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1.
Methods Mol Biol ; 2206: 1-13, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32754806

RESUMO

Most of angiogenesis assays were designed and developed during Folkman's era. But the growth of new blood vessels in several pathologic conditions as tumor development or inflammation were observed long time ago.The development of new blood vessels was early observed by ancient Egyptians who tried to destroy them by applying empirical methods. From the first observations regarding angiogenesis to a personalized therapy targeting newly formed blood vessels a lot of experimental in vitro and in vivo angiogenesis assays have been developed. The present work will overview the oldest and less known part of angiogenesis assays development, and in addition, it will present the newest data in the experimental field of angiogenesis which is rapidly improved by the needs of new antiangiogenic and antivascular therapy development.

2.
Anticancer Res ; 40(10): 5557-5566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988879

RESUMO

BACKGROUND/AIM: E- and P-cadherin (E-cadh, P-cadh) control tumor cell invasion, metastatic or stemness potential and chemotherapy resistance. The study aimed to assess E- and P-cadherin expression in breast cancer molecular subtypes. MATERIALS AND METHODS: Immunohistochemistry for E-cadh and P-cadh was performed for 97 breast cancer cases. Membrane (M), cytoplasmic (C) or mixed (MC) patterns of E-cadh and P-cadh were considered in our evaluation. RESULTS: E-cadh and P-cadh C pattern was significantly correlated in the HER2 subtype (p=0.031). P-cadh M pattern was highly specific for the HER2 subtype (p=0.002). Only P-cadh C characterized the triple negative breast cancer subtype (p=0.015). For Luminal B/HER2 cases, P-cadh M pattern was strongly coexpressed with the E-cadh MC pattern (p=0.012). Progesterone receptor (PR) expression influenced E-cadh M pattern in the Luminal B/HER2 subtype (p=0.042). CONCLUSION: E- and P-cadherins define distinct subgroups within breast cancer molecular subtypes. Our findings support the inclusion of E- and P-cadherin into breast cancer molecular classification.


Assuntos
Antígenos CD/genética , Biomarcadores Tumorais/genética , Caderinas/genética , Neoplasias de Mama Triplo Negativas/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Células-Tronco Neoplásicas/metabolismo , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/patologia
3.
In Vivo ; 33(4): 1157-1163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280205

RESUMO

BACKGROUND: The role of podoplanin (PDPN) and homebox prospero gene 1 (PROX1) in early stages of pancreatic islet changes induced by hypercaloric diet is unclear. The aim of this study was to study PDPN and PROX1 variability in pancreatic islets after a hypercaloric diet in a rat experimental model. MATERIALS AND METHODS: Pancreatic biopsies harvested from Sprague-Dawley rats at 3, 6, and 9 weeks following hypercaloric diet intake were evaluated for morphological and molecular changes of Langerhans islets based on PDPN and PROX1 expression Results: Six weeks of hypercaloric diet induced hypertrophy of pancreatic islets with focal expression of Pdpn and Prox1 mRNA. At 9 weeks of hypercaloric diet, strong peri-insular inflammation was found around hypertrophic islets highly expressing PDPN, and lacking Prox1 mRNA and protein expression. CONCLUSION: This is the first report of Pdpn and Prox1 mRNA expression variability and involvement in early steps of pancreatic islet changes following hypercaloric food intake.


Assuntos
Dieta/efeitos adversos , Ingestão de Energia , Expressão Gênica , Proteínas de Homeodomínio/genética , Glicoproteínas de Membrana/genética , Pancreatopatias/etiologia , Proteínas Supressoras de Tumor/genética , Animais , Biomarcadores , Biópsia , Proteínas de Homeodomínio/metabolismo , Imuno-Histoquímica , Glicoproteínas de Membrana/metabolismo , Pancreatopatias/diagnóstico , Pancreatopatias/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Proteínas Supressoras de Tumor/metabolismo
4.
Cancer Genomics Proteomics ; 16(4): 299-307, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31243111

