Asunto(s)

Células Epitelioides/patología , Neoplasias , Proteína con Dedos de Zinc GLI1/análisis , Biomarcadores de Tumor/análisis , Niño , Femenino , Humanos , Neoplasias/clasificación , Neoplasias/metabolismo , Neoplasias/patología , Fusión de Oncogenes , Dedos del Pie/patología

RESUMEN

BACKGROUND: Glioma-associated oncogene homolog 1(GLI1) expression correlates with the clinical significance and prognosis of several cancers. However, the evaluation of the role GLI1 expression plays in pancreatic ductal adenocarcinoma (PDAC) clinicopathological features and outcomes still lacks. OBJECTIVE: The present study systemic reviewed the association of GLI1 expression and clinical significance as well as patients survival in PDAC. METHODS: We systematically searched the database of The Cochrane Library, PubMed, Embase, CNKI, Weipu data, and Wanfang data according to the inclusion and exclusion criteria. (The search ended on January 1, 2019; no language restrictions). The Newcastle-Ottawa Scale (NOS) scale was implemented to assess the quality of the literature and the Review Manager 5.3 Software was used to conduct a meta-analysis. Finally, 9 studies, a total of 1058 patients, have been included. RESULTS: GLI1 is more likely expressed in PDAC tissue rather than para-carcinoma tissue (OR = 2.86, 95%CI = 1.87-4.36, P < .00001). GLI1 expression is associated with the TNM stage (OR = 3.11, 95%CI = 2.01-4.79, P < .00001), perineural invasion (OR = 2.50, 95%CI = 1.28-4.91, P = .008), and lymphatic metastasis (OR = 2.73, 95%CI = 1.71-4.36, P < .0001). But the association with differentiation (OR = 1.20, 95%CI = 0.74-1.96, P = .46) and tumor size (OR = 2.41, 95%CI = 0.97-6.00, P = .06) was not significant. GLI1 expression is related to the worse overall survival in PDACs (HR = 1.68, 95%CI = 1.40-2.02, P < .00001). CONCLUSION: Positive GLI1 expression promotes the progression and metastasis of PDACs and plays an important role in the clinical significance and the patients survival.

Asunto(s)

Carcinoma Ductal Pancreático/enzimología , Pronóstico , Proteína con Dedos de Zinc GLI1/análisis , Adenocarcinoma/enzimología , Adenocarcinoma/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Carcinoma Ductal Pancreático/genética , Humanos

RESUMEN

BACKGROUND: Gastric Cancer (GC) is a frequently common malignancy. Recent studies have reported Rab1A as an activator of mTORC1, and the mTOR1 pathway is involved in regulating Gli1 expression in several cancers. Only a few studies have been performed to explore the relationship between Rab1A and p-S6K/Gli1in GC. METHODS: Immunohistochemistry (IHC) was performed to explore the association of Rab1A/p-S6K/Gli1 expression and prognosis in 117 GC tissue samples and adjacent normal tissues. RESULTS: Our results indicated that Rab1A/p-S6K/Gli1 was significantly overexpressed in GC tissues. High expression of Rab1A was closely related to the tumor size and the depth of tumor invasion. In addition, Rab1A expression was closely related with p-S6K/Gli1 expression in GC, and high level of Rab1A/p-S6K/Gli1 caused worse prognosis of GC patients. The univariate and multivariate analysis indicated that the expression of Rab1A was an independent prognostic factor. Moreover, both high Rab1A and p-S6K expression led to a worse prognosis when compared to a single positive expression as well as both high Rab1A/Gli1 expression also led to a worse prognosis than the single positive expression of Rab1A/Gli1. Strikingly, the overexpression of p-S6K also led to a worse prognosis in Rab1A positive patients, as did Gli1. CONCLUSION: Our results indicate that Rab1A/mTOR/S6K/Gli1 axis played a crucial role in GC, which may provide a novel field on targeted therapy of GC, especially for mTORC1-targeted therapy-resistant cancers.

