Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 843
Filtrar
1.
Med Sci Monit ; 26: e921162, 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32246704

RESUMO

BACKGROUND This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms. MATERIAL AND METHODS We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed with the STRING platform. The components-targets-disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting. RESULTS Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA. The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted. CONCLUSIONS RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa/métodos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
2.
PLoS One ; 15(2): e0229292, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084210

RESUMO

BACKGROUD: Resection is still the only potentially curative treatment for patients with intrahepatic cholangiocarcinoma (ICC), but the prognosis remains far from satisfactory. However, the benefit of adjuvant therapy (AT) remains controversial, although it has been conducted prevalently. Hence, a meta-analysis was warranted to evaluate the effect of AT for patients with ICC after resection. PATIENTS AND METHODS: PubMed, MedLine, Embase, the Cochrane Library, Web of Science were used to identify potentially eligible studies from Jan.1st 1990 to Aug. 31st 2019, investigating the effect of AT for patients with ICC after resection. Primary endpoint was overall survival (OS), and secondary endpoints was recurrence-free survival (RFS). Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS: 22 studies with 10181 patients were enrolled in this meta-analysis, including 832 patients in the chemotherapy group, 309 patients in the transarterial chemoembolization (TACE) group, 1192 patients in the radiotherapy group, 235 patients in the chemoradiotherapy group, and 6424 patients in the non-AT group. The pooled HR for the OS rate and RFS rate in the AT group were 0.63 (95%CI 0.52~0.74), 0.74 (95%CI 0.58~0.90), compared with the non-AT group. Subgroup analysis showed that the pooled HR for the OS rate in the AT group compared with non-AT group were as follows: chemotherapy group was 0.57 (95%CI = 0.44~0.70), TACE group was 0.56 (95%CI = 0.31~0.82), radiotherapy group was 0.71 (95%CI = 0.39~1.03), chemoradiotherapy group was 0.73 (95%CI = 0.57~0.89), positive resection margin group was 0.60 (95%CI = 0.51~0.69), and lymph node metastasis (LNM) group was 0.67 (95%CI = 0.57~0.76). CONCLUSION: With the current data, we concluded that AT such as chemotherapy, TACE and chemoradiotherapy could benefit patients with ICC after resection, especially those with positive resection margin and LNM, but the conclusion needed to be furtherly confirmed.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Quimioterapia Adjuvante , Colangiocarcinoma/tratamento farmacológico , Humanos , Análise de Sobrevida , Resultado do Tratamento
3.
Bull Cancer ; 107(1): 48-53, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31980143

RESUMO

The adjuvant treatment of biliary tract cancers has long been poorly defined. In recent years, randomized trial data have been used to define treatment references. The French Prodige 12 and Japanese BCAT trials have not demonstrated any benefit of adjuvant chemotherapy. The English BILCAP trial tested adjuvant capecitabine for six months at the usual dose in a randomized, controlled-only trial involving nearly 450 patients. Although the results in intention to treat were borderline significant on the primary endpoint, overall survival (P=0.097), sensitivity analyzes adjusted for prognostic factors and relapse-free survival analyses are clearly positive. The absolute benefit of +5%/+10% overall survival, combined with low and known toxicity profile, leads to recommending treatment for any cancer of the resected bile ducts (with the exception of gallbladder cancer pT1N0).


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Capecitabina/administração & dosagem , Quimioterapia Adjuvante , Colangiocarcinoma/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias da Vesícula Biliar/tratamento farmacológico , Humanos , Análise de Intenção de Tratamento , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
4.
Planta Med ; 86(2): 104-112, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31777055

