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)

N1 non-small cell lung cancer (NSCLC) encompasses a heterogeneous subgroup with differential lymph node involvement. Among 738 patients with NSCLC who underwent surgical resection, including 579 patients (78.5%) with systematic hilar and mediastinal lymph nodal dissection, from 1992 to 2001, 82 patients were pathologically defined as having N1 disease. We retrospectively analyzed the factors influencing survival, including the characteristics of lymph node involvement; the location of involved stations, the number of involved stations, the number of involved nodes, and the status of nodal involvement (microscopic N1, nodal involvement first defined by postoperative histological examination; or macroscopic N1, nodal involvement obviously recognized by preoperative examinations or surgical explorations). The overall 5-year survival rate of the 82 patients with N1 disease was 50.9%. No significant differences in the overall survival were found with regard to gender, age, histologic type, type of resection, or adjuvant therapies. Pathologic T status significantly influenced the overall survival (T1 versus T2 disease, P=0.008). According to the characteristics of lymph node involvement, the prognosis of patients with multiple-node N1 involvement was significantly poorer than that of those with single-node N1 involvement (5-year survival: 29.6% versus 61.5%, p=0.003). The prognosis of patients with macroscopic N1 disease was significantly poorer than that of those with microscopic N1 disease (5-year survival: 43.0% versus 65.0%, P=0.046). By comparison with the survival of patients who underwent surgical resection during the same period for pathologic N0 (pN0) and pathologic N2 (pN2) diseases, no survival differences were observed between microscopic N1/single-node N1 and pN0, or between multiple-node N1 and pN2 diseases. In patients with pathologic N1 disease, microscopic N1 and single-node N1 diseases may be an early stage, whereas multiple-node N1 disease behaves like an advanced stage.
Lung Cancer 2004 Feb
PMID:Survival and characteristics of lymph node involvement in patients with N1 non-small cell lung cancer. 1473 35

Image-guided transthoracic, bronchoscopic, and endoscopic ultrasound fine needle aspiration (FNA) greatly facilitates lung cancer staging by having the potential to precisely biopsy lung lesions and virtually all mediastinal lymph node stations. Imaging modalities alone, including chest x-ray, computed tomography (CT), magnetic resonance imaging, and positron emission tomography identify lesions suspicious for cancer but cannot make a tissue diagnosis. We describe an algorithm for the diagnosis and tumor-node-metastasis staging of lung cancer that uses procedures with the least invasiveness and cost with the highest diagnostic yields. For the anterior mediastinum, fluoroscopic-, ultrasound-, or CT-guided transthoracic FNA (which has a greater yield than bronchoscopy and is less invasive than mediastinoscopy) should be the primary technique for lymph node sampling. In the middle mediastinum, CT-guided transthoracic FNA is preferred for all nodal stations except subcarinal. Endoscopic ultrasound-guided FNA (EUS-FNA), which enables real-time biopsies within 5 cm of the esophagus, is preferred for sampling subcarinal and posterior mediastinal nodes because the yield is similar to CT-guided transthoracic FNA, with minimal risk of pneumothorax. The posterior mediastinum is also accessed by fluoroscopic- or CT-guided transthoracic FNA or video-assisted thoracic surgery. Sampling of the aorticopulmonary window depends on lymph node size; if the nodes are large enough to displace the aortic arch and pulmonary vein, then EUS-FNA is attempted, and if the nodes are not sufficiently enlarged, CT-guided transthoracic FNA should be performed prior to thoracoscopy or thoracotomy.
Clin Lung Cancer 2000 Nov
PMID:Image-guided fine needle aspirate strategies for staging of lung cancer. 1474 Jun 12

Accurate staging of non-small-cell lung cancer (NSCLC) determines prognosis and facilitates decisions regarding treatment options. Unfortunately, even after an apparently complete resection in patients with stage I disease, the recurrence rates range from 25% to 50%, and overall survival is not encouraging. One possible reason for this may be that those patients with a poor outcome actually have more extensive disease, with occult locoregional and/or distant metastasis than originally identified by routine pathologic staging techniques. There is now a sizable body of literature on the detection and possible prognostic role of occult disease in lung cancer. The majority of these studies are based on immunohistochemical analysis of lymph nodes and/or bone marrow, but a handful of studies use molecular approaches. The purpose of this review is to summarize and critique the current literature on occult tumor cell spread to lymph nodes and bone marrow in patients with NSCLC. Based on this literature, we believe that the prognostic significance of bone marrow micrometastasis remains unclear. However, the majority of studies indicate that occult lymph node disease is associated with a poor outcome. Thus, our ability to detect individual tumor cells could result in more accurate staging of NSCLC in patients and would potentially lead to the development of novel therapies, as well as influence decisions regarding the use of appropriate multimodality treatment strategies, the choice of surgical technique, and extent of dissection. As data accumulate, the presence or absence of occult nodal involvement should probably be considered at the next revision of the staging system for NSCLC.
Clin Lung Cancer 2004 Jan
PMID:Prognostic significance of micrometastasis in non-small-cell lung cancer. 1496 73

