scholarly journals Role of Cytokines and Chemokines in NSCLC Immune Navigation and Proliferation

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Sowmya Ramachandran ◽  
Amit K. Verma ◽  
Kapil Dev ◽  
Yamini Goyal ◽  
Deepti Bhatt ◽  
...  

With over a million deaths every year around the world, lung cancer is found to be the most recurrent cancer among all types. Nonsmall cell lung carcinoma (NSCLC) amounts to about 85% of the entire cases. The other 15% owes it to small cell lung carcinoma (SCLC). Despite decades of research, the prognosis for NSCLC patients is poorly understood with treatment options limited. First, this article emphasises on the part that tumour microenvironment (TME) and its constituents play in lung cancer progression. This review also highlights the inflammatory (pro- or anti-) roles of different cytokines (ILs, TGF-β, and TNF-α) and chemokine (CC, CXC, C, and CX3C) families in the lung TME, provoking tumour growth and subsequent metastasis. The write-up also pinpoints recent developments in the field of chemokine biology. Additionally, it covers the role of extracellular vesicles (EVs), as alternate carriers of cytokines and chemokines. This allows the cytokines/chemokines to modulate the EVs for their secretion, trafficking, and aid in cancer proliferation. In the end, this review also stresses on the role of these factors as prognostic biomarkers for lung immunotherapy, apart from focusing on inflammatory actions of these chemoattractants.

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 247-254 ◽  
Author(s):  
Jason Sheehan ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford

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.


Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 56-58
Author(s):  
Motoi Ohba

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.


2019 ◽  
Author(s):  
◽  
Soumavo Mukherjee

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] "Lung carcinoma, also known as lung cancer, is a malignant tumor of lungs characterized by uncontrolled call growth in lung tissue. Tobacco smoking is the reason for nearly 85% of cases of lung cancer. The rest 10-15% are usually a combination of genetic factors, secondhand smoke, environmental pollutants, asbestos and radon gas exposure. Chest radiography and CT scan with confirmation by biopsy are the ways to detect the cancer. The type of cancer, degree of spread and the overall health weigh in on the outcome and eventual possible cure. Still now, most cases are not curable. Surgery, chemotherapy and radiotherapy are the treatments of choice for all types of lung cancer. Being the most common form of cancer in men and second most common form in women, after breast, data of the year 2012 showed 1.8 million incidences of lung cancer resulting to 1.6 million deaths worldwide, with the most common age of diagnosis being 70 years. 5-year survival rate in USA is 17.4%. ... Studies has been done to unravel the downstream effect after knocking down the oncogene via siRNA(42). Malignant cells have a number of secondary pathways, along with the primary pathway, which remain dormant till the disruption of the primary pathway(43). A complex mechanism controls this function which is triggered by the change in downstream protein and gene expression levels. This makes the cancer cells develop drug resistance(44). In this project, we developed a gelatin-based nanoparticle (GelNP) that will act as a vehicle to deliver targeted siRNAs against NSCLC cells in combination with Cisplatin. The cetuximab (Ab), an EGFR targeting antibody, shall be attached to the surface. The AXL and FN14 SiRNAs shall be conjugated to the antibody by the thio-ether linkage. The cetuximab antibody shall be used to specifically target the cell and also to protect the siRNAs from degradation. We predict that 146kDa cetuximab antibody will shield the 15kDa siRNAs and prevent it from exposure to environment. Since AXL and FN14 has been observed to be related to EGFR, we hypothesize that knocking down AXL and FN14 will block EGFR and thus allow the TKI to continue its course of therapeutic action."--Introduction.


2020 ◽  
Author(s):  
Dong-bin Wang ◽  
Xuan Li ◽  
Xi-ke Lu ◽  
Zhong-yi Sun ◽  
Xun Zhang ◽  
...  

Abstract Background: Lung cancer is a leading cause of cancer death around the world, while the Transthyretin (TTR) is a specific biomarkers for clinical diagnosis. However, its role in lung cancer remains to be unknown. Methods: In the present study, we made attempt to investigate effect of abnormal expression of TTR on Non-small-cell lung carcinoma (NSCLC) by overexpression or knockdown of TTR.To further investigate the mechanisms underlying the potential role of TTR in NSCLC, we searched and verified several signal pathways . In vivo experiments, to verify the effect of TTR overexpression on tumors.Results: We finded that up-regulated TTR obviously suppressed cell proliferation, migration, invasion and increased apoptosis.Significant suppression of phosphor-MAPK/ERK was observed in TTR-treated NSCLC cells, implying that TTR was important for cellular progress by regulating MAPK/ERK signaling pathway. In vivo experiment, overexpression of TTR promoted cell apoptosis and inhibited tumor growth. Conclusions: Overall, our results suggest that TTR has a potential anti-tumor effect in human NSCLC progression, which provides theoretical basis for the diagnosis and treatment of NSCLC.Above all, further understanding of TTR was useful for clinical care.


2019 ◽  
Vol 124 ◽  
pp. 98-100 ◽  
Author(s):  
V.V.V. Ravi Kiran Ammu ◽  
Kusuma Kumari Garikapati ◽  
Praveen T. Krishnamurthy ◽  
Pavan Kumar Chintamaneni ◽  
Sai Kiran S.S. Pindiprolu

2019 ◽  
Vol 116 (44) ◽  
pp. 22300-22306 ◽  
Author(s):  
Sara Lázaro ◽  
Miriam Pérez-Crespo ◽  
Corina Lorz ◽  
Alejandra Bernardini ◽  
Marta Oteo ◽  
...  

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.


2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Navdeep Singh ◽  
Sandeep Singh Lubana ◽  
George Constantinou ◽  
Andrea N. Leaf

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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