Asunto(s)

Proteínas Quinasas S6 Ribosómicas/biosíntesis , Neoplasias Gástricas/diagnóstico , Proteína con Dedos de Zinc GLI1/biosíntesis , Proteínas de Unión al GTP rab1/biosíntesis , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Quinasas S6 Ribosómicas/análisis , Proteínas Quinasas S6 Ribosómicas/metabolismo , Neoplasias Gástricas/metabolismo , Proteína con Dedos de Zinc GLI1/análisis , Proteína con Dedos de Zinc GLI1/metabolismo , Proteínas de Unión al GTP rab1/análisis , Proteínas de Unión al GTP rab1/metabolismo

RESUMEN

Overactivation of the Hedgehog (HH) signaling pathway is implicated in many cancers. In this study, we demonstrate that the small molecule RITA, a p53 activator, effectively downregulates HH signaling in human medulloblastoma and rhabdomyosarcoma cells irrespective of p53. This is mediated by a ROS-independent activation of the MAP kinase JNK. We also show that in vitro RITA sensitized cells to the GLI antagonist GANT61, as co-administration of the two drugs had more pronounced effects on cell proliferation and apoptosis. In vivo administration of RITA or GANT61 suppressed rhabdomyosarcoma xenograft growth in nude mice; however, co-administration did not further enhance tumor suppression, even though cell proliferation was decreased. RITA was more potent than GANT61 in downregulating HH target gene expression; surprisingly, this suppressive effect was almost completely eliminated when the two drugs were administered together. Notably, RNA-seq demonstrated a broader response of pathways involved in cancer cell growth in the combination treatment, providing a plausible interpretation for tumor reduction in the absence of HH signaling downregulation.

Asunto(s)

Antineoplásicos/farmacología , Neoplasias Cerebelosas/tratamiento farmacológico , Furanos/farmacología , Proteínas Hedgehog/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Meduloblastoma/tratamiento farmacológico , Rabdomiosarcoma/tratamiento farmacológico , Proteína p53 Supresora de Tumor/metabolismo , Proteína con Dedos de Zinc GLI1/metabolismo , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Cerebelosas/enzimología , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/patología , Femenino , Proteínas Hedgehog/genética , Humanos , Meduloblastoma/enzimología , Meduloblastoma/genética , Meduloblastoma/patología , Ratones Desnudos , Piridinas/farmacología , Pirimidinas/farmacología , Rabdomiosarcoma/enzimología , Rabdomiosarcoma/genética , Rabdomiosarcoma/patología , Transducción de Señal/efectos de los fármacos , Carga Tumoral/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína con Dedos de Zinc GLI1/análisis , Proteína con Dedos de Zinc GLI1/genética

RESUMEN

Colorectal cancer (CRC) is one of the most common cancers worldwide. Recent studies have reported that PI3K/AKT/mTOR pathway regulated the GLI1 expression level via SMO-independent pathway in a variety of tumor types. We detected the expression level of GLI1/p-S6K in CRC tissues. We found the expression of GLI1/p-S6K was apparently close with lymph node metastasis and TNM stage and patients with positive GLI1/p-S6K expression had shorter survival time and patients with both GLI1 and p-S6K positive expression had an even worse overall survival than those with single positive expression. Moreover, GLI1 and p-S6K expression was considered to be independent prognostic factors in CRC patient and the positive co-expression of GLI1/p-S6K had greater influence than single expression positive on the prognosis of postoperative patients with tumor size≥5 cm, well differentiation, positive lymph node metastasis, venous invasion, neural invasion and TNM III-IV. Meanwhile, the GLI1/p-S6K expression had impact on more clinicopathologic features in colon-side carcinoma than in rectum-side carcinoma and the mTOR/S6K/GLI1 axis played an important role in CRC especially in advanced stage. Hence, further studies are underway to explore the molecular mechanism between GLI1 and p-S6K in CRC, and in addition, it offers novel facilities for molecular targeting therapy for CRC.