DNA methyltransferase 1 (DNMT1) catalyzes the post-replication methylation of DNA and is responsible for maintaining the DNA methylation pattern during cell division. A long list of data supports a role for DNMT1 in cellular transformation and inhibitors of DNMT1 were shown to have antitumorigenic effects. It was long believed that DNMT1 promoted tumorigenesis by maintaining the hypermethylated and silenced state of tumor suppressor genes. We have previously shown that DNMT1 knock down by either antisense oligonucleotides directed at DNMT1 or expressed antisense activates a number of genes involved in stress response and cell cycle arrest by a DNA methylation-independent mechanism. In this report we demonstrate that antisense knock down of DNMT1 in human lung carcinoma A549 and embryonal kidney HEK293 cells induces gene expression by a mechanism that does not involve either of the known epigenomic mechanisms, DNA methylation, histone acetylation, or histone methylation. The mechanism of activation of the cell cycle inhibitor p21 and apoptosis inducer BIK by DNMT1 inhibition is independent of the mechanism of activation of the same genes by histone deacetylase inhibition. We determine whether DNMT1 knock down activates one of the nodal transcription activation pathways in the cell and demonstrate that DNMT1 activates Sp1 response elements. This activation of Sp1 response does not involve an increase in either Sp1 or Sp3 protein levels in the cell or the occupancy of the Sp1 elements with these proteins. The methylation-independent regulation of Sp1 elements by DNMT1 unravels a novel function for DNMT1 in gene regulation. DNA methylation was believed to be a mechanism for suppression of CG-rich Sp1-bearing promoters. Our data suggest a fundamentally different and surprising role for DNMT1 regulation of CG-rich genes by a mechanism independent of DNA methylation and histone acetylation. The implications of our data on the biological roles of DNMT1 and the therapeutic potential of DNMT1 inhibitors as anticancer agents are discussed.
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PMID:DNA methyltransferase 1 knock down induces gene expression by a mechanism independent of DNA methylation and histone deacetylation. 1508 53

LUN is a novel RING finger protein that is highly expressed in the lung and might be a transcriptional regulator of E-cadherin [J. Biol. Chem. 276 (2001) 14004]. It might be possible that LUN plays important roles in the development and progression of lung cancer through regulating expression of E-cadherin, but no clinical study on LUN expression has been reported. In the present study, we quantitatively examined gene expression of the LUN in surgical specimens resected from non-small cell lung cancer (NSCLC) patients. In normal lung tissues, the LUN gene expression was down-regulated in smokers (the mean LUN/GAPDH ratios, 0.222 for non-smokers and 0.144 for smokers; P = 0.030). In addition, the mean LUN/GAPDH ratio in lung cancer tissues was significantly lower than that in normal lung tissues (0.072 versus 0.162; P < 0.001). In addition, the LUN gene expression was slightly down-regulated along with progression of primary tumors, and strongly down-regulated along with nodal metastases (the mean LUN/GAPDH ratios, 0.091 for pN0, 0.073 for pN1, and 0.034 for pN2 diseases; P = 0.001). These results suggested that LUN might play important roles in inhibition of nodal metastases as well as in suppression of smoking-related oncogenesis in NSCLC.
Lung Cancer 2004 Oct
PMID:Expression of LUN gene that encodes a novel RING finger protein is correlated with development and progression of non-small cell lung cancer. 1536 29

Merkel-cell carcinoma (MCC) is a rare form of skin cancer of neuroendocrine origin that has been described as the most aggressive cutaneous malignancy. The cell of origin is thought to be the Merkel cell or skin-pressure receptor. It has the propensity for dermal-lymphatic invasion, and nodal and haematogenous spread. Factors that have been implicated in its cause include exposure to sunlight and immunosuppression. The tumour has many similarities to small-cell carcinoma of the lung, with intrinsic sensitivity to ionising radiation and chemotherapy, and an aggressive metastatic potential. The best treatment outcomes can be achieved with early diagnosis and the integration of surgery, radiation, and chemotherapy. The treatment challenges for the clinician are often enormous because many of the patients are elderly and because lesions occur in difficult sites such as the head and neck region and the lower leg.
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PMID:Merkel-cell carcinoma of the skin. 1546 61

90K/Mac-2 Binding Protein (M2BP) plays a role in regulation of immune responses and cell adhesive ability in patients with cancer and infectious diseases. We previously reported that M2BP was highly expressed in lung cancer and that immune responses to M2BP were increased in many patients with lung cancer. To determine the involvement of M2BP in metastatic processes of cancer progression, we examined the ability of M2BP DNA-transduced lung carcinoma cell lines to adhere to extracellular matrices. Although expressions of cell-surface integrins were not modulated in the M2BP transfectants, they showed increased adhesiveness to fibronectin and collagen IV. We next analyzed the serum levels of M2BP in patients with lung cancer and normal donors and the relationships between M2BP expression and clinicopathological factors in the patients. The M2BP level was markedly elevated in the patients and was strongly correlated with nodal involvement and clinical staging. To determine whether expression of M2BP by cancer cells is modulated in the environment of tumor-bearing hosts, M2BP expression in M2BP-positive QG56 cells following exposure of the cells to pro-inflammatory cytokines was examined. The M2BP expression in QG56 cells was up-regulated by many of the cytokines that activate host protective immunity. The findings in this study suggest that M2BP plays a role in cancer metastasis by increased adhesiveness of cancer cells and that M2BP is increasingly produced even in a state of exposure to the host immune system. This molecule may be useful as a predictive factor of disease progression in lung cancer.
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PMID:Involvement of 90K/Mac-2 binding protein in cancer metastases by increased cellular adhesiveness in lung cancer. 1549 95

