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1.
J Cancer Res Clin Oncol ; 150(4): 199, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627278

RESUMO

PURPOSE: Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant and fatal liver tumor with increasing incidence worldwide. Lactate metabolism has been recently reported as a crucial contributor to tumor progression and immune regulation in the tumor microenvironment. However, it remains poorly identified about the biological functions of lactate metabolism in iCCA, which hinders the development of prognostic tools and therapeutic interventions. METHODS: The univariate Cox regression analysis and Boruta algorithm were utilized to identify key lactate metabolism-related genes (LMRGs), and a prognostic signature was constructed based on LMRG scores. Genomic variations and immune cell infiltration were evaluated in the high and low LMRG score groups. Finally, the biological functions of key LMRGs were verified with in vitro and in vivo experiments. RESULTS: Patients in the high LMRG score group exhibit a poor prognosis compared to those in the low LMRG score group, with a high frequency of TP53 and KRAS mutations. Moreover, the infiltration and function of NK cells were compromised in the high LMRG score group, consistent with the results from two independent single-cell RNA sequencing datasets and immunohistochemistry of tissue microarrays. Experimental data revealed that lactate dehydrogenase A (LDHA) knockdown inhibited proliferation and migration in iCCA cell lines and tumor growth in immunocompetent mice. CONCLUSION: Our study revealed the biological roles of LDHA in iCCA and developed a reliable lactate metabolism-related prognostic signature for iCCA, offering promising therapeutic targets for iCCA in the clinic.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Animais , Camundongos , Prognóstico , Colangiocarcinoma/genética , Lactato Desidrogenase 5 , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Lactatos , Microambiente Tumoral/genética
2.
World J Gastroenterol ; 30(10): 1461-1465, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596486

RESUMO

Pancreatobiliary intraductal papillary neoplasms (IPNs) represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated. Despite advances in diagnostic methods, identifying these premalignant lesions is still challenging for treatment providers. Modern imaging, biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up. Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases. The balance between the risk of malignancy and any risk of resection guides management policy; therefore, treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata. IPN of the bile duct is more aggressive; thus, early diagnosis and surgery are crucial. The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/cirurgia , Colangiocarcinoma/genética , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia
3.
J Gastrointest Surg ; 28(4): 434-441, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583893

RESUMO

BACKGROUND: Medicaid expansion (ME) has contributed to transforming the United States healthcare system. However, its effect on palliative care of primary liver cancers remains unknown. This study aimed to evaluate the association between ME and the receipt of palliative treatment in advanced-stage liver cancer. METHODS: Patients diagnosed with stage IV hepatocellular carcinoma or intrahepatic cholangiocarcinoma were identified from the National Cancer Database and divided into pre-expansion (2010-2013) and postexpansion (2015-2019) cohorts. Logistic regression identified predictors of palliative treatment. Difference-in-difference (DID) analysis assessed changes in palliative care use between patients living in ME states and patients living in non-ME states. RESULTS: Among 12,516 patients, 4582 (36.6%) were diagnosed before expansion, and 7934 (63.6%) were diagnosed after expansion. Overall, rates of palliative treatment increased after ME (18.1% [pre-expansion] vs 22.3% [postexpansion]; P < .001) and are more pronounced among ME states. Before expansion, only cancer type and education attainment were associated with the receipt of palliative treatment. Conversely, after expansion, race, insurance, location, cancer type, and ME status (odds ratio [OR], 1.23; 95% CI, 1.06-1.44; P = .018) were all associated with palliative care. Interestingly, the odds were higher if treatment involved receipt of pain management (OR, 2.05; 95% CI, 1.23-2.43; P = .006). Adjusted DID analysis confirmed increased rates of palliative treatment among patients living in ME states relative to non-ME states (DID, 4.4%; 95% CI, 1.2-7.7; P = .008); however, racial disparities persist (White, 5.6; 95% CI, 1.4-9.8; P = .009; minority, 2.6; 95% CI, -2.5 to 7.6; P = .333). CONCLUSION: The implementation of ME contributed to increased rates of palliative treatment for patients residing in ME states after expansion. However, racial disparities persist even after ME, resulting in inequitable access to palliative care.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias Hepáticas , Humanos , Estados Unidos , Medicaid , Cuidados Paliativos , Patient Protection and Affordable Care Act , Cobertura do Seguro , Neoplasias Hepáticas/terapia , Ductos Biliares Intra-Hepáticos
4.
J Exp Clin Cancer Res ; 43(1): 104, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576051

