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)

The epidermal growth factor receptor (EGFR) gene has recently been reported to be mutated in a subset of non-small cell lung cancers (NSCLC), with the mutations being correlated with the patients' drug sensitivity to gefitinib, an EGFR kinase inhibitor. In this study, we searched for EGFR mutations in patients with lung cancer using primary tumor specimens obtained at initial surgery and examined whether their recurrent tumors showed a response to gefitinib depending on the presence of the activating mutation. Among 12 lung cancers that were treated with gefitinib after recurrence, we found that all four tumors which showed a response to gefitinib had an activating mutation in EGFR, whereas none of the remaining eight tumors had a mutation. Southern blot analysis showed that two of the four responsive tumors had the EGFR gene amplification. We also examined another 73 NSCLC specimens (47 males and 26 females; 53 adenocarcinomas and 20 non-adenocarcinomas) which were not treated with gefitinib to determine whether NSCLCs with an EGFR mutation have different clinicopathological properties and/or unique genetic alterations of the other cancer-associated genes. We found that 13 (18%) of 73 tumors had a mutation of the EGFR gene, with the most being detected in female adenocarcinomas. Comparing the alterations in KRAS and P53 with the EGFR mutation, we found that 10 tumors with the KRAS mutation did not have an EGFR mutation, suggesting that each mutation occurs exclusively during the development of lung cancer. These results suggest that the mutation analysis of the EGFR gene using the specimens obtained at surgery might be useful in selecting the appropriate treatment(s) for recurrent lung cancer patients.
Lung Cancer 2005 Dec
PMID:Mutations of epidermal growth factor receptor of non-small cell lung cancer were associated with sensitivity to gefitinib in recurrence after surgery. 1614 Apr 20

Targeting tumor endothelium is an important strategy for cancer therapy. We evaluated the effectiveness of gene therapy, that is, intramuscular delivery of plasmid DNA encoding tumstatin (pSecTag2B-tum), combined with gemcitabine administration in vitro and in vivo, using colon carcinoma (CT26) and Lewis lung carcinoma (LLC) murine models. The in vitro growth-inhibitory and proapoptotic effects of gemcitabine and/or tumstatin on human umbilical vein endothelial cells (HUVECs) and mouse endothelial cells (SVEC4-10), respectively, were assessed. in vitro, conditioned medium from pSecTag2B-tum-transfected COS cells inhibited the growth of endothelial cells but not of CT26 or LLC cells, whereas gemcitabine inhibited the growth of both endothelial cells and CT26 and LLC cells. Mice bearing subcutaneously established CT26 or LLC tumors received pSecTag2B-tum alone or in combination with gemcitabine to assess tumor growth inhibition. in vivo, combined treatment with pSecTag2B-tum and gemcitabine significantly decreased tumor growth through increased inhibition of tumor angiogenesis and increased tumor cell apoptosis compared with either agent alone. Enhanced antiproliferative and proapoptotic activity of the combination therapy on tumor-associated endothelial cells was calculated to be significant. This study suggests that combined treatment by the intramuscular delivery of plasmid DNA encoding tumstatin and gemcitabine augments tumor growth inhibition by suppressing angiogenesis and enhancing apoptosis in murine models. A combination of these agents could be used in future studies and translated into the clinical setting.
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PMID:Enhanced antitumor effect of the combination of tumstatin gene therapy and gemcitabine in murine models. 1614 6

Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.
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PMID:Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor models. 1658 92