RESUMO

Cholangiocarcinoma (CCA) remains a significant public health problem in Thailand. New effective and safe drugs are urgently needed. Zingiber officinale Roscoe (ZO) is a widely used medicinal plant for the treatment of several ailments, and the animal study suggests a potential anti-CCA activity. The present study aimed to develop the oral formulation of standardized extract of ZO and investigate toxicological profiles (acute, repeated dose, and chronic toxicity), including anti-CCA activity of the ZO formulation. The oral pharmaceutical formulation of the standardized ZO extract was successfully developed with an acceptable level of contamination and physicochemical and pharmaceutical properties. Acute, subacute, and chronic toxicity tests were conducted in healthy Sprague Dawley rats according to the OECD guidelines. The results showed no evidence of toxicity and death in the acute and subacute toxicity testing with the maximum tolerated dose (MTD) of 5000 and 2000 mg/kg body weight, respectively. Chronic toxicity revealed MTD and No-Observed-Adverse-Effect level (NOAEL) of 1000 mg/kg body weight. The anti-CCA activity was evaluated in CCA-xenografted mouse model. The formulated ZO powder was fed to animals daily for 30 days. Significant anti-CCA activity on tumor growth inhibition and prolongation of survival time were demonstrated at the high (2000 mg/kg body weight) and moderate (1000 mg/kg body weight) dose levels. Further investigation to elucidate molecular targets of action of ZO against CCA cells is encouraged.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Gengibre/química , Extratos Vegetais/toxicidade , Administração Oral , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Clin Adv Hematol Oncol ; 17(11): 630-637, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31851165

RESUMO

Cholangiocarcinoma (CCA) encompasses a rare group of malignancies arising from epithelial cells lining the biliary tree that connects the liver and gallbladder to the small intestine. Most patients present with advanced incurable disease that has a poor prognosis, and standard treatment options remain limited. Effective nontoxic treatment options for advanced CCA are needed. Fibroblast growth factors (FGFs) and their fibroblast growth factor receptor (FGFR) pathways are crucial to cellular proliferation, cellular survival, and differentiation of many malignancies, but are especially relevant in CCA. The targeting of FGF/FGFR has become the most promising approach to treating patients with advanced/metastatic CCA. Here we review CCA, and discuss the promise of FGFR-directed therapy in advanced CCA.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Terapia de Alvo Molecular , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Ensaios Clínicos como Assunto , Humanos , Resultado do Tratamento
7.
Medicine (Baltimore) ; 98(45): e17832, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702638

RESUMO

INTRODUCTION: The prognosis for recurrent intrahepatic cholangiocarcinoma with bone metastasis remains dismal and its treatment poses a challenge for oncologists. To date, only 2 cases were reported in which pembrolizumab, an agent against programmed cell death protein-1 (PD-1), combined with chemotherapy led to a complete response. The safety and efficacy of nivolumab-based immunotherapy combined with lenvatinibin intrahepatic cholangiocarcinoma is unknown. PATIENT CONCERNS: A 40-year-old female was identified as having a lesion of 7.0 cm in diameter in the right lobe of the liver. In addition, calculi in the main and left hepatic bile ducts as well as the gallbladder were found. DIAGNOSIS: Based on the results of imaging studies and tumor biomarker level, the patient was initially diagnosed as having intrahepatic cholangiocellular carcinoma and cholelithiasis, after which surgery was performed. The pathological examination confirmed that the tumor was cholangiocarcinoma. Adjuvant chemotherapy was administered after surgery. However, the patient developed recurrent lesions at the 5th month after surgery, and the cholangiocarcinoma expanded to the right thoracic vertebral pedicle (T7-8) at the 6th month. INTERVENTIONS: The patient underwent percutaneous microwave ablation after recurrence in the liver was identified. After that, the patient received nivolumab plus lenvatinib. OUTCOMES: The lesions in the liver decreased in size and disappeared after treatment with nivolumab plus lenvatinib. Additionally, the metastases in the right thoracic vertebral pedicle were stable after 9 months of therapy. LESSONS: Immunotherapy has revolutionized the treatment of non-small-cell lung cancer, melanoma, and advanced renal cell carcinoma. In this case, the patient achieved an excellent radiological and symptomatic response after receiving nivolumab plus lenvatinib combination therapy. Patients suffering from cholangiocarcinoma with dMMR status and a high tumor mutation burden (TMB) may have a consistent eutherapeutic effect with anti-PD-1-directed treatment.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Colangiocarcinoma/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Ablação por Radiofrequência , Análise de Sobrevida , Resultado do Tratamento
8.
Asian Pac J Cancer Prev ; 20(9): 2745-2748, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31554372