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) comprises a heterogeneous group of biliary tract cancer. Our previous CCA mutation pattern study focused on genes in the post-transcription modification process, among which the alternative splicing factor RBM10 captured our attention. However, the roles of RBM10 wild type and mutations in CCA remain unclear. METHODS: RBM10 mutation spectrum in CCA was clarified using our initial data and other CCA genomic datasets from domestic and international sources. Real-time PCR and tissue microarray were used to detect RBM10 clinical association. Function assays were conducted to investigate the effects of RBM10 wild type and mutations on CCA. RNA sequencing was to investigate the changes in alternative splicing events in the mutation group compared to the wild-type group. Minigene splicing reporter and interaction assays were performed to elucidate the mechanism of mutation influence on alternative splicing events. RESULTS: RBM10 mutations were more common in Chinese CCA populations and exhibited more protein truncation variants. RBM10 exerted a tumor suppressive effect in CCA and correlated with favorable prognosis of CCA patients. The overexpression of wild-type RBM10 enhanced the ASPM exon18 exon skipping event interacting with SRSF2. The C761Y mutation in the C2H2-type zinc finger domain impaired its interaction with SRSF2, resulting in a loss-of-function mutation. Elevated ASPM203 stabilized DVL2 and enhanced ß-catenin signaling, which promoted CCA progression. CONCLUSIONS: Our results showed that RBM10C761Y-modulated ASPM203 promoted CCA progression in a Wnt/ß-catenin signaling-dependent manner. This study may enhance the understanding of the regulatory mechanisms that link mutation-altering splicing variants to CCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Mutação , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Via de Sinalização Wnt , Ductos Biliares Intra-Hepáticos/metabolismo , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Isoformas de Proteínas , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
5.
World J Gastroenterol ; 30(9): 1018-1042, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577184

RESUMO

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Humanos , Tumor de Klatskin/terapia , Tumor de Klatskin/cirurgia , Resultado do Tratamento , Hepatectomia/métodos , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Ductos Biliares Intra-Hepáticos/patologia , Colangiopancreatografia Retrógrada Endoscópica , Drenagem
6.
BMC Pediatr ; 24(1): 243, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580968

RESUMO

Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Cisto do Colédoco , Masculino , Humanos , Pré-Escolar , Cisto do Colédoco/complicações , Cisto do Colédoco/diagnóstico por imagem , Cisto do Colédoco/cirurgia , Colangiocarcinoma/complicações , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia
7.
Int J Mol Sci ; 25(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38612748

RESUMO

Visceral adiposity is known to be related to poor prognosis in patients with cholangiocarcinoma; however, the prognostic significance of the qualitative features of adipose tissue in cholangiocarcinoma has yet to be well defined. This study investigated the prognostic impact of adipose tissue imaging parameters reflecting the quantity and qualitative characteristics of subcutaneous (SAT) and visceral (VAT) adipose tissue on recurrence-free survival (RFS) and overall survival (OS) in 94 patients undergoing resection of cholangiocarcinoma. The area, mean computed tomography (CT) attenuation, and mean 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of SAT and VAT on positron emission tomography (PET)/CT for staging work-up were measured, and the relationship of these adipose tissue imaging parameters with clinicopathological factors and survival was assessed. TNM stage, histologic grade, lymphovascular invasion, and the size of cholangiocarcinoma showed positive correlations with adipose tissue imaging parameters. Multivariate survival analysis demonstrated that the visceral-to-subcutaneous adipose tissue area ratio (VSR) (p = 0.024; hazard ratio, 1.718) and mean FDG uptake of VAT (p = 0.033; hazard ratio, 9.781) were significant predictors for RFS, but all of the adipose tissue imaging parameters failed to show statistical significance for predicting OS. In addition to visceral adiposity, FDG uptake of VAT might be a promising prognostic parameter for predicting RFS in patients with cholangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Fluordesoxiglucose F18 , Gordura Intra-Abdominal/diagnóstico por imagem , Prognóstico , Tomografia Computadorizada por Raios X , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos
8.
Technol Cancer Res Treat ; 23: 15330338241239139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38613350

