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1.
Mol Med Rep ; 25(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35029280

RESUMO

Silent information regulator factor 2­related enzyme 1 (Sirt1) is involved in the regulation of cell senescence, gene transcription, energy balance and oxidative stress. However, the effect of Sirt1 on atrial natriuretic factor (ANF) secretion, especially under hypoxic conditions is unclear. The present study aimed to investigate the effect of Sirt1, regulated by NADPH oxidase 4 (NOX4), on ANF secretion in isolated beating rat atria during hypoxia. ANF secretion was analyzed using radioimmunoassays and protein expression levels were determined by western blotting and immunofluorescence staining. Intra­atrial pressure was recorded using a physiograph. Hypoxia significantly upregulated Sirt1 and nuclear factor erythroid­2­related factor 2 (Nrf2) protein expression levels, together with significantly increased ANF secretion. Hypoxia­induced protein expression of Sirt1 was significantly blocked by a NOX4 inhibitor, GLX351322, and Nrf2 protein expression levels were significantly abolished using the Sirt1 inhibitor, EX527. Hypoxia also significantly elevated the protein expression levels of phosphorylated­Akt and sequestosome 1 and significantly downregulated Kelch­like ECH­associated protein 1 protein expression levels. These effects were significantly blocked by EX527, preventing hypoxia­induced Nrf2 expression. An Nrf2 inhibitor, ML385, significantly abolished the hypoxia­induced upregulation of activating transcription factor (ATF)3, ATF4, T cell factor (TCF)3 and TCF4/lymphoid enhancer factor 1 (LEF1) protein expression levels, and significantly attenuated hypoxia­induced ANF secretion. These results indicated that Sirt1 and Nrf2, regulated by NOX4, can potentially stimulate TCF3 and TCF4/LEF1 signaling via ATF3 and ATF4 activation, thereby potentially participating in the regulation of ANF secretion in beating rat atria during hypoxia. In conclusion, intervening with the Sirt1/Nrf2/ATF signaling pathway may be an effective strategy for resisting oxidative stress damage in the heart during hypoxia.


Assuntos
Fator 3 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Fator Natriurético Atrial/biossíntese , Átrios do Coração/metabolismo , Hipóxia/metabolismo , NADPH Oxidase 4/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Sirtuína 1/metabolismo , Animais , Imunofluorescência , Expressão Gênica , Hipóxia/genética , Proteína 1 Associada a ECH Semelhante a Kelch , Ratos
2.
Int J Biol Macromol ; 193(Pt B): 2183-2191, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34785197

RESUMO

Biologically active bacterial cellulose (BC) was efficiently synthesized in situ using wine pomace and its hydrolysate. The structural and biomechanical properties together with the biological functions of the BC were investigated. Functional BC from wine pomace and its enzymatic hydrolysate were of high purity and had higher crystallinity indexes (90.61% and 89.88%, respectively) than that from HS medium (82.26%). FTIR results proved the in-situ bindings of polyphenols to the functionalized BC. Compared to BC from HS medium, wine pomace-based BC had more densely packed ultrafine fibrils, higher diameter range distributions of fiber ribbon, but lower thermal decomposition temperatures, as revealed by the SEM micrographs and DSC data. Meanwhile, wine pomace-based BC exhibited higher loads in tensile strength and higher hardness (4.95 ± 0.31 N and 5.13 ± 0.63 N, respectively) than BC in HS medium (3.43 ± 0.14 N). Furthermore, BC synthesized from wine pomace hydrolysate exhibited a slower release rate of phenolic compounds, and possessed more antioxidant activities and better bacteriostatic effects than BC from wine pomace. These results demonstrate that BC synthesized in situ from wine pomace (especially from enzymatic hydrolysate) is a promising biomolecule with a potential application in wound dressing, tissue engineering, and other biomedical fields.


