SUV in the primary lesion, independent of size, correlates with the presence of nodal or distant metastases at the time of presentation. We retrospectively reviewed computed tomography (CT) scan, PET scan, and histologic findings of consecutive patients in our lung cancer referral population evaluated between December 15, 2000 and April 15, 2004. Only patients with primary non-small-cell lung cancer and pathologic confirmation of nodal status or conventionally accepted non-PET proof of distant metastases were included for analysis. One hundred thirty-nine patients had complete results, including CT, PET, and independent confirmation of nodal or distant disease. The stage distribution was as follows: 33 IA, 24 IB, 5 IIA, 9 IIB, 21 IIIA, 8 IIIB, and 39 IV. Simple logistic regression analysis demonstrated a highly significant correlation between SUV of the primary lesion and the presence of nodal or distant metastases at the time of presentation (P = 0.0036). When odds ratios were calculated, a 13% increase in the likelihood of nodal/distant disease was found for every unit increase in SUV. We conclude that PET SUV, independent of size, is a marker of biologic aggression. Elevated SUV in the primary lesion at presentation should prompt high suspicion and mandates meticulous search for nodal or distant disease.
Clin Lung Cancer 2005 Mar
PMID:Increased standardized uptake value in the primary lesion predicts nodal or distant metastases at presentation in lung cancer. 1584 83

FBN2, a large modular extracellular matrix glycoprotein, is known to be a key component of human elastic fiber. A loss of FBN2 expression due to promoter methylation was recently identified in pancreatic cancer. We examined FBN2 expression by reverse transcription PCR and aberrant methylation of FBN2 by methylation specific PCR in lung cancer cell lines. Aberrant methylation of FBN2 was present in 55% (6 of 11) of non-small cell lung cancer (NSCLC) cell lines, but it absent in small cell lung cancer cell lines. The concordance between loss of expression and aberrant methylation of FBN2 was 88% (14 of 16) in the cell lines. FBN2 expression was restored after treatment with the demethylating agent, 5-aza-2'-deoxycytidine in all six cell lines tested that lacked FBN2 expression. Among primary NSCLC, 49% (62/126) of cases had FBN2 methylation, but only 7% (5/69) of the corresponding nonmalignant lung tissues had it. Although FBN2 methylation was detected even in patients with early stage disease, it occurred frequently in large tumors (p=0.022), with nodal metastasis (p=0.037), or with advanced stages of NSCLC (p=0.014). Methylation and silencing of FBN2 in tumor cells may play an important role in carcinogenesis, invasion, and metastasis of NSCLC.
Lung Cancer 2005 Oct
PMID:Aberrant methylation of FBN2 in human non-small cell lung cancer. 1595 Oct 52

The endothelin (ET) system influences tumourigenesis and tumour progression by various mechanisms, including angiogenesis. The aim of this study was to determine whether the expression of endothelin-1 (ET-1) is related to the angiogenic phenomenon in lung cancer and whether it could be involved in its clinical behaviour. Expression of ET-1, endothelin-converting enzyme-1 (ECE-1) and endothelin-receptors ETA and ETB was examined in 201 non-small cell lung carcinoma (NSCLC) and corresponding normal tissues using real-time polymerase chain reaction (RT-PCR). Forty NSCLC were also analysed for vascular endothelial growth factor (VEGF) expression by a competitive-PCR approach to assess whether ET-1 expression was related to this angiogenic factor. A higher number of cases with ET-1, ECE-1 and ETA mRNA expression was observed in malignant lung tumours compared with normal lung tissues (45.7% versus 33% for ET-1 (P < 0.0001); 38.3% versus 16.5% for ECE-1 (P = 0.004); and 42.8% versus 28.5% for ETA (P < 0.0001)). On the other hand, ETB mRNA was higher in normal lung tissues than in tumour samples (58.5% versus 52.8% (P < 0.0001)). Immunohistochemical analysis was also performed in 78 cases, selected from among those with high ET-1 mRNA, to confirm the presence of ET-1 protein and to determine its distribution and localisation. Moreover, an interesting relationship was observed between ET-1 and VEGF mRNA levels (P = 0.02). At univariate analysis, clinical-pathological parameters, such as sex, nodal metastatic involvement and stage, and ET-1 expression were seen to be significant predictors of worse prognosis regarding both overall survival (P = 0.001, P = 0.0003, P = 0.001 and P = 0.03, respectively) and disease-free interval (P = 0.0005, P = 0.0007, P = 0.001 and P = 0.04, respectively). We conclude that ET-1 could be involved in angiogenic phenomena in NSCLC and may represent a further indicator of progression and poor prognosis in this type of cancer, with interesting therapeutic implications.
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PMID:Expression of endothelin-1 is related to poor prognosis in non-small cell lung carcinoma. 1629 24

