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1.
Article in English | MEDLINE | ID: mdl-33572355

ABSTRACT

(1) Background: Health services that were already under pressure before the COVID-19 pandemic to maximize its impact on population health, have not only the imperative to remain resilient and sustainable and be prepared for future waves of the virus, but to take advantage of the learnings from the pandemic to re-configure and support the greatest possible improvements. (2) Methods: A review of articles published by the Special Issue on Population Health and Health Services to identify main drivers for improving the contribution of health services on population health is conducted. (3) Health services have to focus not just on providing the best care to health problems but to improve its focus on health promotion and disease prevention. (4) Conclusions: Implementing innovative but complex solutions to address the problems can hardly be achieved without a multilevel and multisectoral deliberative debate. The CHRODIS PLUS policy dialog method can help standardize policy-making procedures and improve network governance, offering a proven method to strengthen the impact of health services on population health, which in the post-COVID era is more necessary than ever.


Subject(s)
COVID-19 , Delivery of Health Care/trends , Pandemics , Population Health , Humans
2.
Article in English | MEDLINE | ID: mdl-32610433

ABSTRACT

(1) Background: The gap between research findings and their application in routine practice implies that patients and populations are not benefiting from the investment in scientific research. The objective of this work is to describe the process and main lessons obtained from the pilot practices and recommendation that have been implemented by CHRODIS-PLUS partner organizations; (2) Methods: CHRODIS-PLUS is a Joint Action funded by the European Union Health Programme that continues the work of Joint Action CHRODIS-JA. CHRODIS-PLUS has developed an Implementation Strategy that is being tested to implement innovative practices and recommendations in four main areas of action: health promotion and disease prevention, multimorbidity, fostering quality of care of patients with chronic diseases, and employment and chronic conditions; (3) Results: The Three-Stages CHRODIS-PLUS Implementation Strategy, based on a Local Implementation Working Group, has demonstrated that it can be applied for interventions and in situations and contexts of great diversity, reflecting both its validity and generalizability; (4) Conclusions: Implementation has to recognize the social dynamics associated with implementation, ensuring sympathy toward the culture and values that underpin these processes, which is a key differentiation from more linear improvement approaches.


Subject(s)
Health Promotion/methods , Noncommunicable Diseases , Chronic Disease , Cost of Illness , Europe , Humans , Multimorbidity
3.
Health Res Policy Syst ; 16(1): 114, 2018 Nov 23.
Article in English | MEDLINE | ID: mdl-30470236

ABSTRACT

The European Union and Latin America and the Caribbean regions have enjoyed privileged relations since the first bi-regional Summit of Heads of State and Government, held in Rio de Janeiro, Brazil, in 1999, and the lunching of a Strategic Partnership. Health research stands as one of the major areas of research and development expenditure in both regions and has also been the focus of roughly 30% of all bilateral cooperation agreements and programmes.EU-LAC Health, a project funded by the European Union from 2011 to 2017, had the main objective to develop a consensus roadmap to enhance and coordinate the bi-regional collaboration between the European Union member states and Latin America and Caribbean countries in health research. From April 2013, EU-LAC Health has also supported the Working Group on Health created and designated by decision-makers at the highest political level to implement a bi-regional Join Initiative on Research and Innovation.This article collects and summarises the context, methodology (series of workshops, surveys and iterative deskwork by multiple bi-regional stakeholders) of this project, as well as the main outputs of (1) definition of a strategic roadmap, containing a scientific research agenda, to guide policy-makers in equitable and collaborative health research and innovation; (2) launching of the Joint Initiative on Health Research and Innovation, with the vision of being the reference body on the bi-regional health research and innovation collaboration; and (3) funding of 13 bi-regional health research and innovation projects.EU-LAC Health represents a successful example of bi-regional collaboration and the emerging networks and expertise gathered during the lifetime of the project have the potential to tackle common health challenges affecting the quality of life of citizens from the two regions and beyond. The project has also paved the way for more specific bi-regional initiatives such as a new initiative for bi-regional collaboration in personalised medicine that is being arranged by the partnership. Furthermore, it can inspire future initiatives for bi-regional research collaboration on other fields.


