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[PMID]:29408622
[Au] Autor:Zeng Y; Shen Z; Gu W; Wu M
[Ad] Endereço:Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, China; The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China. Ele
[Ti] Título:Inhibition of hepatocellular carcinoma tumorigenesis by curcumin may be associated with CDKN1A and CTGF.
[So] Source:Gene;651:183-193, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:This study aimed to explore crucial genes, transcription factors (TFs), and microRNAs (miRNAs) associated with the effects of curcumin against hepatocellular carcinoma (HCC). We downloaded data (GSE59713) from Gene Expression Omnibus to analyze differentially expressed genes (DEGs) between curcumin-treated and untreated HCC cell lines. Then, we identified the disease ontology (DO) and functional enrichment analysis of these DEGs and analyzed their protein-protein interactions (PPIs). Additionally, we constructed TF-target gene and miRNA-target gene regulatory networks and explored the potential functions of these DEGs. Finally, we detected the expression of CDKN1A, CTGF, LEF1 TF and MIR-19A regulated by curcumin in PLC/PRF/5 cells using RT-PCR. In total, 345 upregulated and 212 downregulated genes were identified. The main enriched pathway of upregulated genes was the TNF signaling pathway. The downregulated genes were significantly enriched in TGF-beta signaling pathway. In addition, most DEGs were significantly enriched in DO terms such as liver cirrhosis, hepatitis, hepatitis C and cholestasis (eg., CTGF). In the constructed PPI network, CDKN1A and CTGF were the key proteins. Moreover, LEF1, CDKN1A, and miR-19A that regulated CTGF were highlighted in the regulatory networks. Furthermore, the expression of CDKN1A, CTGF, LEF1 TF and miR-19A regulated by curcumin in PLC/PRF/5 cells was consistent with the aforementioned bioinformatics analysis results. To conclude, curcumin might exert its protective effects against HCC tumorigenesis by downregulating LEF1 and downregulating CTGF regulated by MIR-19A and upregulating CDKN1A expression.
[Mh] Termos MeSH primário: Carcinogênese/efeitos dos fármacos
Carcinoma Hepatocelular/tratamento farmacológico
Fator de Crescimento do Tecido Conjuntivo/genética
Curcumina/uso terapêutico
Inibidor de Quinase Dependente de Ciclina p21/genética
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/genética
Linhagem Celular Tumoral
Bases de Dados Genéticas
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Neoplasias Hepáticas/genética
Fator 1 de Ligação ao Facilitador Linfoide/genética
MicroRNAs/genética
Proteínas de Neoplasias/genética
Mapas de Interação de Proteínas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CDKN1A protein, human); 0 (CTGF protein, human); 0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (LEF1 protein, human); 0 (Lymphoid Enhancer-Binding Factor 1); 0 (MIRN19 microRNA, human); 0 (MicroRNAs); 0 (Neoplasm Proteins); 139568-91-5 (Connective Tissue Growth Factor); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


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[PMID]:29331379
[Au] Autor:Shinagawa-Kobayashi Y; Kamimura K; Goto R; Ogawa K; Inoue R; Yokoo T; Sakai N; Nagoya T; Sakamaki A; Abe S; Sugitani S; Yanagi M; Fujisawa K; Nozawa Y; Koyama N; Nishina H; Furutani-Seiki M; Sakaida I; Terai S
[Ad] Endereço:Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
[Ti] Título:Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model.
[So] Source:Biochem Biophys Res Commun;496(2):556-561, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model. METHODS: The fli::GFP transgenic medaka fish model has a fluorescently visible systemic vasculature. We fed the fish with SFN with and without histidine to compare blood flow and vascular structure among the differently fed models. The vascular cross-sectional area of each fish was measured to determine vascular diameter changes. RESULTS: Our results demonstrated that SFN-fed medaka developed a narrower vascular diameter. In addition, this narrowing was counteracted by addition of histidine to the medaka diet. We observed no positive effect of histidine on regeneration of cut vessels or on cell growth of endothelial cells and HCC cell lines. CONCLUSION: We proved the efficacy of the medaka model to assess vascular changes after administration of specific chemicals. And our results suggest that SFN causes vascular damage by narrowing peripheral vessel diameter, and that histidine effectively counteracts these changes to maintain blood flow.