Assuntos
Antibacterianos/metabolismo , Antioxidantes/metabolismo , Celulose/metabolismo , Bactérias/metabolismo , Fibras na Dieta/metabolismo , Polifenóis/metabolismo , Resistência à Tração/fisiologia , Vinho
3.
Pharmacol Res ; 174: 105955, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34715330

RESUMO

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Infectologia/tendências , Medicina Tradicional Chinesa/tendências , SARS-CoV-2/efeitos dos fármacos , Antivirais/efeitos adversos , COVID-19/diagnóstico , COVID-19/virologia , Consenso , Técnica Delfos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicina Baseada em Evidências/tendências , Interações Hospedeiro-Patógeno , Humanos , Gravidade do Paciente , SARS-CoV-2/patogenicidade , Resultado do Tratamento
4.
Int J Biol Macromol ; 191: 211-221, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34547311

RESUMO

A cellulose-producing bacterium Komagataeibacter rhaeticus K15 was isolated from kombucha tea, and its metabolic pathways and cellulose synthesis operon were analyzed by genome sequencing. Different from the reported K. rhaeticus, the K15 produced little gluconic acid (2.26 g/L) when glucose was the sole carbon source and has the capacity for high cellulose production (4.76 g/L) with other carbon sources. Furthermore, six nitrogen-fixing genes were found to be responsible for the survival of K15 on a nitrogen-free medium. Based on its fermentation characteristics, K15 was cultured in a kitchen waste medium as a strategy for green and sustainable bacterial cellulose production. The SEM, XRD, and FTIR results indicated that synthesized cellulose has a mean diameter of 40-50 nm nanofiber, good crystallinity, and the same chemical structure. The K15 strain provides a highly viable alternative strategy to reduce the costs of bacterial cellulose production using agro-industrial residues as nutrient sources.


Assuntos
Acetobacteraceae/metabolismo , Celulose/biossíntese , Fermentação , Genes Bacterianos , Microbiologia Industrial/métodos , Eliminação de Resíduos/métodos , Acetobacteraceae/genética , Culinária , Fixação de Nitrogênio/genética , Resíduos
5.
Exp Cell Res ; 404(1): 112618, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33965401

RESUMO

Androgenetic alopecia (AGA) is the most common type of hair loss dysfunction. Secreted frizzled related protein 1 (SFRP1) is found to be associated with hair loss, but its role in AGA and the regulation mechanism of its transcription level is unclear. The aim of our study is to explore the expression of SFRP1 in AGA samples and its transcriptional mechanism. Male frontal and occipital scalp hair follicles from AGA patients were collected, and human dermal papilla cells (DPCs) were isolated and cultured. SFRP1 gene was cloned and constructed into recombinant plasmids to perform dual-luciferase reporter assay. Transcription factor binding sites were predicted through the Jaspar website and further confirmed by the chromatin immunoprecipitation (ChIP) assay. Expression of genes in DPCs was determined by immunofluorescence (IF) staining, quantitative real-time PCR (qRT-PCR) and western blotting. Our findings showed that SFRP1 was highly expressed in DPCs of AGA patients. The core promoter region of SFRP1 was from -100 to +50 bp and was found to be positively regulated by forkhead box C1 (FOXC1), a transcription factor related to hair growth, both at mRNA and protein level in DPCs. Our study suggests that FOXC1 plays an important role in regulating SFRP1 transcription, which may provide new insights into the development of therapeutic strategies for the treatment of AGA.


Assuntos
Alopecia/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Folículo Piloso/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , Alopecia/tratamento farmacológico , Alopecia/genética , Derme/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Fatores de Transcrição/metabolismo
6.
Biomed Environ Sci ; 33(12): 906-915, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472730

RESUMO

OBJECTIVE: Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19. METHODS: A total of 333 consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated in the departments of Internal medicine of Shenzhen Third People's Hospital from January 11 th to February 10 th, 2020 were included. The data were obtained from electronic medical records. The epidemiological data, clinical characteristics, length of hospital stays, and outcomes of pediatric and adult patients were compared. RESULTS: Compared with adult patients, pediatric patients had a shorter time of symptom onset to hospitalization than adults [median time, 1 ( IQR, 1.0-1.0) d vs. 3 ( IQR, 2.0-6.0) d, P < 0.001], milder or fewer symptoms, less severe chest CT findings. The clinical severity classification of children was less severe than adults. Up to 15 th March, the end of the follow-up, 33 (100%) children and 292 (97.3%) adult patients had been discharged from hospital. Only 2 (0.7%) adult patients died, with an overall case mortality of 0.6%. The median length of hospital stay of pediatric patients was shorter than that of adult patients [19 (95% CI: 16.6-21.4) d vs. 21 (95% CI: 19.9-22.1) d, P = 0.024]. CONCLUSION: Pediatric patients with COVID-19 had milder or less clinical symptoms, less evident pulmonary imaging changes, better prognosis, and shorter length of hospital stay.


