Sumario:
The International Journal of Developmental Biology
Linking Development, Stem Cells and Cancer Research
Euskal Herriko Unibertsitateko Argitalpen Zerbitzua / Servicio Editorial de la Universidad del País Vasco / University of the Basque Country Press
Volume 59 - Numbers 1-2-3 (2015) / Pages 1-158 Editor-in-Chief: Juan Aréchaga
MORE INFORMATION [Abstract - FullText / Full Text Open Access]
ISSN: 0214-6282 / ISSN-e: 1696-3547 www.intjdevbiol.com
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Special Issue: Cell Death in Development & Tumors
Guest Editors: Massimo De Felici and Mauro Piacentini
ABSTRACTS
Preface
Programmed Cell death in Development and Tumors
Massimo De Felici and Mauro Piacentini ..... 1-3
Interview
EHU/UPV/UBC - The International Journal of Developmental Biology 59: 5-9 (2015)
doi: 10.1387/ijdb.150167mp / © UBC Press ( www.a360grados.net )
Dying to survive - apoptosis, necroptosis, autophagy as supreme experiments of nature
Mauro Piacentini and Guido Kroemer
Department of Biology, University of Rome ‘Tor Vergata’, Rome, Italy
Abstract: Guido Kroemer has made fundamental contributions to medical research through his pioneering work in the fields of cell death and cancer research. He is best known for the discovery that the permeabilization of mitochondrial membranes constitutes a decisive step in programmed cell death. Kroemer has explored the fine mechanisms of mitochondrial cell death control, the molecular pathways that explain the inhibition of cell death in cancer cells, upstream of or at the level of mitochondria, and the mechanisms that make cancer cell death immunogenic. Moreover, he discovered the AIF protein and clarified its biological role in apoptosis. His important contributions have been recognized with numerous awards. Kroemer currently serves on more than forty Editorial Boards and is a member of the European Molecular Biology Organization (EMBO), German Academy of Sciences, Austrian Academy of Sciences, European Academy of Sciences (EAS), European Academy of Sciences and Arts (EASA), and European Academy of Cancer Sciences (EACS). He is the President of the European Cell Death Organization (ECDO) and the Founding Director of the European Research Institute for Integrated Cellular Pathology (ERI-ICP). Kroemer is the most cited scientist worldwide in the field of cell death as well as in the area of mitochondrial research.
Keywords: apoptosis, autophagy, necrosis, tumor immunology
PCD in Development -------------------------------------------------
EHU/UPV/UBC - The International Journal of Developmental Biology 59: 11-22(2015)
doi: 10.1387/ijdb.150220zz / © UBC Press ( www.a360grados.net )
What cell death does in development
Zahra Zakeri 1, Carlos G. Penaloza 1,2, Kyle Smith 1, Yixia Ye 1 and Richard A. Lockshin 1,3
1. Queens College and Graduate Center, Department of Biology, City University of New York, NY
2. Schenectady County Community College, State University of New York, NY and 3St. John's University, NY, USA
Abstract: Cell death is prominent in gametogenesis and shapes and sculpts embryos. In non-mammalian embryos one sees little or no cell death prior to the maternal-zygotic transition, but, in mammalian embryos, characteristic deaths of one or two cells occur at the end of compaction and are apparently necessary for the separation of the trophoblast from the inner cell mass. Considerable sculpting of the embryo occurs by cell deaths during organogenesis, and appropriate cell numbers, especially in the CNS and in the immune system, are generated by massive overproduction of cells and selection of a few, with death of the rest. The timing, identity, and genetic control of specific cells that die have been well documented in Caenorhabditis, but in other embryos the stochastic nature of the deaths limit our ability to do more than identify the regions in which cells will die. Complete disruption of the cell death machinery can be lethal, but many mutations of the regulatory machinery yield only modest or no phenotypes, indicating substantial redundancy and compensation of regulatory mechanisms. Most of the deaths are apoptotic and are identified by techniques used to recognize apoptosis, but techniques identifying lysosomes (whether in dying or involuting cells or in the phagocytes that invade the tissue) also reveal patterns of cell death. Aberrant cell deaths that produce known phenotypes are typically localized, indicating that the mechanism of activating a programmed death in a specific region, rather than the mechanism of death, is aberrant. These results lead us to conclude that we need to know much more about the conversations among cells that lead cells to commit suicide.