RESUMO

Background: Cholangiocarcinoma (CCA), although is an uncommon liver cancer originating from bile duct epithelial cells, is one of the top 10 most fatal cancers. Chemoresistance is an unmet need always found in CCA patients. Tumor microenvironment conditions such as hypoxia, nutrient starvation and acidic extracellular pH play critical roles in chemoresistance and cancer progression. However, the effect of acidic extracellular pH on cellular response and chemoresistance in CCA has not been studied. Methods: Human CCA cell lines (KKU-M213, KKU-M055 and KKU-100) were cultured under acidic (pH 6.5) or non-acidic (pH 7.4) condition and were used for gene expression, doubling time and cytotoxicity assay. Results: The acidic extracellular pH (pH 6.5) significantly increased doubling times of CCA cell lines compared with non-acidic condition (pH 7.4). Interestingly, extracellular acid condition induced gemcitabine resistance in CCA cell lines. We showed that Octamer-binding transcription factor 4 (Oct4) was upregulated in these cell lines under extracellular acid condition. Conclusion: Our findings demonstrate that CCA cells can adapt to survive in acidic environment after which chemoresistance has been developed. Oct4 may be a key transcriptional regulator which mediates chemoresistance in response to acidic extracellular pH.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Fator 3 de Transcrição de Octâmero/metabolismo , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Desoxicitidina/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Concentração de Íons de Hidrogênio , Fator 3 de Transcrição de Octâmero/genética , Células Tumorais Cultivadas , Microambiente Tumoral
9.
BMC Complement Altern Med ; 19(1): 203, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391034

RESUMO

BACKGROUND: 5-Florouracil (5-FU) is a commonly used chemotherapeutic drug for cholangiocarcinoma, whereas it has unsatisfactory effect, and patients often have chemo-resistance to it. The combination of chemotherapeutic agents and traditional Chinese medicine has already exhibited a promising application in oncotherapy. Huaier extract (Huaier) has been used in clinical practice widely, exhibiting good anti-tumor effect. This paper aims to investigate the possibility of combination 5-FU and Huaier as a treatment for cholangiocarcinoma. METHODS: A series of experiments were performed on the Huh28 cells in vitro, which involved cell proliferation, colony formation, apoptosis, cell cycle, migratory and invasive tests. Besides, western blots were also performed to examine the potential mechanism of 5-FU. RESULTS: The combination effect (antagonism, synergy or additive) was assessed using Chou-Talalay method. Using the CCK-8 and Colony formation assay, the anti-proliferation effect of 5-FU combined with Huaier was observed. Apoptosis inducing and cell cycle arrest effect of the combination of two drugs were assessed by flow cytometry. To determine the combined treatment on cell immigration and invasion ability, wound healing and Transwell assay were performed. The above experiment results suggest that the combined 5-FU and Huaier, compared with treatment using either drug alone, exhibited stronger effects in anti-proliferation, cycle arrest, apoptosis-induced and anti-metastasis. Further, western blot results reveal that the inhibition of STAT3 and its target genes (e.g. Ki67, Cyclin D1, Bcl-2 and MMP-2) might be set as the potential therapeutic targets. Besides, the inhibition of combination treatment in proteins expression associated with proliferation, apoptosis, cell cycle and metastasis was consistent with that of previous phenotypic experiments. CONCLUSIONS: Huaier combined with 5-FU exhibited a synergistic anti-tumor effect in Huh28 cell. Furthermore, the mechanisms might be associated with the activation and translocation of STAT3, as well as its downstream genes.