Assuntos
COVID-19/patologia , COVID-19/epidemiologia , COVID-19/terapia , Criança , China/epidemiologia , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Resultado do Tratamento
7.
Iran J Pharm Res ; 18(2): 631-641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531047

RESUMO

Iguratimod is a new synthetic disease-modifying antirheumatic drug intended to treat patients with rheumatoid arthritis. A new method using recombinant human CYP450s yeast cells containing c-DNA expressed P450s was applied to identify the metabolic pathways of iguratimod and to prepare its metabolite. The metabolite was isolated, and its structure was identified by quadrupole time-of-flight-mass spectrometry and nuclear magnetic resonance. Furthermore, a selective and sensitive high performance liquid chromatography (HPLC) method was developed for the simultaneous quantification of iguratimod and its major metabolite in rat plasma for the first time. The results indicated that iguratimod was mainly metabolized to a metabolite by CYP2C9 and CYP2C19 in in-vitro study. The structure of the metabolite was identified as M2 (N-[3-(acetamido)-4-oxo-6-phenoxy-4H-chromen-7-yl]methanesulfonamide). HPLC assay was achieved on a C18 column using methanol-water containing 0.1% trifluoroacetic acid (55:45 v/v) at a flow rate of 1 mL/min with UV detection at 257 nm. Standard calibration curves were obtained in the concentration range of 0.5-20 µg/mL for iguratimod and its metabolite M2. The lower limits of detection of iguratimod and M2 in rat plasma were 0.1 and 0.25 µg/mL, respectively. The intra- and inter-day precision (RSD%) were within 5% for the two analytes. The average recoveries of the analytes were greater than 90%. In conclusion, recombinant human CYP450s whole-yeast transformation system could be successfully used to identify and prepare the major metabolite of iguratimod. The HPLC method we developed could be successfully applied to evaluate pharmacokinetics of iguratimod and its metabolite M2 in rats.

8.
ANZ J Surg ; 89(7-8): 908-913, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31090189

RESUMO

BACKGROUND: Percutaneous radiofrequency ablation (RFA) is used as a first-line treatment for colorectal liver metastases that recur after first liver resection in our institution. We aim to evaluate its therapeutic efficacy compared to repeated surgical resection. METHODS: A retrospective review was performed in 104 patients treated with curative intent for resectable recurrent colorectal liver metastases. RESULTS: Sixty-one patients underwent RFA and 43 patients underwent surgery. The overall recurrence rates were 82% in the RFA group and 65.1% in the resection group (P = 0.05). The local recurrence rate on a lesion-basis was markedly higher after RFA than that after resection (16.7% versus 7.3%, P = 0.04). The difference remained significant in patients with a maximum lesion diameter >3 cm (24.5% versus 7.6%, P = 0.01). RFA treatment was independently associated with recurrence on multivariate analyses (P = 0.01). 69.7% of RFA patients and 42.6% of surgery patients with intrahepatic recurrence were amenable to repeated local treatment (P = 0.05), leading to the equivalent actuarial 3-year progression free survival rates (RFA: 29.1% versus Resection: 33.1%, P = 0.48) and 5-year overall survival rates in the two treatment groups (RFA: 33% versus Resection: 28.4%, P = 0.36). CONCLUSIONS: Surgery remains the treatment of choice for resectable recurrence. RFA may offer similar benefit in selected patients.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Metastasectomia , Recidiva Local de Neoplasia/cirurgia , Ablação por Radiofrequência , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
9.
J Gastrointest Surg ; 23(12): 2421-2429, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30771211