Subject(s)
Biomedical Research , International Cooperation , Caribbean Region , Europe , European Union , Humans , Latin America
5.
Rev Esp Enferm Dig ; 104(6): 310-4, 2012 Jun.
Article in English, Spanish | MEDLINE | ID: mdl-22738701

ABSTRACT

BACKGROUND: the gastrointestinal (GI) tract is the major target site of the graft-versus-host disease (GVHD). Diagnosis is based on endoscopic and histological findings. MATERIAL AND METHODS: we performed a retrospective study from January 1st, 1990 to December 31st, 2008 on 338 upper gastrointestinal endoscopies (gastroscopies) performed to 197 patients that underwent an allogeneic transplant with clinical suspicion of GI-GVHD. RESULTS: endoscopic findings to the diagnosis of GVHD have a sensitivity (S) of 34%, specificity levels (SP) of 65%, a positive predictive value (PPV) of 73% and a negative predictive value (NPV) of 48%. The histological study of the endoscopic biopsies has a global sensibility of 85.6% SP = 34.6% PPV = 64.2% and NPV = 63.7%. Histological grade was correlated with the clinical grade of acute GVHD (p = 0.018). CONCLUSION: upper gastrointestinal endoscopy is useful for the diagnosis of GVHD, as it allows biopsies that can ultimately lead to the diagnosis, but with limited accuracy because the histological findings have low sensitivity and specificity, while the endoscopic findings are generally nonspecific.


Subject(s)
Duodenum/pathology , Esophagus/pathology , Gastroscopy , Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation , Stomach/pathology , Adult , Aged , Biopsy , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index
6.
Rev. esp. enferm. dig ; 104(6): 310-314, jun. 2012. tab, ilus
Article in Spanish | IBECS | ID: ibc-100732

ABSTRACT

Introducción: el tracto gastrointestinal es la diana principal de afectación en la enfermedad de injerto contra huésped (EICH). Su diagnóstico se basa en los hallazgos endoscópicos e histológicos. Material y métodos: hemos realizado un estudio retrospectivo, desde el 1 de enero de 1990 hasta el 30 de diciembre de 2008, de 338 endoscopias digestivas altas realizadas a 197 pacientes sometidos a trasplante alogénico de células hematopoyéticas con sospecha de EICH gastrointestinal. Resultados: los hallazgos endoscópicos tienen una sensibilidad (S) del 34%, especificidad (E) del 65%, valor predictivo positivo (VPP) del 73% y valor predictivo negativo (VPN) del 48% para el diagnóstico de EICH. El estudio histológico de las biopsias tiene una S del 85,6%, E del 34,6%, VPP del 64,2% y VPN del 63,7%. El grado histológico se correlacionó con el grado clínico en la EICH aguda (p = 0,0018). Conclusión: la endoscopia digestiva alta es útil para el diagnóstico de EICH, ya que permite la toma de biopsias que finalmente pueden llevar al diagnóstico, pero con una rentabilidad limitada ya que los hallazgos histológicos tienen una sensibilidad y especificidad bajas, mientras que los endoscópicos son generalmente inespecíficos(AU)


Background: the gastrointestinal (GI) tract is the major target site of the graft-versus-host disease (GVHD). Diagnosis is based on endoscopic and histological findings. Material and methods: we performed a retrospective study from January 1st, 1990 to December 31st, 2008 on 338 upper gastrointestinal endoscopies (gastroscopies) performed to 197 patients that underwent an allogeneic transplant with clinical suspicion of GI-GVHD. Results: endoscopic findings to the diagnosis of GVHD have a sensitivity (S) of 34%, specificity levels (SP) of 65%, a positive predictive value (PPV) of 73% and a negative predictive value (NPV) of 48%. The histological study of the endoscopic biopsies has a global sensibility of 85.6% SP = 34.6% PPV = 64.2% and NPV = 63.7%. Histological grade was correlated with the clinical grade of acute GVHD (p = 0.018). Conclusion: upper gastrointestinal endoscopy is useful for the diagnosis of GVHD, as it allows biopsies that can ultimately lead to the diagnosis, but with limited accuracy because the histological findings have low sensitivity and specificity, while the endoscopic findings are generally nonspecific(AU)