Assuntos
Antineoplásicos/farmacologia , Colangiocarcinoma/fisiopatologia , Misturas Complexas/farmacologia , Fluoruracila/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/fisiopatologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Medicine (Baltimore) ; 98(31): e16673, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374045

RESUMO

The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The "liver reduction rate" was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median "liver reduction rate" was 21%. The OS had statistically significant difference in nodal status (P = .032) and "liver reduction rate" >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction.


Assuntos
Colangiocarcinoma/radioterapia , Hepatopatias/prevenção & controle , Neoplasias Hepáticas/radioterapia , Lesões por Radiação/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Cisplatino/uso terapêutico , Terapia Combinada , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/uso terapêutico , Piridinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Dosagem Radioterapêutica , Radioterapia Adjuvante , Tegafur/uso terapêutico , Tomografia Computadorizada por Raios X
12.
World J Gastroenterol ; 25(26): 3380-3391, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341363

RESUMO

BACKGROUND: Bile duct cancer is characterized by fast metastasis and invasion and has been regarded as one of the most aggressive tumors due to the absence of effective diagnosis at an early stage. Therefore, it is in the urgent demand to explore novel diagnostic approaches and therapeutic strategies for bile duct cancer to improve patient survival. Raddeanin A (RA) is extracted from the anemone raddeana regel and has been demonstrated to play antitumor roles in various cancers. AIM: To investigate the effects of RA treatment on bile duct cancer cells. METHODS: In this study, four cholangiocarcinoma cell lines (RBE, LIPF155C, LIPF178C, and LICCF) treated with RA were used to test the cell viability. The RA-associated cell functional analysis, 5-fluorouracil (5-Fu) effectiveness as well as cell cycle- and apoptosis-related protein expression were investigated. RESULTS: RA reduced cell viability in a dose-dependent pattern in four cell lines, and the migration and colony formation abilities were also impaired by RA in RBE and LIPF155C cell lines. RA sensitized cell lines to 5-Fu treatment and enhanced the effects of 5-Fu in cholangiocarcinoma. Also, RA decreased protein expression of Wee1, while the combinational effect of RA and 5-Fu decreased protein expressions of cyclooxygenase-2, B cell lymphoma 2, and Wee1 but increased protein levels of Bax, cyclin D1, and cyclin E. CONCLUSION: Taken together, the results suggest that RA acts as an anti-cancer agent and enhancer of 5-Fu in bile duct cancer cells via regulating multiple cell cycle and apoptosis-related proteins. This finding provides novel clues to exploring a novel antitumor drug for bile duct cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Saponinas/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colangiocarcinoma/patologia , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Saponinas/uso terapêutico
13.
Hepatol Int ; 13(4): 490-500, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31214875

RESUMO

BACKGROUND: Although molecular characterization of iCCA has been studied recently, integrative analysis of molecular and clinical characterization has not been fully established. If molecular features of iCCA can be predicted based on clinical findings, we can approach to distinguish targeted treatment. We analyzed RNA sequencing data annotated with clinicopathologic data to clarify molecular-specific clinical features and to evaluate potential therapies for molecular subtypes. METHODS: We performed next-generation RNA sequencing of 30 surgically resected iCCA from Korean patients and the clinicopathologic features were analyzed. The RNA sequences from 32 iCCA resected from US patients were used for validation. RESULTS: Patients were grouped into two subclasses on the basis of unsupervised clustering, which showed a difference in 5-year survival rates (48.5% vs 14.2%, p = 0.007) and similar survival outcome in the US samples. In subclass B (poor prognosis), both data sets were similar in higher carcinoembryonic antigen and cancer antigen 19-9 levels, underlying cholangitis, and bile duct-type pathology; in subclass A (better prognosis), there was more frequent viral hepatitis and cholangiolar-type pathology. On pathway analysis, subclass A had enriched liver-related signatures. Subclass B had enriched inflammation-related and TP53 pathways, with more frequent KRAS mutations. CCA cell lines with similar gene expression patterns of subclass A were sensitive to gemcitabine. CONCLUSIONS: Two molecular subtypes of iCCA with distinct clinicopathological differences were identified. Knowledge of clinical and pathologic characteristics can predict molecular subtypes, and knowledge of different subtype signaling pathways may lead to more rational, targeted approaches to treatment.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Genes Neoplásicos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , República da Coreia/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Regulação para Cima
14.
Medicine (Baltimore) ; 98(24): e15945, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192931