RESUMO

BACKGROUND: Cuproptosis is a novel type of mediated cell death strongly associated with the progression of several cancers and has been implicated as a potential therapeutic target. However, the role of cuproptosis in cholangiocarcinoma for prognostic prediction, subgroup classification, and therapeutic strategies remains largely unknown. METHODS: A systematic analysis was conducted among 146 cuproptosis-related genes and clinical information based on independent mRNA and protein datasets to elucidate the potential mechanisms and prognostic prediction value of cuproptosis-related genes. A 10-cuproptosis-related gene prediction model was constructed, and its effects on cholangiocarcinoma prognosis were significantly connected to poor patient survival. Additionally, the expression patterns of our model included genes that were validated with several cholangiocarcinoma cancer cell lines and a normal biliary epithelial cell line. RESULTS: First, a 10-cuproptosis-related gene signature (ADAM9, ADAM17, ALB, AQP1, CDK1, MT2A, PAM, SOD3, STEAP3, and TMPRSS6) displayed excellent predictive performance for the overall survival of cholangiocarcinoma. The low-cuproptosis group had a significantly better prognosis than the high-cuproptosis group with transcriptome and protein cohorts. Second, compared with the high-risk and low-risk groups, the 2 groups displayed distinct tumor microenvironments, reduced proportions of endothelial cells, and increased levels of cancer-associated fibroblasts based on CIBERSORTx and EPIC analyses. Third, patients' sensitivities to chemotherapeutic drugs and immune checkpoints revealed distinctive differences between the 2 groups. Finally, in replicating the expression patterns of the 10 genes, these results were validated with quantitative real-time polymerase chain reaction results validating the abnormal expression pattern of the target genes in cholangiocarcinoma. CONCLUSIONS: Collectively, we established and verified an effective prognostic model that could separate cholangiocarcinoma patients into 2 heterogeneous cuproptosis subtypes based on the molecular or protein characteristics of 10 cuproptosis-related genes. These findings may provide potential benefits for unveiling molecular characteristics and defining subgroups could improve the early diagnosis and individualized treatment of cholangiocarcinoma patients.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Células Endoteliais , Prognóstico , Colangiocarcinoma/genética , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Microambiente Tumoral/genética , Proteínas de Membrana , Proteínas ADAM
9.
Int J Nanomedicine ; 19: 3461-3473, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617799

RESUMO

Purpose: Ivosidenib (IVO), an isocitrate dehydrogenase-1 (IDH1) used for treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. However, poor solubility, low bioavailability, high dose and side effects limit clinical application of IVO. Methods: Ivosidenib-loaded PLGA nanoparticles (IVO-PLGA-NPs) and Ivosidenib-loaded chitosan coated PLGA nanoparticles (IVO-CS-PLGA-NPs) were prepared using emulsification and solvent evaporation method for the treatment of liver cancer. Results: The developed IVO-PLGA-NPs were evaluated for their particle size (171.7±4.9 nm), PDI (0.333), ZP (-23.0±5.8 mV), EE (96.3±4.3%), and DL (9.66±1.1%); similarly, the IVO-CS-PLGA-NPs were evaluated for their particle size (177.3±5.2 nm), PDI (0.311), ZP +25.9±5.7 mV, EE (90.8±5.7%), and DL (9.42±0.7%). The chitosan coating of IVO-PLGA-NPs was evidenced by an increase in mean particle size and positive ZP value. Because of the chitosan coating, the IVO-CS-PLGA-NPs showed a more stable and prolonged release of IVO than IVO-PLGA-NPs. In comparison to pure-IVO, the IVO-PLGA-NPs and IVO-CS-PLGA-NPs were found to be more effective against HepG2 cells, with IC50 values for the MTT assay being approximately half of those of pure-IVO. In HepG2 cells, the expressions of caspase-3, caspase-9, and p53 were significantly (p < 0.05) elevated. Conclusion: Overall, these findings suggest that chitosan coating of IVO-PLGA-NPs improves the delivery and efficacy of ivosidenib in liver cancer treatment.