Subject(s)
Animals , Male , Female , Rabbits , Mitogen-Activated Protein Kinases , Lipopolysaccharides , Ileal Diseases/diagnosis , Ileum , Ileum/pathology , Myenteric Plexus , Myenteric Plexus/physiopathology , Mitogen-Activated Protein Kinases/pharmacology , Sepsis/diagnosis , Ileal Diseases/veterinary , Analysis of Variance , Immunohistochemistry/methods , Immunohistochemistry , Immunohistochemistry/veterinary
7.
Biol Blood Marrow Transplant ; 17(5): 765-9, 2011 May.
Article in English | MEDLINE | ID: mdl-21093601

ABSTRACT

The gastrointestinal (GI) tract is the main target site of graft-versus-host disease (GVHD). Diagnosis is based on endoscopic and histological findings. Helicobacter pylori (HP) is a Gram-negative spiral bacterium linked to gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and adenocarcinoma and is frequently observed on endoscopy in patients who have undergone transplantation. The role, if any, played by HP infection in the development of acute GVHD is unknown. We conducted a retrospective study between January 1, 1990, and December 31, 2008, of 338 upper GI endoscopies (gastroscopies) performed on patients who underwent allogeneic stem cell transplantation with clinical suspicion of GVHD (198 patients). Acute and chronic GVHD were confirmed from histological features in 97 patients (51.3%) and 68 patients (36%), respectively. HP infection was detected in 69 patients (35%) and had a negative modulating effect on the development of acute GVHD (relative risk [RR], 0.60; 95% confidence interval, 0.46-0.79; P = .001) and chronic GVHD (RR, 0.75; 95% confidence interval, 0.61-0.92; P = .016). Furthermore, the presence of HP was inversely correlated with the histological severity of GVHD (P = .003). Our findings suggest that infection with HP may have a negative modulating effect on GVHD.


Subject(s)
Graft vs Host Disease/complications , Helicobacter Infections/complications , Stomach/microbiology , Anti-Bacterial Agents/administration & dosage , Antineoplastic Agents/administration & dosage , Biopsy , Female , Gastroscopy , Graft vs Host Disease/diagnosis , Graft vs Host Disease/drug therapy , Graft vs Host Disease/physiopathology , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Helicobacter Infections/pathology , Helicobacter pylori/growth & development , Hematologic Neoplasms/physiopathology , Hematologic Neoplasms/therapy , Humans , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Stem Cell Transplantation/adverse effects , Stomach/drug effects , Stomach/pathology , Transplantation, Homologous
8.
Acta Otorrinolaringol Esp ; 60 Suppl 1: 18-23, 2009 Feb.
Article in Spanish | MEDLINE | ID: mdl-19245771

ABSTRACT

Paragangliomas arise from the extra-adrenal paraganglion system. Histologically, paragangliomas are usually easy to diagnose, with well-defined characteristics. These lesions are clearly delimited and highly vascular and are composed of cell balls (Zellballen) separated by thin fibrous septa. These cell balls are composed of two types of cells: chief cells and sustentacular cells. Other, less frequent patterns, which are nearly always focal, can also be found and hamper diagnosis: angiomatoid, fusocellular and clear cell. Some paragangliomas show intense fibrosis, which can compress and distort the cell balls, giving rise to a pseudoinfiltrative appearance (sclerosing paragangliomas). With immunohistochemical techniques, the chief cells are positive for neuroendocrine markers (neuron specific enolase, chromogranin A, synaptophysin, serotonin) while sustentacular cells are positive for S-100 protein. Ultrastructurally, the chief cells contain neurosecretory granules with dense centers and simple intercellular junctions without desmosomes. From a practical point of view, paragangliomas can be divided into three groups: non-invasive (circumscribed or encapsulated), locally invasive and metastatic. Although some invasive tumors can be fatal, there are no histological data that can predict the malignancy of paragangliomas, and the only absolute criterion for malignancy is the presence of metastasis.


