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Updates and controversies in the rapidly evolving field of lung cancer screening, early detection, and chemoprevention.

ABSTRACT: Lung cancer remains the leading cause of cancer-related death in the United States. Cigarette smoking is a well-recognized risk factor for lung cancer, and a sustained elevation of lung cancer risk persists even after smoking cessation. Despite identifiable risk factors, there has been minimal improvement in mortality for patients with lung cancer primarily stemming from diagnosis at a late stage when there are few effective therapeutic options. Early detection of lung cancer and effective screening of high-risk individuals may help improve lung cancer mortality. While low dose computerized tomography (LDCT) screening of high risk smokers has been shown to reduce lung cancer mortality, the high rates of false positives and potential for over-diagnosis have raised questions on how to best implement lung cancer screening. The rapidly evolving field of lung cancer screening and early-detection biomarkers may ultimately improve the ability to diagnose lung cancer in its early stages, identify smokers at highest-risk for this disease, and target chemoprevention strategies. This review aims to provide an overview of the opportunities and challenges related to lung cancer screening, the field of biomarker development for early lung cancer detection, and the future of lung cancer chemoprevention.

SUBMITTER: Kathuria H

PROVIDER: S-EPMC4074822 | biostudies-other | 2014 May

REPOSITORIES: biostudies-other

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Updates and controversies in the rapidly evolving field of lung cancer screening, early detection, and chemoprevention.

Kathuria Hasmeena H Gesthalter Yaron Y Spira Avrum A Brody Jerome S JS Steiling Katrina K

Cancers 20140516 2

Lung cancer remains the leading cause of cancer-related death in the United States. Cigarette smoking is a well-recognized risk factor for lung cancer, and a sustained elevation of lung cancer risk persists even after smoking cessation. Despite identifiable risk factors, there has been minimal improvement in mortality for patients with lung cancer primarily stemming from diagnosis at a late stage when there are few effective therapeutic options. Early detection of lung cancer and effective scree ...[more]

PMID: 24840047

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Project description:Background: Ferroptosis is a newly proposed form of programmed cell death, and accumulating evidence suggests that it plays an essential role in the development of multiple diseases, especially cancers and neurodegenerative diseases. Since officially named in 2012, research on ferroptosis has grown rapidly. There are previous reviews focused on the research progress of ferroptosis from a certain aspect, but no bibliometric studies summarizing this field as a whole. This study aimed to assess the scientific output and activity regarding ferroptosis research from a global perspective. Methods: Publications related to ferroptosis from 2012 to 2020 were identified and selected from the Web of Science Core Collection. Excel 2019 and GraphPad Prism 8.0 was used to analyze quantitative variables including number of publications and citations, H-index, and journal citation reports. VOS viewer and CiteSpace were used to perform co-authorship, co-citation, and co-occurrence analysis of countries/institutes/authors/keywords. Results: A total of 1,285 publications on ferroptosis research were identified. The literature on ferroptosis had been continuously growing since 2012, and the expansion might continue at a rapid pace in the following years. China contributed the greatest proportion (43.74%) of ferroptosis publications, and the United States ranked first in the number of citation frequency (20,980 times) and H-index (70). B. R. Stockwell, D. L. Tang, and R. Kang were key researchers. The journal Cell Death Disease published the highest number of articles, with 42 articles. All the keywords could be divided into two clusters: cluster 1 (pathway and mechanism) and cluster 2 (treatment and effect). In terms of potential hotspots, keywords with the strong bursts and still ongoing recently were "neurodegeneration" (2017-2020), "chemotherapy" (2017-2020), "NF-kappa B" (2017-2020), and "photodynamic therapy" (2018-2020). Conclusion: There will be a dramatically increasing number of publications on ferroptosis research based on the current global trends. China has made significant progress in ferroptosis research, but the United States is actually dominated in this field. More focus will be placed on neurodegeneration, chemotherapy, nuclear factor κB, and photodynamic therapy, which may be the next popular topics in ferroptosis research.

Project description:Cell-autonomous immunity relies on the rapid detection of invasive pathogens by host proteins. Guanylate binding proteins (GBPs) have emerged as key mediators of vertebrate immune defense through their ability to recognize a diverse array of intracellular pathogens and pathogen-containing cellular compartments. Human and mouse GBPs have been shown to target distinct groups of microbes, although the molecular determinants of pathogen specificity remain unclear. We show that rapid diversification of a C-terminal polybasic motif (PBM) in primate GBPs controls recognition of the model cytosolic bacterial pathogen Shigella flexneri By swapping this membrane-binding motif between primate GBP orthologs, we found that the ability to target S. flexneri has been enhanced and lost in specific lineages of New World primates. Single substitutions in rapidly evolving sites of the GBP1 PBM are sufficient to abolish or restore bacterial detection abilities, illustrating a role for epistasis in the evolution of pathogen recognition. We further demonstrate that the squirrel monkey GBP2 C-terminal domain recently gained the ability to target S. flexneri through a stepwise process of convergent evolution. These findings reveal a mechanism by which accelerated evolution of a PBM shifts GBP target specificity and aid in resolving the molecular basis of GBP function in cell-autonomous immune defense.IMPORTANCE Many infectious diseases are caused by microbes that enter and survive within host cells. Guanylate binding proteins (GBPs) are a group of immune proteins which recognize and inhibit a variety of intracellular pathogenic microbes. We discovered that a short sequence within GBPs required for the detection of bacteria, the polybasic motif (PBM), has been rapidly evolving between primate species. By swapping PBMs between primate GBP1 genes, we were able to show that specific sequences can both reduce and improve the ability of GBP1 to target intracellular bacteria. We also show that the ability to envelop bacteria has independently evolved in GBP2 of South American monkeys. Taking the results together, this report illustrates how primate GBPs have adapted to defend against infectious pathogens.

Dataset Information

Updates and controversies in the rapidly evolving field of lung cancer screening, early detection, and chemoprevention.

Publications

Updates and controversies in the rapidly evolving field of lung cancer screening, early detection, and chemoprevention.

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