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)

Between 1968 and 1974, 348 patients with lung cancer were primarily treated with radiation therapy. There were 66 such patients (19%) who survived a minimum of 18 months and are the subject of this report. Of this group, 30 patients have no evidence of disease from 18-96 months, with a median follow-up of 38 months. Thirty-three patients are dead of disease. The five-year actuarial survival of the total group of 348 patients was 5.6%. There were 14 stage I and II patients who survived a minimum of 18 months, of whom 11 had no evidence of disease. Of the 42 Stage III patients, 18 presently show no evidence of disease. There were 13 patients who failed with locally recurrent disease; in this group a dose-response relationship was demonstrated. A local failure rate of 50% (4/8) was observed for patients who received fewer than 5000 rad, 22% (6/27) for patients receiving 5000-5500 rad, 18% (2/11) in patients receiving 5500-5900 rad, and 5% (1/20) for patients who received more than 5900 rad. Radiotherapeutic technique was a significant variable in local failure. Forty-six percent (6/13) of those patient failures may have been eliminated with the use of careful treatment planning with simulation. A statistically significant difference in dose was noted for patients with central recurrence, mean dose 4725 rad, 1561 RET, 81 TDF, when compared with patients with control of gross disease with radiation, mean dose 5740, 1880 RET, 108 TDF. There were four patients with marked early complications (6%) and eight patients with late complications (12%). There were no deaths attributable to radiation. Although most patients with advanced lung carcinoma die of distant disease, a significant number of patients can achieve long-term survival when radically treated with high-dose radiation therapy.
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PMID:The characteristics of long-term survivors of lung cancer treated with radiation. 626 35

RET is a receptor tyrosine kinase expressed in neuroendocrine cells and in tumors of these cell types. RET activation may be mediated by a ligand complex comprising glial cell line-derived neurotrophic factor (GDNF) and GDNF family receptor alpha-1 (GFR alpha-1). Activating RET mutations are found in the inherited cancer syndrome multiple endocrine neoplasia type 2 and in a subset of the related sporadic tumors, medullary thyroid carcinoma and pheochromocytoma, both being derived from neuroendocrine tissues. In one small study, mutations were identified in another tumor with neuroendocrine features, small cell lung carcinoma (SCLC). To determine whether RET mutations contribute to the pathogenesis of SCLC, we examined a panel of 54 SCLC cell lines. No mutations were identified in RET exons 10, 11, and 13-16, regions previously implicated in SCLC or other neuroendocrine tumors. We further examined the expression pattern of RET and the genes encoding the components of its ligand complex GDNF and GFR alpha-1, in 21 SCLC lines by using RT-PCR. Although we found no consistent pattern of expression for these three genes, RET was expressed in 57% of SCLC lines. Thus, although RET mutations appear unlikely to be an important step in the tumorigenesis of SCLC, the frequent expression of this gene suggests that RET may have a mitogenic role in a subset of SCLC cell lines.
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PMID:Investigation of the genes for RET and its ligand complex, GDNF/GFR alpha-I, in small cell lung carcinoma. 955 44

It was recently reported that the human CD109 gene encodes a glycosyl-phosphatidylinositol-anchored glycoprotein that is a member of the alpha(2)-macroglobulin/C3, C4, C5 family of thioester-containing proteins. In this study, we found that the expression of mouse CD109 gene was upregulated in NIH3T3 cells expressing RET tyrosine kinase with a multiple endocrine neoplasia 2B mutation. Northern blot analysis showed a high level of expression of the CD109 gene only in the testis in normal human and mouse tissues. In addition, its expression was high in some human tumor cell lines, which included squamous cell carcinoma and glioblastoma cell lines, whereas it was undetectable in neuroblastoma and small-cell lung carcinoma cell lines. When CD109 expression was examined in 33 cases of human lung cell carcinomas by quantitative RT-PCR, a significant high expression of CD109 was detected in about half of squamous cell carcinomas examined, but not in adenocarcinoma, large-cell carcinoma and small-cell carcinoma. Similarly, upregulation of CD109 was observed in nine out of 17 esophageal squamous cell carcinomas. Thus, these results suggested that CD109 might be a useful molecular target for the development of new therapeutics for malignant tumors, such as squamous cell carcinoma.
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PMID:Expression of CD109 in human cancer. 1511 2