We evaluated the usefulness of a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for detecting occult tumor cells in histologically malignant-negative lymph nodes resected from patients with non-small cell lung cancer. First, we examined the relationship between tumor cell number and carcinoembryonic antigen (CEA) mRNA copy number using a PCR method with a cancer cell line (A549) in a serial dilution study. Next, we evaluated the relationship between nodal metastatic area size and CEA mRNA copy number using lymph nodes with histologically proven metastasis in a serial slice study. On the basis of those results, we performed RT-PCR analyses with 28 primary tumors and 211 lymph nodes from 28 patients who underwent a lobectomy with systematic node dissection. Our results in the serial dilution study showed that the detectable limitation by quantitative RT-PCR was 25-100 neoplastic cells and 20-100 CEA mRNA copy numbers. In the serial slice study, we found a correlation between CEA mRNA copy number and nodal metastatic area. In the clinical samples, amplification of CEA mRNA was obtained with all 28 primary tumors and 13 of the lymph nodes with metastasis shown by hematoxylin-eosin staining. Furthermore, 52 (25%) of 211 histologically negative lymph nodes and the specimens from 14 (64%) of the 22 pN0 patients revealed a significant level of CEA mRNA. These results indicate that micrometastases, which are not detectable with conventional examinations, can be detected by the present method of RT-PCR for CEA mRNA in a proportion of patients with resected pN0 non-small cell lung cancer.
Lung Cancer 2006 May
PMID:Detection of occult tumor cells in lymph nodes from non-small cell lung cancer patients using reverse transcription-polymerase chain reaction for carcinoembryonic antigen mRNA with the evaluation of its sensitivity. 1651 Feb 9

Our previous study demonstrated that bone marrow microinvolvement (BMM) is an epiphenomenon of tumor progression rather than a prognostic factor in non-small cell lung cancer. We hypothesize that an increase in mesenchymal transition power in epithelial tumor cells by up-regulation of the matrix metalloproteinases (MMPs) may contribute to the existence of BMM and poorer prognosis. Hereby we conducted a prospective study of BMM and MMPs expression in a cohort of 57 non-small cell lung cancer patients. Bone aspirates were examined by immunohistochemical stains. Expressions of MMPs were checked by Human MMP primer set kit (Maxim Biotech, USA). Correlations between the MMPs expression and BMM, nodal metastasis, and prognosis were examined. Cox model analysis was used to identify independent prognostic factors. Though positive BMM was identified in 38 (66.7%) of the patients, none of the clinicopathological factors, including sex, age, cell types, tumor differentiation, nodal metastasis and TNM status of the tumor, was related to BMM by the tumor cells. Up-regulation was observed in a broad spectrum of MMPs with the exception of MMP-3. However, only MMP-13 expression correlated with the existence of BMM (p=0.006). Univariate analysis revealed MMP-3, MMP-7 and MMP-13 as negative prognostic factors. Cox model analysis revealed T-status, cell differentiation, and MMP-13 expression of the tumor as independent prognostic factors. The overall 5-year survival rate of the patients was 36.8%. The existence of BMM itself did not influence the prognosis (p=0.109), however, patients with positive MMP-13 expression (N=34) had a poorer 5-year survival rate of 26.5% (p=0.025). In summary, non-small cell lung cancer cells with MMP-13 expression, despite of BMM status, tend to shed and aggregate in the bone marrow, which is subsequently reflected in a poorer survival rate.
Lung Cancer 2006 Jun
PMID:Matrix metalloproteinase-13 expression is associated with bone marrow microinvolvement and prognosis in non-small cell lung cancer. 1656 61

Aims-To determine whether expression of CD44 in neoplasia is associated with tumour grade, stage and prognosis.Methods-The immunohistochemical expression of CD44 was evaluated using the mouse antihuman monoclonal antibody 3G12 which recognises regions shared by all CD44 isoforms to determine whether expression in formalin fixed, paraffin wax embedded tissue correlates with tumour grade, stage or survival in adenocarcinoma of the lung. Thirty one adenocarcinomas of the lung, 16 T2N0 and 15 T2N1, and their nodal metastases were studied.Results-Of the 31 tumours, 25 were positive for the CD44 antigen. CD44 expression correlated with tumour grade, in that intense staining was seen only in moderately and/or poorly differentiated tumours. CD44 did not correlate with nodal status, tumour size, pleural invasion, angiolymphatic invasion, or host inflammatory response, but did correlate with survival. A median survival of 46 months was observed in patients with moderate to strong CD44 expression compared with 24 months for those with no or weak expression. Nine patients were alive without evidence of disease at a median follow up of 61 months. Six (66%) of these nine patients had strong CD44 expression. This contrasts with strong expression in only three (17%) of the 17 patients dying with a median survival of 28 months.Conclusion-In primary adenocarcinoma of the lung loss of CD44 expression is associated with less favorable outcome and may indicate a more aggressive neoplasm. CD44 may be a useful prognostic marker in lung carcinoma.
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PMID:Prognostic significance of CD44 expression in adenocarcinoma of the lung. 1669 7

