4open Pub Date : 2019-01-01 DOI: 10.1051/fopen/2019008

Sirilak Phonin, C. Likasiri

引用次数: 1

Metformin alters signaling induced crosstalk and homeostasis in the carcinogenesis paradigm “Epistemology of the origin of cancer” 二甲双胍改变癌变范式中信号诱导的串扰和稳态“癌症起源的认识论”

4open Pub Date : 2019-01-01 DOI: 10.1051/FOPEN/2019006

B. Brücher, I. Jamall

{"title":"Metformin alters signaling induced crosstalk and homeostasis in the carcinogenesis paradigm “Epistemology of the origin of cancer”","authors":"B. Brücher, I. Jamall","doi":"10.1051/FOPEN/2019006","DOIUrl":"https://doi.org/10.1051/FOPEN/2019006","url":null,"abstract":"The anti-hyperglycemic drug, Metformin, is effective in treating early stages of diabetes and has been associated with a 37% decrease in cancer incidence. While the precise mechanisms for the anti-cancer effects of Metformin remain to be elucidated, this review shows the multiplicity of its effects on interdicting signaling and crosstalk, anti-inflammatory effects and in restoring homeostasis, which, taken together, go beyond its well-known anti-hyperglycemic effect that serves as the basis for its use in type 2 diabetes. Metformin is much more than a one-trick pony. The recent discovery of several signaling pathways influenced by Metformin appears to have potential value in cancer therapy. Based on what we know at present, Metformin promotes beneficial effects attributed to its anti-inflammatory and anti-fibrotic effects largely demonstrated in vitro. Metformin activates or upregulates while it simultaneously inhibits or downregulates multiple signaling pathways of cell-cycle arrest and apoptosis accompanied by oxidative stress, which are in accordance with the 6-step sequence of carcinogenesis. Furthermore, in vivo studies in laboratory animals and in cancer patients are beginning to address the magnitude of the anti-cancer effects and delineate its anti-cancer effects. In this context, results from prior pancreatic and non-pancreatic cancer trials, which contained a significant proportion of the patient population treated with Metformin, will have to be reexamined in light of the observed anti-cancerous effects to gain additional insights. The detailed exploration of Metformin in the context of the “Disruption of signaling homeostasis induced crosstalk in the carcinogenesis paradigm Epistemology of the origin of cancer” can provide helpful insights into the anti-proliferative mechanisms and could play a relevant role in anti-cancer therapy in the future.","PeriodicalId":6841,"journal":{"name":"4open","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74820183","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}

引用次数: 0

The liver fluke Opisthorchis felineus as a group III or group I carcinogen 将肝吸虫视为III类或I类致癌物

4open Pub Date : 2019-01-01 DOI: 10.1051/FOPEN/2019016

M. Pakharukova, J. M. Correia da Costa, V. Mordvinov

{"title":"The liver fluke Opisthorchis felineus as a group III or group I carcinogen","authors":"M. Pakharukova, J. M. Correia da Costa, V. Mordvinov","doi":"10.1051/FOPEN/2019016","DOIUrl":"https://doi.org/10.1051/FOPEN/2019016","url":null,"abstract":"Opisthorchiasis caused by the liver fluke Opisthorchis felineus is one of the most common helminthic infections in the Russian Federation. The largest area affected by opisthorchiasis felinea occupies almost the entire territory of Western Siberia and extends to northern Kazakhstan and a part of the Ural region. Natural endemic regions of opisthorchiasis also exist in the European part of Russia, and in the regions of Western and Eastern Europe. According to the official statistics of the Russian Federation, up to 40 000 patients with opisthorchiasis are registered annually in the country. Opisthorchiasis felinea affects the hepatobiliary system and causes serious liver disorders, including cancer of the biliary tract. Other parasitoses, opisthorchiasis viverrini and clonorchiasis, are widespread in the Southeast Asia and China. The causative agents of these diseases, liver flukes O. viverrini and Clonorchis sinensis, are officially recognized as Group 1 biological carcinogens and are classified as the main risk factors for cholangiocarcinoma. O. felineus is included in Group 3 of biological carcinogens and is not officially considered carcinogenic to humans. Studies on the carcinogenic potential of this liver fluke and the epidemiology of cholangiocarcinoma in the Russian Federation have started in earnest quite recently. Nevertheless, we have some evidence that infection with O. felineus leads to a precancerous state of the bile duct epithelium. This state, combined with additional risk factors, poses a real risk of cholangiocarcinoma. In our opinion, taking into consideration the accumulated facts, the classification of the carcinogenic potential of O. felineus requires revision. In this review, we focus on the relevant characteristics of the biology and epidemiology of this helminth as well as experimental data on opisthorchiasis felinea; this information might clarify the carcinogenicity of O. felineus to humans.","PeriodicalId":6841,"journal":{"name":"4open","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78745379","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}

引用次数: 11

On quaternion applications in obtaining surfaces 四元数在曲面获取中的应用

4open Pub Date : 2019-01-01 DOI: 10.1051/FOPEN/2019019

Özgür Keskin, Y. Yaylı

引用次数: 0

Prelude and premise to the special issue: disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer” 特刊的前奏和前提:癌变范式中体内平衡诱导的信号和串扰的破坏“癌症起源的认识论”

