Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 49
Filtrar
2.
Curr Med Chem ; 31(28): 4534-4548, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38361349

RESUMEN

BACKGROUND: Cholangiocarcinoma (CCA) has a poor prognosis and only limited palliative treatment options. The deficiency of adiponectin and adenosine monophosphate-activated protein kinase (AMPK) signaling was reported in several malignancies, but the alteration of these proteins in CCA is still unclear. OBJECTIVES: This study aimed to assess the role of adiponectin and AMPK signaling in CCA. Furthermore, AdipoRon, a novel adiponectin receptor (AdipoR) agonist, was evaluated in vitro and in vivo as a new anti-tumor therapy for CCA. METHODS: The expression of AdipoR1 and p-AMPKα in human tissue microarrays (TMAs) was evaluated by immunohistochemistry staining (IHC). The effect of 2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide (AdipoRon) was investigated in vitro with proliferation, crystal violet, migration, invasion, colony formation, senescence, cell cycle and apoptosis assays and in vivo using a CCA engineered mouse model (AlbCre/LSL-KRASG12D/p53L/L). RT-qPCR and western blot methods were applied to study molecular alterations in murine tissues. RESULTS: AdipoR1 and p-AMPKα were impaired in human CCA tissues, compared to adjacent non-tumor tissue. There was a positive correlation between the AdipoR1 and p-AMPKα levels in CCA tissues. Treatment with AdipoRon inhibited proliferation, migration, invasion and colony formation and induced apoptosis in a time- and dose-dependent manner in vitro (p<0.05). In addition, AdipoRon reduced the number of CCA and tumor volume, prolonged survival, and decreased metastasis and ascites in the treated group compared to the control group (p<0.05). CONCLUSIONS: AdipoR1 and p-AMPKα are impaired in CCA tissues, and AdipoRon effectively inhibits CCA in vitro and in vivo. Thus, AdipoRon may be considered as a potential anti-tumor therapy in CCA.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Apoptosis , Neoplasias de los Conductos Biliares , Proliferación Celular , Colangiocarcinoma , Receptores de Adiponectina , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Colangiocarcinoma/metabolismo , Receptores de Adiponectina/metabolismo , Receptores de Adiponectina/agonistas , Humanos , Animales , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones , Proliferación Celular/efectos de los fármacos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/metabolismo , Apoptosis/efectos de los fármacos , Piperidinas/farmacología , Piperidinas/química , Piperidinas/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Movimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales
9.
J Gastroenterol Hepatol ; 36(5): 1334-1345, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33091158

RESUMEN

BACKGROUND AND AIM: Cholangiocarcinoma has an unimproved prognosis. Interleukin 6 (IL-6) has an oncogenic potential in some cancer diseases. However, the role of IL-6 in cholangiocarcinoma carcinogenesis is not well understood. The current study investigated the role of IL-6 signaling in cholangiocarcinoma carcinogenesis and efficacy of siltuximab treatment on cholangiocarcinoma in vitro and in vivo. METHODS: The expression of IL-6 was analyzed on human cholangiocarcinoma cell lines and murine and human cholangiocarcinoma tissues, using reverse transcription real-time polymerase chain reaction and immunohistochemistry. In addition, the effect of anti-IL-6 chimeric monoclonal antibody, siltuximab, was investigated in vitro by proliferation, migration, and two-dimensional and three-dimensional invasion assays and in vivo by xenograft mouse model. Western blot was applied to study the molecular alteration. RESULTS: Our result shows high expression of IL-6 in human cholangiocarcinoma cells, and IL-6 stimulants enhance cholangiocarcinoma cell proliferation. In addition, murine and human cholangiocarcinoma tissues express significantly higher levels of IL-6, compared with adjacent non-tumor tissues. On the cholangiocarcinoma engineered mouse model, IL-6 level is associated with tumor volume. Taken together, our data indicate an oncogenic potential of IL-6 in cholangiocarcinoma carcinogenesis. Siltuximab sufficiently abrogates IL-6 signaling and inhibits cholangiocarcinoma progression in vitro and in vivo. The results additionally indicate a relative alteration of IL-6 signaling and its molecular targets, such as STAT3, Wnt/ß-catenin, and mesenchymal markers. CONCLUSIONS: Interleukin 6 plays an essential role in cholangiocarcinoma carcinogenesis, and siltuximab has the potential to be considered as a new treatment option for cholangiocarcinoma patients.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/patología , Carcinogénesis/genética , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Interleucina-6/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Neoplasias de los Conductos Biliares/genética , Línea Celular Tumoral , Colangiocarcinoma/genética , Modelos Animales de Enfermedad , Expresión Génica , Humanos , Interleucina-6/genética , Masculino , Ratones , Persona de Mediana Edad , Terapia Molecular Dirigida , Factor de Transcripción STAT3 , Proteínas Wnt , beta Catenina
10.
Cancers (Basel) ; 12(3)2020 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-32155915

