CT20p as a therapeutic for lung cancer with elevated chaperonin containing TCP1 (CCT) expression levels.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23163-e23163 ◽  
Author(s):  
Priya Vishnubhotla ◽  
Ana C Carr ◽  
Amr Khaled ◽  
Rania Bassiouni ◽  
Annette R. Khaled
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Cell Lines ◽  
Lung Carcinoma ◽  
Small Cell ◽  
Normal Lung ◽  
Lung Cells ◽  
Macromolecular Complex ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

e23163 Background: We previously reported, in breast cancer, the effectiveness of a novel therapeutic peptide called CT20p that displays cancer-selective cytotoxicity. CT20p targets for inhibition a macromolecular complex called Chaperonin-Containing TCP-1 (CCT) that is responsible for folding actin and tubulin and other proteins, like STAT3, into their active forms. CCT is composed of 8 subunits (CCT1-8) that are highly conserved among species. In breast cancer cases, we found that the genes for CCT were frequently amplified (CCT2), upregulating the chaperonin’s activity, which correlated with decreased patient survival. Methods: To determine whether CCT is active in other cancers and thereby a broad therapeutic target, we examined the protein levels of CCT2 in colon, liver, prostate and lung cancer by immunohistochemistry (IHC), using human tissue microarrays (TMAs). Genomic data from The Cancer Genome Atlas (TCGA) was used to support IHC findings. Immunoblot probing of three CCT subunits (CCT2, CCT4, CCT5) was performed to determine their relative expression level in five small cell lung cancer (SCLC) cell lines compared to normal lung cells and these cells tested for susceptibility to killing by CT20p. Results: Results of IHC staining for CCT2 were interpreted on a scale of 1 to 4 (with 4 being the strongest staining). We found that with the exception of colon cancer, all cancers expressed high levels of CCT2 with advancing stage. We identified a significant correlation with cancer progression in both small cell lung carcinoma (SCLC) and squamous cell lung carcinoma (SqCLC). While individual levels of the three probed CCT subunits varied amongst the SCLC cell lines, overall CCT expression was higher in the SCLC cells when compared to normal lung cells and correlated with susceptibility to killing by CT20p. Using the TCGA database, CCT gene alterations were detected in clinical lung cancer cases, with amplification of CCT4 gene in SqCLC cases linked to decreased survival. Conclusions: These results indicate that targeted inhibition of CCT through CT20p treatment is a promising treatment approach for those cancers like SCLC that currently lack effective therapeutics to sustain progression-free survival.

scholarly journals miR-190, CDK1, MCM10 and NDC80 predict the prognosis of the patients with lung cancer

2019 ◽  
Vol 27 (1) ◽  
pp. 15-24
Author(s):  
Li-Wei Gao ◽  
Guo-Liang Wang
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Normal Lung ◽  
Ppi Network ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Network Modules ◽  
Tcga Dataset

Abstract Lung cancer (LC), which includes small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), is common and has a high fatality rate. This study aimed to reveal the prognostic mechanisms of LC. GSE30219 was extracted from the Gene Expression Omnibus (GEO) database, and included 293 LC samples and 14 normal lung samples. Differentially expressed genes (DEGs) were identified using the Limma package, and subjected to pathway enrichment analysis using DAVID. MicroRNAs (miRNAs) targeting the DEGs were predicted using Webgestalt. Cytoscape software was used to build a protein-protein interaction (PPI) network and to identify significant network modules. Survival analysis was conducted using Survminer and Survival packages, and validation was performed using The Cancer Genome Atlas (TCGA) dataset. The good and poor prognosis groups contained 518 DEGs. miR-190, miR-493, and miR-218 for the upregulated genes and miR-302, miR-200, and miR-26 for the downregulated genes were predicted. Three network modules (module 1, 2, and 3) were identified from the PPI network. CDK1, MCM10, and NDC80 were the core nodes of module 1, 2, and 3, respectively. In module 1, CDK1 interacted with both CCNB1 and CCNB2. Additionally, CDK1, CCNB1, CCNB2, MCM10, and NDC80 expression levels correlated with clinical survival and were identified as DEGs in both GSE30219 and the TCGA dataset. miR-190, miR-493, miR-218, miR-200, and miR-302 might act in LC by targeting the DEGs. CDK1, CCNB1, CCNB2, MCM10, and NDC80 might also influence the prognosis of LC.

Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: outcomes and prognostic factors

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 247-254 ◽  
Author(s):  
Jason Sheehan ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
The Brain ◽  
Fine Print

Object. Lung carcinoma is the leading cause of death from cancer. More than 50% of those with small cell lung cancer develop a brain metastasis. Corticosteroid agents, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, median survival for patients with small cell lung carcinoma metastasis is approximately 4 to 5 months after cranial irradiation. In this study the authors examine the efficacy of gamma knife surgery for treating recurrent small cell lung carcinoma metastases to the brain following tumor growth in patients who have previously undergone radiation therapy, and they evaluate factors affecting survival. Methods. A retrospective review of 27 patients (47 recurrent small cell lung cancer brain metastases) undergoing radiosurgery was performed. Clinical and radiographic data obtained during a 14-year treatment period were collected. Multivariate analysis was utilized to determine significant prognostic factors influencing survival. The overall median survival was 18 months after the diagnosis of brain metastases. In multivariate analysis, factors significantly affecting survival included: 1) tumor volume (p = 0.0042); 2) preoperative Karnofsky Performance Scale score (p = 0.0035); and 3) time between initial lung cancer diagnosis and development of brain metastasis (p = 0.0127). Postradiosurgical imaging of the brain metastases revealed that 62% decreased, 19% remained stable, and 19% eventually increased in size. One patient later underwent a craniotomy and tumor resection for a tumor refractory to radiosurgery and radiation therapy. In three patients new brain metastases were demonstrating on follow-up imaging. Conclusions. Stereotactic radiosurgery for recurrent small cell lung carcinoma metastases provided effective local tumor control in the majority of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can extend survival.