Keywords: apoptosis, autophagy, caspase, necrosis, programmed cell death
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 23-32(2015)
doi: 10.1387/ijdb.150055sk / © UBC Press ( www.a360grados.net )
Ecdysone-mediated programmed cell death in Drosophila
Shannon Nicolson, Donna Denton and Sharad Kumar
Centre for Cancer Biology, University of South Australia, Adelaide, Australia
Abstract: During Drosophila development, the steroid hormone ecdysone plays a key role in the transition from embryo into larva and then into pupa. It is during larval-pupal metamorphosis that extensive programmed cell death occurs to remove large obsolete larval tissues. During this transition, ecdysone pulses control the expression of specific transcription factors which drive the expression of key genes involved in cell death, thus spatially and temporally controlling programmed cell death. Ecdysone also controls cell death in specific larval and adult tissues. This review focuses on the current knowledge of ecdysone-mediated cell death in Drosophila.
Keywords: programmed cell death, ecydsone, transcription, apoptosis, autophagy
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 33-39(2015)
doi: 10.1387/ijdb.150047dd / © UBC Press ( www.a360grados.net )
Apaf1 in embryonic development - shaping life by death, and more
Daniela De Zio 1,2, Emiliano Maiani 1 and Francesco Cecconi 1,2
1. Cell Stress and Survival Unit, Danish Cancer Society Research Center, Copenhagen, Denmark
2. IRCCS Fondazione Santa Lucia, and Department of Biology - University of Rome Tor Vergata, Rome, Italy
Abstract: Apaf1 has been studied hitherto for its key role in regulating the formation of the apoptotic core machinery, the apoptosome, to induce programmed cell death. Apaf1 involvement in orchestrating this process during embryonic development has been widely documented and constitutes a breakthrough in developmental biology. In this review, we aim to highlight the origin of Apaf1 discoveries and how findings, mainly based on the analysis of knock-out mouse models, have led us to consider Apaf1 as a master player in fine-tuning apoptosis during embryonic development. Likewise, we also attempt to establish how Apaf1 function is locally time-dependent in regulating neurodevelopment and becomes dispensable during neuron maturation. We go on to discuss Apaf1’s new functions which have been unveiled in recent years and which could revise or, at least, adjust the common view of Apaf1 having merely an apoptotic role. Hence, by presenting clear indications on the pro-survival roles of Apaf1, this review seeks to provide novel and more complex insights into Apaf1 involvement in nervous system development.
Keywords: apoptosis, neurodevelopment, centrosome
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 41-49(2015)
doi: 10.1387/ijdb.150064md / © UBC Press ( www.a360grados.net )
Programmed cell death in mouse primordial germ cells
Massimo De Felici and Francesca G. Klinger
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
Abstract: In a number of mammalian species, the main events of development of the primordial germ cells (PGCs), the embryonic precursors of the oocytes and spermatozoa, were described during the early twentieth century. Actually, the concept of the origin of germ cells in extragonadal sites before the formation of the gonadal anlagen, was put forward for the human embryo around the first decade of the 1900s (for a review, see De Felici, 2013). PGC development is characterized by two major cellular processes, a movement from the wall of the yolk sac, where the germline is determined, to the gonadal anlagen and an increase in number due to active proliferation. As far as we know, the notion that programmed cell death (PCD) might physiologically occur in mammalian PGCs was for the first time put forward by us in 1993 in the case of the mouse. How we arrived to such a concept and the progress made up to now in the characterization of this process in our and other laboratories mainly in the mouse are the topics of the present review.
Keywords: MAPK, ROS, apoptosis
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 51-54(2015)
doi: 10.1387/ijdb.150063fk / © UBC Press ( www.a360grados.net )
Multifaceted programmed cell death in the mammalian fetal ovary
Francesca G. Klinger, Valerio Rossi and Massimo De Felici
Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
Abstract: From previous and more recent works reviewed in the present paper, it appears that mammalian fetal oocytes face several challenges to survive throughout the stages of meiotic prophase I up to the block at the diplotene/dictyate stage and the primordial follicle assembly. Depending on the period of development and experimental conditions, these oocytes can undergo different forms of programmed cell death (PCD) and cross-talking pathways. We hypothesize that they require the continuous support of growth factors to accomplish the activities required to overcome PCD during prophase I. An extraordinary level of DNA double strand break (DSB) tolerance characterizes oocytes during the first stages of meiotic prophase I. However, the activation of a p63/p53-and PCNA-dependent DNA damage checkpoint, plays a major role in eliminating defective oocytes when they reach the diplotene stage. Before oocytes are enclosed into a primordial follicle, the shortness of nutrients/growth factors might activate protective autophagy but this can turn into their death if starvation is prolonged. Actually, clarifying the relationships among growth factor signalling (mainly AKT cascade), apoptotic and autophagic proteins that seem to coexist in fetal oocytes, could be the key to understanding PCD in these cells.
