Clinical Aspects of Inflammation in Non-small Cell Lung Cancer PDF Download
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Author: Andrea Koch
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Andrea Koch
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Steven M. Dubinett
Publisher: Springer
ISBN: 1493927248
Category : Medical
Languages : en
Pages : 215
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Book Description
In recent years there have been various discoveries connecting inflammation and lung cancer and clearly there is growing interest in this area of cancer research. The link between unresolved inflammation and cancer has been well established with estimates that 15% of cancer deaths are inflammation‐related. Evidence for this link includes the following: a) some inflammatory diseases are associated with increased risk of cancer development; b) inflammatory mediators are present surrounding and within most tumors; c) overexpression of inflammatory cytokines increases cancer development and progression in murine studies; d) inhibition of inflammatory mediators decreases cancer development and progression; and e) the use of non‐steroidal anti‐inflammatory drugs (NSAIDs) has been found to decrease cancer incidence and delay progression. The volume will present aspects of the inflammatory tumor microenvironment (TME), its many roles in tumor progression and metastasis, including creation of a hypoxic environment, increased angiogenesis and invasion, changes in expression of micro‐RNAs (miRNAs) and an increase in a stem cell phenotype. The book will also cover the mechanisms of inflammatory mediators. Chronic overexpression of inflammatory mediators in the TME, as seen in smokers and patients with non‐small cell lung cancer (NSCLC), can also lead to increased tumor initiation, progression, invasion and metastasis. The volume will provide a comprehensive perspective of the latest findings and summaries of progress made regarding inflammation and its connection to lung cancer.
Author: RUI LI
Publisher:
ISBN:
Category :
Languages : en
Pages : 183
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Book Description
Lung cancer is the second most common cancer and the leading cause of cancer-associated mortality in the U.S.. The overall 5-year survival of lung cancer patients is less than 20%. The majority of patients are diagnosed with advanced stage disease. While progress has been made with targeted therapies, 5-year survival has so far improved in an incremental manner. Lung cancer is characterized by a prominent inflammatory tumor microenvironment, which in turn represents an important prognostic factor in patients. Unresolved inflammatory conditions promoted by smoking, chronic obstructive pulmonary disease (COPD) and interstitial lung diseases increase the risk of developing lung cancer. Therefore, tumor-promoting inflammation may play a significant role in cancer initiation and progression. The first part of this dissertation focuses on the effect of the tumor suppressor LKB1 on promoting an inflammatory microenvironment in non-small cell lung cancers (NSCLC). Loss of function of LKB1/STK11 is evident in approximately 30% of primary NSCLC. In murine lung cancer models, Kras and Lkb1 double mutation generates highly metastatic lung tumors with different histological types. Although a variety of different mechanisms have been proposed to explain the tumor-promoting effects underlying LKB1 deficiency, no effective therapy has been applied clinically; loss of function mutations presents a therapeutic challenge. Most recently, studies have indicated that LKB1 loss favors an immune-suppressive microenvironment characterized by prominent inflammation, suggesting a new perspective for therapies. Utilizing normal human bronchial epithelial cells (HBECs) which were immortalized in the absence of viral onco-proteins, we find that knockdown of LKB1 elevates the production of multiple inflammatory proteins, among which CXCR2 ligands are the most abundantly secreted. Our data indicate that knockdown of LKB1 in HBECs leads to transcriptional and translational upregulation of CXCR2 ligands and conversely, forced expression of wild-type LKB1 in LKB1-null NSCLC tumor cells decreases CXCR2 ligand production. Non-supervised clustering analysis further reveals KRAS and LKB1 double mutation in human NSCLC cell lines predicts higher levels of CXCR2 ligands. In addition, gene expression analysis shows that CXCR2 ligands are also significantly elevated in murine KrasG12D; Lkb1-/- lung tumors compared to KrasG12D and KrasG12D; Tp53-/- tumors. Dissection of the underlying mechanisms reveals that the NF- B and WNT pathways regulate CXCR2 ligands downstream of LKB1. Surprisingly, regulation of the NF- B pathway by LKB1 is independent of AMPK, but requires the MARK family proteins. Knockdown of MARKs or inhibition of MARK function by a small chemical inhibitor in HBECs recapitulates LKB1 loss-induced NF- B activation and subsequent CXCR2 ligand upregulation. CXCR2 ligands have been reported to play an important role in tumor initiation and progression via recruitment of immune cells and endothelial cells in a variety of cancer types including