{"title":"Lipopolysaccharide challenge of humans as a model for chronic obstructive lung disease exacerbations.","authors":"Sergei A Kharitonov, Ulf Sjöbring","doi":"10.1159/000107056","DOIUrl":"https://doi.org/10.1159/000107056","url":null,"abstract":"<p><p>Endotoxin, or lipopolysaccharide (LPS), is a constituent of the outer cell membrane of Gram-negative bacteria. LPS is a highly potent proinflammatory substance, that, when inhaled, dose-dependently causes fever, chills, and bronchoconstriction. These symptoms are accompanied by a proinflammatory response in sputum and bronchoalveolar lavage fluid with elevation of neutrophils, macrophages and certain cytokines/chemokines. This response can be partially modified with certain drugs. Similar inflammatory changes are observed both in the stable state of chronic obstructive lung disease (COPD) and during exacerbations of this disease. Cigarette smoke, which contains bioactive LPS, is the most common cause of COPD and may also precipitate exacerbations. In addition, the presence of Gram-negative bacteria in the lower airways is a distinguishing feature both of stable COPD and of exacerbations. Based on this knowledge we argue here that inhaled LPS provocation of healthy volunteers can be used as a model or COPD as well as for exacerbations of this disease.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"14 ","pages":"83-100"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000107056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26874357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human rhinovirus models in asthma.","authors":"Anne Marie Singh, William W Busse","doi":"10.1159/000107051","DOIUrl":"https://doi.org/10.1159/000107051","url":null,"abstract":"<p><p>In both children and adults, rhinovirus (RV) infections remain a major cause of exacerbations in asthma. With the use of both in vitro models of RV infection and experimental models of asthma exacerbation in humans, insight into the precise role of RV in this process has been obtained. RV infects the lower airways, and the virus itself, together with the immune response to the virus, leads to increased airway obstruction in some patients with asthma. Defects in the immune response to RV in these patients may also lead to increased symptom severity and to more significant exacerbations. Work further investigating the mechanisms of exacerbation caused by RV infection will ultimately lead to new modalities of treatment and possibly prevention of this common and significant cause of acute asthma.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"14 ","pages":"12-20"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000107051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26877747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cellular and animals models for rhinovirus infection in asthma.","authors":"Maria Xatzipsalti, Nikolaos G Papadopoulos","doi":"10.1159/000107053","DOIUrl":"https://doi.org/10.1159/000107053","url":null,"abstract":"<p><p>Human rhinoviruses (RVs) are responsible for the majority of upper respiratory tract infections. Despite the high prevalence, the pathogenesis is incompletely understood. Experimental models would permit study of the immunological response to infections. Animal models have many limitations because of the anatomic and physiological differences between mammalian species. The only nonhuman animals susceptible to RV are chimpanzees and gibbons. Mouse models are not used because of host cell tropism of RV. This problem may have been partially overcome by transfecting mouse cells with viral RNA, by replacing mouse ICAM-1 with the human counterpart and by using a variant virus. It remains to be seen if these advances will translate into establishment of useful mouse models. In the absence of animal models, epithelial cell lines such as BEAS-2B, A549, 16HBE and HEp-2 have been used. Fibroblasts and smooth muscle cells have also been used. Although transformed cell lines have many properties in common with normal epithelial cells, they lose certain differentiated functions. Therefore, primary and recently well-differentiated cultures are used to study the immune response. In addition to a local inflammatory response, a systemic immune response to RV does develop; therefore peripheral blood mononuclear cells and dendritic cells have been infected with RV, shedding additional light on cell-mediated immunity. Cellular models are invaluable investigational tools for understanding mechanisms of RV-induced asthma and evaluating new targets for therapy.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"14 ","pages":"33-41"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000107053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26874354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Schistosomiasis and neoplasia.","authors":"Ayman Yosry","doi":"10.1159/000092967","DOIUrl":"https://doi.org/10.1159/000092967","url":null,"abstract":"<p><p>Schistosomiasis is endemic in at least 75 tropical and subtropical countries where 600 million people are at risk of which over 200 million are infected. Three species, S. hematobium, S. mansoni and S. japonicum, account for the majority of human infections. There is sufficient evidence that S. hematobium, the predominant etiologic agent for urinary schistosomiasis, is carcinogenic to humans leading to squamous cell carcinoma of the urinary bladder, a relatively uncommon vesical cancer in nonendemic areas. There is limited evidence suggesting that S. japonicum is possibly carcinogenic to humans leading to colorectal cancer and is a risk factor for hepatocellular carcinoma formation. There is inadequate evidence for the carcinogenicity of S. mansoni in humans. S. mansoni may still be linked to hepatocellular carcinoma through potentiating the effects of hepatitis B virus and hepatitis C virus on the liver. In this article, the relationship between schistosomiasis and neoplasia will be reviewed.