Asunto(s)

Neoplasias Colorrectales/patología , Proteínas Quinasas S6 Ribosómicas/análisis , Proteína con Dedos de Zinc GLI1/análisis , Biomarcadores de Tumor/análisis , Colon/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Recto/patología , Análisis de Supervivencia

RESUMEN

OBJECTIVE: To investigate the abnormal expression of sonic hedgehog (SHH) signaling molecules in 52 eutopic endometrial tissues and its diagnostic potency in endometriosis. DESIGN: Retrospective study. SETTING: University hospital. PATIENT(S): Twenty-six women with histologically confirmed endometriosis and 26 women with histologically normal endometria who were undergoing curettage or hysterectomy were selected. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The mRNA and protein levels of molecules in the SHH signaling pathway. RESULT(S): The levels of SHH, smoothened, GLI family zinc finger 3, and its downstream signaling transcription factor (GLI1) not only were upregulated in the eutopic endometrium of endometriosis compared with the control endometrium, but also independently predicted the onset and severity of the disease. CONCLUSION(S): This study is the first to reveal differences in the activation of the SHH signaling pathway between women with and without endometriosis and suggests that the SHH signaling pathway has potential in the diagnosis of endometriosis.

Asunto(s)

Endometriosis/diagnóstico , Endometrio/química , Proteínas Hedgehog/análisis , Proteínas del Tejido Nervioso/análisis , Transducción de Señal , Receptor Smoothened/análisis , Proteína con Dedos de Zinc GLI1/análisis , Proteína Gli3 con Dedos de Zinc/análisis , Adulto , Biomarcadores/análisis , Biopsia , Endometriosis/genética , Endometriosis/metabolismo , Endometriosis/patología , Endometrio/patología , Femenino , Proteínas Hedgehog/genética , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Valor Predictivo de las Pruebas , ARN Mensajero/análisis , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Índice de Severidad de la Enfermedad , Receptor Smoothened/genética , Regulación hacia Arriba , Proteína con Dedos de Zinc GLI1/genética , Proteína Gli3 con Dedos de Zinc/genética

RESUMEN

Activation of the Hedgehog (HH) signaling pathway plays a critical role in the development of basal cell carcinoma (BCC). HH signaling activity is produced by nuclear translocation of transcription factors, glioma-associated oncogene homolog (GLI). Among three GLI subfamilies, GLI1 is the only full-length transcriptional activator, and its nuclear localization is recognized as a signature event in HH signaling activation. However, limited published work has investigated the nuclear staining of GLI1 protein in human tumor tissue samples by immunohistochemical analysis. In this study, we performed immunohistochemical staining of GLI1 in 382 cases of cutaneous epithelial tumors, including 196 BCC cases, using rabbit monoclonal antihuman GLI1 antibody (C68H3). As a result, 98.2% cases of BCC showed a diffuse and strong nuclear staining pattern regardless of the histological subtype. Positive staining was mainly restricted to the tumor nests, while the overlying epidermis was negative suggesting specificity of the antibody. In further analysis of other cutaneous epithelial tumors, 100% (4/4) cases of trichoblastoma, 15.1% (5/33) Bowen's disease, 3.5% (1/28) actinic keratosis and 12.5% (4/32) squamous cell carcinoma showed the nuclear staining pattern of GLI1. This suggested that HH signaling is also dysregulated in some other cutaneous malignant tumors. In conclusion, the C68H3 antibody is a useful tool for revealing activation of HH signaling in immunohistochemical analysis.

Asunto(s)

Enfermedad de Bowen/patología , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Transducción de Señal/genética , Neoplasias Cutáneas/patología , Proteína con Dedos de Zinc GLI1/análisis , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Bowen/genética , Carcinoma Basocelular/genética , Carcinoma de Células Escamosas/genética , Núcleo Celular/metabolismo , Epidermis/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas Hedgehog/metabolismo , Humanos , Inmunohistoquímica/métodos , Queratosis Actínica/patología , Queratosis Seborreica/patología , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Neoplasias Cutáneas/genética , Proteína con Dedos de Zinc GLI1/metabolismo

RESUMEN

BACKGROUND: The hedgehog (Hh) signaling pathway plays important roles in cell proliferation, malignant progression, invasion and metastasis, and the expansion of cancer stem cells (CSCs). Comprehensive immunohistochemical (IHC) analyses have not yet been conducted on the expression levels of Hh signaling molecules in breast cancer tissues. METHODS: A total of 204 patients with invasive breast cancer treated in our institute were study subjects. IHC analyses on the expression levels of the Hh signaling molecules, sonic Hh (SHH), PTCH1, GLI1, GLI2, and GLI3 and the CSC-related factor, SOX2, were investigated. RESULTS: Positive correlations were observed among all of the Hh signaling molecules tested. SOX2 expression correlated with the expression levels of all Hh signaling molecules. SHH expression positively correlated with tumor size, the Ki-67 labeling index, histological grade, estrogen receptor negativity, progesterone receptor negativity, and HER2 positivity. GLI1 expression positively correlated with the histological grade. GLI2 expression positively correlated with the histological grade, Ki-67 labeling index, and HER2 positivity. Univariate analyses revealed that a younger age, larger tumor size, positive lymph node metastasis, higher histological grade, positive lymphatic invasion, and higher Ki-67 labeling index were related to poor relapse-free survival (RFS). The positivity of all Hh signaling molecules and SOX2 did not correlate with poor RFS. A multivariate analysis revealed that positive lymphatic invasion and a younger age were independent worse prognostic factors for RFS. CONCLUSIONS: This comprehensive analysis demonstrated for the first time that SHH, GLI1, and GLI2 expression levels positively correlated with the malignant phenotypes of tumor cells.

Asunto(s)

Neoplasias de la Mama/química , Proteínas Hedgehog/análisis , Proteínas Nucleares/análisis , Proteína con Dedos de Zinc GLI1/análisis , Proteína Gli2 con Dedos de Zinc/análisis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Factores de Transcripción SOXB1/análisis , Transducción de Señal

RESUMEN

Glioma-associated oncogene homolog 1 (Gli1) maintains the cancer stem cell-like characteristics in various tumors. However, its expression in cancer stem cells (CSC) in ductal breast carcinoma has not been well studied. We aimed to characterize Gli1 as a potential CSC marker and investigate its clinical significance in ductal breast carcinoma. Immunohistochemical staining was used to study the relationship of Gli1 to clinicopathologic features, cell cycle regulation-related genes, and CSC markers. Gli1 was expressed to a greater extent in ductal breast carcinoma than in normal breast tissues (P=.002). Its expression was significantly correlated with tumor grade (P=.044), pT stage (P=.017), and molecular subtype (P=.008). Expression was associated, not only with the expression of HIF-1α (P<.001), but also with greater microvessel density (MVD; P=.012). Kaplan-Meier survival analysis revealed that Gli1 was significantly associated with lower overall survival (OS; P=.02). Univariate Cox regression analysis confirmed that Gli1 was a poor prognostic factor for OS (P=.037) and was associated with the expression of the cell cycle-related genes cyclin D1 (P=.011), p21 (P=.009), and pAkt-Thr308 (P=.038). Moreover, Gli1 expression correlated significantly with the expression of two CSC markers, Sox2 (P=.01) and LSD1 (P=.01). Gli1 could be a stem cell marker and an indicator of poor prognosis in patients with ductal breast carcinoma.