RESUMO

BACKGROUND/AIM: Chloride intracellular channel 1 (CLIC1) represents a promising target for personalized therapy. Our aim was to assess CLIC1 expression in clear cell renal cell carcinoma (cc RCC) and identify its possible prognostic role. MATERIALS AND METHODS: Fifty cases of cc RCC were evaluated and selected for immunohistochemistry. CLIC1 expression was correlated with tumor grade, invasion and heterogeneity. RESULTS: A total of 87.5% of the cases were CLIC1 positive, with either a homogeneous (31.42%) or a heterogeneous (68.57%) pattern. Low, mild and strong CLIC1 expressing tumors were defined based on nuclear (N), cytoplasmic (C), membrane (M) or combinations of them (NC, NM, CM, NCM) in terms of CLIC1 distribution. A significant correlation was found between tumor grade and percent of positive tumor cells (p=0.017). For G3 tumors, CLIC1 cytoplasmic expression was strongly correlated with high expression status (p=0.025) and tumor heterogeneity (p=0.004). CLIC1 expression was also correlated with metastasis (p=0.046). CONCLUSION: We defined four cc RCC groups depending on G, CLIC1 expression and pattern: i) G3/NM/low CLIC1+, ii) G2/CM/mild CLIC1+ iii) G1 or G2/NM or CM /high CLIC1+, and iv) G2/M /high CLIC1.


Assuntos
Carcinoma de Células Renais/genética , Canais de Cloreto/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Humanos , Masculino
5.
Surg Innov ; 26(4): 408-419, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31056009

RESUMO

Purpose. Clinically apparent anastomotic leakage (AL) after low anterior rectal resection (LAR; <7 cm from anal verge) using circular double-stapled anastomosis without defunctioning stoma is up to 37.5%. However, it is unclear whether there is reduction of LAR after 21 postoperative days without defunctioning stoma but with extraluminal anastomotic application of fibrin sealant. Methods. Forty-eight-week-old pigs underwent LAR and circular double-stapled anastomosis in end-to-end technique (descendo-rectostomy). Animals were randomized into therapy and control group (cg). Therapy group (n = 20) received additional extraluminal circular anastomotic application of fibrin sealant. Objective was to assess incidence of clinically apparent and nonclinically apparent leakage through the 21st postoperative day. Remaining animals were sacrificed on the 21st day, and anastomotic region was analyzed. In case of earlier diagnosed AL, animals were sacrificed. Results. In cg, we observed clinically and nonclinically AL in 20% (n = 4). No animal was identified with a nonclinical-apparent leakage in this group, and all 4 animals with leakages presented clinical signs. In the therapy group, no animal (0/20) developed clinically apparent leakage signs. There were no leakages in this group, but 3 animals had ulcerative lesions without leak and without clinical signs. These lesions were observed intraluminally at crossing of staple lines after 21 days. In one of these animals, incomplete leakage was observed, blocked by fibrin sealant. Conclusion. In circular stapled colorectal anastomosis, circular fibrin glue sealant successfully protected anastomotic intraluminal wall defects at crossing of staple lines, reducing leakage rate from 20% to 0% (cg vs therapy group) after 21 postoperative days.


Assuntos
Anastomose Cirúrgica/métodos , Fístula Anastomótica/prevenção & controle , Adesivo Tecidual de Fibrina/uso terapêutico , Reto/cirurgia , Grampeamento Cirúrgico/métodos , Animais , Modelos Animais , Suínos
6.
In Vivo ; 33(3): 743-748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028192

RESUMO

BACKGROUND/AIM: Mast cells (MCs) represent the most controversial non-malignant element of the tumor microenvironment. Our aim was to study how MCs density and distribution (intratumoral-MCit versus peritumoral-MCpt) relate to tumor grade and molecular subtypes. MATERIALS AND METHODS: MCs tryptase immunohistochemistry was performed on 80 cases of breast carcinomas. RESULTS: For Luminal A tumors, a partial correlation was detected between MCit and progesterone receptor (PR) (p=0.005). Luminal B tumors showed a significant correlation between MCpt and age (p=0.009), estrogen receptor (ER) (p=0.017) and PR (p=0.035). MCit and MCpt were strongly interrelated in this subtype (p=0.002) and in triple-negative breast cancers (p=0.002). In HER2 subtype, MCpt tumors were significantly correlated with HER2 (p=0.044). In G2 tumors, MCpt correlated with ER (p=0.015) and PR (p=0.038) while in G3 tumors ER correlated with both MCit (p=0.009) and MCpt (p=0.000487) tumors. CONCLUSION: MCs dynamics are strongly influenced by hormone receptors and HER2 status. MCit increased in aggressive tumor types and is a worse prognostic factor.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Mastócitos/imunologia , Mastócitos/metabolismo , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biomarcadores Tumorais , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Gradação de Tumores , Neovascularização Patológica/metabolismo , Prognóstico , Resultado do Tratamento
7.
Eur J Histochem ; 63(1)2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30838843

