It is increasingly evident that carcinogenesis, in the vast majority of cancers, cannot be explained simply through an accumulation of somatic mutations, or epigenetics, the stem cell theory, or the Warburg effect. Here, decades of thinking based on incorrect assumptions has resulted in an incorrect hypothesis on the origin of cancer. Many papers studying DNA, genetics, RNA, miRNA, proteomics, and epigenetics have increased our understanding of biology. Our paradigm, though more complex, is more reliable and plausible. It states that cancer originates from a disruption of homeostasis. This essential biological phenomenon, homeostasis, maintains the interrelationships of various signaling pathways and induced crosstalk which modify cellular functions together with the interactions of surrounding cells and structures such that the equilibrium lies towards the optimal health of the organism. This Special Issue “Disruption of signaling homeostasis induced crosstalk in the carcinogenesis paradigm Epistemology of the origin of cancer” provides compelling evidence that carcinogenesis is explained by a six-step sequence of events for the vast majority of cancers. These six steps include, (1) a pathogenic stimulus followed by (2) chronic inflammation, from which develops (3) fibrosis with associated remodeling in the cellular microenvironment. From these changes a (4) pre-cancerous niche develops which triggers the deployment of (5) a chronic stress escape strategy, and when this fails to resolve, and (6) the transition of a normal cell to a cancer cell occurs. This paradigm provides opportunities to move away from a symptom-oriented understanding of cancer and is much closer to a cause-based understanding, which opens the door for early preventative strategies to mitigate cancer as a disease, and to interdict metastases. This is underpinned by the fact that an independent recently published proof of this paradigm showed how a stimulus trigger the proposed multi-sequence cascade of events as abrupt involution-induced chronic inflammation, followed by fibrosis with remodeling, which describes the pre-cancerous niche followed by hyperplasia, metaplasia, and cancer.
{"title":"Synopsis: Special Issue on “Disruption of signaling homeostasis induced crosstalk in the carcinogenesis paradigm Epistemology of the origin of cancer”","authors":"B. Brücher, I. Jamall","doi":"10.1051/fopen/2019023","DOIUrl":"https://doi.org/10.1051/fopen/2019023","url":null,"abstract":"It is increasingly evident that carcinogenesis, in the vast majority of cancers, cannot be explained simply through an accumulation of somatic mutations, or epigenetics, the stem cell theory, or the Warburg effect. Here, decades of thinking based on incorrect assumptions has resulted in an incorrect hypothesis on the origin of cancer. Many papers studying DNA, genetics, RNA, miRNA, proteomics, and epigenetics have increased our understanding of biology. Our paradigm, though more complex, is more reliable and plausible. It states that cancer originates from a disruption of homeostasis. This essential biological phenomenon, homeostasis, maintains the interrelationships of various signaling pathways and induced crosstalk which modify cellular functions together with the interactions of surrounding cells and structures such that the equilibrium lies towards the optimal health of the organism. This Special Issue “Disruption of signaling homeostasis induced crosstalk in the carcinogenesis paradigm Epistemology of the origin of cancer” provides compelling evidence that carcinogenesis is explained by a six-step sequence of events for the vast majority of cancers. These six steps include, (1) a pathogenic stimulus followed by (2) chronic inflammation, from which develops (3) fibrosis with associated remodeling in the cellular microenvironment. From these changes a (4) pre-cancerous niche develops which triggers the deployment of (5) a chronic stress escape strategy, and when this fails to resolve, and (6) the transition of a normal cell to a cancer cell occurs. This paradigm provides opportunities to move away from a symptom-oriented understanding of cancer and is much closer to a cause-based understanding, which opens the door for early preventative strategies to mitigate cancer as a disease, and to interdict metastases. This is underpinned by the fact that an independent recently published proof of this paradigm showed how a stimulus trigger the proposed multi-sequence cascade of events as abrupt involution-induced chronic inflammation, followed by fibrosis with remodeling, which describes the pre-cancerous niche followed by hyperplasia, metaplasia, and cancer.","PeriodicalId":6841,"journal":{"name":"4open","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89899649","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}