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) represents a major health burden with limited curative treatment options. There is a substantial unmet need to develop innovative approaches to impact the progression of advanced HCC. Haprolid is a novel natural component isolated from myxobacteria. Haprolid has been reported as a potent selective cytotoxin against a panel of tumor cells in recent studies including HCC cells. The aims of this study are to evaluate the antitumor effect of haprolid in HCC and to understand its underlying molecular mechanisms. METHODS: The efficacy of haprolid was evaluated in human HCC cell lines (Huh-7, Hep3B and HepG2) and xenograft tumors (NMRI-Foxn1nu mice with injection of Hep3B cells). Cytotoxic activity of haprolid was determined by the WST-1 and crystal violet assay. Wound healing, transwell and tumorsphere assays were performed to investigate migration and invasion of HCC cells. Apoptosis and cell-cycle distribution were measured by flow cytometry. The effects of haprolid on the Rb/E2F and Akt/mTOR pathway were examined by immunoblotting and immunohistochemistry. RESULTS: haprolid treatment significantly inhibited cell proliferation, migration and invasion in vitro. The epithelial-mesenchymal transition (EMT) was impaired by haprolid treatment and the expression level of N-cadherin, vimentin and Snail was downregulated. Moreover, growth of HCC cells in vitro was suppressed by inhibition of G1/S transition, and partially by induction of apoptosis. The drug induced downregulation of cell cycle regulatory proteins cyclin A, cyclin B and CDK2 and induced upregulation of p21 and p27. Further evidence showed that these effects of haprolid were associated with Rb/E2F downregulation and Akt/mTOR inhibition. Finally, in vivo nude mice experiments demonstrated significant inhibition of tumor growth upon haprolid treatment. CONCLUSION: Our results show that haprolid inhibits the growth of HCC through dual inhibition of Rb/E2F and Akt/mTOR pathways. Therefore, haprolid might be considered as a new and promising candidate for the palliative therapy of HCC.

11.
Exp Cell Res ; 385(2): 111671, 2019 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-31634481

RESUMEN

Aberrant activation of Sonic Hedgehog (SHH) pathway has been implicated in a variety of cancers including cholangiocarcinoma (CC); however, the influencing factors are still unknown. Additionally, intratumoral hypoxia is known to contribute towards therapeutic resistance through modulatory effects on various pathways. In this study, we investigated the relationship between hypoxia and SHH pathway activation and the effect of this interplay on cancer stemness and epithelial-to- mesenchymal transition (EMT) during cholangiocarcinogenesis. Hypoxia promoted SHH pathway activation, evidenced by upregulated SHH and SMO levels, and enhanced glioma-associated oncogene homolog 1 (GLI1) nuclear translocation; whereas silencing of HIF-1α impaired SHH upregulation. Hypoxia also enhanced the expression of cancer stem cell (CSC) transcription factors (NANOG, Oct4, SOX2), CD133 and EMT markers (N-cadherin, Vimentin), thereby supporting invasion. Cyclopamine treatment suppressed hypoxia induced SHH pathway activation, consequently reducing invasiveness by downregulating the expression of CSC transcription factors, CD133 and EMT. Cyclopamine induced apoptosis in CC cells under hypoxia, suggesting that hypoxia induced activation of SHH pathway has modulatory effects on CC progression. Therefore, SHH signaling is proposed as a target for CC treatment, which is refractory to standard chemotherapy.