RESUMO

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.


Assuntos
Adenoma/metabolismo , Hormônios Hipofisários/análise , Neoplasias Hipofisárias/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/metabolismo , Adenoma/genética , Adenoma/patologia , Adenoma Acidófilo/genética , Adenoma Acidófilo/metabolismo , Adenoma Acidófilo/patologia , Adenoma Basófilo/genética , Adenoma Basófilo/metabolismo , Adenoma Basófilo/patologia , Adenoma Cromófobo/genética , Adenoma Cromófobo/metabolismo , Adenoma Cromófobo/patologia , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/genética
8.
In Vivo ; 33(1): 79-83, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30587606

RESUMO

BACKGROUND/AIM: The aim of this study was to evaluate SOX2 expression in pituitary adenomas and its correlation to their secretory state and clinicopathological parameters. PATIENTS AND METHODS: Thirty-four patients were clinically evaluated and surgery was recommended for tumor removal. Histopathological diagnosis by hematoxylin eosin staining was followed by immunohistochemistry for pituitary hormones and SOX2 co-expression. RESULTS: Fourteen of the 34 cases were GH-secreting adenomas, 10 were prolactinomas and 10 non-functioning pituitary adenomas. SOX2-positive expression was detected in 47.05% of total cases: 8 GH-secreting adenomas (57.14%), 6 prolactinomas (60%) and 2 non-functioning adenomas (20%). SOX2 positivity was significantly higher amongst secreting adenomas (p=0.041). SOX2-negative tumors were significantly associated with corticotrophin deficiency (p=0.047) and gonadotrophin deficiency (p=0.041). No correlation with tumor size or extrasellar extension was detected. CONCLUSION: SOX2 is differentially expressed in pituitary adenomas and influences the secretory state or clinical behavior of pituitary adenomas.


Assuntos
Hipófise/metabolismo , Neoplasias Hipofisárias/genética , Fatores de Transcrição SOXB1/genética , Feminino , Regulação da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Masculino , Hipófise/patologia , Neoplasias Hipofisárias/patologia
9.
Int J Mol Sci ; 19(12)2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30572565

RESUMO

Microscopic and molecular events related to alveolar ridge augmentation are less known because of the lack of experimental models and limited molecular markers used to evaluate this process. We propose here the chick embryo chorioallantoic membrane (CAM) as an in vivo model to study the interaction between CAM and bone substitutes (B) combined with hyaluronic acid (BH), saline solution (BHS and BS, respectively), or both, aiming to point out the microscopic and molecular events assessed by Runt-related transcription factor 2 (RUNX 2), osteonectin (SPARC), and Bone Morphogenic Protein 4 (BMP4). The BH complex induced osteoprogenitor and osteoblastic differentiation of CAM mesenchymal cells, certified by the RUNX2 +, BMP4 +, and SPARC + phenotypes capable of bone matrix synthesis and mineralization. A strong angiogenic response without inflammation was detected on microscopic specimens of the BH combination compared with an inflammatory induced angiogenesis for the BS and BHS combinations. A multilayered organization of the BH complex grafted on CAM was detected with a differential expression of RUNX2, BMP4, and SPARC. The BH complex induced CAM mesenchymal cells differentiation through osteoblastic lineage with a sustained angiogenic response not related with inflammation. Thus, bone granules resuspended in hyaluronic acid seem to be the best combination for a proper non-inflammatory response in alveolar ridge augmentation. The CAM model allows us to assess the early events of the bone substitutes⁻mesenchymal cells interaction related to osteoblastic differentiation, an important step in alveolar ridge augmentation.


