The Impact of lncRNAs and miRNAs on Apoptosis in Lung Cancer

Apoptosis is a coordinated cellular process that occurs in several physiological situations. Dysregulation of apoptosis has been documented in numerous pathological situations, particularly cancer. Non-coding RNAs regulate apoptosis via different mechanisms. Lung cancer is among neoplastic conditions in which the role of non-coding RNAs in the regulation of apoptosis has been investigated. Non-coding RNAs that regulate apoptosis in lung cancer have functional interactions with PI3K/Akt, PTEN, GSK-3β, NF-κB, Bcl-2, Bax, p53, mTOR and other important cancer-related pathways. Globally, over-expression of apoptosis-blocking non-coding RNAs has been associated with poor prognosis of patients, while apoptosis-promoting ones have the opposite effect. In the current paper, we describe the impact of lncRNAs and miRNAs on cell apoptosis in lung cancer.

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Do we Need Maintenance Chemotherapy in Advanced NSCLC in the Era of Immune and Targeted Therapy?

Current Cancer Therapy Reviews ◽

10.2174/1573394714666180417160205 ◽

2019 ◽

Vol 15 (1) ◽

pp. 50-55

Author(s):

Ahmed Nagy ◽

Omar Abdel Rahman ◽

Heba Abdullah ◽

Ahmed Negida

Keyword(s):

Lung Cancer ◽

Maintenance Therapy ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Statistical Significance ◽

Small Cell ◽

Maintenance Chemotherapy ◽

Small Cell Lung ◽

The Impact

Background: Although well established for the effective management of hematologic cancers, maintenance chemotherapy has only been recently incorportated as a treatment paradigm for advanced non–small-cell lung cancer. Maintenance chemotherapy aims to prolong a clinically favorable response state achieved after finishing induction therapy which is usually predefined in number before startng treatment. There are 2 modalities for maintenance therapy; continuation maintenance (involving a non-platinum component which was a part of the induction protocol or a targeted agent) and switch maintenance therapy (utilizing a new agent which was not a part of the induction regimen). Methods: The purpose of this article is to review the role of maintenance therapy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC) and provide a brief overview about induction chemotherapy in NSCLC to address the basis of maintenance therapy as a treatment option. We will also compare the impact of maintenance chemotherapy with the now evolving role of immunotherapy in NSCLC. Results: There have been 4 maintenance studies to date showing prolonged PFS and OS with statistical significance. However, Three out of the four studies (ECOG4599, JMEN, and PARAMOUNT) did not report tumor molecular analysis. As regard Immunotherapy, current data is in favour of strongly an increasing role for immunotherapy in NSCLC. Conclusion: Maintenance therapy in NSCLC continues to be an important therapeutic line to improve outcome in patients with metastatic and recurrent disease.

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Covid-19 In Man: A Very Dangerous Affair.

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530321666210101123801 ◽

2021 ◽

Vol 21 ◽

Author(s):

Giuseppe Lisco ◽

Vito A. Giagulli ◽

Giovanni De Pergola ◽

Anna De Tullio ◽

Edoardo Guastamacchia ◽

...

Keyword(s):

Poor Prognosis ◽

Metabolic Diseases ◽

Systemic Disease ◽

Public Health Issue ◽

Immune System Dysfunction ◽

Data Support ◽

Systemic Spread ◽

The Impact

Background: The novel pandemic of Coronavirus disease 2019 (COVID-19) has becoming a public health issue since March 2020 considering that more than 30 million people were found to be infected worldwide. Particularly, recent evidences suggested that men may be considered as at higher risk of poor prognosis or death once the infection occurred and concerns surfaced in regard of the risk of a possible testicular injury due to SARS-CoV-2 infection. Results: Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, younger man with normal testicular function compared to women of similar age are prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that SARS-CoV-2 genome is not normally found in gonads and gametes, therefore sex transmission could be excluded as a possible way to spread the COVID-19. Conclusion: Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection even in case it occurred asymptomatically but no long-term evidences are currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.

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Differential Impacts of Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) in Epithelial IGF-Induced Lung Cancer Development

Endocrinology ◽

10.1210/en.2010-0693 ◽

2011 ◽

Vol 152 (6) ◽

pp. 2164-2173 ◽

Cited By ~ 13

Author(s):

Woo-Young Kim ◽

Mi-Jung Kim ◽

Hojin Moon ◽

Ping Yuan ◽

Jin-Soo Kim ◽

...

Keyword(s):

Lung Cancer ◽

Lung Tumor ◽

Binding Protein ◽

Cancer Development ◽

Lung Carcinogenesis ◽

Tobacco Carcinogen ◽

Igf I ◽

The Impact ◽

Igfbp 3

The IGF axis has been implicated in the risk of various cancers. We previously reported a potential role of tissue-derived IGF in lung tumor formation and progression. However, the role of IGF-binding protein (IGFBP)-3, a major IGFBP, on the activity of tissue-driven IGF in lung cancer development is largely unknown. Here, we show that IGF-I, but not IGF-II, protein levels in non-small-cell lung cancer (NSCLC) were significantly higher than those in normal and hyperplastic bronchial epithelium. We found that IGF-I and IGFBP-3 levels in NSCLC tissue specimens were significantly correlated with phosphorylated IGF-IR (pIGF-IR) expression. We investigated the impact of IGFBP-3 expression on the activity of tissue-driven IGF-I in lung cancer development using mice carrying lung-specific human IGF-I transgene (Tg), a germline-null mutation of IGFBP-3, or both. Compared with wild-type (BP3+/+) mice, mice carrying heterozygous (BP3+/−) or homozygous (BP3−/−) deletion of IGFBP-3 alleles exhibited decreases in circulating IGFBP-3 and IGF-I. Unexpectedly, IGFTg mice with 50% of physiological IGFBP-3 (BP3+/−; IGFTg) showed higher levels of pIGF-IR/IR and a greater degree of spontaneous or tobacco carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung tumor development and progression than did the IGFTg mice with normal (BP3+/+;IGFTg) or homozygous deletion of IGFBP-3 (BP3−/−; IGFTg). These data show that IGF-I is overexpressed in NSCLC, leading to activation of IGF-IR, and that IGFBP-3, depending on its expression level, either inhibits or potentiates IGF-I actions in lung carcinogenesis.

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Structural insights and evaluation of the potential impact of missense variants on the interactions of SLIT2 with ROBO1/4 in cancer progression

Scientific Reports ◽

10.1038/s41598-020-78882-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Debmalya Sengupta ◽

Gairika Bhattacharya ◽

Sayak Ganguli ◽

Mainak Sengupta

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Structural Parameters ◽

Homology Modelling ◽

Missense Variants ◽

Potential Impact ◽

The Impact ◽

Structural Insights ◽

Rigid Docking

AbstractThe cognate interaction of ROBO1/4 with its ligand SLIT2 is known to be involved in lung cancer progression. However, the precise role of genetic variants, disrupting the molecular interactions is less understood. All cancer-associated missense variants of ROBO1/4 and SLIT2 from COSMIC were screened for their pathogenicity. Homology modelling was done in Modeller 9.17, followed by molecular simulation in GROMACS. Rigid docking was performed for the cognate partners in PatchDock with refinement in HADDOCK server. Post-docking alterations in conformational, stoichiometric, as well as structural parameters, were assessed. The disruptive variants were ranked using a weighted scoring scheme. In silico prioritisation of 825 variants revealed 379 to be potentially pathogenic out of which, about 12% of the variants, i.e. ROBO1 (14), ROBO4 (8), and SLIT2 (23) altered the cognate docking. Six variants of ROBO1 and 5 variants of ROBO4 were identified as "high disruptors" of interactions with SLIT2 wild type. Likewise, 17 and 13 variants of SLIT2 were found to be "high disruptors" of its interaction with ROBO1 and ROBO4, respectively. Our study is the first report on the impact of cancer-associated missense variants on ROBO1/4 and SLIT2 interactions that might be the drivers of lung cancer progression.

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Glyceraldehyde-3-phosphate dehydrogenase gene over expression correlates with poor prognosis in non small cell lung cancer patients

Molecular Cancer ◽

10.1186/1476-4598-12-97 ◽

2013 ◽

Vol 12 (1) ◽

pp. 97 ◽

Cited By ~ 20

Author(s):

Roberto Puzone ◽

Graziana Savarino ◽

Sandra Salvi ◽

Maria Dal Bello ◽

Giulia Barletta ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Poor Prognosis ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancer Patients ◽

Over Expression ◽

Dehydrogenase Gene

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Regulation of Macrophage Activation and Polarization by HCC-Derived Exosomal lncRNA TUC339

International Journal of Molecular Sciences ◽

10.3390/ijms19102958 ◽

2018 ◽

Vol 19 (10) ◽

pp. 2958 ◽

Cited By ~ 41

Author(s):

Xue Li ◽

Yi Lei ◽

Miao Wu ◽

Nan Li

Keyword(s):

Macrophage Activation ◽

Cell Function ◽

Regulatory Function ◽

Receptor Interaction ◽

Loss Of Function ◽

Critical Function ◽

Over Expression ◽

Ifn Γ ◽

Non Coding Rnas

Exosomes released by cells can serve as vehicles for delivery of biological materials and signals. Long non-coding RNAs (lncRNAs) are non-coding RNAs longer than 200 nt, which roles are increasingly appreciated in various biological content. Tumor-derived exosomal lncRNAs have been implicated as signaling mediators to orchestrate cell function among neighbor tumor cells. However, the role of tumor-derived lncRNAs in cross-talk with environmental macrophages has yet to be explored. In this paper, we demonstrated that hepatocellular carcinoma (HCC) cells–derived exosomes contain elevated levels of lncRNA TUC339 and that HCC-derived exosomes could be taken up by THP-1 cells. In seeking to dissect the biological function of tumor secreting TUC339 in macrophages, we applied loss-of-function and gain-of-function strategies. We observed increased pro-inflammatory cytokine production, increased co-stimulatory molecule expression, and enhanced phagocytosis upon suppression of TUC339 by siRNA in THP-1 cells, and the opposite effect upon over-expression of this lncRNA, which indicates that TUC339 was involved in the regulation of macrophage activation. Moreover, we detected an elevated level of TUC339 in M(IL-4) macrophages as compared to M(IFN-γ + LPS) macrophages and a down-regulation of TUC339 expression during M(IL-4)-to-M(IFN-γ + LPS) repolarization and vice versa. Furthermore, suppression of TUC339 in macrophages diminished the expression of M(IL-4) markers upon IL-4 treatment while overexpression of TUC339 in macrophages enhanced M(IL-4) markers upon IFN-γ + LPS treatment, which suggests a critical function of TUC339 in the regulation of macrophage M1/M2 polarization. Lastly, using microarray analysis, we identified cytokine-cytokine receptor interaction, CXCR chemokine receptor binding, Toll-like receptor signaling, FcγR-mediated phagocytosis, regulation of the actin cytoskeleton, and cell proliferation are related with TUC339 function in macrophages. Our results provide evidence for a novel regulatory function of tumor-derived exosomal lncRNA TUC339 in environmental macrophages and shed light on the complicated interactions between tumor and immune cells through exosomal lncRNAs.

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Re-evaluation of the Role of Postoperative Radiotherapy and the Impact of Radiation Dose for Non–Small-Cell Lung Cancer Using the National Cancer Database

Journal of Thoracic Oncology ◽

10.1097/jto.0000000000000406 ◽

2015 ◽

Vol 10 (1) ◽

pp. 148-155 ◽

Cited By ~ 35

Author(s):

Christopher D. Corso ◽

Charles E. Rutter ◽

Lynn D. Wilson ◽

Anthony W. Kim ◽

Roy H. Decker ◽

...

Keyword(s):

Lung Cancer ◽

Radiation Dose ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Postoperative Radiotherapy ◽

Small Cell ◽

National Cancer Database ◽

Small Cell Lung ◽

The Impact

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Impact of erlotinib activity on overall survival in non small cell lung cancer patients: Is the post progression survival a new paradigm?

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e19086 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e19086-e19086

Author(s):

Tindara Franchina ◽

Alessandro Russo ◽

Claudia Proto ◽

Giuseppe Chiofalo ◽

Maria Picciotto ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Statistical Tests ◽

Small Cell ◽

Cancer Evolution ◽

Small Cell Lung ◽

The Impact

e19086 Background: In the last few years, the treatment of non-small cell lung cancer (NSCLC) has been dramatically changed with the introduction of EGFR TK (Epidermal Growth Factor Tyrosine Kinase) inhibitors. Given its objectivity and the benefits derived by patients, overall survival (OS) has been historically considered the most important therapeutic objective in advanced NSCLC. However, little is known about postprogression survival (PPS) in NSCLC. This study evaluates the correlation between response to erlotinib and post progression survival (i.e. the time between disease progression and death) to estimate the impact of this drug on overall survival. Methods: We retrospectively analyzed 68 NSCLC unselected patients consecutively treated with second or third line erlotinib at our institution from 2007 to 2010, including in the responder group patients who progressed after stable disease on erlotinib for at least six months (n=20). The relationship between OS and PPS was evaluated by standard statistical tests. P-values <0.05 were considered statistically significant. Results: Survival was significantly prolonged in responders patients (18.6 vs 11.3) suggesting the important role of EGFR TK inhibitors in NSCLC management. In addition a significant increase of PPS was recorded in these patients (9.1 vs 4.6 p=0.02), allowing to perform further therapy lines to better control cancer evolution. Conclusions: These data underline the key role of EGFR in NSCLC growth and progression and the impact of erlotinib in cancer control evolution. Post progression therapy influence the effect on overall survival. This analysis suggests that a treatment strategy incorporating all active agents over the course of disease optimizes OS. Further investigations will be needed in selected patients harboring EGFR-activating mutations to better define the role of PPS as new indicator of erlotinib efficacy.

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