Subject(s)
Head and Neck Neoplasms/pathology , Paraganglioma/pathology , Humans
9.
Acta otorrinolaringol. esp ; 60(supl.1): 18-23, feb. 2009. ilus, tab
Article in Spanish | IBECS | ID: ibc-59845

ABSTRACT

Los paragangliomas son tumores que derivan del sistema paragangliónico extra adrenal. Desde el punto de vista histológico, los paragangliomas son, por lo general, tumores de fácil diagnóstico, con unas características bien definidas. Son lesiones bien delimitadas, muy vascularizadas y formadas por nidos celulares (Zellballen) separados por finos septos conjuntivos. Los nidos celulares están constituidos por 2 tipos de células: las principales y las sustentaculares. En ocasiones, existen otros patrones, menos frecuentes y casi siempre focales, que pueden dificultar el diagnóstico: angiomatoide, fusocelular y de células claras. Algunos paragangliomas se acompañan de intensa fibrosis, que puede comprimir y distorsionar los nidos celulares, dando una apariencia seudoinfiltrativa (paragangliomas esclerosantes). Con técnicas inmunohistoquímicas, las células principales son positivas para marcadores neuroendocrinos (enolasaneuronal específica, cromogranina A, sinaptofisina, serotonina) y las células sustentaculares para proteína S-100. Desde el punto de vista ultra estructural, las células principales muestran gránulos de centro denso, de tipo neurosecretor y uniones simples intercelulares sin desmosomas. Desde un punto de vista práctico, los paragangliomas pueden dividirse en 3 grupos: no invasivos (circunscritos o encapsulados), localmente invasivos y metastásicos. A pesar de que algunos tumores de crecimiento infiltrante pueden ser letales, no existe ningún dato histopatológico que pueda predecir el comportamiento maligno de los paragangliomas, y sólo la existencia de metástasis es criterio absoluto de malignidad (AU)


Paragangliomas arise from the extra-adrenal paraganglion system. Histologically, paragangliomas are usually easy to diagnose, with well-defined characteristics. These lesions are clearly delimited and highly vascular and are composed of cell balls (Zellballen) separated by thin fibrous septa. These cell balls are composed of two types of cells: chief cells and sustentacular cells. Other, less frequent patterns, which are nearly always focal, can also be found and hamper diagnosis: angiomatoid, fusocellular and clear cell. Some paragangliomas show intense fibrosis, which can compress and distort the cell balls, giving rise to a pseudo -infiltrative appearance (sclerosing paragangliomas). Withimmunohistochemical techniques, the chief cells are positive for neuroendocrine markers (neuron specific enolase, chromogran in A, synaptophys in, serotonin) while sustentacular cells are positive for S-100 protein. Ultrastructurally, the chief cells contain neurosecretory granules with densecenters and simple intercellular junctions without desmosomes. From a practical point of view, paragangliomas can be divided into three groups: non-invasive (circumscribed or encapsulated), locally invasive and metastatic. Although some invasive tumors can be fatal, there are no histological data that can predict the malignancy of paragangliomas, and the only absolute criterion for malignancy is the presence of metast (AU)


Subject(s)
Humans , Head and Neck Neoplasms/pathology , Paraganglioma/pathology
10.
Carcinogenesis ; 28(10): 2069-73, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17468515

ABSTRACT

FUS-DDIT3 is a chimeric oncogene generated by the most common chromosomal translocation t(12;16)(q13;p11) associated to liposarcomas. The application of transgenic methods and the use of primary mesenchymal progenitor cells to the study of this sarcoma-associated FUS-DDIT3 gene fusion have provided insights into their in vivo functions and suggested mechanisms by which lineage selection may be achieved. These studies indicate that FUS-DDIT3 contributes to differentiation arrest acting at a point in the adipocyte differentiation process after induction of peroxisome proliferator-activated receptor gamma (PPARgamma) expression. To test this idea within a living mouse, we generated mice expressing FUS-DDIT3 within aP2-positive cells, because aP2 is a downstream target of PPARgamma expressed at the immature adipocyte stage. Here, we report that FUS-DDIT3 expression was successfully induced at the aP2 stage of differentiation both in vivo and in vitro. aP2-FUS-DDIT3 mice do not develop liposarcomas and exhibit an increase in white adipose tissue size. Consistent with in vivo data, mouse embryonic fibroblasts (MEFs) obtained from aP2-FUS-DDIT3 mice not only were capable of terminal differentiation but also showed an increased capacity for adipogenesis in vitro compared with wild-type MEFs. Taken together, this study provides genetic evidence that the presence of FUS-DDIT3 in an aP2-positive cell is not enough to cause liposarcoma development and establishes that PPARgamma inactivation is required for liposarcoma development.