Keywords: apoptosis, fetal ovary, oocyte, autophagy
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 55-62(2015)
doi: 10.1387/ijdb.150065jh / © UBC Press ( www.a360grados.net )
Interdigital tissue regression in the developing limb of vertebrates
Carlos I. Lorda-Diez, Juan A. Montero, Juan A. Garcia-Porrero and Juan M. Hurle
Departamento de Anatomía y Biología Celular and IDIVAL, Universidad de Cantabria. Santander, Spain
Abstract: Here we have chosen the regression of the interdigital tissue which sculpts the digits from the hand/foot plate in tetrapod embryos to review the most relevant aspects concerning the regulation and biological significance of programmed cell death. We gather abundant information showing that the initiation of the degenerative process is the result of a complex interplay between the different signaling pathways which are also responsible for limb outgrowth and skeletal tissue differentiation, rather than being regulated by a specific signaling pathway. The model further shows that once the death response is triggered, several different routes of cell disruption, including caspase-dependent apoptosis, lysosomal-mediated cell death, and even a cell senescence process, are activated in the interdigits to ensure their elimination. Transcriptional and structural changes accompanying the degenerative process, and their posible contribution to the control of the death process, are also revised in detail. Finally we survey a number of issues still awaiting clarification, such as the functional implication of interdigital cell death as a source of signals acting on the surrounding tissues, as occurs in the so called “regenerative cell death”.
Keywords: cell death, apoptosis, limb development, developmental senescence, lysosomal cell death
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 63-71(2015)
doi: 10.1387/ijdb.150070ev / © UBC Press ( www.a360grados.net )
Development and programed cell death in the mammalian eye
Elena Vecino and Arantxa Acera
Experimental Ophthalmo-Biology Group (GOBE), Department of Cell Biology and Histology, University of the Basque Country (UPV/EHU), Leioa, Vizcaya, Spain
Abstract: Programmed cell death (PCD) is a major mechanism for patterning of a variety of complex structures. Cells are initially organized into fairly loose patterns; then, selective death removes the cells between pattern elements to create the correct structures, as a sculptor removes some material to reveal the hidden image. The life or death of a cell is mostly affected by extracellular signals because the intracellular machinery responsible for PCD is constitutively expressed in most animal cells. The optic vesicle originates during gastrulation when the endoderm and mesoderm interact with the adjacent prospective head ectoderm to create a lens. To be formed correctly, the lens must have a precise spatial relationship with the retina. Ganglion cells are the first neurons to be differentiated in the retina. Vertical networks in the inner and outer retina are later interconnected when bipolar cells are formed and connections with ganglion cells are established. This sequential pattern of retinal circuit development is common across vertebrate species. During development of the retina, far more neurons are generated than are ultimately needed with almost one half of them undergoing PCD shortly before establishing meaningful contacts within their targets. However, apoptosis in other eye tissues is not a key event but rather a refinement. Thus, for the final development of the cornea, the control of keratocyte proliferation is more important than cell death events. The molecular mechanisms underlying apoptotic cell death have been conserved throughout evolution; however further investigations are needed to understand the key mechanisms of PCD in different tissues during development.