Assuntos
Substitutos Ósseos/farmacologia , Diferenciação Celular , Membrana Corioalantoide/metabolismo , Ácido Hialurônico/farmacologia , Inflamação/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Osteoblastos/citologia , Animais , Proteína Morfogenética Óssea 4/metabolismo , Diferenciação Celular/efeitos dos fármacos , Embrião de Galinha , Membrana Corioalantoide/citologia , Membrana Corioalantoide/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteoblastos/efeitos dos fármacos , Osteonectina/metabolismo
10.
Crit Rev Oncol Hematol ; 131: 46-52, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30293705

RESUMO

PDGFs/PDGFRs axis is documented as an important tumor-promoting agent and potential therapeutic target for several human carcinomas, including breast cancer. However, little is known about the role played by the PDGF family members in the normal development of the breast tissue, breast carcinogenesis and tumor-microenvironment dynamics Despite its potent pro-lymphangiogenic effects, PDGF-B/PDGFR-beta axis remains controversial and incompletely elucidated in the field of breast cancer, with emphasis to its differential implications in breast cancer molecular subtypes. Although some data are available concerning this aspect, little or no information is found regarding the role of the PDGF-B/PDGFR-beta axis in rare and aggressive types of breast cancers, such as triple negative breast cancers (TNBCs) and its associated subtypes This review attempted to gather as many data as possible concerning PDGFs family members in the normal breast tissue and in breast carcinogenesis with special focus on their role in diagnosis and therapeutic approach.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Carcinogênese/patologia , Proteínas Proto-Oncogênicas c-sis/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Microambiente Tumoral , Animais , Mama/metabolismo , Neoplasias da Mama/metabolismo , Carcinogênese/metabolismo , Feminino , Humanos
11.
J Pathol ; 246(4): 447-458, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30101525

RESUMO

Aggressive tumor cells can adopt an endothelial cell-like phenotype and contribute to the formation of a tumor vasculature, independent of tumor angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it is associated with poor survival in cancer patients. To what extent tumor cells capable of vascular mimicry phenocopy the angiogenic cascade is still poorly explored. Here, we identify pericytes as important players in vascular mimicry. We found that pericytes are recruited by vascular mimicry-positive tumor cells in order to facilitate sprouting and to provide structural support of the vascular-like networks. The pericyte recruitment is mediated through platelet-derived growth factor (PDGF)-B. Consequently, preventing PDGF-B signaling by blocking the PDGF receptors with either the small tyrosine kinase inhibitor imatinib or blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the current study identifies an important role for pericytes in the formation of vascular-like structures by tumor cells. Moreover, the mechanism that controls the pericyte recruitment provides therapeutic opportunities for patients with aggressive vascular mimicry-positive cancer types. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Mimetismo Biológico/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , Melanoma Experimental/irrigação sanguínea , Melanoma Experimental/tratamento farmacológico , Neovascularização Patológica , Pericitos/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Animais , Comunicação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Técnicas de Cocultura , Humanos , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Nus , Pericitos/metabolismo , Pericitos/patologia , Fator de Crescimento Derivado de Plaquetas/imunologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Front Pediatr ; 6: 223, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30131951

RESUMO

In children, lymphangiomas are extremely rare pathologic entities that are characterized by unusual locations. The mesenteric localization is extremely rare in children, and the clinical signs usually mimic an acute abdominal syndrome. For most of the cases, their diagnosis is established by the radiologist, and the main therapeutic option is represented by surgery for lesion removal. We hereby describe the case of a 4 year old girl admitted to the pediatric emergency department for continuous abdominal pain, more intense in the orthostatic position, associated with abdominal distension, nausea, and vomiting. These symptoms raised the clinical suspicion of acute abdominal syndrome. The patient had no previous clinically significant events. Radiologic examination suggested a mesenteric multicystic lymphangioma certified by surgical and histopathological evaluation. No specific targeted therapy is currently available; moreover, no specific criteria for recurrences have been stated. A new approach of infantile lymphangiomas following surgery, regarding the use of specific lymphatic markers panel including D2-40, Prox-1, VEGFR-3, PDGFs, and Ki67 may improve the characterization of such lesions regarding their prognosis, recurrence rate and targeted therapy implementation especially for those with a more aggressive or recurrent behavior.