Subject(s)
Adipocytes/cytology , Liposarcoma/genetics , PPAR gamma/antagonists & inhibitors , RNA-Binding Protein FUS/genetics , Transcription Factor CHOP/genetics , Animals , Cell Differentiation , Chromosomes, Human, Pair 16 , Chromosomes, Human, Pair 2 , Fibroblasts/physiology , Humans , Liposarcoma/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Nude , Mice, Transgenic , Promoter Regions, Genetic , RNA/genetics , RNA/isolation & purification , Translocation, Genetic
11.
BMC Biotechnol ; 7: 17, 2007 Apr 05.
Article in English | MEDLINE | ID: mdl-17411439

ABSTRACT

BACKGROUND: Embryonated chicken eggs have been used since the mid-20th century to grow a wide range of animal viruses to high titers. However, eggs have found so far only limited use in the production of recombinant proteins. We now describe a system, based on a Sendai virus minigenome, to produce large amounts of heterologous viral glycoproteins in the allantoic cavity of embryonated eggs. RESULTS: Soluble forms of human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) fusion (F) proteins, devoid of their transmembrane and cytoplasmic domains, were produced in allantoic fluids using the Sendai minigenome system. The first step was rescuing in cell cultures Sendai virus minigenomes encoding the proteins of interest, with the help of wild type Sendai virus. The second step was propagating such recombinant defective viruses, together with the helper virus, in the allantoic cavity of chicken embryonated eggs, and passage to optimize protein production. When compared with the production of the same proteins in the culture supernatant of cells infected with vaccinia recombinants, the yield in the allantoic fluid was 5-10 fold higher. Mutant forms of these soluble proteins were easily constructed by site-directed mutagenesis and expressed in eggs using the same approach. CONCLUSION: The simplicity and economy of the Sendai minigenome system, together with the high yield achieved in the allantoic fluid of eggs, makes it an attractive method to express soluble glycoproteins aimed for structural studies.


Subject(s)
Allantois/metabolism , Body Fluids/metabolism , Genome, Viral/genetics , Glycoproteins/biosynthesis , Glycoproteins/genetics , Ovum/metabolism , Sendai virus/genetics , Animals , Chick Embryo , Chickens , Cricetinae , Glycoproteins/isolation & purification , Glycoproteins/ultrastructure , Humans , Solubility , Viral Proteins/biosynthesis , Viral Proteins/genetics , Viral Proteins/isolation & purification , Viral Proteins/ultrastructure
12.
J Cell Physiol ; 197(2): 214-24, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14502561

ABSTRACT

Neurofibromin (NF1) (the product of Nf1 gene) is a large cytosolic protein known as a negative regulator of Ras. A fragment of some 400 residues located at the center of the NF1 GAP-Related Domain (NF1-GRD) has strong identity with other molecules of the GAP family, which comprises, among others, the mammalian proteins NF1 and p120GAP, and the yeast proteins IRA1 and IRA2. GAP family members are known by their ability to promote the GTPase activity of Ras proteins, facilitating the transit of those proteins to their inactive state. Recent findings (Tong et al., 2002, Nat Neurosci 5:95-96) indicate that NF1 may be involved in the regulation of adenyl cyclase activity. Our results show that NF1-GRD cooperates with Ras in the anchorage-independent growth capacity of Ras-expressing fibroblasts, without affecting: (i) their ability to grow in low serum, (ii) their cellular adhesion capability, or (iii) the expression of key proteins involved in cell-cell and cell-matrix interactions. On the other hand, NF1 overexpression induces an increase in the expression levels of the focal adhesion kinase (FAK), and specific changes in the activation status of the mitogen-activated protein kinases (MAPKs). These results suggest the existence of a Ras-independent NF1-dependent pathway able to modify the levels of expression of FAK and the levels of activation of MAPKs. Because FAK and many proteins recently found to bind NF1 have a role in the cytoskeleton, this pathway may involve rearrangement of cytoskeletal components that facilitate anchorage independence.