Lung resection remains the therapy of choice offering the greatest potential for cure in non-spread lung cancer. Prognostic importance of lymph-node involvement has been underlined by several studies. So, exploration of the mediastinum is of major importance for defining the therapeutic strategy in a possibly curative setting. Pre-resectional exploration of the mediastinal lymph-nodal status is mandatory to define tumour stage exactly and establish specific therapy. Cervical mediastinoscopy is the primary diagnostic procedure and remains the gold standard in invasive surgical staging. Complementary, parasternal mediastinoscopy, extended mediastinoscopy, and video-assisted thoracoscopy may be performed. These techniques allow accurate assessment of mediastinal lymph-node involvement, resulting in an appropriate judgement as to resectability and possible treatment options. Different techniques are established for intraoperative exploration and staging. In terms of curative surgery of lung cancer we demand accurate staging which is achieved by systematic and complete Lymph-node dissection. So, individually and dependent on primary tumour site, accurate mediastinal staging of Lung cancer should be performed in combination with definitive lung resection.
Lung Cancer 2004 Aug
PMID:Surgical exploration of the mediastinum: mediastinoscopy and intraoperative staging. 1555 82

Surgical resection of early-stage non-small-cell lung cancer (NSCLC) remains the standard of care in patients fit for surgery. Careful preoperative staging is imperative, as is pathologic documentation of the mediastinal nodal contents. Adjuvant postoperative thoracic radiation therapy (RT) clearly has an impact in reducing locoregional recurrence but has no clear impact on survival. The Postoperative RT (PORT) metaanalysis raised concerns about PORT, particularly in stage I/II NSCLC, suggesting it may negatively impact survival. This was not a concern in stage III NSCLC, in which the risk of locoregional recurrence is higher. However, distant recurrence remains the dominant pattern in resected NSCLC, suggesting that the majority of patients with early-stage resected NSCLC harbor occult micrometastatic disease. Historically, the role of adjuvant chemotherapy has been controversial, and its routine use was not supported by the published data, which consisted of a small number of underpowered trials using inadequately delivered, antiquated chemotherapy. More recently, larger trials have been reported with conflicting results. Like adjuvant PORT, chemotherapy combined with RT has not improved survival over PORT alone. The use of adjuvant cisplatin-based therapy did not show a survival advantage in the Adjuvant Lung Project Italy study but did in the International Adjuvant Lung Trial, creating controversy in the routine implementation of adjuvant therapy in all patients. Recently completed randomized trials by the Cancer and Leukemia Group B and the National Cancer Institute of Canada provide convincing evidence of a substantial benefit from adjuvant therapy in well-staged and completely resected stage I/II NSCLC. Currently, the totality of the data supports a discussion with patients with resected NSCLC regarding the potential benefits of adjuvant therapy.
Clin Lung Cancer 2004 Nov
PMID:Adjuvant therapy of resected non-small-cell lung cancer. 1555 17

Sialyl Lewis antigens (sLe(x/a)) are cancer-associated carbohydrate determinants, serve as ligands of the selectin family and are associated with hematogenous metastasis of cancer. So far, the clinicopathologic values of sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) in lung cancer have remained controversial. Using immunohistochemistry, the expressions of sLe(x) and sLe(a) antigens, and an airway mucin (MUC5AC) protein, which was supposed to be the major carrying protein of sialyl Lewis moieties, were studied in surgically resected tumor tissues of 61 patients with stages I or II NSCLC. Thirty-two (52.5%) of the 61 studied subjects were found to be positive for expression of sLe(a), 40 (65.6%) were positive for expression of sLe(x), and 16 (26.2%) were positive for MUC5AC protein. Both the expression of sLe(x) and MUC5AC were associated with adenocarcinoma subtype. Patients bearing tumors with MUC5AC and/or sLe(x) expression had a higher probability of post-operative distant metastasis. Survival analysis demonstrated that patients bearing tumors with expression of sLe(x) antigen or MUC5AC had shorter overall survival. The multivariate logistic regression showed that age >65 years old (OR = 0.207, 95% CI = 0.075-0.569, P = 0.002), nodal status (OR = 6.575, 95% CI = 2.459-17.583, P < 0.001), and MUC5AC (OR = 5.545, 95% CI = 1.998-15.386, P = 0.001) were independent factors affecting survival. We concluded that the expression of sLe(x) was related to MUC5AC protein, while patients with tumors co-expressing both MUC5AC and sLe(x) antigen had the worst survival.
Lung Cancer 2005 Jan
PMID:Sialyl Lewis antigens: association with MUC5AC protein and correlation with post-operative recurrence of non-small cell lung cancer. 1560 55


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