Assuntos
Neoplasias dos Ductos Biliares , Quitosana , Glicina/análogos & derivados , Neoplasias Hepáticas , Nanopartículas , Piridinas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Ductos Biliares Intra-Hepáticos
10.
Cancer Med ; 13(7): e7186, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597789

RESUMO

BACKGROUND: The definition of textbook outcome in biliary system cancers is a developing concept in need of expansion and investigation of its association with survival and quality of life. METHODS: In this original research, we developed a novel "all or none" textbook outcome definition which addresses the rapid recovery of post-surgical indexes, in addition to short-term mortality, hospital re-admission, prolonged stay, surgical margin and postoperative complications. Based on the fulfillment of relevant criteria, patients were divided into textbook outcome and non-textbook outcome groups and their characteristics and survival data were analyzed. A customized "quality of life" questionnaire was developed to address short-term recovery and post-discharge life quality of patients. Association with quality of life improvement was then investigated. RESULTS: A total of 129 patients were included. Textbook outcome was achieved in 25.58% of patients (37.04% of gallbladder cancer patients and 17.8% of cholangiocarcinoma patients). Compared to non-textbook outcome group, patients with textbook outcome had lower rate of pre-operative biliary drainage (p = 0.026), higher rate of normal preoperative liver function (p < 0.001) and tumor markers (p = 0.001), reduced perioperative bleeding (p = 0.006) and blood transfusion (p = 0.005), and higher rate of N0 stage cases (p = 0.008). Textbook outcome was also associated with enhanced survival, significantly in older patients (<65 years) (1-year survival rate: 100% vs. 78.57% (p = 0.108), 2-year survival rate: 87.5% vs. 44% (p = 0.046)). Finally, textbook outcome was significantly associated with enhanced basic daily performance (p < 0.001), social life performance (p = 0.033), and personal evaluation (p < 0.001), and thus improved quality of life (p < 0.001). CONCLUSIONS: The novel definition of textbook outcome was able to address the specific nature of recovery after resection of biliary system cancers. Expanding the scope of textbook outcome and addressing the influence on survival and quality of life provides a comprehensive concept able to reflect physical, psychological and functioning enhancements in patients recovery.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Humanos , Idoso , Qualidade de Vida , Assistência ao Convalescente , Alta do Paciente , Neoplasias do Sistema Biliar/cirurgia , Ductos Biliares Intra-Hepáticos
12.
BMC Surg ; 24(1): 102, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600548

RESUMO

BACKGROUNDS: Radical resection is the most effective treatment for perihilar tumors. Biliary tract reconstruction after resection is one of the key steps in this surgery. Mucosa-to-mucosa cholangiojejunostomy is traditionally performed, in which the bile ducts at the resection margin are separately anastomosed to the jejunum. However, this approach is associated with long operative time and high risk of postoperative complications. The present study presents a modified technique of hepatojejunostomy and its outcomes. METHODS: The data of patients who underwent hepatojejunostomy using the modified technique at the Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China, from January 2016 to December 2021, were retrospectively analyzed. RESULTS: A total of 13 patients with perihilar tumors underwent R0 resection and bilioenteric reconstruction using the modified hepatojejunostomy technique during the study period. During the operation, the alignment of the bile duct stumps was improved, the posterior wall of the anastomosis was reinforced, internal stents were placed in the smaller bile ducts, external stents were placed in the larger bile ducts, and hepatojejunostomy was performed using 4 - 0 prolene. No serious postoperative complications, such as death or bile leakage, occurred during the hospitalization. Furthermore, there were no cases of biliary stricture or cholangitis after the six-month follow-up period. CONCLUSION: The modified hepatojejunostomy technique is a safe and effective technique of biliary reconstruction after the resection of perihilar tumors. This can be easily performed for difficult cases with multiple bile ducts that require reconstruction after resection.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias , Humanos , Estudos Retrospectivos , Ductos Biliares/cirurgia , Anastomose Cirúrgica/métodos , Hepatectomia/métodos , Complicações Pós-Operatórias/etiologia , Neoplasias dos Ductos Biliares/cirurgia
13.
Pharm Biol ; 62(1): 314-325, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38571483

RESUMO

CONTEXT: Cholangiocarcinoma with highly heterogeneous, aggressive, and multidrug resistance has a poor prognosis. Although babaodan (BBD) combined with cisplatin improved non-small cell lung cancer efficacy, its impact on overcoming resistance in cholangiocarcinoma remains unexplored. OBJECTIVE: This study explored the role and mechanism of BBD on cisplatin resistance in cholangiocarcinoma cells (CCAs). MATERIALS AND METHODS: Cisplatin-resistant CCAs were exposed to varying concentrations of cisplatin (25-400 µg/mL) or BBD (0.25-1.00 mg/mL) for 48 h. IC50 values, inhibition ratios, apoptosis levels, DNA damage, glutathione (GSH) levels, oxidized forms of GSH, total GSH content, and glutaminase relative activity were evaluated using the cell counting kit 8, flow cytometry, comet assay, and relevant assay kits. RESULTS: BBD-reduced the cisplatin IC50 in CCAs from 118.8 to 61.83 µg/mL, leading to increased inhibition rate, apoptosis, and DNA damage, and decreased expression of B-cell lymphoma-2, p-Yes-associated protein 1/Yes-associated protein 1, solute carrier family 1 member 5, activating transcription factor 4, and ERCC excision repair 1 in a dose-dependent manner with maximum reductions of 78.97%, 51.98%, 54.03%, 56.59%, and 63.22%, respectively; bcl2-associated X and gamma histone levels were increased by 0.43-115.77% and 22.15-53.39%. The impact of YAP1 knockdown on cisplatin-resistant CCAs resembled BBD. GSH, oxidized GSH species, total GSH content, and glutaminase activity in cisplatin-resistant CCAs with BBD treatment also decreased, while YAP1 overexpression countered BBD's effects. DISCUSSION AND CONCLUSION: This study provides a scientific basis for BBD clinical application and provides a new direction for BBD biological mechanism research.


Assuntos
Antineoplásicos , Neoplasias dos Ductos Biliares , Carcinoma Pulmonar de Células não Pequenas , Colangiocarcinoma , Neoplasias Pulmonares , Humanos , Cisplatino/farmacologia , Proteínas de Sinalização YAP , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glutaminase/metabolismo , Glutaminase/farmacologia , Glutaminase/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Resistencia a Medicamentos Antineoplásicos , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral
16.
Front Immunol ; 15: 1377722, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550587

RESUMO

Liver cancer is the third leading of tumor death, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Immune checkpoint inhibitors (ICIs) are yielding much for sufferers to hope for patients, but only some patients with advanced liver tumor respond. Recent research showed that tumor microenvironment (TME) is critical for the effectiveness of ICIs in advanced liver tumor. Meanwhile, metabolic reprogramming of liver tumor leads to immunosuppression in TME. These suggest that regulating the abnormal metabolism of liver tumor cells and firing up TME to turn "cold tumor" into "hot tumor" are potential strategies to improve the therapeutic effect of ICIs in liver tumor. Previous studies have found that YAP1 is a potential target to improve the efficacy of anti-PD-1 in HCC. Here, we review that YAP1 promotes immunosuppression of TME, mainly due to the overstimulation of cytokines in TME by YAP1. Subsequently, we studied the effects of YAP1 on metabolic reprogramming in liver tumor cells, including glycolysis, gluconeogenesis, lipid metabolism, arachidonic acid metabolism, and amino acid metabolism. Lastly, we summarized the existing drugs targeting YAP1 in the treatment of liver tumor, including some medicines from natural sources, which have the potential to improve the efficacy of ICIs in the treatment of liver tumor. This review contributed to the application of targeted YAP1 for combined therapy with ICIs in liver tumor patients.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Ductos Biliares Intra-Hepáticos , Microambiente Tumoral
17.
Chirurgia (Bucur) ; 119(Ahead of print): 1-13, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38484362

RESUMO

Introduction: intrahepatic cholangiocarcinoma (ICCA) are rare, aggressive cancers that develop in second order or smaller bile ducts. The aim of this review is to systematically review the most important prognostic factors affecting the long-term outcomes of these patients. Material and Methods: articles conducted on this issue, written in English, published between from January 2000 to December 2023 in Cochrane Library, PubMed, Embase, MedLine, Web of Science, Elsevier, Google Scholar were systematically researched and reviewed. Results: ICCA are usually late diagnosed cancers because of the asymptomatic character, and curative procedures are often not feasible, only 20 to 30% of patients being fit for surgery. With the prognostic of this aggressive malignancy being baleful, the most important risk factors but also prognosis factors seem to be represented by socioeconomic factors, morphological presentation, dimensions, number and extension of the tumor as well as resection margins. Conclusions: once these factors are widely recognized and identified in each case, the clinician will be able to find the best treatment for these patients in order to improve the long-term outcomes.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Prognóstico , Resultado do Tratamento , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia
18.
J Pharmacol Sci ; 154(4): 301-311, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38485348