Keywords: retina, cornea, lens, ciliary body, iris, programed cell death, eye, development
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 73-78(2015)
doi: 10.1387/ijdb.150050ac / © UBC Press ( www.a360grados.net )
Programmed cell death in the skin
Antonio Costanzo 1, Francesca Fausti 2, Giulia Spallone 2, Francesca Moretti 2, Alessandra Narcisi 1 and Elisabetta Botti 1
1. Dermatology Unit, NESMOS Department, Sapienza University of Rome
2. Department of Dermatology, Tor Vergata University of Rome, Italy
Abstract: Differently from the other cells of the body, epidermal cells of the skin undergo a specific programmed cell death form named cornification. Many events take part to control this process, which has been described as a terminal differentiation program. Going from the innermost layer to the outermost, epidermal cells stop dividing, change their shape, acquire new cellular structures and strengthen their cytoskeleton. This is corroborated by the fact that during this physical transition they change their gene expression, reprogramming in some way their biochemical activity. The activation of critical enzymes, including proteases and transglutaminases is a fundamental cellular event. These enzymes are involved in building the supramolecular and cornified structures which confer resistance to the epidermis which carries out a vital function as a skin barrier, preserving the organism from various insults. Here we review current concepts about cornification and the mechanisms by which this process is preserved in species.
Keywords: Cornification, apoptosis, skin disease
PCD in Cancer ----------------------------------------------
EHU/UPV/UBC - The International Journal of Developmental Biology 59: 79-86(2015)
doi: 10.1387/ijdb.150081gm / © UBC Press ( www.a360grados.net )
Cell competition, apoptosis and tumour development
Ginés Morata and Luna Ballesteros-Arias
Centro de Biología Molecular Severo Ochoa, Madrid, Spain
Abstract: The phenomenon of cell competition is an interactive process originally discovered in the imaginal discs of Drosophila; it is a developmental mechanism that identifies and eliminates cells that are weaker than their neighbours or have features that make them different or not well adapted to their surroundings. It appears to be an important homeostatic mechanism to contribute to the general fitness of developing tissues. Here we discuss some of the basic features of cell competition and then focus on results indicating that cell competition is responsible for the removal of malignant or aberrant cells that may appear during development, although in certain circumstances it can revert its role to promote tumour growth. We also consider several recent studies that indicate that cell competition also occurs in vertebrates where it performs similar functions.
Keywords: cell competition, tumour development, apoptosis, Drosophila, vertebrates
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 87-93(2015)
doi: 10.1387/ijdb.150045sg / © UBC Press ( www.a360grados.net )
P63 in health and cancer
Stefania Gonfloni, Valerio Caputo and Valentina Iannizzotto
Department of Biology, University of Rome "Tor Vergata", Rome, Italy
Abstract: TP63 is the most ancient member of the p53 gene family. The p53 family comprises three transcription factors (p53/p63/p73). They share a high degree of homology and similar domain structure. Yet, they can exist as truncated isoforms. Alternative promoters and splicing sites lead to the generation of several molecules. P53/p63/p73 are important to maintain cell homeostasis. P63 and p73 regulate many p53 target genes. This is due to their common structural features. Both proteins may compensate the loss of p53. This is a common event occurring in more than 50% of malignancies. Yet, p63 (or p73) has its own role. Studies from p63-null mice have shown the key role of p63 in embryo development. Several reports have supported the p63 role in epidermal development and in skin homeostasis. P63 involvement in heart development is currently being researched. Recent studies have found p63 to be “the guardian of human reproduction”. In addition, p63 has an important, even controversial, role in cancer. Here, we provide a general overview of p63 regulation and activity. We discuss emerging concepts about its role in germ line protection, metabolism and cancer.
Keywords: p63, genome stability, DNA damage response, metabolism, cancer
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 95-108(2015)
doi: 10.1387/ijdb.150082iv / © UBC Press ( www.a360grados.net )
Role of autophagy in the maintenance and function of cancer stem cells
Ilio Vitale 1,2, Gwenola Manic 1, Vito Dandrea 3 and Ruggero De Maria 1
1. Regina Elena National Cancer Institute
2. Department of Biology, University of Rome "Tor Vergata"
3. Department of Surgical Sciences, University of Rome “La Sapienza”, Rome, Italy
Abstract: Recent advances in experimental technologies and cancer models have made possible to demonstrate that the tumor is a dynamic system comprising heterogeneous populations of cancer cells organized in a hierarchical fashion with cancer stem cells (CSCs) at the apex. CSCs are immature cells characterized by self-renewal property and long-term repopulation potential. CSCs have been causally linked to cancer initiation, propagation, spreading, recurrence and relapse as well as to resistance to anticancer therapy. A growing body of evidence suggests that the function and physiology of CSCs may be influenced by genetic/epigenetic factors and tumor environment. In this context, macroautophagy is a lysosomal degradative process (herein referred to as autophagy) critical for the adaptive response to stress and the preservation of cellular and tissue homeostasis in all eukaryotes that may have a crucial role of in the origin, maintenance and invasiveness of CSCs. The activation of the autophagic machinery is also considered as an adaptive response of CSCs to perturbation of tumor microenvironment, caused for instance by anticancer therapy. Nevertheless, compelling preclinical and clinical evidence on the cytoprotective role of autophagy for CSCs is still missing. Here, we summarize the results on the contribution of autophagy in CSCs and how it impacts tumorigenesis and tumor progression. We also discuss the therapeutical potential of the modulation of autophagy as a means to eradicate CSCs.