RESUMO

BACKGROUND: Fluoxetine has been reported to treat anorexia nervosa (AN) caused by chemotherapy in patients with cholangiocarcinoma effectively. However, no study systematically investigated its efficacy and safety. Thus, this study will systematically assess its efficacy and safety for AN caused by chemotherapy in patients with cholangiocarcinoma. METHODS: A comprehensive literature search for relevant studies will be conducted from the following databases from inception to the present: MEDILINE, EMBASE, Cochrane Library, Web of Science, PSYCINFO, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All randomized controlled trials on assessing the efficacy and safety of fluoxetine for AN caused by chemotherapy in patients with cholangiocarcinoma will be considered for inclusion in this study. RevMan V.5.3 software will be used for risk of bias assessment and statistical analysis. RESULTS: This study will summarize the latest evidence of fluoxetine for AN caused by chemotherapy in patients with cholangiocarcinoma through assessing outcomes of weight, depression, anxiety, and quality of life. Additionally, any adverse events will also be analyzed. CONCLUSION: The findings of this study will provide most recent evidence of fluoxetine for AN caused by chemotherapy in patients with cholangiocarcinoma. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019131583.


Assuntos
Anorexia Nervosa/tratamento farmacológico , Antidepressivos de Segunda Geração/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Fluoxetina/uso terapêutico , Anorexia Nervosa/induzido quimicamente , Neoplasias dos Ductos Biliares/psicologia , China , Colangiocarcinoma/psicologia , Feminino , Humanos , Masculino , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Resultado do Tratamento
15.
Top Companion Anim Med ; 35: 1-5, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31122681

RESUMO

A 4-year-old, neutered male Golden Retriever was presented with a 1-week history of weight loss, polyuria, and polydipsia. The diagnostic workup showed an increased ionized calcium concentration, mild increase in serum creatinine and urea concentration, and severe hyperlipasemia. A complete abdominal ultrasound revealed multiple hepatic nodules. A cytological diagnosis of malignant epithelial neoplasia, highly suggestive of bile duct adenocarcinoma was made. In order to confirm the presumptive diagnosis of hypercalcemia of malignancy due to the presence of a hepatic neoplasia, serum parathormone-related peptide concentration was measured, and the result revealed an increased concentration. The dog was hospitalized and received supportive treatments consisting of intravenous furosemide and fluid therapy. After ruling out lymphoma and hypoadrenocorticism, oral prednisone was initiated and ionized calcium concentration decreased gradually down to normal concentration after 7 days of hospitalization. Chemotherapy with intravenous epirubicin was initiated based on the cytological diagnosis. One month after diagnosis and due to the worsening of its clinical condition, the dog was humanely euthanized. Postmortem examination confirmed a cholangiocellular carcinoma. To our knowledge, this is the first report of malignant hypercalcemia associated with cholangiocellular carcinoma in a dog.