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"13 ","pages":"81-100"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000092967","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25985534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christoph Heyder, Eva Gloria-Maercker, Wolfgang Hatzmann, Kurt S Zaenker, Thomas Dittmar
{"title":"Visualization of tumor cell extravasation.","authors":"Christoph Heyder, Eva Gloria-Maercker, Wolfgang Hatzmann, Kurt S Zaenker, Thomas Dittmar","doi":"10.1159/000092974","DOIUrl":"https://doi.org/10.1159/000092974","url":null,"abstract":"<p><p>In cancer the blood-borne spread of tumor cells leads to the formation of secondary tumors at distant loci, whereby the extravasation of tumor cells is a prerequisite step during hematogenous metastasis. In regard to the fate of endothelial cells located at the site of tumor cell infiltration, tumor cell-endothelial interactions were analyzed using an in vitro real-time model. This model shows the complete sequence of the transmigration process and gave new insights into the complex and dynamic cell-cell and cell-matrix interactions which occur during tumor cell transmigration across the endothelial barrier. An in vitro real-time apoptosis assay permits the distinction between apoptotic cell death from necrotic cell death. This model indicates that transmigration of tumor cell clusters derived from the invasive human bladder carcinoma cell line T24 irreversibly damages the endothelial cells by inducing apoptosis at the site of tumor cell infiltration. It is postulated here that apoptosis induction facilitates the removal of detached endothelial cells, thereby forestalling a local inflammatory response which might be detrimental to extravasating tumor cells.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"13 ","pages":"200-208"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000092974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25984953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Helicobacter pylori and gastric neoplasia.","authors":"Wai K Leung","doi":"10.1159/000092966","DOIUrl":"https://doi.org/10.1159/000092966","url":null,"abstract":"<p><p>Helicobacter pylori is present in the stomach of more than half of the world population. Based on compelling epidemiological evidences, it was classified by the World Health Organization as a type I gastric carcinogen. It is generally believed that gastric cancer development is a multi-step progression from chronic gastritis to atrophy, intestinal metaplasia, dysplasia, and cancer. Individuals infected with H. pylori have at least a 2-fold increase in risk of gastric cancer development though only a small proportion of infected individuals will ultimately develop this malignancy. The exact mechanisms underlying how H. pylori triggers or causes gastric cancer remain elusive. Certain H. pylori genotypes like cagA, vacA s1 or babA1 are considered to be of higher virulent potential. Apart from the bacterial factors, the host response to chronic H. pylori infection may also attribute to the cancer risk. It was found that individuals who carry pro-inflammatory cytokine gene polymorphism have a substantial increase in risk of cancer development. The combination of bacterial and host genotypes may have a synergistic effect on cancer development. Despite the strong causal link between chronic H. pylori infection and gastric cancer, the role of H. pylori eradication in preventing gastric cancer remains controversial. More long-term data may be necessary to clarify this controversy.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"13 ","pages":"66-80"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000092966","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25985533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The inflammatory tumor microenvironment and its impact on cancer development.","authors":"Karin E de Visser, Lisa M Coussens","doi":"10.1159/000092969","DOIUrl":"https://doi.org/10.1159/000092969","url":null,"abstract":"<p><p>The role of the immune system during cancer development is complex involving extensive reciprocal interactions between genetically altered cells, adaptive and innate immune cells, their soluble mediators and structural components present in the neoplastic microenvironment. Each stage of cancer development is regulated uniquely by the immune system; whereas full activation of adaptive immune cells at the tumor stage may result in eradication of malignant cells, chronic activation of innate immune cells at sites of premalignant growth may actually enhance tumor development. In addition, the balance between desirable antitumor immune responses and undesirable pro-tumor chronic inflammatory responses largely depends on the context in which a malignancy is developing. The following chapter focuses on the inflammatory components and processes engaged during cancer development and the impact of the inflammatory microenvironment.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"13 ","pages":"118-137"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000092969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25985536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chemokine-directed metastasis.","authors":"Brigitte N Gomperts, Robert M Strieter","doi":"10.1159/000092972","DOIUrl":"https://doi.org/10.1159/000092972","url":null,"abstract":"<p><p>Over the last 20 years, the biology of chemokines has expanded beyond their initial role in mediating migration of specific subsets of leukocytes. Chemokines have been found to display pleiotropic effects for enhancing immunity to tumor-associated antigens, regulating angiogenesis, promoting proliferation/anti-apoptosis of tumor cells; and mediating tumor cell invasion and trafficking in an organ-specific manner that leads to metastases. Here, we review the importance of chemokines, especially CXC chemokines in regulating angiogenesis, tumor cell invasion and metastases; and demonstrate why they can be seen as important therapeutic targets for intervention in cancer.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"13 ","pages":"170-190"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000092972","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25984951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Involvement of chemokine receptors in organ-specific metastasis.","authors":"Albert Zlotnik","doi":"10.1159/000092973","DOIUrl":"https://doi.org/10.1159/000092973","url":null,"abstract":"<p><p>The chemokines are a family of small proteins known for their ability to control cell migration in the body. Their receptors belong to the class A subfamily of G protein-coupled receptors. In recent years, chemokines have grown in importance, because they are involved in inflammation and autoimmune disease. Some of them are also involved in infectious disease, since two chemokine receptors, CXCR4 and CCR5, are used by the human immunodeficiency virus (HIV) to gain entry to cells. Several years ago it also became clear that chemokines can also influence tumor cells. Specifically, tumor cells express chemokine receptors in a nonrandom manner, and this suggested a role for chemokines in the metastatic destination of tumor cells. By far the most common chemokine receptor expressed by many cancer cells is CXCR4. Its ligand, CXCL12, is strongly expressed in lung, liver, bone marrow and lymph nodes, places that represent common metastatic destinations in many cancers. Many studies have now validated the concept that chemokines and their receptors influence metastasis. The potential therapeutic importance of these observations depends on the role that each metastatic destination such as liver, lung, bone marrow, etc., plays in the prognosis of a cancer patient.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"13 ","pages":"191-199"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000092973","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25984952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Pawelek, Ashok Chakraborty, Rossita Lazova, Yesim Yilmaz, Dennis Cooper, Douglas Brash, Tamara Handerson
{"title":"Co-opting macrophage traits in cancer progression: a consequence of tumor cell fusion?","authors":"John Pawelek, Ashok Chakraborty, Rossita Lazova, Yesim Yilmaz, Dennis Cooper, Douglas Brash, Tamara Handerson","doi":"10.1159/000092970","DOIUrl":"https://doi.org/10.1159/000092970","url":null,"abstract":"<p><p>Tumor-associated macrophages (TAMs) play multiple roles in tumor initiation and progression. Tumors frequently appear in areas of chronic inflammation. This is likely aided by the mutagenic actions of macrophages. Tumor growth and progression is supported by macrophage-induced neoangiogenesis and stroma production, and macrophages produce tumor-stimulating growth factors. In most cancers a high density of TAMs predicts poor outcome. But not only do cancer cells depend upon macrophages for growth and invasion, they also co-opt macrophage traits. These include a wide diversity of molecules and pathways regulating adhesion, matrix alterations, neoangiogenesis, motility, chemotaxis, immune signaling pathways and even multidrug resistance proteins. Evidence is presented that these traits could be generated through macrophage-tumor cell fusion. Fusion has been reported in numerous animal tumor models and was recently documented in 2 human cases. Fusion could also account for the high degree of aneuploidy and plasticity in cancer, and for immune evasion. One common trait of myeloid-tumor fusion is the high expression of Beta1,6-branched N-glycans, used by macrophages in systemic migration. Beta1,6-branched oligosaccharides have long been associated with metastasis in animal models and were recently found to be common in a wide diversity of human cancers. We suggest that Beta1,6-branched oligosaccharides in human cancer may reflect widespread tumor cell fusion. Viewing the cancer cell as a myeloid hybrid provides new approaches towards understanding and treating this complex disease.</p>","PeriodicalId":79855,"journal":{"name":"Contributions to microbiology","volume":"13 ","pages":"138-155"},"PeriodicalIF":0.0,"publicationDate":"2006-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000092970","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25985537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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