MIG (monokine induced by interferon-gamma) is a CXC chemokine ligand (CXCL9) that can potently inhibit angiogenesis, and displays thymus-dependent antitumor effects. The effectiveness of a treatment combining gene therapy with plasmid-borne MIG (pORF-MIG) and low-dose cisplatin chemotherapy was determined using colon carcinoma (CT26) and Lewis lung carcinoma (LL/2c) murine models. The program was carried out via intramuscular delivery of pORF-MIG at 100 mug/mouse twice a week for 4 weeks, and/or intraperitoneal delivery of cisplatin at 0.6 mg/kg/mouse every 3 days for 48 days. Tumor volume and survival time were evaluated after treatment. CD31 immunohistochemical staining in tumor tissues and alginate capsule models in vivo was used to evaluate angiogenesis. Induction of apoptosis and cytotoxic T-lymphocyte (CTL) activity were also assessed. The combination of pORF-MIG and low-dose cisplatin produced significant antitumor activity, with complete tumor regression in 4/10 of CT26 colon carcinomas and 3/10 of LL/2c lung carcinomas, low vascularity, in alginate capsules, apparently degraded tumor microvessel density, and increased induction of apoptotic and CTL activities compared with either treatment alone. This study suggests that the combination of pORF-MIG plus cisplatin augments the inhibition of angiogenesis and the induction of apoptosis or CTL activity, all of which enhance antitumor activity. These findings may prove useful in further explorations of the application of combinatorial approaches to the treatment of solid tumors.
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PMID:Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma. 1667 84

H60 is a murine minor histocompatibility antigen that binds to NKG2D and activates an effector phenotype in NK and T cells. In the present study, H60 was genetically fused to the tumor-targeting murine MAb TNT-3. The resultant fusion protein, named H60/TNT-3, was produced in NS0 cells and determined by ELISA to possess an H60 epitope. The Ka of H60/TNT-3 (2.43 x 10(9) M(-1)) was nearly identical to that of the parental Ab (2.22 x 10(9) M(-1)), demonstrating that addition of the H60 moiety to the N-terminus of TNT-3 heavy chain did not affect antigen affinity. In vitro, H60/TNT-3 bound and activated murine NK cells, eliciting IFN-gamma production in a higher percentage of cells than the activating NKG2D Ab A10. In vivo, H60/TNT-3 possessed a half-life of approximately 12 hours and effectively targeted tumor tissue versus control organs, with nearly 2% injected dose per gram of tumor retained after 48 hours. Finally, H60/TNT-3 was tested for antitumor efficacy in BALB/c and C57BL/6 mice bearing subcutaneous syngeneic carcinomas. Tumor volume reduction was observed in both CT26 and Lewis Lung models (53% and 52%, respectively) relative to untreated control mice. Further, Lewis Lung carcinoma-bearing mice treated with H60/TNT-3 experienced a statistically significant survival advantage. Taken together, these data characterize a new immunotherapeutic MAb with antitumor efficacy that prolonged overall survival in a resistant solid tumor model.
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PMID:H60/TNT-3 fusion protein activates NK cells in vitro and improves immunotherapeutic outcome in murine syngeneic tumor models. 1669 70

We analysed the biologic properties of a small cell lung carcinoma cell line (designated KK0206) established from a patient with SCLC who had cancer-associated retinopathy (CAR). Morphological and immunohistochemical studies showed that KK0206 cells have features of the classic type of SCLC. KK0206 cells grew in suspension, forming relatively small clumps of cells with a doubling time of 72 h. On light microscopy, the cells were relatively small with little cytoplasm. On immunohistochemistry using anti-bovine recoverin rabbit antibody, the cells were intensely positive for recoverin. In addition, they were positive for NSE, Ki-67, and TP53. They also expressed human recoverin, a photoreceptor protein, whose presence was confirmed by RT-PCR analysis with cDNA sequencing and Western blot analysis. The point mutation of their TP53 gene (exon 156) was detected as well. The present study demonstrates that human recoverin is expressed in SCLC cells cultured from an anti-recoverin antibody-negative patient with CAR. KK0206 might be important for further research on SCLC related retinopathy.
Lung Cancer 2007 Jun
PMID:Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy. 1737 19

Patients with malignant mesothelioma (MM), an aggressive cancer associated with asbestos exposure, usually present clinically with advanced disease and this greatly reduces the likelihood of curative treatment. MM is difficult to diagnose without invasive techniques; the development of non-invasively detectable molecular markers would therefore be highly beneficial. DNA methylation changes in cancer cells provide powerful markers that are potentially detectable non-invasively in DNA shed into bodily fluids. Here we examined the methylation status of 28 loci in 52 MM tumors to investigate their potential as molecular markers for MM. To exclude candidate MM markers that might be positive in biopsies/pleural fluid due to contaminating surrounding non-tumor lung tissue/DNA, we also examined the methylation of these markers in lung samples (age- or environmentally induced hypermethylation is frequently observed in non-cancerous lung). Statistically significantly increased methylation in MM versus non-tumor lung samples was found for estrogen receptor 1 (ESR1; p = 0.0002), solute carrier family 6 member 20 (SLC6A20; p = 0.0022) and spleen tyrosine kinase (SYK; p=0.0003). Examination of associations between methylation levels of the 28 loci and clinical parameters suggest associations of the methylation status of metallothionein genes with gender, histology, asbestos exposure, and lymph node involvement, and the methylation status of leucine zipper tumor suppressor 1 (LZTS1) and SLC6A20 with survival.
Lung Cancer 2007 Nov
PMID:DNA methylation profile of 28 potential marker loci in malignant mesothelioma. 1765 10