A pathogenic (biological or chemical) stimulus is the earliest information received by a cell that can result in the disruption of homeostasis with consequent development of disease. Chronic inflammation involves many cell types with numerous cytokines and signaling pathways, the release of different components by the cells, and the crosstalk provoked by such stimuli involving subclinical chronic inflammation and is mechanistically manifold. Exosomes secrete chemicals that trigger the epithelium to produce exosome-like nanoparticles promoting chronic inflammation. Small molecules, together with various cytokines, selectively target signaling pathways inducing crosstalk that suppress apoptosis. 16S rRNA gene sequencing has become routine to provide information on the composition and abundance of bacteria found in human tissues and in reservoirs. The deregulation of autophagy with chronic stimulation of inflammation is an early phenomenon in carcinogenesis. The disruption of cell–cell integrity enables transcellular CagA migration and triggers deregulation of autophagy with the net result being chronic inflammation. The complex and insidious nature of chronic inflammation can be seen both inside and outside the cell and even with intracellular nuclear fragments such as chromatin, which itself can elicit a chronic inflammatory response within the cytoplasm and affect autophagy. The ultimate result of unresolved chronic inflammation is fibrosis, a step before tissue remodeling results in the formation of a precancerous niche (PCN). Various pathogenic stimuli associated with different neoplasms result in persistent inflammation. This ongoing disruption of homeostasis in the micromilieu of cells, tissues, and organs is an essential preamble to carcinogenesis and occurs early in that process.
{"title":"Chronic inflammation evoked by pathogenic stimulus during carcinogenesis","authors":"B. Brücher, I. Jamall","doi":"10.1051/FOPEN/2018006","DOIUrl":"https://doi.org/10.1051/FOPEN/2018006","url":null,"abstract":"A pathogenic (biological or chemical) stimulus is the earliest information received by a cell that can result in the disruption of homeostasis with consequent development of disease. Chronic inflammation involves many cell types with numerous cytokines and signaling pathways, the release of different components by the cells, and the crosstalk provoked by such stimuli involving subclinical chronic inflammation and is mechanistically manifold. Exosomes secrete chemicals that trigger the epithelium to produce exosome-like nanoparticles promoting chronic inflammation. Small molecules, together with various cytokines, selectively target signaling pathways inducing crosstalk that suppress apoptosis. 16S rRNA gene sequencing has become routine to provide information on the composition and abundance of bacteria found in human tissues and in reservoirs. The deregulation of autophagy with chronic stimulation of inflammation is an early phenomenon in carcinogenesis. The disruption of cell–cell integrity enables transcellular CagA migration and triggers deregulation of autophagy with the net result being chronic inflammation. The complex and insidious nature of chronic inflammation can be seen both inside and outside the cell and even with intracellular nuclear fragments such as chromatin, which itself can elicit a chronic inflammatory response within the cytoplasm and affect autophagy. The ultimate result of unresolved chronic inflammation is fibrosis, a step before tissue remodeling results in the formation of a precancerous niche (PCN). Various pathogenic stimuli associated with different neoplasms result in persistent inflammation. This ongoing disruption of homeostasis in the micromilieu of cells, tissues, and organs is an essential preamble to carcinogenesis and occurs early in that process.","PeriodicalId":6841,"journal":{"name":"4open","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89963793","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}
We consider discrete analogues of pseudo-differential operators and related discrete equations and boundary value problems. Existence and uniqueness results for special elliptic discrete boundary value problem and comparison for discrete and continuous solutions are given for certain smooth data in discrete Sobolev–Slobodetskii spaces.
{"title":"To the theory of discrete boundary value problems","authors":"O. Tarasova, V. Vasilyev","doi":"10.1051/FOPEN/2019009","DOIUrl":"https://doi.org/10.1051/FOPEN/2019009","url":null,"abstract":"We consider discrete analogues of pseudo-differential operators and related discrete equations and boundary value problems. Existence and uniqueness results for special elliptic discrete boundary value problem and comparison for discrete and continuous solutions are given for certain smooth data in discrete Sobolev–Slobodetskii spaces.","PeriodicalId":6841,"journal":{"name":"4open","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74840411","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}
The system of two-sided quaternion matrix equations with η-Hermicity, A1XA1η* = C1, A2XA2η* = C2 is considered in the paper. Using noncommutative row-column determinants previously introduced by the author, determinantal representations (analogs of Cramer’s rule) of a general solution to the system are obtained. As special cases, Cramer’s rules for an η-Hermitian solution when C1 = Cη*1 and C2 = Cη*2 and for an η-skew-Hermitian solution when C1 = −Cη*1 and C2 = −Cη*2 are also explored.