13.
In Vivo ; 32(4): 791-798, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29936460

RESUMO

AIM: To characterize baby hamster kidney fibroblast (BHK 21/C13) cells and test the effects of antibodies against podoplanin and disodium cromolyn on BHK 21/C13 cell line-derived tumors grown on chick embryo chorioallantoic membrane (CAM). MATERIAL AND METHODS: BHK 21/C13 cell-derived fibrosarcomas developed in hamsters were implanted on CAM and treated with anti-podoplanin antibodies and disodium cromolyn. BHK 21/C13 cell immunophenotype was assessed. RESULTS: Fibrosarcoma cells were positive for vimentin, CD117, smooth muscle actin, vascular endothelial growth factor epidermal growth factor receptor, homebox prospero gene 1 and negative for platelet-derived growth factor B, neuron-specific enolase, S100, CD34, Ewing sarcoma and podoplanin. CAM-grown fibrosarcomas were highly sensitive to disodium cromolyn and anti-podoplanin antibodies. CONCLUSION: Immunophenotyping BHK 21/C13 cells and their response to drugs represent the first step in revealing cell line utility and a reliable tool for experimental cancer research.


Assuntos
Membrana Corioalantoide/efeitos dos fármacos , Fibrossarcoma/tratamento farmacológico , Glicoproteínas de Membrana/antagonistas & inibidores , Proteínas de Neoplasias/genética , Animais , Anticorpos Anti-Idiotípicos/administração & dosagem , Linhagem Celular Tumoral , Embrião de Galinha , Membrana Corioalantoide/imunologia , Cricetinae , Cromolina Sódica/administração & dosagem , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Fibrossarcoma/genética , Fibrossarcoma/imunologia , Fibrossarcoma/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicoproteínas de Membrana/imunologia , Proteínas Proto-Oncogênicas c-kit/genética , Vimentina/genética
14.
Cancer Manag Res ; 10: 33-40, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29379318

RESUMO

Background/purpose: Lung cancer is a major stress factor for the affected individual, leading to psychological distress in over 50% of the diagnosed patients. Since coping styles describe different patterns in approaching serious problems, our study aimed at ascertaining if the diagnosis of lung cancer has an impact on the patient's coping styles and if there is a difference in psychical response among patients with different coping styles, as assessed by variance of anxiety and depression scores after diagnosis. Patients and methods: In this prospective study, a cohort of 50 patients were evaluated using the COPE scale, Generalized Anxiety Disorder Questionnaire 7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9), both prior to and 1 month after learning about their lung cancer diagnosis. The baseline and the final parameters were compared and stratified with respect to coping styles. Results: We observed that 1 month after learning the diagnosis, the patients had a significantly higher GAD-7 score (median score 12 vs 4 points; p<0.001). At the same time, the PHQ-9 score was significantly higher at the 1 month follow-up time-point (median score 16 vs 7; p=0.002). The increases in the anxiety scores were significant in patients with initial social support (13 vs 3; p=0.014) and avoidance coping style (14 vs 6; p=0.003). Regarding the depression scores, after the diagnosis, the only significant increase was observed in patients with initial avoidance coping style (18 vs 5; p=0.014). Conclusion: Our study demonstrates that patients who receive the diagnosis for cancer show a significant increase in anxiety and depression intensity. The most adaptive coping style turned out to be the problem-focused one while the least adaptive one was the avoidant style.

15.
Anticancer Res ; 38(2): 811-816, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29374706

RESUMO

BACKGROUND: Few data are available regarding the epithelial to mesenchymal transition (EMT) /mesenchymal to epitheilal transition (MET) in the liver metastasis of digestive cancers. The aim of this study was to establish EMT/MET metastatic tumor cell plasticity according to the histological growth pattern of liver metastases. MATERIALS AND METHODS: Biopsies from 25 patients with liver metastasis (desmoplastic, replacement and pushing type) were evaluated. Double immunostaining of E-cadherin/vimentin, keratin 8,18/vimentin and E-cadherin/ keratin 8,18 were performed. RESULTS: The following cell types were noted: epithelial, mesenchymal, non-differentiated and differentiated hybrid mesenchymal/ epithelial and non-hybrid phenotype. All cases had mesenchymal/ epithelial phenotype cells. A significant correlation was found between the non-differentiated hybrid mesenchymal/ epithelial phenotype metastatic cells and histological growth pattern for gastric and colorectal cancer. CONCLUSION: A MET-targeting strategy, in conjunction with conventional chemotherapy, may be useful for the treatment of liver metastases.