[Mh] Termos MeSH primário: Antineoplásicos/efeitos adversos
Velocidade do Fluxo Sanguíneo/efeitos dos fármacos
Vasos Sanguíneos/efeitos dos fármacos
Vasos Sanguíneos/patologia
Histidina/farmacologia
Niacinamida/análogos & derivados
Compostos de Fenilureia/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Carcinoma Hepatocelular/tratamento farmacológico
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Niacinamida/efeitos adversos
Oryzias
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Phenylurea Compounds); 25X51I8RD4 (Niacinamide); 4QD397987E (Histidine); 9ZOQ3TZI87 (sorafenib)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE


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[PMID]:29267507
[Au] Autor:Liu N; Ding D; Wang L; Zhao H; Zhu L; Geng X
[Ad] Endereço:Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
[Ti] Título:Two novel Mg(II)-based and Zn(II)-based complexes: inhibiting growth of human liver cancer cells.
[So] Source:Braz J Med Biol Res;51(2):e6929, 2017 Dec 18.
[Is] ISSN:1414-431X
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Two new Mg(II)-based and Zn(II)-based coordination polymers, {[Mg3(BTB)(DMA)4](DMA)2}n (1, H3BTB=1,3,5-benzenetrisbenzoic acid, DMA=N,N-dimethylacetamide) and {(H2NMe2)2[Zn3(BTB)2(OH)(Im)](DMF)9(MeOH)7}n (2, Im=imidazole, DMF=N,N-dimethylformamide), have been successfully synthesized and structurally characterized under solvothermal conditions. 1 contains a linear [Mg3(COO)6] cluster that connected by the fully deprotonated BTB3- ligands to give a kgd-type 2D bilayer structure; 2 represents a microporous 3D pillar-layered system based on the binuclear Zn units and pillared Im ligands, which shows a (3,5)-connected hms topological net. In addition, in vitro anticancer activities of compounds 1 and 2 on 4 human liver cancer cells (HB611, HHCC, BEL-7405 and SMMC-7721) were determined.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Benzimidazóis/farmacologia
Neoplasias Hepáticas/tratamento farmacológico
Estruturas Metalorgânicas/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Benzimidazóis/síntese química
Linhagem Celular Tumoral
Seres Humanos
Ligantes
Neoplasias Hepáticas/patologia
Magnésio/química
Estruturas Metalorgânicas/síntese química
Estrutura Molecular
Zinco/química
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Benzimidazoles); 0 (Ligands); 0 (Metal-Organic Frameworks); I38ZP9992A (Magnesium); J41CSQ7QDS (Zinc)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE


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[PMID]:29249005
[Au] Autor:Trevisani F; Brandi G; Garuti F; Barbera MA; Tortora R; Casadei Gardini A; Granito A; Tovoli F; De Lorenzo S; Inghilesi AL; Foschi FG; Bernardi M; Marra F; Sacco R; Di Costanzo GG
[Ad] Endereço:Department of Medical and Surgical Sciences, Medical Semeiotics, University of Bologna, via Albertoni 15, 40138, Bologna, Italy. franco.trevisani@unibo.it.
[Ti] Título:Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation.
[So] Source:J Cancer Res Clin Oncol;144(2):403-414, 2018 Feb.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Metronomic capecitabine (MC) is a well-tolerated systemic treatment showing promising results in one retrospective study, as second-line therapy after sorafenib failure, in patients with hepatocellular carcinoma (HCC). METHODS: 117 patients undergoing MC were compared to 112 patients, eligible for this treatment, but undergoing best supportive care (BSC) after sorafenib discontinuation for toxicity or HCC progression. The two groups were compared for demographic and clinical features. A multivariate regression analysis was conducted to detect independent prognostic factors. To balance confounding factors between the two groups, a propensity score model based on independent prognosticators (performance status, neoplastic thrombosis, causes of sorafenib discontinuation and pre-sorafenib treatment) was performed. RESULTS: Patients undergoing MC showed better performance status, lower tumor burden, lower prevalence of portal vein thrombosis, and better cancer stage. Median (95% CI) post-sorafenib survival (PSS) was longer in MC than in BSC patients [9.5 (7.5-11.6) vs 5.0 (4.2-5.7) months (p < 0.001)]. Neoplastic thrombosis, cause of sorafenib discontinuation, pre-sorafenib treatment and MC were independent prognosticators. The benefit of capecitabine was confirmed in patients after matching with propensity score [PSS: 9.9 (6.8-12.9) vs. 5.8 (4.8-6.8) months, (p = 0.001)]. MC lowered the mortality risk by about 40%. MC achieved better results in patients who stopped sorafenib for adverse events than in those who progressed during it [PSS: 17.3 (10.5-24.1) vs. 7.8 (5.2-10.1) months, (p = 0.035)]. Treatment toxicity was low and easily manageable with dose modulation. CONCLUSIONS: MC may be an efficient and safe second-line systemic therapy for HCC patients who discontinued sorafenib for toxicity or tumor progression.