{"title":"Cramer’s rules for the system of quaternion matrix equations with η-Hermicity","authors":"Ivan Kyrchei","doi":"10.1051/FOPEN/2019021","DOIUrl":"https://doi.org/10.1051/FOPEN/2019021","url":null,"abstract":"The system of two-sided quaternion matrix equations with η-Hermicity, A1XA1η* = C1, A2XA2η* = C2 is considered in the paper. Using noncommutative row-column determinants previously introduced by the author, determinantal representations (analogs of Cramer’s rule) of a general solution to the system are obtained. As special cases, Cramer’s rules for an η-Hermitian solution when C1 = Cη*1 and C2 = Cη*2 and for an η-skew-Hermitian solution when C1 = −Cη*1 and C2 = −Cη*2 are also explored.","PeriodicalId":6841,"journal":{"name":"4open","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77110644","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}
The attempt to restore homeostasis, once disrupted, such that complex signaling, crosstalk between ubiquitous proteins, and a diverse range of pathways gone awry is near impossible, especially in the presence of an ongoing pathogenic stimuli with incessant inflammation. This persistent inflammation, when unresolved, induces fibrosis with consequent remodeling of the extracellular matrix (ECM) which leads to the formation of the precancerous niche (PCN), the tipping point in the transition of normal to cancerous cells. Thus, the sustained disruption of homeostasis when confronted with limited adaptation capabilities either of cells or of the surrounding matrix and faced with chronic stress in the tissue microenvironment results in an escape strategy which, if unsuccessful, causes cells, tissue, or the organism to become unable to recover over the long term. All conditions necessary for cell–cell transition such as deregulation of cell–cell complexes, decrease in the stability of adherens junctions, together with the apical-basal polarity, and the loss of the cytoskeletal architecture occurs as a cascade of events inducing inappropriate and diverse signaling pathways and crosstalk. In biology, the transition of one cell type to another and the transition from one cell function to another is incompletely understood mechanistically, but within the context of embryogenesis and morphogenesis is acknowledged as a physiologically routine event. The constant stress that can result in the development of the PCN leads to a chronic stress escape strategy (CSES) which, if unsuccessful, eventually triggers a normal cell- to-cancer cell- transition (NCCCT).
{"title":"Transition from normal to cancerous cell by precancerous niche (PCN) induced chronic cell-matrix stress","authors":"B. Brücher, I. Jamall","doi":"10.1051/FOPEN/2018996","DOIUrl":"https://doi.org/10.1051/FOPEN/2018996","url":null,"abstract":"The attempt to restore homeostasis, once disrupted, such that complex signaling, crosstalk between ubiquitous proteins, and a diverse range of pathways gone awry is near impossible, especially in the presence of an ongoing pathogenic stimuli with incessant inflammation. This persistent inflammation, when unresolved, induces fibrosis with consequent remodeling of the extracellular matrix (ECM) which leads to the formation of the precancerous niche (PCN), the tipping point in the transition of normal to cancerous cells. Thus, the sustained disruption of homeostasis when confronted with limited adaptation capabilities either of cells or of the surrounding matrix and faced with chronic stress in the tissue microenvironment results in an escape strategy which, if unsuccessful, causes cells, tissue, or the organism to become unable to recover over the long term. All conditions necessary for cell–cell transition such as deregulation of cell–cell complexes, decrease in the stability of adherens junctions, together with the apical-basal polarity, and the loss of the cytoskeletal architecture occurs as a cascade of events inducing inappropriate and diverse signaling pathways and crosstalk. In biology, the transition of one cell type to another and the transition from one cell function to another is incompletely understood mechanistically, but within the context of embryogenesis and morphogenesis is acknowledged as a physiologically routine event. The constant stress that can result in the development of the PCN leads to a chronic stress escape strategy (CSES) which, if unsuccessful, eventually triggers a normal cell- to-cancer cell- transition (NCCCT).","PeriodicalId":6841,"journal":{"name":"4open","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90849811","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}
V. González-López, Marina Capelari Piovesana, N. Romano
In this paper, we estimate tail conditional probabilities by incorporating copula models and adopting a Bayesian estimation process for the copula’s parameter. Based on the records of student’s classifications in (a) Mathematics and (b) Natural Sciences/Physics (of the entrance exam to the University of Campinas, from 2013 to 2015), by means of tail conditional probabilities we predict the performance, of the same students, in Calculus I which is a mandatory subject of the undergraduate course of Statistics, and we compare the conditional probabilities year after year. We see that (a), (b) and Calculus I show maximal trivariate correlations in tail events given by classifications which are jointly high/low in the three subjects. We compare the evolution of the tail conditional probabilities from 2013 to 2015 and, according to our results there has been an improvement (from 2013 to 2015) of at most 12%. This improvement being more incisive in the settings with conditional events given by jointly high classifications in comparison with settings with conditional events given by jointly lower classifications.