Keywords: autophagosomes, beclin 1, CD133, chloroquine, lysosomes, tumor initiating cells
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 109-117(2015)
doi: 10.1387/ijdb.150057mp / © UBC Press ( www.a360grados.net )
AMBRA1-regulated autophagy in vertebrate development
Manuela Antonioli 1,2, Federica Albiero 1, Gian María Fimia 1,3 and Mauro Piacentini 1,2
1. National Institute for Infectious Diseases I.R.C.C.S. ‘Lazzaro Spallanzani’ Rome
2. Department of Biology, University of Rome ‘Tor Vergata’, Rome
3. Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce, Italy
Abstract: Autophagy is a catabolic process that mediates the lysosomal turn over of organelles and macromolecules, and is strongly activated in stress conditions to ensure cell survival. Autophagy core genes are highly conserved from yeast to mammals, with an increasing number of positive and negative regulators that have evolved in higher eukaryotes. Autophagy takes part in different stages of development, as revealed by alterations in cell proliferation, differentiation and survival during the embryogenesis of organisms carrying mutations in autophagy genes. These defects are ascribed to the ability of autophagy to provide elements for new synthesis or energy production in limiting conditions during embryogenesis, as well as to contribute to the profound cell remodeling that occurs during differentiation. However, many differences have been observed in the phenotypes of autophagy mutant organisms, indicating that these genes have acquired specific functions in particular tissues, which may reflect the ability of autophagy to crosstalk with the main developmental processes. In this review, we discuss the role of upstream regulators of autophagy in the development of different model systems, focusing, in particular, on AMBRA1 (autophagy/beclin-1 regulator-1) and its role in the central nervous system.
Keywords: AMBRA1, autophagy, BECLIN1, LC3, ULK
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 119-129(2015)
doi: 10.1387/ijdb.150044bz / © UBC Press ( www.a360grados.net )
Cell death in cancer therapy of lung adenocarcinoma
Anna Zagryazhskaya 1, Katarina Gyuraszova 1,2 and Boris Zhivotovsky 1,3
1. Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden
2. Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University in Košice, Košice, Slovakia
3. Lomonosov Moscow State University, Moscow, Russia
Abstract: Lung cancer is the main cause of all cancer-related deaths in the world, with lung adenocarcinoma (ADC) being the most common subtype of this fatal disease. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors. This is particularly important for the successful development of new cancer therapy approaches. The high resistance of lung ADC to conventional radio- and chemotherapies represents a major challenge to treatment effectiveness. Here we discuss recent progress in understanding the mechanisms of ADC’s broad resistance to treatment and its possible therapeutic implications. A number of driving oncogenic alterations were identified in a subset of lung ADCs, making them suitable for targeted therapies directed towards specific cancer-associated molecular changes. In addition, we discuss the molecular aberrations common in lung ADC that are currently being exploited or are potentially important for targeted cancer therapy, as well as limitations of this type of therapy. Furthermore, we highlight possible treatment modalities that hold promise for overcoming resistance to targeted therapies as well as alternative treatment options such as immunotherapies that are potentially promising for improving the clinical outcome of lung ADC patients.
Keywords: cell death, apoptosis, lung adenocarcinoma, targeted therapy, chemotherapy, radiotherapy
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 131-140(2015)
doi: 10.1387/ijdb.150061pa / © UBC Press ( www.a360grados.net )
Immunogenic cell death
Abhishek D. Garg, Aleksandra M. Dudek-Peric, Erminia Romano and Patrizia Agostinis
Cell Death Research & Therapy (CDRT) Laboratory, Department for Cellular and Molecular Medicine, KULeuven University of Leuven, Leuven, Belgium
Abstract: Currently, it is widely acknowledged that a proactive anticancer immunosurveillance mechanism takes part in the rejection of neoplastic lesions before they progress towards a benign or malignant tumour. However in cases of very aggressive neoplastic lesions consisting of cells with high mutational diversity, cancer cell variants might be formed that are capable of evading host defence systems against uncontrolled proliferation and anticancer immunosurveillance. This is mainly accomplished through the exhibition of low immunogenicity, which is a particularly important stumbling block in the revival of long-lasting as well as stable anticancer immunity. Recently, it has emerged emphatically that inciting a cancer cell death routine, associated with the activation of danger signalling pathways evoking emission of damage-associated molecular patterns (DAMPs), markedly increases the immunogenicity of dying cancer cells. This cell death pathway has been termed “immunogenic cell death” (ICD). In the present review we introduce this concept and discuss its characteristics in detail. We also discuss in detail the various molecular, immunological and operational determinants of ICD.
Keywords: immunogenicity, immunogenic cell death, cancer, danger signals, antigen, damage-associated molecular patterns, danger signalling, ER stress, photodynamic therapy (PDT), chemotherapy
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 141-147(2015)
doi: 10.1387/ijdb.150084el / © UBC Press ( www.a360grados.net )
Combinatorial cancer immunotherapy strategies with proapoptotic small-molecule IAP antagonists
Shawn T. Beug 1, David P. Conrad 1,2, Tommy Alain 1,3, Robert G. Korneluk 1,3 and Eric C. Lacasse 1
1. Solange Gauthier Karsh Molecular Genetics Laboratory, Apoptosis Research Centre, Children’s Hospital of Eastern Ontario (CHEO) Research Institute
2. Celverum Inc., Ottawa, Canada; 3Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada
Abstract: Members of the inhibitor of apoptosis (IAP) family control several critical aspects of innate immunity, cell death, and tumorigenesis. Small molecule antagonists that target specific IAP oncoproteins, primarily cIAP1 and cIAP2, but potentially also XIAP and Livin, modulate distinct immune signal transduction pathways that can lead to an increased sensitivity of tumors cells to cytokine-mediated apoptosis. These antagonists are based on the structure of an endogenous cellular IAP inhibitor called Smac. Smac is normally sequestered within the mitochondria and is released into the cytoplasm upon cell death stimuli, thereby overcoming the anti-apoptotic action of the IAPs. The therapeutic usefulness of recombinant tumoricidal cytokines to treat cancer patients is principally limited due to their unacceptable adverse side effects. Therefore, investigators have sought to develop alternative regimens that do not rely on exogenously delivered death ligands. These approaches include the stimulation of the immune system with oncolytic virus-based agents or Toll-like receptor agonists in combination with Smac mimetics. Similarly, preclinical combination immunotherapy studies reveal that recombinant interferon synergizes with Smac mimetics to kill cancer. This strategy opens up new therapeutic avenues for anti-cancer therapy by modulating specific immune-mediated death pathways employing unique dual-pronged combinatorial approaches.
Keywords: Smac mimetic, XIAP, cIAP1, cIAP2, TNFα, interferon, oncolytic virus, TLR agonist, virotherapy, apoptosis
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EHU/UPV/UBC - The International Journal of Developmental Biology 59: 149-158(2015)
doi: 10.1387/ijdb.150037fs / © UBC Press ( www.a360grados.net )
Regulated cell death in diagnostic histopathology
Faruk Skenderi 1, Semir Vranic 1 and Ivan Damjanov 2
1. Department of Pathology, University of Sarajevo Clinical Center, Sarajevo, Bosnia and Herzegovina
2. Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, Kansas City, Kansas, USA
Abstract: Regulated cell death (RCD) is a controlled cellular process, essential for normal development, tissue integrity and homeostasis, and its dysregulation has been implicated in the pathogenesis of various conditions including developmental and immunological disorders, neurodegenerative diseases, and cancer. In this review, we briefly discuss the historical perspective and conceptual development of RCD, we overview recent classifications and some of the key players in RCD; finally we focus on current applications of RCD in diagnostic histopathology.
Keywords: regulated cell death, programmed cell death, apoptosis, histopathology, diagnostic markers
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