[Mh] Termos MeSH primário: Capecitabina/administração & dosagem
Carcinoma Hepatocelular/tratamento farmacológico
Neoplasias Hepáticas/tratamento farmacológico
Niacinamida/análogos & derivados
Compostos de Fenilureia/administração & dosagem
[Mh] Termos MeSH secundário: Administração Metronômica
Idoso
Antimetabólitos Antineoplásicos/administração & dosagem
Feminino
Seres Humanos
Masculino
Niacinamida/administração & dosagem
Niacinamida/efeitos adversos
Compostos de Fenilureia/efeitos adversos
Inibidores de Proteínas Quinases/administração & dosagem
Inibidores de Proteínas Quinases/efeitos adversos
Estudos Retrospectivos
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (Phenylurea Compounds); 0 (Protein Kinase Inhibitors); 25X51I8RD4 (Niacinamide); 6804DJ8Z9U (Capecitabine); 9ZOQ3TZI87 (sorafenib)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171218
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2556-6


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[PMID]:28468916
[Au] Autor:Vujanovic L; Stahl EC; Pardee AD; Geller DA; Tsung A; Watkins SC; Gibson GA; Storkus WJ; Butterfield LH
[Ad] Endereço:University of Pittsburgh Cancer Institute, University of Pittsburgh, Pennsylvania.
[Ti] Título:Tumor-Derived α-Fetoprotein Directly Drives Human Natural Killer-Cell Activation and Subsequent Cell Death.
[So] Source:Cancer Immunol Res;5(6):493-502, 2017 Jun.
[Is] ISSN:2326-6074
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hepatocellular carcinoma (HCC) patients with reduced natural killer (NK)-cell numbers and function have been shown to have a poor disease outcome. Mechanisms underlying NK-cell deficiency and dysfunction in HCC patients remain largely unresolved. α-Fetoprotein (AFP) is an oncofetal antigen produced by HCC. Previous studies demonstrated that tumor-derived AFP (tAFP) can indirectly impair NK-cell activity by suppressing dendritic cell function. However, a direct tAFP effect on NK cells remains unexplored. The purpose of this study was to examine the ability of cord blood-derived AFP (nAFP) and that of tAFP to directly modulate human NK-cell activity and longevity Short-term exposure to tAFP and, especially, nAFP proteins induced a unique proinflammatory, IL2-hyperresponsive phenotype in NK cells as measured by IL1ß, IL6, and TNF secretion, CD69 upregulation, and enhanced tumor cell killing. In contrast, extended coculture with tAFP, but not nAFP, negatively affected long-term NK-cell viability. NK-cell activation was directly mediated by the AFP protein itself, whereas their viability was affected by hydrophilic components within the low molecular mass cargo that copurified with tAFP. Identification of the distinct impact of circulating tAFP on NK-cell function and viability may be crucial to developing a strategy to ameliorate HCC patient NK-cell functional deficits. .
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/imunologia
Células Matadoras Naturais/imunologia
Neoplasias Hepáticas/imunologia
alfa-Fetoproteínas/imunologia
[Mh] Termos MeSH secundário: Morte Celular
Linhagem Celular Tumoral
Proliferação Celular
Células Cultivadas
Citocinas/imunologia
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AFP protein, human); 0 (Cytokines); 0 (alpha-Fetoproteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1158/2326-6066.CIR-16-0216


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[PMID]:28467999
[Au] Autor:Thorgeirsson SS
[Ad] Endereço:Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
[Ti] Título:Stemness in Liver Cancer.