Asunto(s)

Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Carcinoma Ductal de Mama/química , Células Madre Neoplásicas/química , Proteína con Dedos de Zinc GLI1/análisis , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/terapia , Proteínas de Ciclo Celular/análisis , Distribución de Chi-Cuadrado , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Estadificación de Neoplasias , Células Madre Neoplásicas/patología , Neovascularización Patológica , Fosforilación , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-akt/análisis , Factores de Riesgo

RESUMEN

BACKGROUND: Predictive biomarkers or signature(s) for oesophageal cancer (OC) patients undergoing preoperative therapy could help administration of effective therapy, avoidance of ineffective ones, and establishment new strategies. Since the hedgehog pathway is often upregulated in OC, we examined its transcriptional factor, Gli-1, which confers therapy resistance, we wanted to assess Gli-1 as a predictive biomarker for chemoradiation response and validate it. METHODS: Untreated OC tissues from patients who underwent chemoradiation and surgery were assessed for nuclear Gli-1 by immunohistochemistry and labelling indices (LIs) were correlated with pathologic complete response (pathCR) or

Asunto(s)

Adenocarcinoma/química , Adenocarcinoma/terapia , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/terapia , Núcleo Celular/química , Quimioradioterapia Adyuvante , Neoplasias Esofágicas/química , Neoplasias Esofágicas/terapia , Proteína con Dedos de Zinc GLI1/análisis , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Sistemas CRISPR-Cas , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos , Métodos Epidemiológicos , Neoplasias Esofágicas/patología , Esofagectomía , Femenino , Edición Génica , Proteínas Hedgehog/análisis , Proteínas Hedgehog/genética , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , ARN Mensajero/metabolismo , Tolerancia a Radiación , Proteína con Dedos de Zinc GLI1/antagonistas & inhibidores , Proteína con Dedos de Zinc GLI1/genética

RESUMEN

The paper presents an example of differential diagnostic studies for pyogenic granuloma and oral squamous cell carcinoma (SCC). In the described case immunohistochemistry with antibodies to Ki-67 and Gli1 was used as conventional histological procedure proved to be inconvenient for adequate diagnostics. The immunohistochemical study established increased proliferative activity of epithelial cells specific both pyogenic granuloma and oral SCC, but intensive Gli1 protein expression in membranes and cytoplasm of epithelial cells with malignant transformation allowed differentiation of these neoplasms.

Asunto(s)

Carcinoma de Células Escamosas/diagnóstico , Granuloma Piogénico/diagnóstico , Antígeno Ki-67/análisis , Neoplasias de la Boca/diagnóstico , Proteína con Dedos de Zinc GLI1/análisis , Anticuerpos/inmunología , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Membrana Celular/química , Transformación Celular Neoplásica/química , Transformación Celular Neoplásica/patología , Diagnóstico Diferencial , Granuloma Piogénico/patología , Humanos , Inmunohistoquímica , Antígeno Ki-67/inmunología , Mucosa Bucal/química , Mucosa Bucal/patología , Neoplasias de la Boca/química , Neoplasias de la Boca/patología , Proteína con Dedos de Zinc GLI1/inmunología

RESUMEN

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that mostly occurs in the elderly. Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of MCCs and is associated with carcinogenesis. Hedgehog signaling pathway plays a role in human embryogenesis and organogenesis. In addition, reactivation of this pathway later in life can cause tumors. Twenty-nineMCPyV-positive and 21 MCPyV-negative MCCs were immunohistochemically stained with primary antibodies for hedgehog signaling (SHH, IHH, PTCH1, SMO, GLI1, GLI2, and GLI3) and evaluated using H-score. Polymerase chain reaction and sequence analysis for SHH and GLI1 exons were also performed. Expression of SHH was higher in MCPyV-positive MCCs than in MCPyV-negative MCCs (P<.001). Higher expression of GLI1, MCPyV infection, male sex, and Japanese ethnicity were associated with better overall survival (P=.034, P=.001, P=.042, and P=.036, respectively). Higher expression of SHH and MCPyV infection were associated with improved MCC-specific survival (P=.037 and P=.002, respectively). The mutation analysis of prognosis-related GLI1 and SHH genes in our study revealed a low frequency of mutations in the 10 exons examined, except GLI1 exon 5 (18/22 cases), all having the same silent mutation of c.576G>A. Only 2 mutations with amino acid changes were detected in MCPyV-negative MCCs only: 1 missense mutation in GLI1 exon 4 and 1 nonsense mutation in SHH-3B. Expression of SHH and GLI1 may be useful prognostic markers of MCC because increased expression was associated with better prognosis. The high rate of c.576G>A silent mutation in GLI1 exon 5 was a feature of MCC.