A few series in the literature were published before 1987 on syndrome of inappropriate antidiuretic hormone secretion (SIADH) in small cell lung cancer (SCLC). This study examines the outcome in more recent era. From 1981-1998, there were 1417 new cases of SCLC diagnosed in the provincial registry, of which 244 were of limited stage (LS). A chart review and statistical analyses were performed using Mann-Whitney test, chi-square test and Kaplan-Meier method. Fourteen LS patients (group A) had SIADH at presentation. Group B consisted of 230 LS patients without SIADH. There were more patients with poorer performance status (ECOG 2-4) in group A than B (28.6% versus 7.8%, P=0.03). Otherwise, sex, age at diagnosis, nodal spread, pleural effusion, bronchial obstruction, superior vena cava obstruction, performance status, weight loss, and lactic dehydrogenase at presentation, were comparable between the two groups. Treatments given, e.g., extent of surgical resection (if performed, whether complete/incomplete), total number of chemotherapy cycles, radiotherapy doses, were comparable (P>0.05). The response to chemo-radiation was not significantly different (P=0.7). Five-year overall survival (8% versus 19%, P=0.08), and cause-specific survival (16% versus 20%, P=0.13) showed that group A patients had a worse outcome, though of borderline significance. Symptoms related to SIADH included: weakness, 4 patients; tiredness, 3; change in level of consciousness, 1; seizure, 1. The range of lowest sodium level was 110-129. Two patients also had paraneoplastic myopathy. SIADH resolved in 12 patients at 1.6-44.7 weeks (median: 4.3). Among the 14 patients who initially presented with SIADH and recurred later, 10 had recurrence of SIADH at the time of tumor recurrence. Serum sodium was useful for post-treatment surveillance in SCLC patients who presented with SIADH, with 71% (10/14) developing SIADH again at the time of recurrence. SIADH is a poor prognostic factor for LS SCLC.
Lung Cancer 2006 Aug
PMID:Syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with limited stage small cell lung cancer. 1678 84

Although considerable knowledge exists on the tumor biology of lung cancer, there is still a need to assess molecular events for the clinical management of the disease. We studied the pattern of chromosomal imbalances in 45 non-small cell lung carcinomas (NSCLC) by comparative genomic hybridization (CGH) and correlated the results with clinicopathological features including immunohistochemical (IHC) expression of the epidermal growth factor receptor (EGFR). Twenty-one tumors were squamous cell carcinomas (SCC) and 24 non-squamous cell lung carcinomas (NSCC) comprising 9 adenocarcinomas (ADC), 9 large cell carcinomas (LCC), 4 sarcomatoid carcinomas and 2 adenosquamous carcinomas. The mean number of individual imbalances was 7.1 for SCC (mean gains, 3.8; mean losses, 3.4) and 6.4 for NSCC (mean gains, 4.5; mean losses, 1.9). Several individual imbalances correlated significantly with increasing number of imbalances, that were +1q, -3p, +3q, -5q, -8p, +8q, +7p, +12p, and +14q. Altogether, the most frequent imbalances were +3q (49%), +5p (49%), -5q (36%), +8q (29%), -8p (24%), -3p (22%), +7p (22%), +12p (22%), +14q (20%), +18p (20%), +1q (18%), and +7q (18%). Among these, +3q and +18p correlated significantly with SCC, and +5p and +14q with NSCC. Remarkably, overlapping imbalances included +3q26, +7p11 in SCC and +1q21, +3q24, +12p11, and +14q12 in NSCC. EGFR expression was higher in SCC than in NSCC and correlated with +3q in the entire series. In addition, +12p correlated significantly with disease progress with the exception of nodal involvement in NSCC as well as with disease progress, regardless of nodal involvement, in the entire series. In conclusion, the present study contributes to the molecular biological characterization of NSCLC histological subtypes and through evaluation of molecular events to the recently emergent focus on novel markers for lung cancer treatment.
Lung Cancer 2006 Dec
PMID:Assessment of molecular events in squamous and non-squamous cell lung carcinoma. 1701 Oct 66

Primary neuroendocrine neoplasms of the lung represent a clinical spectrum of tumors ranging from the relatively benign and slow-growing typical carcinoid to the highly aggressive small-cell lung carcinoma. The rarity of carcinoids has made the role of radiation therapy in their management controversial. This review considers the results of published studies to generate treatment recommendations and identify areas for future research. Surgery remains the standard of care for medically operable disease. Histology plays the most important role in determining the role of adjuvant radiation. Resected typical carcinoids likely do not require adjuvant therapy irrespective of nodal statius. Resected atypical carcinoids and large-cell neuroendocrine carcinomas have a significant risk of localfailure, for which adjuvant radiation likely improves local control. Definitive radiation is warranted in unresectable disease. Palliative radiation for symptomatic lesions has demonstrated efficacy for all histologies. Collaborative group trials are warranted.
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PMID:Primary carcinoid tumors of the lung: a role for radiotherapy. 1715 7


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