Subject(s)
Cytoskeleton/metabolism , Genes, ras , Neurofibromin 1/metabolism , ras GTPase-Activating Proteins/metabolism , 3T3 Cells , Animals , Cell Adhesion/physiology , Cytoskeleton/genetics , Eukaryotic Cells/metabolism , Extracellular Matrix/metabolism , Focal Adhesion Kinase 1 , Focal Adhesion Protein-Tyrosine Kinases , MAP Kinase Signaling System/physiology , Mice , Neurofibromin 1/genetics , Protein Isoforms/metabolism , Protein Structure, Tertiary/genetics , Protein-Tyrosine Kinases/metabolism , Transfection , ras GTPase-Activating Proteins/genetics
13.
Cytometry B Clin Cytom ; 51(1): 14-20, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12500293

ABSTRACT

BACKGROUND: In recent years important information has accumulated on the genetic alterations present in colorectal tumors. However, thus far few studies have analyzed the impact of numerical abnormalities of chromosomes 17 and 18, which carry the p53 and DCC plus SHAD4/DPC4 genes involved in colorectal cancer, on the clinical and biological behaviors of the disease. METHODS: With the use of interphase fluorescence in situ hybridization (FISH), we analyzed the incidence of numerical abnormalities of chromosomes 17 and 18 in a series of malignant colorectal tumors and explored its potential association with clinicobiological behavior and the prognosis of the disease. For this purpose, 94 consecutive patients newly diagnosed with colorectal cancer were analyzed. In all cases, FISH analyses of the number of copies and nuclei of chromosomes 17 and 18 were performed in interphase nuclei with the use of double stainings. For all patients, information on age, sex, tumor size, Dukes' stage, tumor localization, DNA ploidy status, and the proportion of S-phase tumor cells was recorded. Median follow-up was 38 months. RESULTS: Numerical abnormalities of chromosomes 17 and 18 were present in most patients with colorectal cancer (57% and 52%, respectively). Gains of chromosome 17 and monosomy 18 were found in 51% and 29% of cases, respectively, and they were the most frequent individual abnormalities for each chromosome. The simultaneous analysis of the number of copies of both chromosomes in the same cell showed that, in most cases displaying numerical abnormalities for these chromosomes, two or more different tumor cell clones were present. From a clinical point of view, numerical abnormalities of chromosome 17, especially monosomy 17, were associated with a significantly higher incidence of rectal tumors (P = 0.001) and Dukes' stage D (P = 0.02) and a lower median of disease-free survival among patients who underwent curative surgery (P = 0.05), as compared with diploid cases. In addition, cases with an altered number of copies of chromosome 17 showed a higher incidence of DNA aneuploidy (P = 0.0001) and a greater proportion of S-phase cells (P = 0.001) by flow cytometry. In contrast, no clear association was found between the presence of numerical abnormalities of chromosome 18 and clinicobiological disease characteristics, except for a higher incidence of DNA aneuploidy by flow cytometry (P = 0.001) and a lower median of disease-free survival (P = 0.06). Multivariate analysis showed that numerical abnormalities of chromosome 17, but not of chromosome 18, are an independent prognostic factor for predicting disease-free survival in patients with colorectal cancer. CONCLUSIONS: Numerical abnormalities of chromosomes 17 and 18 were relatively common findings in patients with colorectal cancer, with chromosome 17 being associated with a higher incidence of tumors localized to the rectum and a worse clinical outcome. Cytometry Part B (Clin. Cytometry) 51B:14-20, 2003.


Subject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 18 , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Flow Cytometry , Genes, DCC/genetics , Genes, p53/genetics , Humans , In Situ Hybridization, Fluorescence , Incidence , Male , Middle Aged , Prognosis
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