Asunto(s)

Carcinoma de Células de Merkel/química , Carcinoma de Células de Merkel/virología , Proteínas Hedgehog/análisis , Poliomavirus de Células de Merkel/aislamiento & purificación , Transducción de Señal , Neoplasias Cutáneas/química , Neoplasias Cutáneas/virología , Proteína con Dedos de Zinc GLI1/análisis , Biomarcadores de Tumor/genética , Carcinoma de Células de Merkel/genética , Carcinoma de Células de Merkel/patología , Transformación Celular Viral , Análisis Mutacional de ADN , Exones , Femenino , Proteínas Hedgehog/genética , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Pronóstico , Factores de Riesgo , Mutación Silenciosa , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Proteína con Dedos de Zinc GLI1/genética

RESUMEN

BACKGROUND: Several evidences suggest a marked angiogenic dependency in triple-negative breast cancer (TNBC) tumorigenesis and a potential sensitivity to anti-angiogenic agents. Herein, the putative role of Hedgehog (Hh) pathway in regulating TNBC-dependent angiogenesis was investigated. METHODS: Expression and regulation of the Hh pathway transcription factor glioma-associated oncogene homolog1 protein (GLI1) were studied on the endothelial compartment and on TNBC-initiated angiogenesis. To evaluate the translational relevance of our findings, the combination of paclitaxel with the Smo inhibitor NVP-LDE225 was tested in TNBC xenografted mice. RESULTS: Tissue microarray analysis on 200 TNBC patients showed GLI1 overexpression paired with vascular endothelial growth factor receptor 2 (VEGFR2) expression. In vitro, Hh pathway promotes TNBC progression in an autocrine manner, regulating the VEGF/VEGFR2 loop on cancer cell surface, and in a paracrine manner, orchestrating tumour vascularisation. These effects were counteracted by Smo pharmacological inhibition. In TNBC xenografted mice, scheduling NVP-LDE225 rather than bevacizumab provided a better sustained inhibition of TNBC cells proliferation and endothelial cells organisation. CONCLUSIONS: This study identifies the Hh pathway as one of the main regulators of tumour angiogenesis in TNBC, thus suggesting Hh inhibition as a potential new anti-angiogenic therapeutic option to be clinically investigated in GLI1 overexpressing TNBC patients.

Asunto(s)

Proteínas Hedgehog/metabolismo , Neovascularización Patológica/metabolismo , Transducción de Señal , Neoplasias de la Mama Triple Negativas/metabolismo , Proteína con Dedos de Zinc GLI1/genética , Proteína con Dedos de Zinc GLI1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/farmacología , Compuestos de Bifenilo/administración & dosificación , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Células Endoteliales/efectos de los fármacos , Femenino , Silenciador del Gen , Proteínas Hedgehog/antagonistas & inhibidores , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células MCF-7 , Proteínas de la Membrana , Ratones , Ratones Desnudos , Persona de Mediana Edad , Trasplante de Neoplasias , Neovascularización Patológica/tratamiento farmacológico , Paclitaxel/administración & dosificación , Piridinas/administración & dosificación , ARN Mensajero/metabolismo , Trombospondina 1/genética , Trombospondina 1/metabolismo , Análisis de Matrices Tisulares , Transfección , Neoplasias de la Mama Triple Negativas/química , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/análisis , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven , Proteína con Dedos de Zinc GLI1/análisis