Asunto(s)
Neoplasias de los Conductos Biliares/metabolismo , Colangiocarcinoma/metabolismo , Transición Epitelial-Mesenquimal , Proteínas Hedgehog/metabolismo , Oxígeno/metabolismo , Transducción de Señal , Antígeno AC133/genética , Antígeno AC133/metabolismo , Apoptosis , Hipoxia de la Célula , Línea Celular Tumoral , Movimiento Celular , Proteínas Hedgehog/genética , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Proteína Homeótica Nanog/genética , Proteína Homeótica Nanog/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/fisiología , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Factores de Transcripción SOXC/genética , Factores de Transcripción SOXC/metabolismo , Receptor Smoothened/genética , Receptor Smoothened/metabolismo , Alcaloides de Veratrum/farmacología , Proteína con Dedos de Zinc GLI1/genética , Proteína con Dedos de Zinc GLI1/metabolismo
12.
13.
Exp Cell Res ; 364(1): 59-67, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29366806

RESUMEN

Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. CC treatment options are very limited especially for patients with distant metastasis. Kangai 1 C-terminal interacting tetraspanin (KITENIN) is highly expressed in numerous cancers, but the role of KITENIN in CC remains unknown. Here, we have investigated for the first time the function of KITENIN in human CC cell lines (TFK-1, SZ-1), tissues and a CC mouse model (Alb-Cre/LSL-KRASG12D/p53L/L). KITENIN was expressed in 92.2% of human CC tissues, in murine CC samples and also in human CC cell lines. Knockdown of KITENIN by small interfering RNA (siRNA) effectively reduced proliferation, migration, invasion and colony formation in both intra- and extra-hepatic CC cells. The expression of epithelial-mesenchymal transition (EMT) markers like N-cadherin, Vimentin, Snail and Slug were suppressed in KITENIN knockdown CC cells. Our results indicate that KITENIN is crucial for cholangiocarcinogenesis and it might become a potential therapeutic target for human CC treatment.


Asunto(s)
Neoplasias de los Conductos Biliares/prevención & control , Proteínas Portadoras/antagonistas & inhibidores , Proliferación Celular , Colangiocarcinoma/prevención & control , Silenciador del Gen , Proteínas de la Membrana/antagonistas & inhibidores , ARN Interferente Pequeño/genética , Animales , Apoptosis , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Movimiento Celular , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Femenino , Humanos , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Células Tumorales Cultivadas
14.
Cancer Lett ; 399: 20-28, 2017 07 28.
Artículo en Inglés | MEDLINE | ID: mdl-28408354

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited treatment options. The proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. We hypothesize that his analogue Argyrin F (AF) may also prevent PDAC progression. We have used PDAC cells and engineered mice (Pdx1-Cre; LSL-KrasG12D; p53 lox/+) to assess AF anticancer activity. We analyzed the effect of AF on proliferation and epithelial plasticity using MTT-, wound healing-, invasion-, colony formation-, apoptosis-, cell cycle- and senescence assays. In vivo treatment with AF, Gemcitabine (G) and combinational treatment (AF + G) was performed for survival analysis. AF inhibited cell proliferation, migration, invasion and colony formation in vitro. AF impaired epithelial-mesenchymal transition (EMT), caused considerable apoptosis and senescence in a dose- and time-dependent manner and affected cell cycle G1/S phase transition. G treatment achieved longest mice survival, followed by AF + G and AF compared to vehicle group. However, AF + G treatment induced the largest reduction in tumor spread and ascites. In conclusion, we have demonstrated that AF prevents PDAC progression and that combined therapy was superior to AF monotherapy. Therefore, AF treatment might be useful as an additional therapy for PDAC.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Péptidos Cíclicos/farmacología , Animales , Apoptosis/efectos de los fármacos , Carcinoma Ductal Pancreático/irrigación sanguínea , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/secundario , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Ciclooxigenasa 2/metabolismo , Relación Dosis-Respuesta a Droga , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Ratones Transgénicos , Invasividad Neoplásica , Neovascularización Patológica , Neoplasias Pancreáticas/irrigación sanguínea , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Estabilidad Proteica , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Carga Tumoral/efectos de los fármacos
15.
Stem Cells Transl Med ; 6(3): 819-829, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28186678