{"title":"Tail conditional probabilities to predict academic performance","authors":"V. González-López, Marina Capelari Piovesana, N. Romano","doi":"10.1051/FOPEN/2019012","DOIUrl":"https://doi.org/10.1051/FOPEN/2019012","url":null,"abstract":"In this paper, we estimate tail conditional probabilities by incorporating copula models and adopting a Bayesian estimation process for the copula’s parameter. Based on the records of student’s classifications in (a) Mathematics and (b) Natural Sciences/Physics (of the entrance exam to the University of Campinas, from 2013 to 2015), by means of tail conditional probabilities we predict the performance, of the same students, in Calculus I which is a mandatory subject of the undergraduate course of Statistics, and we compare the conditional probabilities year after year. We see that (a), (b) and Calculus I show maximal trivariate correlations in tail events given by classifications which are jointly high/low in the three subjects. We compare the evolution of the tail conditional probabilities from 2013 to 2015 and, according to our results there has been an improvement (from 2013 to 2015) of at most 12%. This improvement being more incisive in the settings with conditional events given by jointly high classifications in comparison with settings with conditional events given by jointly lower classifications.","PeriodicalId":6841,"journal":{"name":"4open","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90235633","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}
R. Ciriminna, Vin Morreale, Mario Pecoraino, M. Pagliaro
Providing a case study of general applicability in all world's semi-arid regions where the plant is increasingly harvested, we describe the use and outcomes of solar air heating and ventilation coupled to a conventional kiln to dehydrate Opuntia ficus-indica cladodes. For the first time, the dried cladodes and the ground dehydrated ‘Nopal’ cladodes retain their natural green-yellow color. New applications to functionalize foodstuff and to formulate nutraceutical, personal care and cosmetic products of even higher efficacy and broader scope are anticipated.
{"title":"Solar air drying for innovative Opuntia ficus-indica cladode dehydration","authors":"R. Ciriminna, Vin Morreale, Mario Pecoraino, M. Pagliaro","doi":"10.1051/FOPEN/2019001","DOIUrl":"https://doi.org/10.1051/FOPEN/2019001","url":null,"abstract":"Providing a case study of general applicability in all world's semi-arid regions where the plant is increasingly harvested, we describe the use and outcomes of solar air heating and ventilation coupled to a conventional kiln to dehydrate Opuntia ficus-indica cladodes. For the first time, the dried cladodes and the ground dehydrated ‘Nopal’ cladodes retain their natural green-yellow color. New applications to functionalize foodstuff and to formulate nutraceutical, personal care and cosmetic products of even higher efficacy and broader scope are anticipated.","PeriodicalId":6841,"journal":{"name":"4open","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78543244","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}
The role of ubiquitous proteins (UPs) and their corresponding enzymes have been underestimated in carcinogenesis as the focus of much research revolved around measuring mutations and/or other genetic epiphenomena as surrogate markers of cancer and cancer progression. Over the past three decades, the scientific community has come to realize that the concentration on microdissection of cancer cells without accounting for the neighborhood in which these cells reside, i.e., the stroma, fails to reflect the true nature of cancer biology. UPs are fundamental for cellular homeostasis and phylogenetic development as well as for the integrity of the cytoskeleton and for the stability of cells and tissues in regards to intercellular signaling, cell shape and mobility, apoptosis, wound healing, and cell polarity. Corresponding enzymes are used by microorganisms to gain entry into the host by degradation of UPs and play a role to cleave peptide bonds for killing disease-causing life forms along for the creation of the precancerous niche (PCN) during carcinogenesis, cancer invasion, and in metastasis. The language used by such proteins as well as their complementary enzymes with its influence on multiple pathways and the cross-linked extracellular matrix is incompletely understood. The role of UPs in the disruption of signaling homeostasis and resulting interference with crosstalk in carcinogenesis appears sufficiently delineated to warrant a much more refined examination of their qualitative and quantitative contribution to the development of cancer and cancer therapy.