RESUMO

BACKGROUND: In predicting the risk for posthepatectomy complications, hepatectomy is traditionally classified into minor or major resection based on the number of resected segments. Recently, a new hepatectomy complexity classification was proposed. This study aimed to compare the value of the traditional and that of the new classification in perioperative outcomes prediction. METHODS: Demographics, perioperative laboratory tests, intraoperative and postoperative outcomes, and follow-up data of patients with hepatocellular carcinoma who underwent liver resection were retrospectively analyzed. RESULTS: A total of 302 patients were included in our study. Multivariable analysis of intraoperative variables showed that the complexity classification could independently predict the occurrence of blood loss > 800 mL, operation time > 4 h, intraoperative transfusion, and the use of Pringle's maneuver (all p < 0.05). For postoperative outcomes, the high-complexity group was independently associated with severe complications, and hepatic-related complications (all p < 0.05); the traditional classification was independently associated only with posthepatectomy liver failure (PHLF) (p = 0.004). CONCLUSIONS: Complexity classification could be used to assess the difficulty of surgery and was independently associated with postoperative complications. The traditional classification did not reflect operation complexity and was associated only with PHLF.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Hepatectomia/classificação , Complicações Intraoperatórias/etiologia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Prognóstico , Estudos Retrospectivos
10.
J Gastrointest Surg ; 23(3): 563-570, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30066069

RESUMO

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is a marker of inflammation and is associated with poor outcomes. We aimed to evaluate the role of the pretreatment NLR in predicting the outcomes after preoperative chemotherapy in patients with colorectal liver metastases (CRLM). METHODS: A retrospective review was performed for 183 patients with CRLM. The NLR was measured before chemotherapy, and a receiver operating characteristic (ROC) curve was used to estimate the cutoff value. Logistic regressions were applied to analyze potential predictors of the pathological response. The Cox proportional hazard method was used to analyze survival. RESULTS: The pre-chemotherapy NLR was 2.4 ± 1.1, whereas the post-chemotherapy NLR was 2.1 ± 1.6 (p < 0.001). The pretreatment NLR of 2.3 was a significant predictive marker for the pathological response. The pathological response rates were 67.1% in the patients with an NLR ≤ 2.3 and 48.1% in patients with an NLR > 2.3 (p = 0.01). Multivariate analysis revealed that the factors independently associated with pathological responses were a low pretreatment NLR (p = 0.043), radiological response to chemotherapy (p < 0.001), first-line chemotherapy (p = 0.001), and targeted therapy (p = 0.002). The median overall survival (OS) and recurrence-free survival (RFS) were worse in the increased NLR cohort than in the low NLR cohort (OS: 31.1 vs. 43.1 months, p = 0.012; RFS: 6.5 vs. 9.4 months, p = 0.06). According to multivariate analyses, a high pretreatment NLR was a significant predictor for both worse OS (HR = 2.43, 95%CI = 1.49-3.94, p < 0.001) and RFS (HR = 1.53, 95%CI = 1.08-2.18, p = 0.017). CONCLUSIONS: An increased pretreatment NLR was a significant predictor of a poor pathological response and worse prognosis after preoperative chemotherapy. The NLR is a simple biomarker for assessing chemotherapy efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/terapia , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Neoplasias Colorretais/terapia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/secundário , Masculino , Metástase Neoplásica , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos
11.
Transl Cancer Res ; 8(2): 422-428, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35116774

RESUMO

BACKGROUND: We aimed to study the incidence rate of hypoparathyroidism, its risk factors, and identify its predictive factors among patients with papillary thyroid carcinoma (PTC) who had undergone total or near-total thyroidectomy and central neck dissection (CND). METHODS: Ninety-three PTC patients who had undergone total or near-total thyroidectomy and CND were analyzed for hypoparathyroidism. The association between clinicopathological factors and hypoparathyroidism was tested by χ2 test and multivariate logistic regression. The ROC curve and a 2×2 contingency table were used to evaluate the performance of postoperative parathyroid hormone (PTH) and serum calcium concentration in prediction of hypothyroidism. RESULTS: Hypothyroidism was observed in 46 patients (49.5%), among whom 2 had permanent hypothyroidism. Univariate analysis showed that tumor size (P=0.034), extraglandular invasion (P=0.028), bilateral tumors (P=0.045), and bilateral CND (P=0.028) were significant risk factors of hypothyroidism. Multivariate analysis showed that extraglandular invasion (P=0.003) and bilateral CND (P=0.044) were independent risk factors. The patients with hypothyroidism had an average PTH level of 8.51 ng/L on the first day after surgery, and those without, 21.39 ng/L (P<0.001). When the PTH level on the first day after surgery was used to predict postoperative hypothyroidism, the ROC curve analysis showed that the area under curve (AUC) was 0.875. CONCLUSIONS: Hypothyroidism is a common complication of total or near-total thyroidectomy and CND, for which extraglandular invasion and bilateral CND are independently significant risk factors and the level of PTH is a reliable and early predictor.

12.
Cancer Manag Res ; 10: 2315-2324, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30104900

RESUMO

Background: Systemic inflammation (SI) is associated with tumor progression and overall survival (OS) in patients with hepatocellular carcinoma (HCC). The presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can influence the prognosis of patients with hepatitis B virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed to analyze the correlations between HLA gene polymorphisms and SI. Patients and methods: This study included 330 patients with HCC. The clinical parameters were reviewed, and five SNPs, namely rs2647073, rs3997872, rs3077, rs7453920, and rs7768538, were genotyped using the MassARRAY system. Results: The rs3997872, rs7453920, and rs7768538 genotypes were found to be significantly associated with OS (P<0.05). The rs7453920 genotype was significantly associated with the neutrophil/lymphocyte ratio (NLR; P=0.001), which was used as an SI index with a threshold determined by receiver operating characteristic analysis. An elevated NLR was also an independent predictor of OS according to univariate and multivariate analyses (P<0.001). Conclusion: Our data show that HLA gene polymorphisms are associated with SI in patients with HBV-related HCC, and the absence of minor allele A (rs7453920) promotes SI and shortens OS.

13.
J Med Chem ; 61(20): 8947-8980, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-29870668

RESUMO

DNA topoisomerase II (topo II) is an important enzyme involved in DNA replication, recombination, and repair. Despite the popular applications of topo II inhibitors in cancer therapy, there is still an urgent need to upgrade topo II inhibitors to cope with drug resistance and severe adverse effects. Accordingly, novel topo II catalytic or multitarget topo II inhibitors are gaining more attention and make it possible to ease the toxic limitations of topo II poisons. In this review, medicinal chemistry approaches are mainly discussed toward the development of potent topo II inhibitors with low toxicities.


Assuntos
DNA Topoisomerases Tipo II/metabolismo , Descoberta de Drogas/métodos , Inibidores da Topoisomerase II/farmacologia , Animais , Biocatálise , Química Farmacêutica , DNA Topoisomerases Tipo II/química , Humanos
14.
Br J Pharmacol ; 175(14): 3034-3049, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29722898

RESUMO

BACKGROUND AND PURPOSE: Indoleamine 2,3-dioxygenase 1 (IDO1) is emerging as an important new therapeutic target for treatment of malignant tumours characterized by dysregulated tryptophan metabolism. However, the antitumour efficacy of existing small-molecule inhibitors of IDO1 is still unsatisfactory and the underlying mechanism remains largely undefined. Hence, we discovered a novel potent small-molecule inhibitor of IDO1, LW106, and studied its antitumour effects and the underlying mechanisms in two tumour models. EXPERIMENTAL APPROACH: C57BL6 mice, athymic nude mice or Ido1-/- mice were inoculated with IDO1-expressing and -nonexpressing tumour cells and treated with vehicle, epacadostat or increasing doses of LW106. Xenografted tumours, plasma, spleens and other vital organs were harvested and subjected to kynurenine/tryptophan measurement and flow cytometric, histological and immunohistochemical analyses. KEY RESULTS: LW106 dose-dependently inhibited the outgrowth of xenografted tumours that were inoculated in C57BL6 mice but not nude mice or Ido1-/- mice, showing a stronger antitumour efficacy than epacadostat, an existing IDO1 inhibitor. LW106 substantially elevated intratumoural infiltration of proliferative Teff cells, while reducing recruitment of proliferative Treg cells and non-haematopoietic stromal cells such as endothelial cells and cancer-associated fibroblasts. LW106 treatment resulted in a reduced subpopulation of cancer stem cells (CSCs) in xenografted tumours in which fewer proliferative/invasive tumour cells and more apoptotic tumour cells were observed. CONCLUSIONS AND IMPLICATIONS: LW106 inhibits tumour outgrowth by limiting stroma-immune crosstalk and CSC enrichment in the tumour micro-environment. LW106 has potential as a immunotherapeutic agent for use in combination with immune checkpoint inhibitors and (or) chemotherapeutic drugs for cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Dioxigenases/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dioxigenases/genética , Dioxigenases/metabolismo , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Nus , Neoplasias/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
15.
Int J Surg ; 53: 371-377, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29229309

