Research, Clinics, Teaching and Society Journal of the Portuguese Experimental Pathology Association

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1 Experimental Pathology and Health Sciences Research, Clinics, Teaching and Society Journal of the Portuguese Experimental Pathology Association Editor: Associated Editors: António M. Silvério Cabrita, MD, PhD, Coimbra, Portugal Manuel Luís Correia Matos Beja, MD, PhD, Coimbra, Portugal Daniel Cartucho, MSci, MD, Faro, Portugal Editorial Board: Redactorial Board: António Silvério Cabrita, MD, PhD, Coimbra, Portugal Américo Afonso, DMD, PhD, Porto, Portugal Artur Varejão, DVM, PhD, Vila Real, Portugal Aura Colaço, DVM, PhD, Vila Real, Portugal Carlos A. Fontes Ribeiro, MD, PhD, Coimbra, Portugal Carlos Gonçalves, MD, PhD, Coimbra, Portugal Carlos Lopes, MD, PhD, Porto, Portugal Carlos Viegas, DVM, PhD, Vila Real, Portugal Fátima Gartner, DVM, PhD, Porto, Portugal Fátima Martins, MD, PhD, Coimbra, Portugal Felisbina Luisa Queiroga, PhD, Vila Real, Portugal Fernanda Seixas Travassos, DVM, PhD, Vila Real, Portugal Fernando Capela e Silva, PhD, Evora, Portugal Fidel San Roman, DVM, PhD, Madrid, Spain Francelina da Cruz Lopes, MD, PhD, Coimbra, Portugal Graça Dias, DVM, PhD, Lisbon, Portugal Helena Fernandes, PhD, Porto, Portugal Isabel Dias, DVM, PhD, Vila Real, Portugal Isabel Poiares Baptista, DMD, PhD, Coimbra, Portugal Ivone Souza, PhD, Recife, Brasil João A. B. Patrício, MD, PhD, Coimbra, Portugal Jorge Colaço, DVM, PhD, Vila Real, Portugal Jorge Rodrigues, DVM, PhD, Vila Real, Portugal José A. S. Medeiros, MD, PhD, Coimbra, Portugal José Manuel Almeida, DVM, Vila Real, Portugal L. Boyanova, Sofia, Bulgaria Luís Antunes, DVM, Vila Real, Portugal Luis de la Cruz Palomino, DVM, PhD, Lugo, Spain Margarida Caramona, PhD, Coimbra, Portugal Maria de Lurdes Pinto, DVM, PhD, Vila Real, Portugal Maria dos Anjos Pires, DVM, Vila Real, Portugal Maria Helena Gil, PhD, Coimbra, Portugal Maria João Pires, PhD, Vila Real, Portugal Maria Manuela Estima Gomes, PhD, Minho, Portugal Paula Oliveira, DVM, PhD, Vila Real, Portugal Paula Pereira, PhD, Lisbon, Portugal Paula Rodrigues, DVM, PhD, Vila Real, Portugal Rita Payan Carreira, PhD, Vila Real, Portugal Rogério Branco, MD, PhD, Porto, Portugal Rui M. B. Alves, MD, PhD, Coimbra, Portgual Stefano Geuna, MD, Turino, Italy Vasco Bairos, PhD, Coimbra, Portugal Rodrigo Farinha, DMD, Coimbra, Portugal Ana I. V. Rafael, MSci, Coimbra, Portugal Karen Cavalcanti, MSci, Recife, Brasil Experimental Pathology and Health Sciences Clinics, Teaching, Research and Society Correspondence: Two issues each year António M Silvério Cabrita ISSN Exinlab Legal deposit: /07 Centro de Empresas de Taveiro Founded: Taveiro 2008: Volume 2 (2) Portugal Language: English Hsjournal@appept.org 1

2 Experimental Pathology andhealth Sciences Research, Clinics, Teaching and Society STATEMENT OF PURPOSE As the beginning of a new century, there is a need to promote scientific and technological development applicable to the entire community, only possible if research is primarily devoted to solving the basic problems and the financial gains are, instead of being the goal, only the means to sustain research. Scientific knowledge and technological capacity should be translated into practical applications for clinicians which in turn will be applicable to the population. New information and capacities can be transferred to teaching programs to prepare new health technicians. Experimental Pathology and Health Sciences Journal belonging to the Portuguese Experimental Pathology Association means to be a forum to bring together scientists, clinicians and those who can voice health social problems. Our objective is to contribute to pluritranslational health work and in so doing provide better conditions for our citizens. INSTRUCTIONS TO AUTHORS Manuscript Categories The journal comprises articles, organized under the following subjects: Editorial, History, Invited Opinion, Invited Review, Review, Minireview, Reports, Student's