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.

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.

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.

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.

Lung cancer (including management of an isolated lung lesion)

2018 ◽  
Author(s):  
Raman Verma ◽  
Sarah Deacon
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Primary Lung Cancer ◽  
Small Cell ◽  
The Body ◽  
Small Cell Lung ◽  
Rare Type ◽  
Cell Lung Carcinoma ◽  
Isolated Lung

Lung cancer is the second most common type of cancer in the UK. It is termed ‘primary’ if it originates in the lungs. and ‘secondary’ if it manifests elsewhere in the body but then spreads to the lungs. The main types of primary lung cancer are small cell lung carcinoma and non-small cell lung carcinoma. Bronchial carcinoids account for up to 5% of lung cancer. These are generally small when diagnosed and occur most commonly in people under 40 years of age. Unrelated to cigarette smoking, carcinoid tumours can metastasize and a small proportion of these tumours secrete hormone-like substances that may cause specific symptoms related to the hormone being produced. Carcinoids generally grow and spread more slowly than bronchogenic cancers, and many are detected early enough to be amenable to surgical resection. Mesothelioma is a rare type of cancer that affects the pleura.

scholarly journals ADRB3 expression in tumor cells is a poor prognostic factor and promotes proliferation in non-small cell lung carcinoma

2020 ◽  
Vol 69 (11) ◽  
pp. 2345-2355
Author(s):  
Meng Zheng ◽  
Zhiling Zhou ◽  
Xiangting Tian ◽  
Dingzhang Xiao ◽  
Xinghua Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Poor Prognostic Factor

Abstract The cross-talk between cancer cells and monocyte-derived alveolar macrophages (Mo-AMs) promotes non-small cell lung carcinoma (NSCLC) progression. In this study, we report that both cancer cells and Mo-AMs robustly express beta 3-adrenergic receptor (ADRB3) in NSCLC. ADRB3 supports lung cancer cells proliferation and promotes chronic inflammation. Genetic and pharmacologic inhibition of ADRB3 reverses tumor growth and inflammation in mouse. Furthermore, we demonstrate that M5D1, a novel anti-ADRB3 monoclonal antibody, inhibits human lung cancer cells proliferation and inflammation via affecting the intracellular mTOR pathway and activating p53. In NSCLC patients, we confirmed that upregulation of ADRB3 expression correlates with tumor progression and poor prognosis. Altogether, these results shed light on the role of ADRB3 in NSCLC and suggest that M5D1 could become powerful antitumor weapons.

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