[So] Source:Dig Dis;35(4):387-389, 2017.
[Is] ISSN:1421-9875
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Cancer cells possessing "stemness," or stem-cell properties, are referred to as cancer stem cells (CSC) or cancer-initiating cells. The concept that these cells rest at the apex of the cancer hierarchy is an evolving theme in cancer research. These cells are by definition primarily responsible for the initiation and propagation of tumors as well as relapse after therapy, and they are therefore of major scientific interest. Several studies indicate that hepatocellular carcinomas that harbor phenotypic features of stem cells and progenitor cells constitute a subclass of therapeutically challenging cancers that are associated with a particularly poor prognosis. We recently demonstrated that any cell type in the mouse hepatic lineage can undergo oncogenic reprogramming into a CSC by activating different cell type-specific pathways [1]. Identification of common and cell of origin-specific phenotypic and genetic changes could provide new therapeutic targets for liver cancer.
[Mh] Termos MeSH primário: Neoplasias Hepáticas/patologia
Células-Tronco Neoplásicas/patologia
[Mh] Termos MeSH secundário: Animais
Carcinogênese/patologia
Carcinoma Hepatocelular/patologia
Seres Humanos
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1159/000456592


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[PMID]:28453695
[Au] Autor:Suenaga M; Schirripa M; Cao S; Zhang W; Yang D; Murgioni S; Rossini D; Marmorino F; Mennitto A; Ning Y; Okazaki S; Berger MD; Miyamoto Y; Gopez R; Barzi A; Yamaguchi T; Loupakis F; Lenz HJ
[Ad] Endereço:Department of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA.
[Ti] Título:Genetic variants of DNA repair-related genes predict efficacy of TAS-102 in patients with refractory metastatic colorectal cancer.
[So] Source:Ann Oncol;28(5):1015-1022, 2017 05 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib. Single nucleotide polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX, RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1, PCNA) were analyzed by PCR-based direct sequencing. Results: In univariate analysis for the evaluation cohort, patients with any G allele in ATM rs609429 had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4 months, HR 0.37, 95% CI: 0.14-0.99, P = 0.022). Patients carrying any A allele in XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs. 2.3 months, HR 0.44, 95% CI: 0.21-0.92, P = 0.024) and OS (15.6 vs. 6.3 months, HR 0.25, 95% CI: 0.08-0.79, P = 0.012) than those with the G/G variant. In multivariable analysis, ATM rs609429 remained significant for OS (P = 0.020). In the validation cohort, patients having ATM rs609429 with any G allele showed longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though without statistical significance. Conclusion: Genetic variants in the HR pathway may predict clinical outcome in mCRC patients receiving TAS-102.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Neoplasias Colorretais/genética
Enzimas Reparadoras do DNA/genética
Neoplasias Hepáticas/genética
Trifluridina/uso terapêutico
Uracila/análogos & derivados
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/farmacologia
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/mortalidade
Neoplasias Colorretais/patologia
Intervalo Livre de Doença
Combinação de Medicamentos
Resistência a Medicamentos Antineoplásicos/genética
Feminino
Estudos de Associação Genética
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/mortalidade
Neoplasias Hepáticas/secundário
Masculino
Meia-Idade
Compostos de Fenilureia/farmacologia
Compostos de Fenilureia/uso terapêutico
Modelos de Riscos Proporcionais
Piridinas/farmacologia
Piridinas/uso terapêutico
Estudos Retrospectivos
Resultado do Tratamento
Trifluridina/farmacologia
Uracila/farmacologia
Uracila/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Drug Combinations); 0 (Phenylurea Compounds); 0 (Pyridines); 0 (TAS 102); 24T2A1DOYB (regorafenib); 56HH86ZVCT (Uracil); EC 6.5.1.- (DNA Repair Enzymes); RMW9V5RW38 (Trifluridine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx035


  8 / 125406 MEDLINE  
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[PMID]:28922789
[Au] Autor:Mlecnik B; Van den Eynde M; Bindea G; Church SE; Vasaturo A; Fredriksen T; Lafontaine L; Haicheur N; Marliot F; Debetancourt D; Pairet G; Jouret-Mourin A; Gigot JF; Hubert C; Danse E; Dragean C; Carrasco J; Humblet Y; Valge-Archer V; Berger A; Pagès F; Machiels JP; Galon J
[Ad] Endereço:Laboratory of Integrative Cancer Immunology, INSERM, UMRS1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMRS1138, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS1138, Centre de Recherche des Cordeliers, Paris, France; Inovarion, Paris, France; Department of Medic
[Ti] Título:Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not. Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis.