Tribune, Technical Notes, Research and Experimental Models, Clinical Cases, Clinics and Society, Teaching in Health Science Courses, Student and Research Matters, Applyed Technology. All submissions should be made using the address hsjournal@appept.org. All manuscripts are evaluated first by the Editor and Associated Editors and then submitted to a blinded peer-review process, where we preserve the confidentiality of the authors. After 60 days after the receiving date, the authors are informed about the result of the review: accepted, rejected of acceptable after some changes. If there is any Conflict of Interest, the journal should be informed by the author on the submission of the manuscript. The Portuguese Association of Experimental Pathology holds copyright of published papers. All correspondence concerning editorial matters should be addressed to: António M Silvério Cabrita Editor of Experimental Pathology and Health Sciences Exinlab Centro de Empresas de Taveiro Taveiro - Portugal or by to: hsjournal@appept.org. Manuscript Structure Manuscripts should be prepared in the style of the Journal and according to the Uniform Requirements for Manuscripts Submitted tobiomedical Journals (Available at: Reviews should have a maximum of 8,000 words, 150 references, and six tables or figures. First Page: Should contain an intelligible to the general reader abstract, with no more than 250 words. For research papers the abstract should clearly summarize the background, methodology, results and their significance. Second Page: The second page must include a concise title; complete names of all authors; departments, institution and address where the research was performed; grant numbers and sources of support; name, address, and fax of the corresponding author. Any affiliations with any organization or entity having a direct financial or personal interest in the subject matter or materials discussed in the article should also be stated. The title page is the only page where the authors and their affiliations are identified. Please refer the number of text pages, tables and figures of the manuscript. Body Text: Starts on the third page of the manuscript. For research papers the remaining sections of the text, should include: Introduction, Materials and Methods, Results, Discussion, and Acknowledgments. Commonly abbreviated terms should be spelled out in their first occurrence and then may be referenced in abbreviation through the remainder of the manuscript. Authors must say if the appropriate boards or ethics committee approved the research protocol. If applicable authors should inform about the existence of informed permission of the patients. Tables: Tables should be typed double-spaced and submitted on separate pages, as part of the manuscript. Tables should be black and white text only and should not include figures or other non-typeset images. Figures: One figure consists on one or multiple related panels described under one legend. During the paper construction, figures will be sized to fit one or two columns. Figures without the appropriate size will be sized at the publisher's discretion. If the exact scale is critical, scale bars should be used on the photograph and specified in the legend. The legends are submitted as part of the manuscript, in the place where the related figure should appear in the paper. An adjustment of brightness, contrast, or color balance is only acceptable if applied to the whole image and does not change the conclusions taken from the picture. All pictures should be sent separately, in JPEG or TIFF format, with the best resolution possible. References References should be double-spaced and numbered in order of citation in the text, including citations in tables and figure legends. Complete author citation is required. References should conform to the style of the Journal, as follows (examples): References of Journals: Pereira JE, Cabrita AM, Filipe VM, Bulas-Cruz J, Couto PA, Melo-Pinto P, Costa LM, Geuna S, Mauricio AC, Varejao AS. A comparison analysis of hindlimb kinematics during overground and treadmill locomotion in rats. Behav Brain Res. 2006:172; References of Books: Ted A. Looms, A. Wallace Hayes. Numbers in Toxicology. Loomis's Essentials of Toxicology. Edited by Academic Press. 1996; pp References of Websites: Cited in text only. Include the name of the institution sponsoring the web site, URL address and date of access. Authors will receive an electronic (PDF) reprint. 2

