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)

Osteopontin (OPN) is a multifunctional protein, which has recently been shown to be linked to tumorigenesis, progression and metastasis in different malignancies. Since non-small-cell lung cancer (NSCLC)'s prognosis remains bad, with few predictors of outcome, the purpose of this study was to evaluate if OPN might be involved in NSCLC's biology and therefore represent a prognostic marker and a target for new therapeutic trials. Immunohistochemistry was used to detect OPN expression, evaluated as percentage of neoplastic cells with cytoplasmic immunoreactivity, in a wide cohort of patients with stage I NSCLC (136 cases). The median value of this series (20% of positive cells) was used as the cutoff value to distinguish tumours with low (<20%) from tumours with high (> or =20%) OPN expression. A statistically significant correlation between high levels of OPN and shorter overall (P = 0.034) and disease-free (P = 0.011) survival in our patients was shown. Our results support the hypothesis that high OPN expression is a significantly unfavourable prognostic factor for the survival of patients with stage I NSCLC. This conclusion has notable importance in terms of the biological characterization of early-stage tumours and therapeutic opportunities.
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PMID:Prognostic significance of osteopontin expression in early-stage non-small-cell lung cancer. 1609 64

Despite advances in the detection and treatment of lung cancer, the prognosis for patients with lung cancer is poor, partly as a result of recurrences. We retrospectively analyzed the relationship between recurrence and survival in patients with non-small cell lung cancers (NSCLC), and the promoter methylation of p16, GSTP1, FHIT, H-cadherin, and RARbeta2 genes to identify a prognostic molecular marker associated with the recurrence of NSCLC. Methylation status from 335 paraffin blocks was determined by methylation-specific PCR. Of the 335 NSCLC samples, promoter methylation was detected in 35% for p16, 39% for RARbeta2, 42% for H-cadherin, 7% for GSTP1, and 21% for FHIT. Recurrence was observed in 39% (132 of 335) of the patients. Recurrence was significantly associated with histology (P = 0.001) and pathologic stage (P = 0.009). Hypermethylation of any single gene was not associated with recurrence in patients. However, cohypermethylation of p16 and FHIT genes in stage I NSCLCs was associated with an increased risk of recurrence [odds ratio, 6.43; 95% confidence interval (CI), 1.04-20.19; P = 0.02] and poor recurrence-free survival after surgery (hazard ratio, 2.03; 95% CI, 1.09-6.23; P = 0.02). In addition, their survival after recurrence was also 4.62 times poorer (95% CI, 1.27-16.48; P = 0.005) than for those without cohypermethylation of both genes. In conclusion, the present study suggests that cohypermethylation of p16 and FHIT genes in patients with stage I NSCLC may be a valuable biomarker for predicting the recurrence-associated prognosis of the disease.
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PMID:Cohypermethylation of p16 and FHIT promoters as a prognostic factor of recurrence in surgically resected stage I non-small cell lung cancer. 1661 24

DNA hypermethylated gene promoter sequences are extremely promising cancer markers. Their use for risk assessment, early diagnosis, or prognosis depends on the timing of this gene change during tumor progression. We studied this for the proapoptotic gene ASC/TMS1 in lung cancer and used the findings to develop a sputum marker. ASC/TMS1 protein levels are reduced in all lung cancer types (30 of 40; 75%) but not in 10 preinvasive lesions. Hypermethylation of ASC/TMS1 is also associated with invasive cancers (41 of 152 or 27.0% of all lung cancer types) with variation in incidence between histopathologic types including 32.1% (26 of 81) of adenocarcinomas, 13.2% (7 of 53) of squamous cell carcinomas, 38.5% (5 of 13) of large-cell carcinomas, and 60% (3 of 5) of small-cell lung cancers. The hypermethylation is particularly correlated with late tumor stages being present in only 14% of stage I but 60% of later-stage tumors. The incidence of ASC/TMS1 hypermethylation in sputum DNA fully mimics the tissue findings being present in only 2% (2 of 85) of high-risk, cancer-free smokers, 15% (3 of 18) of patients with stage I non-small-cell lung cancer (NSCLC), but 41% of patients with stage III NSCLC (18 of 44), including 56% (10 of 18) of those with adenocarcinoma. Importantly, sputum is positive for this marker in 24% (10 of 42) of very high risk, clinically cancer-free individuals previously resected for stage I NSCLC. Thus, hypermethylation of ASC/TMS1 is a marker for late-stage lung cancer and, in sputum, could predict prognosis in patients resected for early-stage disease.
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PMID:Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer. 1677 95

Starting in 2002, the Radiation Therapy Oncology Group in North America began the process of developing multicenter prospective trials in lung cancer using Stereotactic Body Radiation Therapy (SBRT). Much of the work was based on the prospective single institution trials from Indiana University that had been presented and published. In late 2004, RTOG 0236 using SBRT for medically inoperable patients with clinical stage I non-small cell lung cancer (NSCLC) was activated for accrual. Prior to activation, representatives from the Lung, Image-Guided Therapy, Physics, and Radiobiology Committees met on regular occasions to design the multicenter study and quality assurance measures. SBRT is not a black box, and the essence of the therapy had to be distilled via guidelines. Issues related to patient selection, method of dosimetry construction, equipment requirements, motion assessments and control, site accreditation, data exchange, and follow-up policies were worked out by compromise and consensus. RTOG 0236 has nearly completed its accrual. The Lung Committee has initiated the development of several other trials, each building on the last, to investigate the therapy in central tumors, in combinations with systemic therapy, in operable patients, and in lung metastases patients. The guidelines developed for RTOG 0236 will be refined to take advantage of more modern innovations including heterogeneity corrections and intensity modulation when appropriate. The development of RTOG 0618 using SBRT in operable patients with early stage NSCLC is a testament to both the enthusiasm from already published works and prospective multicenter clinical testing using SBRT techniques.
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PMID:Accreditation and quality assurance for Radiation Therapy Oncology Group: Multicenter clinical trials using Stereotactic Body Radiation Therapy in lung cancer. 1698 40

We reviewed results of SBRT treatment of 138 patients with medically inoperable stage I NSCLC treated during 1996-2003 at five different centres in Sweden and Denmark. Mean age was 74 years (range 56-90) with 69 men and 72 women. SBRT was delivered using a 3D conformal multifield technique and a stereotactic body frame. Doses delivered were 30-48 Gy (65% isodose at the periphery of planning target volume, PTV) in 2-4 fractions. Equivalent dose in 2 Gy fractions (EQD2) was in the range of 50-100 Gy. Mean gross tumour volume (GTV) was 39 cm3 (2-436), and planning target volume was 101 cm3 (11-719). Overall response rate (CR, PR) was 61% (84/138). SD was noted in 36% (50/138). During a median follow-up period of 33 months (1-107), 16 (12%) local failures occurred, ten of which also included distant metastases. Local failure was associated with tumour size, target definition and central or pleura proximity. Distant metastases occurred in 25% (35/138) of the patients. Ninety-one (65%) patients died during follow-up of which 55 patients (60%) died of other causes than lung cancer. Three- and 5-year overall survival was 52 and 26% respectively. Lung cancer specific 3- and 5-year overall survival was 66 and 40% respectively. Fifty nine percent (83/138) of the patients had no side effects. Fourteen patients experienced grade 3-4 toxicity according to radiation therapy oncology group (RTOG). EQD2 (> v.s.<55.6 Gy) showed a statistically significant benefit survival for the higher doses. SBRT for stage I NSCLC results in favourable local control not inferior to fractionated RT and with acceptable toxicity.
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PMID:Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. A retrospective analysis of patients treated in the Nordic countries. 1698 41

Insulin receptor substrate-1 (IRS-1) is an adaptor protein for insulin-like growth factor (IGF) signaling and it is presumed associated with cancer development, progression or clinical outcome of patients harboring solid tumors. Therefore, we investigated by immunohistochemistry, the expression of IRS-1 in the tumor tissues from 94 patients who were diagnosed as stage I non-small cell lung cancer (NSCLC) and had undergone a curative lung resection. The relationships between its intratumoral expression and various clinical parameters were explored. IRS-1 is consistently expressed in the cytoplasm of intrapulmonary bronchial and bronchiolar epithelial cells comprising normal appearing adjacent lung tissues. Forty-one (43.6%) of 94 specimens showed loss of IRS-1 expression. In a subset analysis, IRS-1 was more frequently lost in stage IB than in IA tumors (50.0 vs. 22.7%, p=0.024, chi(2) test), which was reflected by the facts that tumors which showed down-regulation of IRS-1 had larger area than those with IRS-1 expression (18.1 vs. 12.1 cm(2), p=0.044, t-test). Down-regulation of IRS-1 is more frequently observed in squamous cell carcinoma than other cell type lung cancer (p=0.002, chi(2) test) and its expression was not affected by histological grade of differentiation. Comparing pack-years (P.Y.) between groups of smokers whose tumor expressed IRS-1 and those that did not, smokers whose tumor showed loss of IRS-1 expression had higher P.Y. than those whose tumor did express IRS-1 (39.2+/-23.67 vs. 25.6+/-26.61 P.Y., p=0.034, t-test). Intratumoral expression of IRS-1 did not influence disease-free survival, disease-specific survival or overall survival of stage I NSCLC patients, whose median follow-up duration is 7.5 years (95% CI; 7.21-7.86 years). These results suggest that loss of IRS-1 might rather be an early event in NSCLC development than a prognostic factor and that it is more strongly related with squamous cell carcinoma and with smoking.
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PMID:Clinical significance of insulin receptor substrate-I down-regulation in non-small cell lung cancer. 1708 38

Completely resected non small-cell lung cancer (NSCLC) patients frequently experience local or systemic relapse of their disease. In order to decrease the risk of relapse, postoperative (adjuvant) treatments have been studied. To date, the several published or reported randomised trials on postoperative chemotherapy show that adjuvant chemotherapy should be regarded as a standard of care for stage II and IIIA completely resected NSCLC. On the other hand, available data suggest that adjuvant radiotherapy has a detrimental effect on survival of completely resected stage I and II NSCLC patients. The relevance of adjuvant radiotherapy for stage IIIAN2 NSCLC patients has not been demonstrated to date. Choice of drugs, combination with targeted therapies, optimal treatment schedules, the management of stage I NSCLC patients and individually-based adjuvant therapeutic strategies are currently being evaluated in clinical trials in which the participation of all investigators is essential.
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PMID:[Early stages of non small cell lung cancer (I. II. IIIA). Postoperative treatments for resected non small-cell lung cancer]. 1726 36

We evaluated the clinical characteristics of 18 patients with lung cancer complicated by chronic renal failure at our department between November 1983 and September 2004. The 18 patients consisted of 17 men and 1 woman aged 60-81 years (mean, 70 years). Fifteen patients had non-small cell lung cancer (NSCLC), and 3 had small cell lung cancer (SCLC). The stage of NSCLC was I in 7 patients, II in 2, and IV in 6. The stage of SCLC was localized disease (LD) in 2 patients and extensive disease (ED) in 1. The lung cancer was often detected due to symptoms such as cough and bloody sputum. Concerning treatment, surgery was mainly selected in patients with stage I NSCLC, but radiotherapy alone was often performed due to the wishes of patients in those with stage III or IV NSCLC. The outcome of patients who underwent chemotherapy with stage III or IV NSCLC was similar to patients with lung cancer not complicated by renal failure. In lung cancer patients with chronic renal failure, new hepatic excretion type anti-cancer drugs can be also used, but further evaluation is necessary.
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PMID:[Lung cancer in patients with chronic renal failure]. 1731 20

Clinical outcomes following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) are excellent, with local control rates ranging from 80% to 95% in medically inoperable patients. Toxicity following SBRT has been lower than expected, with exception for grade 3 to 5 events occurring in patients treated with high doses to mediastinal structures. In considering a randomized head-to-head comparison of SBRT versus surgery for stage I lung cancer, the interpretation of clinical response based on imaging is of great importance. This is because of the opportunity to salvage SBRT local failure with surgery in operable patients. The current literature is reviewed with respect to computed tomography (CT) and positron emission tomography (PET) with respect to response following SBRT. The reported toxicities following SBRT for both peripheral and central lung cancers are also reviewed.
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PMID:Radiographic response and clinical toxicity following SBRT for stage I lung cancer. 1760 7

Non-small cell lung carcinoma (NSCLC) is one of the leading causes of death from cancer in both Eastern and Western countries. For patients with stage I NSCLC, full lobar or more extensive surgical resection is the treatment of choice. However, even among patients with surgically resected, stage I NSCLC, up to 30% of patients die of the disease within 5 years. At present, apart from clinical stage, there are no established cancer-specific clinical variables or biomarkers that reliably identify individuals at increased risk of death after surgical resection-individuals who could be candidates for adjuvant therapy or alternative management strategies. At a recent international workshop, participants discussed a clinical trial to compare radiation therapy with surgery among patients with stage I NSCLC. This study offers the opportunity to prospectively obtain, bank, and analyze tissue and other clinical specimens, which should facilitate the identification of new biomarkers for early detection, prognosis, and therapy in lung cancer.
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PMID:Molecular pathogenesis of early-stage non-small cell lung cancer and a proposal for tissue banking to facilitate identification of new biomarkers. 1760 9


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