[Mh] Termos MeSH primário: Linfócitos B
Neoplasias Colorretais/imunologia
Neoplasias Hepáticas/imunologia
Neoplasias Pulmonares/imunologia
Linfócitos do Interstício Tumoral
Linfócitos T
[Mh] Termos MeSH secundário: Idoso
Antígenos CD20/análise
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linfócitos B/química
Complexo CD3/análise
Linfócitos T CD8-Positivos
Quimioterapia Adjuvante
Neoplasias Colorretais/patologia
Neoplasias Colorretais/terapia
Intervalo Livre de Doença
Seguimentos
Fatores de Transcrição Forkhead/análise
Hepatectomia
Seres Humanos
Antígenos Comuns de Leucócito/análise
Neoplasias Hepáticas/secundário
Neoplasias Hepáticas/terapia
Neoplasias Pulmonares/secundário
Neoplasias Pulmonares/terapia
Contagem de Linfócitos
Metastasectomia
Meia-Idade
Metástase Neoplásica
Pneumonectomia
Período Pré-Operatório
Critérios de Avaliação de Resposta em Tumores Sólidos
Taxa de Sobrevida
Linfócitos T/química
Microambiente Tumoral/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (CD3 Complex); 0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx123


  9 / 125406 MEDLINE  
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[PMID]:28453918
[Au] Autor:Vannas MJ; Boyd S; Färkkilä MA; Arola J; Isoniemi H
[Ad] Endereço:Transplantation and Liver Surgery Clinic, Helsinki University Hospital, Helsinki, Finland.
[Ti] Título:Value of brush cytology for optimal timing of liver transplantation in primary sclerosing cholangitis.
[So] Source:Liver Int;37(5):735-742, 2017 May.
[Is] ISSN:1478-3231
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND AIMS: Primary sclerosing cholangitis is associated with a high risk of cholangiocarcinoma. Here, we investigated the value of surveillance for dysplasia using brush cytology, to determine the optimal timing of liver transplantation in primary sclerosing cholangitis. We compared our preoperative findings, with the final explanted liver histopathology. METHODS: 126 consecutive patients were transplanted for primary sclerosing cholangitis from 1984 to 2012. Patients were divided into two groups: symptomatic (n=91), and asymptomatic (n=35). RESULTS: Brush cytology was available for 101 patients; 66 symptomatic and 35 asymptomatic. Suspicious cytological findings were found in nine patients (14%) in the symptomatic group and 17 (49%) in the asymptomatic group. DNA flow cytometry was available for 49 patients (25 symptomatic, 24 asymptomatic), with aneuploidy detected in six patients (24%) in the symptomatic group and 15 (63%) in the asymptomatic group. Explanted liver histology showed biliary dysplasia or cholangiocarcinoma in 11 symptomatic patients (12%) and 15 asymptomatic patients (43%). A combination of cytological and DNA flow cytometry findings resulted in a test sensitivity of 68%, with a specificity of 86%. Ten-year survival in the asymptomatic group was 91%. CONCLUSIONS: Dysplasia surveillance using brush specimens may help to select those patients likely to benefit from early liver transplantation. It remains unclear as to whether surveillance with brush cytology improves long-term survival, but there is presently no better method with which to predict transplantation timing.