RESUMO

Amino acid transporter LAT1 is highly upregulated in various cancer types, including cholangiocarcinoma (CHOL), and contributes to the rapid proliferation of cancer cells and disease progression. However, the molecular mechanisms underlying the pathological upregulation of LAT1 remain largely unknown. This study pursued the possibility of miRNA-mediated regulation of the LAT1 expression in CHOL cells. Using online target prediction methods, we extracted five candidate miRNAs commonly predicted to regulate the LAT1 expression. Three of them, miR-194-5p, miR-122-5p, and miR-126-3p, were significantly downregulated in CHOL cancer compared to normal tissues. Correlation analysis revealed weak-to-moderate negative correlations between the expression of these miRNAs and LAT1 mRNA in CHOL cancer tissues. We selected miR-194-5p and miR-122-5p for further analyses and found that both miRNAs functionally target 3'UTR of LAT1 mRNA by a luciferase-based reporter assay. Transfection of the miRNA mimics significantly suppressed the LAT1 expression at mRNA and protein levels and inhibited the proliferation of CHOL cells, with a trend of affecting intracellular amino acids and amino acid-related signaling pathways. This study indicates that the decreased expression of these LAT1-targeting tumor-suppressive miRNAs contributes to the upregulation of LAT1 and the proliferation of CHOL cells, highlighting their potential for developing novel cancer therapeutics and diagnostics.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Linhagem Celular Tumoral , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , RNA Mensageiro/genética , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética
19.
Best Pract Res Clin Gastroenterol ; 68: 101893, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38522890

RESUMO

Cholangiocarcinoma (CCA) are primary malignancies of biliary system and usually unresectable at the time of diagnosis. As a consequence, majority of these cases are candidates for palliative care. With the advances in chemotherapeutic agents and multidisciplinary care, the survival rate has improved in cases with inoperable malignant biliary obstruction. As a consequence, there is a need to provide effective and durable palliative care in these patients. The main role of endoscopic palliation in the vast majority of CCA includes biliary stenting for obstructive jaundice. Recent advances in the endoscopic palliation and multimodal approach appear promising in imparting durable relief of symptoms. Use of radiofrequency ablation, photodynamic therapy and intraluminal brachytherapy has been shown to improve the survival rates as well as the patency of biliary stents. Infact, intraductal ablation may act synergistically with chemotherapy by modulating tumour signalling pathways and immune microenvironment.


Assuntos
Neoplasias dos Ductos Biliares , Ablação por Cateter , Colangiocarcinoma , Fotoquimioterapia , Humanos , Colangiopancreatografia Retrógrada Endoscópica , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/cirurgia , Cuidados Paliativos , Ductos Biliares Intra-Hepáticos/cirurgia , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/cirurgia , Stents , Ablação por Cateter/efeitos adversos , Microambiente Tumoral
20.
BMC Cancer ; 24(1): 358, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509498

RESUMO

BACKGROUND: The prognostic significance of tumor burden score (TBS) in relation to carcinoembryonic antigen (CEA) has not been investigated among patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). This study aimed to develop and validate a simplified model, a combination of TBS and CEA (CTC grade), for predicting the long-term outcomes of postoperative ICC patients. METHODS: Patients who underwent curative - intent resection of ICC between 2011 and 2019 were identified from a large multi - institutional database. The impact of TBS, CEA, and the CTC grade on overall survival (OS) and recurrence - free survival (RFS) was evaluated in both the derivation and validation cohorts. The receiver operating characteristic curve was utilized for assessing the predictive accuracy of the model. Subgroup analyses were performed across 8th TNM stage system stratified by CTC grade to assess the discriminatory capacity within the same TNM stage. RESULTS: A total of 812 patients were included in the derivation cohort and 266 patients in the validation cohort. Survival varied based on CEA (low: 36.7% vs. high: 9.0%) and TBS (low: 40.3% vs. high: 17.6%) in relation to 5 - year survival (both p < 0.001). As expected, patients with low CTC grade (i.e., low TBS/low CEA) were associated with the best OS as well as RFS, while high CTC grade (i.e., high TBS/high CEA) correlated to the worst outcomes. The model exhibited well performance in both the derivation cohort (area under the curve of 0.694) and the validation cohort (0.664). The predictive efficacy of the CTC grade system remains consistently stable across TNM stages I and III/IV. CONCLUSION: The CTC grade, a composite parameter derived from the combination of TBS and CEA levels, served as an easy - to - use tool and performed well in stratifying patients with ICC relative to OS and RFS.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Hepatectomia , Antígeno Carcinoembrionário , Carga Tumoral , Colangiocarcinoma/patologia , Prognóstico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Estudos Retrospectivos
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