NSCLC. Therefore, our findings suggest that elevation of CXCR2 ligands by LKB1 deficiency facilitates tumor development by creating a tumor-favored microenvironment. Investigating the contribution of CXCR2 ligands to LKB1-dependent malignancy may aid in the development of novel prevention as well as therapeutic strategies against LKB1-null NSCLC. The second part of this dissertation examines the impact of dysregulated inflammation on cancer progression. The plasticity of epithelial to mesenchymal transition (EMT) program has been considered to be an essential element regulating cancer metastasis. Cancer cells undergoing EMT need to maintain the mesenchymal phenotype during metastasis but revert back to epithelial phenotypes for successful outgrowth of clones at metastatic sites. However, the determinants of EMT plasticity are not yet clear and the underlying mechanisms have not been fully explored. Recently, we have found that a subset of NSCLC cells undergo EMT in the presence of cytokines including IL-1 , TNF- and TGF- (within 7 days), and this occurs concomitantly with increased cell migration and invasion. In addition, chronic exposure to these inflammatory cytokines leads to EMT memory, which refers to the phenomenon in which cells are able to maintain EMT despite withdrawal of the original stimulus. Intriguingly, in contrast to the acute EMT process, EMT memory uniquely depends on chronic cytokine exposure, and not on the signaling pathways (JNK/ERK) and transcription factors (fra-1/slug) mediating the acute EMT. Further studies demonstrate that E-cadherin is repressed via a dynamic alteration of histone modifications and subsequent DNA methylation during chronic IL-1 exposure. Furthermore, a pathway analysis of the RNA profile of these cells indicates that a large portion of the altered genes can be methylated. Phenotypically, EMT memory allows cancer cells to maintain highly migratory and invasive features during metastasis. These findings, for the first time, demonstrate that EMT memory is uniquely induced by chronic inflammation and identifies epigenetic modifications as its underlying mechanism. Better understanding of EMT will ultimately assist in the identification of targets for preventing and treating metastatic behaviors in lung cancer.
Author: Bharat B. Aggarwal
Publisher: Springer
ISBN: 3034808372
Category : Medical
Languages : en
Pages : 489
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Book Description
This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.
Author: Heine H. Hansen
Publisher: Springer
ISBN: 9781461294146
Category : Medical
Languages : en
Pages : 274
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Book Description
Lung cancer is one of the biggest challenges in oncology today. The challenge is due to the recognition of the possibility of prevention in at least 70-80 % of all the cases and the extreme difficulties encountered in the treatment of this neoplasm. Despite the knowledge of prevention measures such as cessation of cigarette smoking the incidence continues to increase in many countries. The increase is particularly notable in females in the west ernized countries where the death rate in females in certain regions sur passes that of breast cancer. Furthermore, in many developing countries lung cancer is now being diagnosed with increasing frequency in both sexes and it is expected to be a major cause of death in those countries later in this century or the beginning of next century if the tobacco consumption will continue its rapid rise. With respect to therapy the 1970'es brought considerable progress in understanding of the clinical behaviour of lung cancer thereby establishing the importance of distinguishing between the major histologic types. Thera peutic advancement was particularly experienced in small cell carcinoma with the introduction of combination chemotherapy after this special dis ease entity among lung cancers was recognized as being a disseminated dis ease in almost all cases at the time of diagnosis. It was expected that the improvement in therapy would have continued in the early 1980'es, not only for small cell lung cancer but also for the other cell types.
Author: Juerg Hodler
Publisher: Springer
ISBN: 3030111490
Category : Medical
Languages : en
Pages : 238
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Book Description
This open access book focuses on diagnostic and interventional imaging of the chest, breast, heart, and vessels. It consists of a remarkable collection of contributions authored by internationally respected experts, featuring the most recent diagnostic developments and technological advances with a highly didactical approach. The chapters are disease-oriented and cover all the relevant imaging modalities, including standard radiography, CT, nuclear medicine with PET, ultrasound and magnetic resonance imaging, as well as imaging-guided interventions. As such, it presents a comprehensive review of current knowledge on imaging of the heart and chest, as well as thoracic interventions and a selection of "hot topics". The book is intended for radiologists, however, it is also of interest to clinicians in oncology, cardiology, and pulmonology.