{"title":"Undervalued ubiquitous proteins","authors":"B. Brücher, I. Jamall","doi":"10.1051/FOPEN/2019002","DOIUrl":"https://doi.org/10.1051/FOPEN/2019002","url":null,"abstract":"The role of ubiquitous proteins (UPs) and their corresponding enzymes have been underestimated in carcinogenesis as the focus of much research revolved around measuring mutations and/or other genetic epiphenomena as surrogate markers of cancer and cancer progression. Over the past three decades, the scientific community has come to realize that the concentration on microdissection of cancer cells without accounting for the neighborhood in which these cells reside, i.e., the stroma, fails to reflect the true nature of cancer biology. UPs are fundamental for cellular homeostasis and phylogenetic development as well as for the integrity of the cytoskeleton and for the stability of cells and tissues in regards to intercellular signaling, cell shape and mobility, apoptosis, wound healing, and cell polarity. Corresponding enzymes are used by microorganisms to gain entry into the host by degradation of UPs and play a role to cleave peptide bonds for killing disease-causing life forms along for the creation of the precancerous niche (PCN) during carcinogenesis, cancer invasion, and in metastasis. The language used by such proteins as well as their complementary enzymes with its influence on multiple pathways and the cross-linked extracellular matrix is incompletely understood. The role of UPs in the disruption of signaling homeostasis and resulting interference with crosstalk in carcinogenesis appears sufficiently delineated to warrant a much more refined examination of their qualitative and quantitative contribution to the development of cancer and cancer therapy.","PeriodicalId":6841,"journal":{"name":"4open","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74626981","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}
Fibroblasts are actively involved in the creation of the stroma and the extracellular matrix which are important for cell adhesion, cell–cell communication, and tissue metabolism. The role of fibrosis in carcinogenesis can be examined by analogy to tissues of various cancers. The orchestration of letters in the interplay of manifold components with signaling and crosstalk is incompletely understood but available evidence suggests a hitherto underappreciated role for fibrosis in carcinogenesis. Complex signaling and crosstalk by pathogenic stimuli evoke persistent subclinical inflammation, which in turn, results in a cascade of different cell types, ubiquitous proteins and their corresponding enzymes, cytokine releases, and multiple signaling pathways promoting the onset of fibrosis. There is considerable evidence that the body's attempt to resolve such a modified extracellular environment leads to further disruption of homeostasis and the genesis of the precancerous niche as part of the six-step process that describes carcinogenesis. The precancerous niche is formed and can be understood to develop as a result of (1) pathogenic stimulus, (2) chronic inflammation, and (3) fibrosis with alterations of the extracellular matrix, stromal rigidity, and mechano-transduction. This is why carcinogenesis is not just a process of aberrant cell growth with damaged genetic material but the role of the PCN in its entirety reveals how carcinogenesis can occur without invoking the need for somatic mutations.