RESUMEN

Cancer stem cells (CSC) are associated with tumor resistance and are characterized in gastric cancer (GC). Studies have indicated that Notch and wnt-beta-catenin pathways are crucial for CSC development. Using CD44+ CSCs, we investigated the role of these pathways in GC carcinogenesis. We performed cell proliferation, wound healing, invasion, tumorsphere, and apoptosis assays. Immunoblot analysis of downstream signaling targets of Notch and wnt-beta-catenin were tested after gamma-secretase inhibitor IX (GSI) treatment. Immunohistochemistry, immunofluorescence, and Fluorescence activated cell sorting (FACS) were used to determine CD44 and Hairy enhancer of split-1 (Hes1) expression in human GC tissues. CD44+ CSCs were subcutaneously injected into NMR-nu/nu mice and treated with vehicle or GSI. GC patients with expression of CD44 and Hes1 showed overall reduced survival. CD44+ CSCs showed high expression of Hes1. GSI treatment showed effective inhibition of cell proliferation, migration, invasion, tumor sphere formation of CD44+ CSCs, and induced apoptosis. Importanly, Notch1 was found to be important in mediating a crosstalk between Notch and wnt-beta-catenin in CD44+ CSCs. Our study highlights a crosstalk between Notch and wnt-beta-catenin in gastric CD44+ CSCs. Expression of CD44 and Hes1 is associated with patient overall survival. GSI could be an alternative drug to treat GC. Stem Cells Translational Medicine 2017;6:819-829.


Asunto(s)
Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Receptores de Hialuranos/metabolismo , Células Madre Neoplásicas/metabolismo , Receptores Notch/metabolismo , Neoplasias Gástricas/patología , Vía de Señalización Wnt , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Ratones Desnudos , Invasividad Neoplásica , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/patología , Análisis de Supervivencia , Factor de Transcripción HES-1/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
16.
PLoS One ; 11(9): e0162673, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27649309

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0095605.].

18.
Int J Oncol ; 48(5): 2025-34, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26935541

RESUMEN

Cholangiocarcinoma (CC) worldwide is the most common biliary malignancy with poor prognostic value and new systemic treatments are desirable. Plant extracts like bromelain and papain, which are cysteine proteases from the fruit pineapple and papaya, are known to have antitumor activities. Therefore, in this study for the first time we investigated the anticancer effect of bromelain and papain in intra- and extrahepatic human CC cell lines. The effect of bromelain and papain on human CC cell growth, migration, invasion and epithelial plasticity was analyzed using cell proliferation, wound healing, invasion and apoptosis assay, as well as western blotting. Bromelain and papain lead to a decrease in the proliferation, invasion and migration of CC cells. Both plant extracts inhibited NFκB/AMPK signalling as well as their downstream signalling proteins such as p-AKT, p-ERK, p-Stat3. Additionally, MMP9 and other epithelial-mesenchymal-transition markers were partially found to be downregulated. Apoptosis was induced after bromelain and papain treatment. Interestingly, bromelain showed an overall more effective inhibition of CC as compared to papain. siRNA mediated silencing of NFκB on CC cells indicated that bromelain and papain have cytotoxic effects on human CC cell lines and bromelain and partially papain in comparison impair tumor growth by NFκB/AMPK signalling. Especially bromelain can evolve as promising, potential therapeutic option that might open new insights for the treatment of human CC.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de los Conductos Biliares/metabolismo , Bromelaínas/farmacología , Colangiocarcinoma/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Papaína/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Apoptosis , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colangiocarcinoma/tratamiento farmacológico , Humanos , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos
19.
Pancreas ; 45(7): 1018-26, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26784907