Assuntos
Neoplasias do Sistema Digestório/patologia , Neoplasias Hepáticas/secundário , Antígenos CD , Caderinas/metabolismo , Plasticidade Celular/fisiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias do Sistema Digestório/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Imuno-Histoquímica , Queratinas/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Vimentina/metabolismo
16.
In Vivo ; 32(1): 79-83, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29275302

RESUMO

BACKGROUND: Angiogenesis plays a pivotal role in tumor development. Although microvessel density (MVD) is the most common method used for evaluation of angiogenesis, it has several limitations. Our aim was to evaluate MVD and microvessel proliferation (MVP) in a series of invasive breast carcinomas and analyze whether angiogenesis is influenced by the molecular phenotype of each tumor. MATERIALS AND METHODS: We examined vascular proliferation using double immunohistochemistry (CD34/Ki67) in a series of 54 invasive breast carcinomas and compared the results with standard MVD, molecular subtypes and other classical parameters. RESULTS: Increased MVD and MVP values were recorded in basal-like subtype, but only the MVP value reached significance among this group of patients (p=0.0001). For all cases combined, increased MVP was significantly correlated with negative estrogen receptor (ER) status (p=0.010) and higher histological grade (p=0.002). CONCLUSION: MVP more accurately reflects the state of angiogenesis in breast cancer, compared with standard MVD. Vascular proliferation was associated with aggressive tumor features, indicating its contribution to tumor progression. The strong association between vascular proliferation and basal-like tumors suggests that this marker can be used for stratification of patients who might benefit from therapies targeting angiogenesis.


Assuntos
Neoplasias da Mama/metabolismo , Proliferação de Células , Microvasos/metabolismo , Neovascularização Patológica/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/metabolismo , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/classificação , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Microvasos/patologia , Pessoa de Meia-Idade , Prognóstico
17.
Anticancer Res ; 38(1): 259-263, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29277781

RESUMO

BACKGROUND/AIM: Probably due to their low occurrence, chromophobe and papillary renal cell carcinomas are less well characterized and, currently, there are no reliable prognostic markers for this group of patients. Moreover, the optimal therapy for patients with non-clear renal cell carcinoma (RCC) is unknown yet. Although elevated levels of Galectin-3 (Gal-3) were associated with poor prognosis in conventional RCC, the impact of this protein on carcinogenesis of chromophobe and papillary entities has not been previously described. MATERIALS AND METHODS: Gal-3 expression was investigated in 34 consecutive cases of RCCs, including 19 papillary carcinomas and 15 chromophobe carcinomas. RESULTS: Immunohistochemical analysis of Gal-3 in tumor cells showed 3 patterns of expression: membranous, cytoplasmic and nuclear staining. Most tumors included in our study showed a cytoplasmic expression and it was almost equally distributed between the histologic subtypes. However, only nuclear staining of Gal-3 was associated with both Fuhrman grade and tumor stage (p=0.016 and p=0.032, respectively) in chromophobe subtype. CONCLUSION: Our results indicate that the nuclear expression of Gal-3 has an essential role in the development of chromophobe carcinoma. The association with advanced tumor stage and nuclear grade suggests that this protein is an indicator of aggressiveness in the chromophobe subtype, thus targeting anti-nuclear transport may prove an effective therapy for this particular group of patients.