Assuntos
Neoplasias dos Ductos Biliares/veterinária , Colangiocarcinoma/veterinária , Doenças do Cão/diagnóstico , Hipercalcemia/veterinária , Síndromes Paraneoplásicas/veterinária , Animais , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Cães , Epirubicina/uso terapêutico , Hipercalcemia/tratamento farmacológico , Masculino , Síndromes Paraneoplásicas/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/sangue , Prednisona/uso terapêutico
16.
PLoS One ; 14(5): e0216721, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31120926

RESUMO

Although cholangiocarcinoma (CCA) has a low incidence globally, this is extremely high in Northeast Thailand. The lack of both early detection measures and effective therapeutic drugs is the major problem for the poor prognosis of CCA patients. Based on regional knowledge, it would be advantageous to search for effective natural phyto-products for the treatment of CCA. Cardiospermum halicacabum L., Gomphrena celosioides Mart. and Scoparia dulcis L., very well-known medicinal herbs in Asian countries, were selected for the investigation of inhibitory effects on CCA cells. Of the three different ethanolic extracts, S. dulcis L extract showed most inhibitory effects on cell growth of CCA cell lines KKU-100 and KKU-213, at percentages of 56.06 and 74.76, respectively, compared to the untreated group after treatment with 250 µg/mL of extracts for 72 hrs. At 400 and 500 µg/mL of the extracts, the inhibitory effect of KKU-213 was indicated by a significant increase in the BAX/Bcl-2 ratio and cell membrane permeability. Moreover, metabolic profiling-based screening employed in the current study revealed a significant positive association between the lignin compound and a decrease in CCA cell viability. Our study suggests, for the first time, that ESD has the ability to inhibit CCA cell growth through the induction of apoptosis.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Fitoterapia , Amaranthaceae/química , Apoptose/efeitos dos fármacos , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Sapindaceae/química , Scoparia/química , Tailândia , Ensaio Tumoral de Célula-Tronco
17.
Cells ; 8(5)2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126020

RESUMO

Cholangiocarcinoma (CCA) is a deadly malignant tumor of the liver. It is a significant health problem in Thailand. The critical obstacles of CCA diagnosis and treatment are the high heterogeneity of disease and considerable resistance to treatment. Recent multi-omics studies revealed the promising targets for CCA treatment; however, limited models for drug discovery are available. This study aimed to develop a patient-derived xenograft (PDX) model as well as PDX-derived cell lines of CCA for future drug screening. From a total of 16 CCA frozen tissues, 75% (eight intrahepatic and four extrahepatic subtypes) were successfully grown and subpassaged in Balb/c Rag-2-/-/Jak3-/- mice. A shorter duration of PDX growth was observed during F0 to F2 transplantation; concomitantly, increased Oct-3/4 and Sox2 were evidenced in 50% and 33%, respectively, of serial PDXs. Only four cell lines were established. The cell lines exhibited either bile duct (KKK-D049 and KKK-D068) or combined hepatobiliary origin (KKK-D131 and KKK-D138). These cell lines acquired high transplantation efficiency in both subcutaneous (100%) and intrasplenic (88%) transplantation models. The subcutaneously transplanted xenograft retained the histological architecture as in the patient tissues. Our models of CCA PDX and PDX-derived cell lines would be a useful platform for CCA precision medicine.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Xenoenxertos , Transplante Heterólogo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Adulto , Idoso , Animais , Neoplasias dos Ductos Biliares/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/tratamento farmacológico , Modelos Animais de Doenças , Descoberta de Drogas/métodos , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Medicina de Precisão , Tailândia
18.
Anticancer Res ; 39(4): 2155-2161, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952762

RESUMO

BACKGROUND/AIM: The impact of adjuvant chemotherapy (AC) for extrahepatic cholangiocarcinoma (ECC) remains unclear. This study evaluated the efficacy and limitations of AC. PATIENTS AND METHODS: Between 2006 and 2016, 106 patients with stage II-IV ECC who underwent curative resection with biliary tract reconstruction were retrospectively analyzed. Patients were divided into two groups: Those who received AC (n=57) and those who did not (n=49). RESULTS: Fewer grade 3-4 complications were observed in the AC group compared to the non-AC group (38.6 vs. 61.2%, p=0.03). In the non-AC group, complications were the most frequent reason for omitting AC (n=21, including 13 with biliary fistula). In the AC group, the therapy completion rate was 56.1% and the main reason for discontinuation was adverse events (n=12, including six with cholangitis). AC was not associated with survival benefits (median survival: 50.4 vs. 37.3 months, p=0.916). CONCLUSION: AC for ECC might be inadequate as a standard strategy due to the low implementation and completion rates because complications often hamper administration.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Desoxicitidina/análogos & derivados , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Quimioterapia Adjuvante/efeitos adversos , Colangiocarcinoma/cirurgia , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Ácido Oxônico/uso terapêutico , Piridinas/uso terapêutico , Procedimentos Cirúrgicos Reconstrutivos , Recidiva , Tegafur/uso terapêutico
19.
J Hepatobiliary Pancreat Sci ; 26(6): 242-243, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30945442