3 Experimental Pathology and Health Sciences 2008: 2(2) 5 7 EDITORIAL Science and Goodwill for Health Care António M. Silvério Cabrita OPINION A Regenerative Approach for Cancer Treatment and Understanding António M. Silvério Cabrita and Manuel C. de Matos Beja MINIREVIEW Muscle Regeneration António Cabral, Vanessa Machado, Nuno Machado and Rodrigo Farinha REPORT 2008 Food For Health HISTORY - INTEMPORAL DOCTORS Zhang Zhongjing Catarina Amaro RESEARCH PAPERS Comparison of Animal Models for the Study of Inflammation Maria dos Anjos Pires, Filomena Adega, Rita Payan-Carreira, Fernanda Seixas, Fernando Oliveira-Torres Inhibition of Serotonin-induced Contractions of Guinea-pig Ileum by Tilia europeae L. Aqueous Extract M. Dulce Cotrim, Isabel Vitória Figueiredo, T. Baptista, Carlos A. Fontes Ribeiro Bowel Mucosa-associated Lymphoid Tissue in Experimental Red Wine, De-alcoholized Red Wine, Ethanol and DMH Administration Tiago F. Rama, Isabel S. Carneiro, Ana Rita P. Fonseca, José C. B. Silva, Karen Cavalcanti and António M. Silvério Cabrita Assessment of the Cytotoxicity of Microparticles for Controlled Drug Release in Oftalmology Ana Cristina Santos, Cláudia Matos, Rosemeyre Cordeiro, Ana Rita Brás, Bárbara Oliveiros, Elisa Campos, Patrícia Alves, Maria Graça Rasteiro, Maria Helena Gil CLINICAL CASES Use of Intratumural Cisplatin in Lung Cancer Daniel Cartucho... STUDENT AND RESEARCH MATTERS Basic Indexes for Small Rodents in Experimental Pathology António M. Silvério Cabrita, Rodrigo Farinha, Karen Cavalcanti, Ana Calado, Pedro Barreto and M.L. Matos Beja Allergy Diagnosis - an Application to Dog Luís M.L. Martins, Ana Goicoa Valdevira, Juan Rejas López Workshop in Pharmaceutical and Biomedical Sciences - Programme Abstracts of Oral Presentations News Rat tooth germen H&E; 100X in the original 3

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5 OPINION Experimental Pathology and Health Sciences 2007; 2 (2): zzzzz Figure António M. Silvério Cabrita MD, PhD, Faculty of Medicine of Coimbra s University, President of the Portuguese Experimental Pathology Association scabrita@mac.com M. L. Matos Beja MD, PhD Portuguese Experimental Pathology Association A Regenerative Approach for Cancer Treatment and Understanding António M. Silvério Cabrita and Manuel C. de Matos Beja For many years we have been accepting a unified theory of carcinogenesis, the classical explanation that divides the process in three sequential basic steps. During the last decades an increasing number of molecular studies on carcinogenesis have demonstrated that neoplasm may arise from several different ways and so, being actually different entities. If this is the case, a different approach for cancer prevention and treatment may be needed. It is not to exclude that many neoplasm may have their origin in non mature cells, which by malignant transformation show several properties of active stem cells (1-10). A new hypothesis has been introduced which indicates that neoplastic cells may be originated in stem cells and that cancer cells with stem cell characteristics may be identified in neoplastic lesions. In this case instead of trying to kill these cells the treatment approach could be directing them to a normal differentiation process. If we assume that at least some neoplastic cells are transformed into malignant stem cells it would be a possible therapeutic choice to induce dedifferentiation of these cells and then to direct the rededifferentiation to a normal and stable phenotype. Also it should