RESUMEN

OBJECTIVES: Differentiation of pancreatic cancer (PCA) from chronic pancreatitis (CP) is challenging. We searched for peptide markers in urine to develop a diagnostic peptide marker model. METHODS: Capillary electrophoresis-mass spectrometry was used to search for peptides in urine of patients with PCA (n = 39) or CP (n = 41). Statistical different peptides were included in a peptide multimarker model. Peptide markers were sequence identified and validated by immunoassay and immunohistochemistry (IHC). RESULTS: Applied to a validation cohort of 54 patients with PCA and 52 patients with CP, the peptide model correctly classified 47 patients with PCA and 44 patients with CP (area under the curve, 0.93; 87% sensitivity; 85% specificity). All 5 patients with PCA with concomitant CP were classified positive. Urine proteome analysis outperformed carbohydrate antigen 19-9 (area under the curve, 0.84) by a 15% increase in sensitivity at the same specificity. From 99 healthy subjects, only four were misclassified. Fetuin-A was the most prominent peptide marker source for PCA as verified by immunoassay and IHC. In silico protease mapping of the peptide markers' terminal sequences pointed to increased meprin-A activity in PCA, which in IHC was associated with neoangiogenesis. CONCLUSIONS: Urinary proteome analysis differentiates PCA from CP and may serve as PCA screening tool.


Asunto(s)
Biomarcadores/orina , Neoplasias Pancreáticas/orina , Pancreatitis Crónica/orina , Péptidos/orina , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Electroforesis Capilar , Femenino , Humanos , Inmunoensayo/métodos , Inmunohistoquímica , Masculino , Espectrometría de Masas , Metaloendopeptidasas/análisis , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Pancreáticas/diagnóstico , Pancreatitis Crónica/diagnóstico , Curva ROC , alfa-2-Glicoproteína-HS/análisis
20.
Mol Carcinog ; 55(12): 2037-2050, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-26757360

RESUMEN

Palliative treatment options for human cholangiocarcinoma (CCC) are quite limited and new therapeutic strategies are of utmost need. c-MET has been shown to be deregulated in many cancers, but the role of c-MET in the carcinogenesis of CCC remains unclear. The main purpose of this study is to evaluate the expression and also to investigate the role of c-MET and its effective inhibition for the treatment of CCC. In this study we investigated the effects of LY2801653, a small-molecule inhibitor with potent activity against MET kinase, in human CCC cell lines and in vivo using a xenograft mouse model. We have investigated the role of c-MET and its inhibitory effects on migration, invasion, colony formation, MET downstream targets, and CCC tumor growth. We also analyzed the role of apoptosis and senescence as well as the influence of hypoxia in this context. c-MET and p-MET were expressed in 72% and 12.5% of human CCC tissues and in TFK-1, SZ-1 cell lines. MET inhibition was achieved by blocking phosphorylation of MET with LY2801653 and subsequent down regulation of c-MET downstream targets. Treatment showed in a xenograft model potent anti-tumor activity. LY2801653 is an effective inhibitor and suppress the proliferation of CCC cells as well as the growth of xenograft tumors. Therefore, inhibition of c-MET could be a possible alternative approach for the treatment of human CCC. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Conductos Biliares/efectos de los fármacos , Colangiocarcinoma/tratamiento farmacológico , Indazoles/uso terapéutico , Niacinamida/análogos & derivados , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/metabolismo , Animales , Apoptosis/efectos de los fármacos , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Conductos Biliares/metabolismo , Conductos Biliares/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Femenino , Humanos , Ratones Desnudos , Terapia Molecular Dirigida , Invasividad Neoplásica/patología , Invasividad Neoplásica/prevención & control , Niacinamida/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-met/análisis , Transducción de Señal/efectos de los fármacos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...