[Mh] Termos MeSH primário: Sistema Biliar/patologia
Colangite Esclerosante/patologia
Colangite Esclerosante/cirurgia
Citodiagnóstico/métodos
Células Epiteliais/patologia
Transplante de Fígado
[Mh] Termos MeSH secundário: Adulto
Neoplasias dos Ductos Biliares/patologia
Carcinoma Hepatocelular/patologia
Colangiocarcinoma/patologia
Colangiopancreatografia Retrógrada Endoscópica
Diagnóstico Diferencial
Feminino
Finlândia
Seres Humanos
Estimativa de Kaplan-Meier
Neoplasias Hepáticas/patologia
Masculino
Meia-Idade
Sistema de Registros
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/liv.13276


  10 / 125406 MEDLINE  
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[PMID]:27770401
[Au] Autor:Schulte ML; Hight MR; Ayers GD; Liu Q; Shyr Y; Washington MK; Manning HC
[Ad] Endereço:Vanderbilt Center for Molecular Probes, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
[Ti] Título:Non-Invasive Glutamine PET Reflects Pharmacological Inhibition of BRAF In Vivo.
[So] Source:Mol Imaging Biol;19(3):421-428, 2017 06.
[Is] ISSN:1860-2002
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: This study aimed to study whether cancer cells possess distinguishing metabolic features compared with surrounding normal cells, such as increased glutamine uptake. Given this, quantitative measures of glutamine uptake may reflect critical processes in oncology. Approximately, 10 % of patients with colorectal cancer (CRC) express BRAF , which may be actionable with selective BRAF inhibitors or in combination with inhibitors of complementary signaling axes. Non-invasive and quantitative predictive measures of response to these targeted therapies remain poorly developed in this setting. The primary objective of this study was to explore 4-[ F]fluoroglutamine (4-[ F]F-GLN) positron emission tomography (PET) to predict response to BRAF -targeted therapy in preclinical models of colon cancer. PROCEDURES: Tumor microarrays from patients with primary human colon cancers (n = 115) and CRC liver metastases (n = 111) were used to evaluate the prevalence of ASCT2, the primary glutamine transporter in oncology, by immunohistochemistry. Subsequently, 4-[ F]F-GLN PET was evaluated in mouse models of human BRAF -expressing and BRAF wild-type CRC. RESULTS: Approximately 70 % of primary colon cancers and 53 % of metastases exhibited positive ASCT2 immunoreactivity, suggesting that [ F]4-F-GLN PET could be applicable to a majority of patients with colon cancer. ASCT2 expression was not associated selectively with the expression of mutant BRAF. Decreased 4-[ F]F-GLN predicted pharmacological response to single-agent BRAF and combination BRAF and PI3K/mTOR inhibition in BRAF -mutant Colo-205 tumors. In contrast, a similar decrease was not observed in BRAF wild-type HCT-116 tumors, a setting where BRAF -targeted therapies are ineffective. CONCLUSIONS: 4-[ F]F-GLN PET selectively reflected pharmacodynamic response to BRAF inhibition when compared with 2-deoxy-2[ F]fluoro-D-glucose PET, which was decreased non-specifically for all treated cohorts, regardless of downstream pathway inhibition. These findings illustrate the utility of non-invasive PET imaging measures of glutamine uptake to selectively predict response to BRAF-targeted therapy in colon cancer and may suggest further opportunities to inform colon cancer clinical trials using targeted therapies against MAPK activation.
[Mh] Termos MeSH primário: Glutamina/química
Mutação/genética
Tomografia por Emissão de Pósitrons
Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores
Proteínas Proto-Oncogênicas B-raf/genética
[Mh] Termos MeSH secundário: Sistema ASC de Transporte de Aminoácidos/metabolismo
Animais
Linhagem Celular Tumoral
Neoplasias do Colo/tratamento farmacológico
Neoplasias do Colo/metabolismo
Neoplasias do Colo/patologia
Feminino
Seres Humanos
Neoplasias Hepáticas/secundário
Camundongos Nus
Antígenos de Histocompatibilidade Menor/metabolismo
Inibidores de Proteínas Quinases/farmacologia
Inibidores de Proteínas Quinases/uso terapêutico
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acid Transport System ASC); 0 (Minor Histocompatibility Antigens); 0 (Protein Kinase Inhibitors); 0 (SLC1A5 protein, human); 0RH81L854J (Glutamine); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1007/s11307-016-1008-z



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