be a priority to understand what cell group or niche in each tissue is the possible target for carcinogenesis etiologic factors. It is said that cancer stem cells only represent a minor tumoral cell population and that this number only represents those that have been identified up until now. It is now supposed that only cancer stem cells are responsible for the capacity to propagate tumor transplanted into nude mice (8,9). Several studies describe a series of events that bench mark the beginning of the complex process, in various stages, of carcinogenesis. Even though It is not yet clear, recent data points to stem cells as the possible target of this process, possibly while in a susceptible stage with already some degree of maturation (11,12) (Figure1). The Figure

6 cells subject to this process should have their dedifferentiation capacity on a normal mature tissue blocked and their proliferation capacity stimulated. In this case the process of malignant transformation would initially affect the balance between the forces that point towards maturation and the forces that stimulate proliferation (Figure 2). On a next stage, the cell having its dedifferentiation system affected would come to express molecules that could correspond to different stages of the dedifferentiation of its respective original tissue or even another type of tissue, in what we can call of molecular anachronism (Figure 3). This plastic capacity and of adaptation to the envolving environment would allow the transformed cells to adapt, survive and proliferate. If this is infact the process, then the treatment of neoplastic lesions could be regarded as a group of procedures that would restitute the capacity of maturation and that would naturally oppose to proliferative activity. In this case treatment should succeed with chemical stimuli capable of directioning maturation, consequently silencing the proliferative process (Figures 4 and 5), a therapeutic approach by reprogramming tumoral cell which is now done in some conditions (13,14). Similar to what we do in vitro with stem cell cultures, in a first stage we expand and in the second we direct maturation which happens through mechanisms that reduce or suppress cell proliferation. Figure Figure References: 1. Pitot HC and Dragan YP. Facts and Theories concerning the mechanisms of carcinogenesis. The Faseb Journal. 1991:5; Sell, S and Pierce GB. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab. Invest. 1994:70; Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature Nov 1;414(6859): Behbod F and Rosen JM. Will cancer stem cells provide new therapeutic targets?. Carcinogenesis. 2004:26; Woodward WA, Chen MS, Behbod F and Rosen JM. On mammary stem cells. Jounarl of Cell Science. 2005:118; Tai M-H, Chang C-C, Olson LK and Trosko JE. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 2005:26; Vermeulen L, Sprick MR, Kemper K, Stassi G, Medema JP. Cancer Figure stem cells--old concepts, new insights. Cell Death Differ Jun;15(6): Hart LS, El-Deiry WS.. Invincible, but not invisible: imaging approaches toward in vivo detection of cancer stem cells. J Clin Oncol Jun 10;26(17): Gsteiger S, Morgenthaler S. Heterogeneity in multistage carcinogenesis and mixture modeling. Theor Biol Med Model Jul 21;5: Ashkenazi R, Gentry SN, Jackson TL. Pathways to tumorigenesis--modeling mutation acquisition in stem cells and their progeny. Neoplasia Nov;10(11): Ye F, Zhou C, Cheng Q, Shen J, Chen H. Stem-cell-abundant proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells. BMC Cancer Apr 18;8: Sotomayor P, Godoy A, Smith GJ, Huss WJ. Oct4A is expressed by a subpopulation of prostate neuroendocrine cells. Prostate Dec Bru T, Clarke C, McGrew MJ, Sang HM, Wilmut I, Blow JJ. Rapid induction of pluripotency genes after exposure of human somatic cells to mouse ES cell extracts. Exp Cell Res Aug 15;314(14): Cabral AJ, Machano V, Machado NV, Farinha R. Reversine: A New Promising Compound. Experimental Pathology and Health Sciences. 2008; 1 (1):