Introduction of spinal surgery into lung cancer operations has made extensive operations feasible with an acceptable long-term survival. We report our successful experience of en bloc total vertebrectomy for lung cancer invading the spine. A 49-year-old man was found to have squamous cell carcinoma of the posterior apex of the right lung with an invasion of the body of the second and third thoracic vertebra. After induction chemoradiotherapy, we performed en bloc resection through thoracotomy and posterior median approach. Vertebral stabilization was achieved with a rod fixation and a placement of titanium mesh cage packed with autogenous bone chips.
Lung Cancer 2008 Jul
PMID:En bloc total vertebrectomy for lung cancer invading the spine. 1824 63

Mouse PNAS-4 (mPNAS-4) has 96% identity with human PNAS-4 (hPNAS-4) in primary sequence and has been reported to be involved in the apoptotic response to DNA damage. However, there have been no studies reported of the biological functions of mPNAS-4. In studies conducted by our group (unpublished data), it was interesting to note that overexpression of mPNAS-4 promoted apoptotic death in Lewis lung carcinoma cells (LL2) and colon carcinoma cells (CT26) of mice both in vitro and in vivo. In our studies, mPNAS-4 was cloned into the pGEX-6P-1 vector with GST tag at N-terminal in Escherichia coli strain BL21(DE3). The soluble and insoluble expression of recombinant protein mPNAS-4 (rmPNAS-4) was temperature-dependent. The majority of rmPNAS-4 was insoluble at 37 degrees C, while it was almost exclusively expressed in soluble form at 20 degrees C. The soluble rmPNAS-4 was purified by one-step affinity purification, using a glutathione Sepharose 4B column. The rmPNAS-4 protein was further identified by electrospray ionization-mass spectrometry analysis. The search parameters of the parent and fragment mass error tolerance were set at 0.1 and 0.05 kDa, respectively, and the sequence coverage of search result was 28%. The purified rmPNAS-4 was further used as immunogen to raise polyclonal antibodies in New Zealand white rabbit, which were suitable to detect both the recombinant and the endogenous mPNAS-4 in mouse brain tissue and LL2 cells after immunoblotting and/or immunostaining. The purified rmPNAS-4 and our prepared anti-mPNAS-4 polyclonal antibodies may provide useful tools for future biological function studies for mPNAS.
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PMID:Prokaryotic expression of a novel mouse pro-apoptosis protein PNAS-4 and application of its polyclonal antibodies. 1862 94

It is unusual for a malignant lung tumor to present clinically as a cystic lesion. A case of large cell carcinoma of the lung mimicking pulmonary hydatid cyst is reported herein. The patient was a 65-year-old male who presented with history of slowly progressive breathlessness and painful swelling over the left chest wall. Computed tomography of the chest showed a well defined cystic lesion in the left upper lobe with outward extension through the left 2nd-3rd intercostal space in the absence of bony destruction. The patient was found to have positive serological test for Echinococcus granulosus and therefore the preoperative diagnosis was that of complicated pulmonary hydatid cyst. Intra-operative findings included presence of a large cavity filled with necrotic material and "daughter cysts". Dense adhesions between the cavity wall and the thoracic cage prevented complete surgical resection. Histopathological evaluation of the excised specimen showed large cell carcinoma. The case highlights the fact that a lung carcinoma may rarely have clinical, radiological, and serological features similar to those of a pulmonary hydatid cyst.
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PMID:Lung carcinoma mimicking hydatid cyst: a case report and review of the literature. 1906 56


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