Author: International Agency for Research on Cancer
Publisher: World Health Organization
ISBN: 9789283224365
Category : Health & Fitness
Languages : en
Pages : 410
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Book Description
WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart is the seventh volume in the Fourth Edition of the WHO series on histological and genetic typing of human tumors. This authoritative, concise reference book provides an international standard for oncologists and pathologists and will serve as an indispensable guide for use in the design of studies monitoring response to therapy and clinical outcome.
Author: W. H. O. Classification WHO Classification of Tumours Editorial Board
Publisher:
ISBN: 9789283245063
Category :
Languages : en
Pages : 500
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Book Description
****When not purchasing directly from the official sales agents of the WHO, especially at online bookshops, please note that there have been issues with counterfeited copies. Buy only from known sellers and if there are quality issues, please contact the seller for a refund.***** Thoracic Tumoursis the fifth available volume in the fifth edition of the WHO series on the classification of human tumours. This series (also known as the WHO Blue Books) is regarded as the gold standard for the diagnosis of tumours and comprises a unique synthesis of histopathological diagnosis with digital and molecular pathology. These authoritative and concise reference books provide indispensable international standards for anyone involved in the care of patients with cancer or in cancer research, underpinning individual patient treatment as well as research into all aspects of cancer causation, prevention, therapy, and education. What's new in this edition? The fifth edition, guided by the WHO Classification of Tumours Editorial Board, establishes a single coherent cancer classification presented across a collection of individual volumes organized on the basis of anatomical site (digestive system, breast, soft tissue and bone, etc.) and structured in a systematic manner, with each tumour type listed within a taxonomic classification: site, category, family (class), type, and subtype. In each volume, the entities are now listed from benign to malignant and are described under an updated set of headings, including histopathology, diagnostic molecular pathology, staging, and easy-to-read essential and desirable diagnostic criteria. Who should read this book? * Pathologists * Oncologists * Respiratory physicians * Thoracic radiologists * Cancer researchers * Surgeons * Epidemiologists * Cancer registrars This volume: * Prepared by 217 authors and editors * Contributors from around the world * More than 1000 high-quality images * More than 3500 references
Author: Andrew W. Bruce
Publisher: Springer Science & Business Media
ISBN: 1447113985
Category : Medical
Languages : en
Pages : 363
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Book Description
Carcinoma of the prostate increasingly dominates the attention of urologists for both scientific and clinical reasons. The search for an explanation and the prediction of the variable behaviour of the malignant prostatic cell continues unabated. The search for more precise tumour staging and more effective treatment is equally vigorous. Editors Andrew Bruce and John Trachtenberg have assembled acknowledged leaders in prostate cancer to present those areas of direct interest to the clinician. There are a number of other topics that might have been considered but most of these, such as experimental tumour models or biochemical factors affecting cell growth, still lack immediate application for the clinician. Carcinoma of the prostate continues to have its highest incidence in the western world, and the difference in comparison with the incidence in the Far East appears to be real and not masked by diagnostic or other factors. A number of other epidemiological aspects need careful analysis: Is the incidence increasing? Is the survival improving? Is the prognosis worse in the younger patient? Epidemiological data are easily misused and misinterpreted so that a precise analysis of the known facts makes an important opening chapter to this book.
Author: Guoping Cai
Publisher: Springer Nature
ISBN: 303021799X
Category : Medical
Languages : en
Pages : 432
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Book Description
This book introduces basic ROSE techniques and resources required to set up ROSE service. It reviews the cytomorphologic features that are recognizable during ROSE, including those important for sample adequacy, specimen triage, preliminary interpretation, and potential diagnostic pitfalls. Economic and regulatory aspects are discussed as well as the pros and cons of telecytology. The book is formatted for clinical settings, simulating the ROSE process that occurs in the ultrasound room, CT room, bronchoscopy suite, and endoscopy suite. Each chapter focuses on the cytomorphologic clues and pitfalls of the entities specific to that clinical setting. Rapid On-Site Evaluation: A Practical Guide will be a valuable resource for pathologists, cytotechnologists, physicians who perform biopsies and/or ROSE evaluation, and trainees for utilizing ROSE and improving diagnostic performance of biopsies.