Assuntos
Carcinoma Papilar/metabolismo , Carcinoma de Células Renais/metabolismo , Galectina 3/metabolismo , Neoplasias Renais/metabolismo , Adulto , Idoso , Carcinoma Papilar/patologia , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias
18.
In Vivo ; 31(6): 1139-1144, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29102936

RESUMO

BACKGROUND/AIM: To analyze the interaction between the human mesenchymal stem cells (hMSC) and the chick embryo chorioallantoic membrane (CAM), in order to assess the still obscure process of vasculogenesis. MATERIALS AND METHODS: We implanted hMSC onto CAM and we analyzed the morphology and the immunohistochemical profile of CAM. RESULTS: hMSC adhered to CAM, few of them entered the chorionic epithelium and the mesoderm and developed a CD44-/Ki67- status. hMSC stimulated the CAM mesenchymal cells (cMSC) to acquire endothelial and pericyte-like features and to generate cord/capillary-like structures (CLS) in the chorionic epithelium and the mesoderm, but they also entered these structures (CD34+/SMA (smooth muscle actin)+ hMSC). Simultaneously, hMSC induced a process of sprouting angiogenesis in the mesoderm, CD105+ hMSC being identified in the proximity of the angiogenic areas. CONCLUSION: hMSC and CAM establish a genuine hotspot of vasculogenesis, which may evolve to a valuable experimental model for this research field.


Assuntos
Adesão Celular/genética , Diferenciação Celular/genética , Membrana Corioalantoide/crescimento & desenvolvimento , Neovascularização Fisiológica/genética , Animais , Antígenos CD34/genética , Linhagem da Célula/genética , Embrião de Galinha , Membrana Corioalantoide/metabolismo , Endoglina/genética , Epitélio/crescimento & desenvolvimento , Epitélio/metabolismo , Humanos , Receptores de Hialuronatos/genética , Antígeno Ki-67/genética , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Mesoderma/crescimento & desenvolvimento , Mesoderma/metabolismo
19.
Anticancer Res ; 37(9): 4935-4942, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28870915

RESUMO

BACKGROUND/AIM: To assess the concordance between IHC and FISH and its influence on tumor type, grade and lympho-vascular invasion (LVI). MATERIALS AND METHODS: HER2 immunohistochemistry (IHC) to 45 cases of bladder carcinoma, followed by fluorescent in situ hybridization (FISH) were applied. RESULTS: 31.12% cases were IHC positive. Less than 35% of HER2-negative cases presented LVI and this percent increased to 54.54% for +1 HER2 cases. LVI increases up to 57.14% for +2 HER2 cases and slightly decreased for +3 HER2 cases to 42.85%. IHC/FISH concordance was found for 73.34% cases but 31.57% were previously negative and 36.36% scored as +1 by IHC had gene amplification as shown by FISH analysis. T3 was correlated with HER2-IHC (p=0.05) and HER2-FISH (p=0.01). CONCLUSION: Improved HER2 assessement is needed for urothelial carcinomas. HER2-IHC scored as 0-2 should be validated by and reclassified according to FISH analysis.


Assuntos
Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Diagnóstico Diferencial , Amplificação de Genes , Humanos , Técnicas Imunoenzimáticas , Hibridização in Situ Fluorescente , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
20.
Cancer Genomics Proteomics ; 14(5): 383-387, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28871005

RESUMO

BACKGROUND: Podoplanin (PDPN), a mucin-type transmembrane glycoprotein, is expressed in a variety of human cancer types, and contributes to tumor progression. Our goal was to evaluate PDPN expression in hepatocellular carcinoma (HCC) using both immunohistochemistry (IHC) and RNAscope in situ hybridization. MATERIALS AND METHODS: Twenty patients with HCC who underwent partial hepatectomy with curative intent were retrospectively analyzed. RESULTS: IHC gave positive results in 11 cases, while RNAscope assay for PDPN detected amplification in 16 cases. A significant association was noted between PDPN protein expression and histological tumor grade (p=0.036). Four cases that had negative PDPN results by RNAscope were also negative by IHC, while the remaining five cases with negative results by IHC were positive by RNAscope. A positive relationship was found between PDPN mRNA protein expression (p<0.001). CONCLUSION: Our preliminary results suggest that PDPN contributes to the malignant potential of HCC. RNAscope proved to be a more sensitive and reliable method than IHC in PDPN detection.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica/métodos , Neoplasias Hepáticas/genética , Glicoproteínas de Membrana/genética , RNA Neoplásico/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
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