RESUMO

Highlight Tanaka and Kubo reported the first case of recurrent occupational cholangiocarcinoma treated with programmed death-1 inhibitor. A programmed death-1 inhibitor was administered every 2 weeks for para-aortic lymph node metastasis after curative hepatectomy. After seven cycles of administration, positron emission tomography demonstrated diminished lymph node size without 18 F-fluorodeoxy glucose uptake.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias dos Ductos Biliares/induzido quimicamente , Neoplasias dos Ductos Biliares/tratamento farmacológico , Compostos Clorados/toxicidade , Colangiocarcinoma/induzido quimicamente , Colangiocarcinoma/tratamento farmacológico , Nivolumabe/uso terapêutico , Exposição Ocupacional/efeitos adversos , Solventes/toxicidade , Adulto , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Biomarcadores Tumorais/sangue , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Fluordesoxiglucose F18 , Hepatectomia , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
20.
Photodiagnosis Photodyn Ther ; 26: 218-223, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30965145

RESUMO

BACKGROUND: The five-year survival rate for successful surgical treatment of cholangiocellular cancer is only 20-40%, and in the case of an unresectable tumor, the life expectancy does not usually exceed 6 months. Survival decreases with the presence of jaundice, due to the spread of the tumor process along the bile ducts, leading to their obstruction. We report outcomes of patients with nonresectable bile duct carcinoma complicated by obstructive jaundice treated with Photodynamic Therapy (PDT). METHODS: Combined diagnosis and treatment included percutaneous cholangiostomy, intraductal video fluorescence diagnostics, photodynamic therapy, and bile duct stenting. All patients were treated at the Sechenov University Oncology Center in Moscow. The results of treatment of 33 patients have been presented. The intraductal diagnosis of malignant bile duct lesions was performed after cholangiostomy using the endovideofluorescence module for minimally invasive surgery and endoscopy. With the use of this method, it is the first time in Russia that it has become possible to obtain a videofluorescent image of the tumor and to determine the high level of photosensitizer accumulation in all cholangiocarcinoma patients. The preparations Photolon, Radachlorin, and Photosens were employed as photosensitizers (PS). Intraductal photodynamic therapy was used to achieve the antitumor effect. Laser power density was about 200 mW/cm2. RESULTS: We present initial results, improved the diagnostic possibilities in this difficult localization of carcinoma, and demonstrated the feasibility of prolongation of life without significant deterioration of its quality. The average survival time in the treatment group is 9.5 months. CONCLUSION: The treatment of patients with nonresectable cholangiocarcinoma with Photodynamic Therapy should be an available option. In this context, the additional use of intraductal endovideofluorescence diagnostics is a highly specific technique that allows reliable detection of the photosensitizer accumulation predominantly by the tumor tissue and appears promising. As shown by our experience, flourescent localization followed by Photodynamic Therapy, enabled us to improve diagnostic techniques and treat the tumor with improved outcome.


Assuntos
Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/complicações , Colangiocarcinoma/tratamento farmacológico , Icterícia Obstrutiva/complicações , Icterícia Obstrutiva/tratamento farmacológico , Fotoquimioterapia/métodos , Idoso , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Colangiocarcinoma/diagnóstico por imagem , Feminino , Humanos , Icterícia Obstrutiva/diagnóstico por imagem , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA