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Anti-tumor immunity,autophagy and chemotherapy

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World Journal of Gastroenterology 2012年第45期18卷 6537-6540页

作者： gyrgyi mzes Ferenc Sipos 2nd Department of Internal medicine Semmelweis University1088 BudapestHungary

Autophagy or self-digestion of cells is activated upon various stressful stimuli and has been found to be a survival and drug resistance pathway in ***,genetic studies support that autophagy can act as a tumor ***,defective autophagy is implicated in tumorigenesis,as *** precise impact of autophagy on malignant transformation has not yet been clarified,but recent data suggest that this complex process is mainly directed by cell types,phases,genetic background and *** of autophagy to anticancer immune responses may indicate a novel aspect in cancer chemotherapy.

关键词： Cancer Autophagy Chemotherapy Antitu-mor immunity Cell death

Injury-associated reacquiring of intestinal stem cell function

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World Journal of Gastroenterology 2015年第7期21卷 2005-2010页

作者： Ferenc Sipos gy?rgyi m?zes 2~(nd) Department of Internal medicine Semmelweis University

Epithelial layer of the intestine relies upon stem cells for maintaining homeostasis and *** types of stem cells are currently defined in intestinal crypts:the cycling crypt base columnar cells and quiescent *** several candidate markers and regulators of rapidly cycling and quiescent stem cells have been identified so far,the exact nature of quiescent cells is still questionable since investigations mainly focused on candidate markers rather than the label-retaining population *** results,however,have streng-thened the argument for functional *** a lineage tracing strategy label-retaining cells(LRCs)of the intestinal epithelium were marked,then followed by a pulse-chase analysis it was found that during homeostasis,LRCs were Lgr5-positive and were destined to become Paneth and neuroendocrine ***,it was demonstrated that LRCs are capable of clonogenic growth by recall to the self-renewing pool of stem cells in case of epithelial *** new findings highlight on the hierarchical and spatial organization of intestinal epithelial homeostasis and the important plasticity of progenitors during tissue regeneration,moreover,provide a motivation for studying their role in disorders like colorectal cancer.

关键词： Epithelium Injury Label-retaining cells Stem cell

Issues and opportunities of stem cell therapy in autoimmune diseases

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World Journal of Stem Cells 2019年第4期11卷 212-221页

作者： gy?rgyi m?zes Ferenc Sipos Immunology Team 2nd Department of Internal MedicineSemmelweis University

The purpose of regenerative medicine is to restore or enhance the normal function of human cells, tissues, and organs. From a clinical point of view, the use of stem cells is more advantageous than differentiated cells because they can be collected more easily and in larger quantities, their proliferation capacity is more pronounced, they are more resistant in cell culture, their aging is delayed, they are able to form a number of cell lines, and they are able to promote vascularization of tissue carriers. The therapeutic use of stem cells for disease modification, immunomodulation, or regenerative purposes are undoubtedly encouraging, but most studies are still in their early stages, and the clinical results reported are not clear with regard to therapeutic efficacy and potential side effects. Uniform regulation of the clinical application of stem cells is also indispensable for this highly customizable, minimally invasive, individualized therapeutic method to become a successful and safe treatment alternative in many different autoimmune and autoinflammatory disorders.

关键词： Stem cell therapy Autoimmune Autoinflammatory Immunomodulation Disease modification

Disagreements in the therapeutic use of mesenchymal stem cellderived secretome

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World Journal of Stem Cells 2022年第6期14卷 365-371页

作者： Ferenc Sipos györgyi műzes Department of Internal medicine and Hematology Semmelweis UniversityBudapest 1088Hungary

In a recent article,the authors provide a detailed summary of the characteristics and biological functions of mesenchymal stem cells(mSCs),as well as a discussion on the potential mechanisms of action of mSC-based *** describe the morphology,biogenesis,and current isolation techniques of exosomes,one of the most important fractions of the mSC-derived *** also summarize the characteristics of mSC-derived exosomes and highlight their functions and therapeutic potential for tissue/organ regeneration and for kidney,liver,cardiovascular,neurological,and musculoskeletal diseases,as well as cutaneous wound *** the fact that mSCs are regarded as an important pillar of regenerative medicine,their regenerative potential has been demonstrated to be limited in a number of pathological *** negative effects of mSC-based cell therapy have heightened interest in the therapeutic use of mSC-derived *** the other hand,mSC-derived exosomes and microvesicles possess the potential to have a significant impact on disease development,including *** can interact with tumor cells and promote mutual exchange and induction of cellular markers by exchanging ***,enzymes secreted into and activated within exosomes can result in tumor cells acquiring new *** a result,therapeutic applications of mSC-derived secretomes must be approached with extreme caution.

关键词： mesenchymal stem cells Secretome Exosomes Regeneration Therapy Cancer

Controversies in therapeutic application of mesenchymal stem cell-derived secretome

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BIOCELL 2022年第4期46卷 903-906页

作者： FERENC SIPOS gyÖrgyi mŰzes Department of Internal medicine and Hematology Semmelweis UniversityBudapest1088Hungary

Though mesenchymal stem cells(mSCs)are considered as an important pillar of regenerative medicine,their regenerative potential has been shown to be limited in several pathological *** adverse properties of mSCbased cell therapy have drawn attention to the therapeutic use of mSC-derived ***,mSC-originated exosomes and microvesicles can also possess a significant impact on disease development,including *** interchanging secretome,mSCs can interact with tumor cells and promote mutual exchange/induction of cellular *** addition,enzymes secreted into and activated within exosomes can result in the acquisition of new tumor cell ***,therapeutic applications of mSC-derived secretome require much caution.

关键词： mesenchymal stem cells Secretome Exosomes Cancer

Regulatory T cells in inflammatory bowel diseases and colorectal cancer

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World Journal of Gastroenterology 2012年第40期18卷 5688-5694页

作者： gyrgyi mzes Béla molnár Ferenc Sipos 2nd Department of Internal medicine Semmelweis University molecular medicine Research Unit Hungarian Academy of Sciences

Regulatory T cells(T regs) are key elements in immunological *** number of T regs may alter in both peripheral blood and in colonic mucosa during pathological *** local cellular,microbiological and cytokine milieu affect immunophenotype and function of T *** box P3+ T regs function shows altered properties in inflammatory bowel diseases(IBDs).This alteration of T regs function can furthermore be observed between Crohn's disease and ulcerative colitis,which may have both clinical and therapeutical *** mucosal inflammation may also influence T regs function,which together with the intestinal bacterial flora seem to have a supporting role in colitis-associated colorectal carcinogenesis.T regs have a crucial role in the immunoevasion of cancer cells in sporadic colorectal ***,their number and phenotype correlate closely with the clinical outcome of the disease,even if their contribution to carcinogenesis has previously been *** knowledge of the clinical relationship between IBD and colitis-associated colon cancer,and the growing number of immunological aspects encompassing sporadic colorectal carcinogenesis,the molecular and cellular links amongst T regs,regulation of the inflammation,and cancer development are still not well *** this paper,we aimed to review the current data surrounding the role of T regs in the pathogenesis of IBD,colitis-associated colon cancer and sporadic colorectal cancer.

关键词： Regulatory T cells Forkhead box P3 Inflam-matory bowel diseases Colitis-associated colon cancer Colorectal cancer

Interplay of autophagy and innate immunity in Crohn's disease: A key immunobiologic feature

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World Journal of Gastroenterology 2013年第28期19卷 4447-4454页

作者： gyrgyi müzes Zsolt Tulassay Ferenc Sipos 2nd Department of Internal medicine Semmelweis University 1088 Budapest Hungary

Crohn's disease representing a clinical phenotype of inflammatory bowel disease is a polygenic immune disorder with complex multifactor etiology. Recent genome-wide association studies of susceptibility loci have highlighted on the importance of the autophagy pathway, which previously had not been implicated in disease pathology. Autophagy represents an evolutionarily highly conserved multi-step process of cellular self-digestion due to sequestration of excessive, damaged, or aged proteins and intracellular organelles in double-membranous vesicles of autophagosomes, terminally self-digested in lysosomes. Autophagy is deeply involved in regulation of cell development and differentiation, survival and senescence, and it also fundamentally affects the inflammatory pathways, as well as the innate and adaptive arms of immune responses. Autophagy is mainly activated due to sensors of the innate immunity, i.e., by pattern recognition receptor signaling. The interplay of genes regulating immune functions is strongly influenced by the environment, especially gut resident microbiota. The basic challenge for intestinal immune recognition is the requirement of a simultaneous delicate balance between tolerance and responsiveness towards microbes. On the basis of autophagy-related risk genetic polymorphisms (ATG16L1, IRGm , NOD2 , XBP1 ) impaired sensing and handling of intracellular bacteria by innate immunity, closely interrelated with the autophagic and unfolded protein pathways seem to be the most relevant immunobiologic events. Autophagy is now widely considered as a key regulator mechanism with the capacity to integrate several aspects of Crohn's disease pathogenesis. In this review, recent advances in the exciting crosstalk of susceptibility coding variants-related autophagy and innate immunity are discussed.

关键词： Crohn’s disease Innate immunity Autophagy genes Autophagy Gut microbiota

Therapeutic aspects of c-mYC signaling in inflammatory and cancerous colonic diseases

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World Journal of Gastroenterology 2016年第35期22卷 7938-7950页

作者： Ferenc Sipos Gábor Firneisz györgyi mũzes 2nd Department of Internal medicine Semmelweis UniversityH-1088 Budapest Hungary

Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host's protective immunity. In cells upon DNA damage several protooncogenes, including c-mYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-mYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and microRNA expression. The transcriptional program regulated by c-mYC is context dependent, therefore the final cellular response to elevated c-mYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-mYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-mYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-mYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-mYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. molecules directly targeting c-mYC, or agents acting on other genes involved in the c-mYC pathway could be sele

关键词： c-mYC Therapy Apoptosis Autophagy Colon Inflammation Colorectal cancer

Changes of the cytokine profile in inflammatory bowel diseases

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World Journal of Gastroenterology 2012年第41期18卷 5848-5861页

作者： gyrgyi mzes Béla molnár Zsolt Tulassay Ferenc Sipos 2nd Department of Internal medicine Semmelweis University1088 BudapestHungary molecular medicine Research Unit Hungarian Academy of Sciences1051 BudapestHungary

Cytokines are indispensable signals of the mucosaassociated immune system for maintaining normal gut *** imbalance of their profile in favour of inflammation initiation may lead to disease states,such as that is observed in inflammatory bowel diseases(IBD).Although Crohn's disease(CD) is often described as a prototype of T-helper 1-type diseases,and ulcerative colitis(UC) is traditionally viewed as a T-helper 2-mediated condition,the classic paradigm,which categorises cytokines into pro-and anti-inflammatory groups,has recently been *** inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological *** the less there are many common immunological responses in IBD that are mediated by *** they regulate and influence the development,course and recurrence of the inflammatory process,the concrete pathogenic role of these small signaling molecules is sometimes not unambiguous in the subtypes of the *** aim is to review the current information about pro-and anti-inflammatory effects of traditionally studied and recently discovered cytokines in the pathogenesis of UC and *** better understanding of their production and functional activity may lead to the development of new therapeutic modalities.

关键词： Ulcerative colitis Crohn's disease Interleu-kin-33 Tumor necrosis factor-like factor Interleukin-8 Interleukin-35 Interleukin-25 Interleukin-4 Tumornecrosis factor ligand superfamily member 14