Lung cancer is the most widely diagnosed malignancy in the world. Understanding early-stage disease will give insight into its pathogenesis. Despite the fact that pre-invasive lesions are challenging to isolate, and often yield insufficient DNA for the analysis of multiple loci, genomic profiling of such lesions will lead to the discovery of causal genetic alterations, which may be otherwise masked by the gross instability associated with tumors. In this study, we report the identification of multiple early genetic events on chromosome 5p in lung cancer progression. Using a high-resolution 5p-specific genomic array, which contains a tiling path of DNA segments for comparative genomic hybridization, nine novel minimal regions of loss and gain were discovered in bronchial carcinoma in situ (CIS) specimens. Within these regions we identified two candidate genes novel to lung cancer. The 0.27 Mbp region at 5p15.2 contains a single gene, Triple Functional Domain, which we determined to be differentially expressed in tumors. The 0.34 Mbp region at 5p13.2 contains Glial Cell Line-Derived Neurotrophic Factor (GDNF), which is a ligand for the RET oncogene product and is normally expressed during lung development (but absent in adult lung tissue). Our data showed not only that GDNF is overexpressed at the transcript level in squamous non-small-cell lung carcinoma, but also that the GDNF protein is present in early-stage lesions. Reactivation of the fetal lung expressed GDNF in early lesions and its amplification in CIS suggests an early role in tumorigenesis. These results highlight the value of examining the genomes of pre-invasive stages of cancer at tiling resolution.
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PMID:Chromosome 5p aberrations are early events in lung cancer: implication of glial cell line-derived neurotrophic factor in disease progression. 1587 Jul

This review is focused on "new drugs" that might be developed for thyroid cancer treatment. Thyroid cancer is frequently associated to the activation of specific protein (RET, BRAF) and lipid [PI(3)K] kinases. There is good evidence that these genetic lesions are causative events in thyroid cancer initiation or progression. Therefore, novel compounds able to target these kinases might be useful for thyroid cancer treatment. The power of this approach is witnessed by the examples of BCR-ABL, c-KIT and EGFR inhibitors in the treatment of chronic myelogenous leukemia (CML), gastro-intestinal stromal tumors (GIST) and non-small cell lung carcinoma (NSCLC).
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PMID:New drugs in thyroid cancer. 1789 Dec 51

Molecular testing in anatomic pathology is going to become more and more important during the next decade as we develop assays that can aid in diagnosis, prognosis, and predicting response to therapy. The anatomic pathologist needs to be familiar with the different assays available but also needs to be able to discern which are going to become standard of care and which will not. Three different types of tumors are reviewed: thyroid cancer, oligodendroglioma, and lung carcinoma. Molecular assays that are currently in use or on the near horizon, including translocation analyses for RET-PTC and PPARgamma-PAX8, point mutation analysis for BRAF and epidermal growth factor receptor, and genetic loss for 1p and 19q, are discussed.
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PMID:Molecular testing in solid tumors: an overview. 1825 69

We herein show that Artemin (ARTN), one of the glial cell line-derived neurotrophic factor family of ligands, promotes progression of human non-small cell lung carcinoma (NSCLC). Oncomine data indicate that expression of components of the ARTN signaling pathway (ARTN, GFRA3, and RET) is increased in neoplastic compared with normal lung tissues; increased expression of ARTN in NSCLC also predicted metastasis to lymph nodes and a higher grade in certain NSCLC subtypes. Forced expression of ARTN stimulated survival, anchorage-independent, and three-dimensional Matrigel growth of NSCLC cell lines. ARTN increased BCL2 expression by transcriptional upregulation, and inhibition of BCL2 abrogated the oncogenic properties of ARTN in NSCLC cells. Forced expression of ARTN also enhanced migration and invasion of NSCLC cells. Forced expression of ARTN in H1299 cells additionally resulted in larger xenograft tumors, which were highly proliferative, invasive, and metastatic. Concordantly, either small interfering RNA-mediated depletion or functional inhibition of endogenous ARTN with antibodies reduced oncogenicity and invasiveness of NSCLC cells. ARTN therefore mediates progression of NSCLC and may be a potential therapeutic target for NSCLC.
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PMID:Artemin-stimulated progression of human non-small cell lung carcinoma is mediated by BCL2. 2053 Jul 13