The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

2019 ◽  
Vol 22 (4) ◽  
pp. 238-244 ◽  
Author(s):  
Gang Chen ◽  
Bo Ye
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

New lung cancer treatment strategy with molecular target of PKCeta

Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 56-58
Author(s):  
Motoi Ohba
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Surgical Removal ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Nucleotide Mutation

Lung cancer is one of the most prevalent and lethal forms of the disease accounting for almost 20 per cent of all deaths from cancer. It is therefore the leading cause of cancer death in men and second most fatal in women. There are between 1.5 and 2 million new cases of cancer globally every year. A similar number die from the disease annually. There are two forms of lung cancer – small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). SCLC is the more aggressive form being faster growing and more metastatic, however it also responds more effectively to treatments such as chemotherapy. NSCLC is the more common form of the disease, accounting for 85 per cent of cases. They develop more slowly than SCLCs, however they are largely unresponsive to chemotherapy and require precise surgical removal. Both present a huge medical problem in terms of diagnosis and treatment. Due to its far higher prevalence, NSCLC is the most studied of the two forms. A chemotherapeutic treatment has been developed that targets the epidermal growth factor receptor (EGFR). EGFR is majorly upregulated in most cases and plays a key role in the tumour's growth and survival. The treatment blocks the receptor and is usually very effective in the first instances. However, it is typically unable to clear the cancer as a single nucleotide mutation is capable of rendering the inhibitor unable to act on the receptor. Therefore, the cancer returns and continues to develop. New treatments are also required. This is the work of Dr Motoi Ohba of the Advanced Cancer Translational Research Institute, Showa University, Japan. His work is aimed at both uncovering novel targets for cancer treatment and finding and developing molecules that could effectively manipulate these targets.

Expression of the Vasopressin and Gastrin-Releasing Peptide Genes in Small Cell Lung Carcinoma Cell Lines

Pathobiology ◽  
1992 ◽  
Vol 60 (3) ◽  
pp. 136-142 ◽  
Author(s):  
Marleen A.E. Verbeeck ◽  
Jack P.M. Elands ◽  
Lou F.M.H. de Leij ◽  
Charles H.C.M. Buys ◽  
Desmond N. Carney ◽  
...  
Keyword(s):  
Cell Lines ◽  
Lung Carcinoma ◽  
Carcinoma Cell ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Gastrin Releasing Peptide ◽  
Carcinoma Cell Lines ◽  
Lung Carcinoma Cell

scholarly journals Differential development of large-cell neuroendocrine or small-cell lung carcinoma upon inactivation of 4 tumor suppressor genes

2019 ◽  
Vol 116 (44) ◽  
pp. 22300-22306 ◽  
Author(s):  
Sara Lázaro ◽  
Miriam Pérez-Crespo ◽  
Corina Lorz ◽  
Alejandra Bernardini ◽  
Marta Oteo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
Imaging Method ◽  
Cancer Type ◽  
High Grade ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

High-grade neuroendocrine lung malignancies (large-cell neuroendocrine cell carcinoma, LCNEC, and small-cell lung carcinoma, SCLC) are among the most deadly lung cancer conditions with no optimal clinical management. The biological relationships between SCLC and LCNEC are still largely unknown and a current matter of debate as growing molecular data reveal high heterogeneity with potential therapeutic consequences. Here we describe murine models of high-grade neuroendocrine lung carcinomas generated by the loss of 4 tumor suppressors. In an Rbl1-null background, deletion of Rb1, Pten, and Trp53 floxed alleles after Ad-CMVcre infection in a wide variety of lung epithelial cells produces LCNEC. Meanwhile, inactivation of these genes using Ad-K5cre in basal cells leads to the development of SCLC, thus differentially influencing the lung cancer type developed. So far, a defined model of LCNEC has not been reported. Molecular and transcriptomic analyses of both models revealed strong similarities to their human counterparts. In addition, a 68Ga-DOTATOC–based molecular-imaging method provides a tool for detection and monitoring the progression of the cancer. These data offer insight into the biology of SCLC and LCNEC, providing a useful framework for development of compounds and preclinical investigations in accurate immunocompetent models.

scholarly journals Immunocheckpoint Inhibitor- (Nivolumab-) Associated Hypereosinophilia in Non-Small-Cell Lung Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Navdeep Singh ◽  
Sandeep Singh Lubana ◽  
George Constantinou ◽  
Andrea N. Leaf
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Lung Carcinoma ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Eosinophil Counts

Immunocheckpoint inhibitor (ICI) therapy has provided significant clinical improvements in the treatment of several malignancies. The purpose of this report is to increase awareness of hypereosinophilia associated with checkpoint inhibitors, a topic that has been rarely reported. Hypereosinophilia may need to be addressed especially if eosinophil counts increase to levels where hypereosinophilic visceral complications can occur. We are presenting a case of a 57-year-old male with hypereosinophilia that was seen in the setting of progression of metastatic non-small-cell lung cancer during and after nivolumab treatment.

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