{"title":"Precancerous niche (PCN), a product of fibrosis with remodeling by incessant chronic inflammation","authors":"B. Brücher, I. Jamall","doi":"10.1051/FOPEN/2018009","DOIUrl":"https://doi.org/10.1051/FOPEN/2018009","url":null,"abstract":"Fibroblasts are actively involved in the creation of the stroma and the extracellular matrix which are important for cell adhesion, cell–cell communication, and tissue metabolism. The role of fibrosis in carcinogenesis can be examined by analogy to tissues of various cancers. The orchestration of letters in the interplay of manifold components with signaling and crosstalk is incompletely understood but available evidence suggests a hitherto underappreciated role for fibrosis in carcinogenesis. Complex signaling and crosstalk by pathogenic stimuli evoke persistent subclinical inflammation, which in turn, results in a cascade of different cell types, ubiquitous proteins and their corresponding enzymes, cytokine releases, and multiple signaling pathways promoting the onset of fibrosis. There is considerable evidence that the body's attempt to resolve such a modified extracellular environment leads to further disruption of homeostasis and the genesis of the precancerous niche as part of the six-step process that describes carcinogenesis. The precancerous niche is formed and can be understood to develop as a result of (1) pathogenic stimulus, (2) chronic inflammation, and (3) fibrosis with alterations of the extracellular matrix, stromal rigidity, and mechano-transduction. This is why carcinogenesis is not just a process of aberrant cell growth with damaged genetic material but the role of the PCN in its entirety reveals how carcinogenesis can occur without invoking the need for somatic mutations.","PeriodicalId":6841,"journal":{"name":"4open","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79550663","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}
The microbiome, the relationship between environmental factors, a high-fat diet, morbid obesity, and host response have been associated with cancer, only a small fraction of which (<10%) are genetically triggered. This nongenetic association is underpinned by a worldwide increase in morbid obesity, which is associated with both insulin resistance and chronic inflammation. The connection of the microbiome and morbid obesity is reinforced by an approximate shift of about 47% in the estimated total number of bacteria and an increase from 38,000,000,000,000 in a reference man to 56,000,000,000,000 in morbid obesity leading to a disruption of the microbial ecology within the gut. Humans contain 6,000,000,000 microbes and more than 90% of the cells of the human body are microorganisms. Changes in the microflora of the gut are associated with the polarization of ion channels by butyrate, thereby influencing cell growth. The decrease in the relative proportion ofBacteroidetestogether with a change in the fermentation of carbohydrates by bacteria is observed in morbid obesity. The disruption of homeostasis of the microflora in the obese changes signaling and crosstalk of several pathways, resulting in inflammation while suppressing apoptosis. The interactions between the microbiome and morbid obesity are important to understand signaling and crosstalk in the context of the progression of the six-step sequence of carcinogenesis. This disruption of homeostasis increases remodeling of the extracellular matrix and fibrosis followed by the none-resolvable precancerous niche as the internal pathogenic stimuli continue. The chronic stress explains why under such circumstances there is a greater proclivity for normal cells to undergo the transition to cancer cells.
{"title":"Microbiome and morbid obesity increase pathogenic stimulus diversity","authors":"B. Brücher, I. Jamall","doi":"10.1051/FOPEN/2018007","DOIUrl":"https://doi.org/10.1051/FOPEN/2018007","url":null,"abstract":"The microbiome, the relationship between environmental factors, a high-fat diet, morbid obesity, and host response have been associated with cancer, only a small fraction of which (<10%) are genetically triggered. This nongenetic association is underpinned by a worldwide increase in morbid obesity, which is associated with both insulin resistance and chronic inflammation. The connection of the microbiome and morbid obesity is reinforced by an approximate shift of about 47% in the estimated total number of bacteria and an increase from 38,000,000,000,000 in a reference man to 56,000,000,000,000 in morbid obesity leading to a disruption of the microbial ecology within the gut. Humans contain 6,000,000,000 microbes and more than 90% of the cells of the human body are microorganisms. Changes in the microflora of the gut are associated with the polarization of ion channels by butyrate, thereby influencing cell growth. The decrease in the relative proportion ofBacteroidetestogether with a change in the fermentation of carbohydrates by bacteria is observed in morbid obesity. The disruption of homeostasis of the microflora in the obese changes signaling and crosstalk of several pathways, resulting in inflammation while suppressing apoptosis. The interactions between the microbiome and morbid obesity are important to understand signaling and crosstalk in the context of the progression of the six-step sequence of carcinogenesis. This disruption of homeostasis increases remodeling of the extracellular matrix and fibrosis followed by the none-resolvable precancerous niche as the internal pathogenic stimuli continue. The chronic stress explains why under such circumstances there is a greater proclivity for normal cells to undergo the transition to cancer cells.","PeriodicalId":6841,"journal":{"name":"4open","volume":"18 8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79608133","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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