A 55-year-old Caucasian woman with lung adenocarcinoma stage IV presented with repeated relapse after treatment with cytotoxic chemotherapy (carboplatin, gemcitabine, docetaxel, pemetrexed) and targeted agents (erlotinib, cetuximab, sunitinib). Comprehensive molecular diagnostics (EGFR-, ALK-, RAS-, BRAF-, PIK3CA-, HER2- and DDR2-aberrations) were performed and failed initially to detect any driver mutation. While the patient suffered from rapid deterioration of her general condition, in particular from progressive dyspnea due to lung metastases, we implemented screening for RET- and ROS1 translocations into our molecular diagnostic program based on recent reports of these new molecular subgroups in lung adenocarcinoma. On retesting the patient's tumor sample was found to harbor a ROS1-translocation. The patient was subsequently treated with crizotinib and experienced a pronounced clinical improvement corresponding to a complete metabolic response in (18)F-FDG-PET and a good and confirmed partial response in CT (RECIST 1.1). Our case exemplifies the need for rapid implementation of newly discovered rare genetic lung cancer subtypes in routine molecular diagnostics.
Lung Cancer 2013 Jul
PMID:Complete metabolic response in a patient with repeatedly relapsed non-small cell lung cancer harboring ROS1 gene rearrangement after treatment with crizotinib. 2355 10

Thymic tumors are epithelial tumors of the thymus for which multimodal therapies are often ineffective because of a lack of standardized regimens. Due to the low incidence, the molecular pathology and genomic abnormalities of thymic epithelial tumors are largely unknown. In this study, we report our comprehensively genomic study on a case of metastatic thymic tumor. Using next generation deep DNA sequencing technology, we sequenced 190 segments of 46 cancer genes of the cancer genome to cover 739 COSMIC mutations in 604 loci. Among these sequenced cancer genes, we identified that three low frequency (~10% of cells) mutations in the TP53 gene (c.782+1G>T), ALK gene (c.3551C>T), and RET gene (c.2651A>T). To the best of our knowledge, this is the first study to show those mutations in thymic tumor. Of note, our study further indicates comprehensive molecular analysis may facilitate development of novel diagnostic and therapeutic strategies for thymic tumors.
Lung Cancer 2013 Jul
PMID:Identification of novel mutations of TP53, ALK and RET gene in metastatic thymic squamous cell carcinoma and its therapeutic implication. 2363 85

A new RET fusion gene has been recently described in a subset of non-small cell lung cancer (NSCLC) identified by specific clinico-pathologic characteristics. This transforming gene arise from the fusion of KIF5B and the RET proto-oncogene, and it is mutually exclusive with EGFR, KRAS and EML4/ALK alterations. For this reason it could represent a putative target for specific inhibitory drugs and its evaluation could be necessary in the future daily molecular characterization of NSCLCs. One of the major challenge in diagnostic molecular pathology is to optimize genotyping tests with the minimally invasive techniques used to acquire diagnostic tumor tissue or cells. This is a significant relevant issue for approximately 60% of NSCLC patients presenting with unresectable disease, where the only pathologic materials available for diagnostic use are small biopsy or cytological specimens. Thus, the aim of this study was to verify the possibility to use RNA purified from cytological specimens to perform KIF5B/RET gene fusion expression analysis. Accordingly, we looked for the presence of the rearrangement in formalin fixed paraffin embedded tissues (FFPETs) and cytological specimens (CSs) of a selected series of "triple-marker" negative adenocarcinomas. The tests conducted revealed the presence of 1 positive patient for variant 1 of KIF5B/RET among the 49 analyzed. The presence of this fusion transcript was found in both FFPET and CS of the same patient demonstrating that the RNA obtained from minimally invasive techniques is perfectly suitable for this kind of tests. The presence of the rearrangement was also confirmed by FISH analysis. In conclusion, our findings confirm that the performance of cytology-based molecular testing for KIF5B/RET rearrangements is at least as effective as histology-based analysis, both with regard to the success rate for nucleic acid isolation and the ability to detect gene alterations.
Lung Cancer 2013 Sep
PMID:KIF5B/RET fusion gene analysis in a selected series of cytological specimens of EGFR, KRAS and EML4-ALK wild-type adenocarcinomas of the lung. 2389 10


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