RESUMO
AIMS AND BACKGROUND: The aims of this study were to investigate the correlation between topoisomerase II alpha (TOP2A), microtubule-associated protein-tau (MAP-tau) and other prognostic factors in breast cancer and to evaluate the predictive value of TOP2A and MAP-tau in breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy. METHODS AND STUDY DESIGN: Seventy patients with axillary lymph node positive breast cancer who underwent curative surgery between January 2000 and December 2005 were evaluated retrospectively. The levels of protein expression of TOP2A and MAP-tau were assessed using immunohistochemistry. RESULTS: Among the 70 patients, 43 (61.4%) showed TOP2A overexpression and 30 (42.9%) showed MAP-tau positivity. TOP2A overexpression was associated with p53 positivity and high histological grade. MAP-tau positivity was associated with a lower positive lymph node ratio, lower proliferative activity, and hormone receptor positivity. Based on the TOP2A and MAP-tau expression, there was no significant difference in disease-free survival in the breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy. CONCLUSIONS: We conclude that immunohistochemical analysis of TOP2A and MAP-tau protein expression may not predict the benefits of adjuvant anthracycline and taxane chemotherapy in axillary node positive breast cancer.
Assuntos
Antígenos de Neoplasias/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/patologia , DNA Topoisomerases Tipo II/análise , Proteínas de Ligação a DNA/análise , Linfonodos/patologia , Proteínas tau/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/administração & dosagem , Axila , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama Masculina/química , Neoplasias da Mama Masculina/patologia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/química , Carcinoma Lobular/patologia , Carcinoma Medular/química , Carcinoma Medular/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Proteínas de Ligação a Poli-ADP-Ribose , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do Tratamento , Regulação para CimaRESUMO
Human mesenchymal stem cells (MSCs) communicate with other cells in the human body and appear to "home" to areas of injury in response to signals of cellular damage, known as homing signals. This review of the state of current research on homing of MSCs suggests that favorable cellular conditions and the in vivo environment facilitate and are required for the migration of MSCs to the site of insult or injury in vivo. We review the current understanding of MSC migration and discuss strategies for enhancing both the environmental and cellular conditions that give rise to effective homing of MSCs. This may allow MSCs to quickly find and migrate to injured tissues, where they may best exert clinical benefits resulting from improved homing and the presence of increased numbers of MSCs.
RESUMO
A number of studies have postulated that efficiency in mammalian cloning is inversely correlated with donor cell differentiation status and may be increased by using undifferentiated cells as nuclear donors. Here, we attempted the recloning of dogs by nuclear transfer of canine adipose tissue-derived mesenchymal stem cells (cAd-MSCs) from a transgenic cloned beagle to determine if cAd-MSCs can be a suitable donor cell type. In order to isolate cAd-MSCs, adipose tissues were collected from a transgenic cloned beagle produced by somatic cell nuclear transfer (SCNT) of canine fetal fibroblasts modified genetically with a red fluorescent protein (RFP) gene. The cAd-MSCs expressed the RFP gene and cell-surface marker characteristics of MSCs including CD29, CD44 and thy1.1. Furthermore, cAd-MSCs underwent osteogenic, adipogenic, myogenic, neurogenic and chondrogenic differentiation when exposed to specific differentiation-inducing conditions. In order to investigate the developmental potential of cAd-MSCs, we carried out SCNT. Fused-couplets (82/109, 75.2%) were chemically activated and transferred into the uterine tube of five naturally estrus-synchronized surrogates. One of them (20%) maintained pregnancy and subsequently gave birth to two healthy cloned pups. The present study demonstrated for the first time the successful production of cloned beagles by nuclear transfer of cAd-MSCs. Another important outcome of the present study is the successful recloning of RFP-expressing transgenic cloned beagle pups by nuclear transfer of cells derived from a transgenic cloned beagle. In conclusion, the present study demonstrates that adipose stem cells can be a good nuclear donor source for dog cloning.
Assuntos
Tecido Adiposo/citologia , Células-Tronco Adultas/fisiologia , Animais Geneticamente Modificados , Clonagem de Organismos/métodos , Clonagem de Organismos/veterinária , Cães , Células-Tronco Adultas/citologia , Animais , Animais Recém-Nascidos , Diferenciação Celular/fisiologia , Células Cultivadas , Cães/genética , Transferência Embrionária/veterinária , Feminino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Técnicas de Transferência Nuclear/veterinária , Gravidez , Taxa de GravidezRESUMO
Adipose tissue-derived mesenchymal stem cells (AdMSCs) represent an attractive and ethical cell source for stem cell therapy. With the recent demonstration of MSC homing properties, intravenous applications of MSCs to cell-damaged diseases have increased. In the present study, the toxicity and tumorigenicity of human AdMSCs (hAdMSCs) were investigated for clinical application. Culture-expanded hAdMSCs showed the typical appearance, immunophenotype, and differentiation capacity of MSCs, and were genetically stable at least 12 passages in culture. Cells suspended in physiological saline maintained their MSC properties in a cold storage condition for at least 3 days. To test the toxicity of hAdMSCs, different doses of hAdMSCs were injected intravenously into immunodeficient mice, and the mice were observed for 13 weeks. Even at the highest cell dose (2.5×10(8) cells/kg body weight), the SCID mice were viable and had no side effects. A tumorigenicity test was performed in Balb/c-nu nude mice for 26 weeks. Even at the highest cell dose (2×10(8) MSCs/kg), no evidence of tumor development was found. In a human clinical trial, 8 male patients who had suffered a spinal cord injury >12 months previous were intravenously administered autologous hAdMSCs (4×10(8) cells) one time. None of the patients developed any serious adverse events related to hAdMSC transplantation during the 3-month follow-up. In conclusion, the systemic transplantation of hAdMSCs appears to be safe and does not induce tumor development.
Assuntos
Tecido Adiposo , Infusões Intravenosas , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Traumatismos da Medula Espinal/terapia , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Adulto , Animais , Antígenos de Superfície , Testes de Carcinogenicidade , Diferenciação Celular , Feminino , Humanos , Cariótipo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos SCID , Pessoa de Meia-Idade , NeoplasiasRESUMO
The HOX family of genes plays a fundamental role in the morphogenesis of vertebrate embryonic cells. HOX genes are thought to be important for the regulation of stem cells. We investigated HOX gene expression in mesenchymal stem cells (MSCs) from human placentas. We isolated MSCs from human placentas and confirmed stemness by fluorescence-activated cell sorting (FACS) analysis and differentiation studies. Using reverse transcription PCR, mRNA expression of 39 Class I HOX genes was measured in the MSCs. The expression of HOXB6, C4, C8, C10, D3, D4, and D10 were measured by Western blot analysis. HOXC10 was expressed in 10 of 10 amnion-derived MSCs but in only 2 of 10 decidua-derived MSCs. HOXC4 and D10 were expressed in 100% of both amnion-derived MSCs and deciduas-derived MSCs. HOXD4 was silent in all amnion-derived MSCs and deciduas-derived MSCs (n = 10). HOX gene activation patterns might be a useful indicator for the detection of MSCs of different tissue origins. We demonstrated that HOXC10 is a gene that may discriminate between amnion-derived MSCs and decidua-derived MSCs.