4open Pub Date : 2019-01-01 DOI: 10.1051/FOPEN/2019005

B. Brücher, I. Jamall

{"title":"Prelude and premise to the special issue: disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”","authors":"B. Brücher, I. Jamall","doi":"10.1051/FOPEN/2019005","DOIUrl":"https://doi.org/10.1051/FOPEN/2019005","url":null,"abstract":"The vast majority of anticancer strategies are symptomatic but in order to achieve some tangible progress, we need to identify the cause(s) of the majority of cancers. There is a kind of zeitgeist that findings in genetics, namely somatic mutations, are reflexively viewed as being causative for carcinogenesis, although some 80% of all cancers are presently termed “sporadic” (i.e., with no proven cause). The observation that one inch of cancerous liver tissue can have more than 100 000 000 mutations and an identical mutation can result in different phenotypes, depending on the environment surrounding that mutation, makes it very unlikely that mutations by themselves are causative of most cancers. 4open debuts its Special Issue series with papers that provide strong evidence that carcinogenesis consists of a 6-step sequence (1) a pathogenic stimulus followed by (2) chronic inflammation from which develops (3) fibrosis with associated remodeling of the extracellular microenvironment, and from these changes a (4) precancerous niche (PCN), a product of fibrosis with remodeling by persistent inflammation develops which triggers the deployment of (5) a chronic stress escape strategy and when this fails to be resolved it results in (6) the normal cell to cancerous cell transition. This Special Issue contains separate papers discussing undervalued ubiquitous proteins, chronic inflammation, eicosanoids, microbiome and morbid obesity, PCN, cell transition, followed by altered signaling induced by Metformin, NF-κB signaling and crosstalk during carcinogenesis, and a brief synopsis. In essence, the available evidence, both in vitro and in vivo, lends credence to the proposition that the majority of cancers occur from a disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”.","PeriodicalId":6841,"journal":{"name":"4open","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85765805","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}

引用次数: 2

Mathematical models for optimising bi-enzyme biosensors 优化双酶生物传感器的数学模型

4open Pub Date : 2019-01-01 DOI: 10.1051/FOPEN/2019015

Qi Wang, Yupeng Liu

引用次数: 1

Periodic solutions for a class of conservative Liénard-type equations 一类保守型limedard方程的周期解

4open Pub Date : 2019-01-01 DOI: 10.1051/FOPEN/2019003

E. R. Korfanty, Ankai Liu, W. Feng

引用次数: 0

Eicosanoids in carcinogenesis 二十烷类化合物在癌变中的作用

4open Pub Date : 2019-01-01 DOI: 10.1051/FOPEN/2018008

B. Brücher, I. Jamall

{"title":"Eicosanoids in carcinogenesis","authors":"B. Brücher, I. Jamall","doi":"10.1051/FOPEN/2018008","DOIUrl":"https://doi.org/10.1051/FOPEN/2018008","url":null,"abstract":"Inflammation is the body's reaction to pathogenic (biological or chemical) stimuli and covers a burgeoning list of compounds and pathways that act in concert to maintain the health of the organism. Eicosanoids and related fatty acid derivatives can be formed from arachidonic acid and other polyenoic fatty acids via the cyclooxygenase and lipoxygenase pathways generating a variety of pro- and anti-inflammatory mediators, such as prostaglandins, leukotrienes, lipoxins, resolvins and others. The cytochrome P450 pathway leads to the formation of hydroxy fatty acids, such as 20-hydroxyeicosatetraenoic acid, and epoxy eicosanoids. Free radical reactions induced by reactive oxygen and/or nitrogen free radical species lead to oxygenated lipids such as isoprostanes or isolevuglandins which also exhibit pro-inflammatory activities. Eicosanoids and their metabolites play fundamental endocrine, autocrine and paracrine roles in both physiological and pathological signaling in various diseases. These molecules induce various unsaturated fatty acid dependent signaling pathways that influence crosstalk, alter cell–cell interactions, and result in a wide spectrum of cellular dysfunctions including those of the tissue microenvironment. Although the complete role of eicosanoids, including that of the recently elucidated anti-inflammatory specialized pro-resolving lipid mediators (SPMs), e.g. lipoxins, resolvins, protectins and maresins, is not completely understood, the result of unremitting chronic inflammation is fostering early stages of carcinogenesis. Chronic inflammation facilitates the transition from a normal cell to a cancerous one. The disruption of homeostasis across a wide, but identifiable, swath of diverse molecular pathways creates a micromilieu which constitutes an early and necessary step in the 6-step sequence of carcinogenesis for the vast majority of cancers, termed “sporadic cancers”.","PeriodicalId":6841,"journal":{"name":"4open","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85255817","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}

引用次数: 9

On Sheffer polynomial families 关于Sheffer多项式族

4open Pub Date : 2019-01-01 DOI: 10.1051/FOPEN/2019004

S. Pinelas, P. Ricci

引用次数: 1

Map production and data analysis with local parameters 根据当地参数进行地图制作和数据分析

4open Pub Date : 2019-01-01 DOI: 10.1051/FOPEN/2019022

H. D. de Oliveira, Fernando M. Granja-Martins, H. Fernandez

引用次数: 0

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