RESUMO

PURPOSE: We sought to determine the impact of surgical margin status on overall survival (OS) and recurrence pattern stratified by tumor burden. MATERIALS AND METHODS: Data were collected from patients undergoing resection for colorectal liver metastases (CRLM). Tumor burden was calculated according to a newly proposed Tumor Burden Score (TBS) system, defined as the distance from the origin on a Cartesian plane that incorporated maximum tumor size and number of liver lesions. Patients were divided into low tumor burden group and high tumor burden group accordingly, and the impact of resection margin on overall survival was examined. RESULTS: A total of 286 patients were available, among which R1 resection was observed in 88 patients. The median TBS for the entire cohort was 3.84. Metastases in the R1 group were characterized by more advanced disease and more complex resections. Compared with a R0 resection, a R1 resection offered an lower 5-year overall survival rate (46.8% vs. 22.1%, p = 0.001). Multivariate analysis identified R1 resection (p = 0.03), high TBS (p = 0.002), lymph nodes metastases (p = 0.003) and lymphovascular invasion (p = 0.03) of the primary colorectal tumor as the factors independently associated with worse survival. The survival benefit associated with negative margins was greater in patients with low TBS (55.7% vs. 21.7%, p = 0.021) than in patients with high TBS (31.8% vs. 24.5%, p = 0.116). R1 resection was associated with an increased true margin recurrence rate in patients with low TBS (32.3% vs. 13.4%; p = 0.014) and an increased risk of new intrahepatic metastases in patients with high TBS (43.9% vs. 26.7%; p = 0.034). CONCLUSIONS: Negative margin is an important determinant of survival. The impact of positive margins is more pronounced in patients with low tumor burden.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Margens de Excisão , Carga Tumoral , Adulto , Idoso , Estudos de Coortes , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estudos Retrospectivos
16.
J Asian Nat Prod Res ; 20(2): 117-121, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28644689

RESUMO

Two new prenylflavonoids, morusalbols A and B (1 and 2), were isolated from the branches and leaves of Morus alba, together with three known compounds, kuwanon C (3), morusin (4), morusinol (5). The structures of these two prenylflavonoids were elucidated by extensive analyzes of the spectroscopic data.


Assuntos
Flavonoides/isolamento & purificação , Morus/química , Flavonoides/química , Flavonoides/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química
17.
Oncotarget ; 8(60): 102531-102539, 2017 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-29254268

RESUMO

The aims of this study were to assess early recurrence predictive factors and elucidate the best early recurrence management. 255 patients with colorectal liver metastases (CRLM) who underwent hepatectomy were retrospectively analyzed. A total of 87 patients (34.1%) developed early recurrence, defined as recurrence that occurred within 6 months after resection. Multivariate analysis showed that preoperative carcino-embryonic antigen (CEA) level ≥ 30 ng/ml, primary tumor lymphovascular invasion (LVI), number of metastases ≥ 4, R1 resection and initially unresectable disease were independent predictors of early recurrence. A predictive scoring system for early recurrence was created by incorporating these factors, and this system showed good discrimination (concordance index of 0.78). In early recurrent patients who underwent salvage treatment, those with 0-2 risk factors demonstrated a significantly longer median survival after recurrence than patients with 3-5 risk factors (33.4 months vs. 20.2 months, p = 0.001). For patients who underwent chemotherapy alone, the median survival after recurrence between two groups was comparable (18.3 months vs. 22.6 months, p = 0.926). Multivariate analysis revealed that primary tumor lymph node metastases (HR = 1.96, p = 0.032), early recurrence (HR = 1.67, p = 0.045), salvage treatment for recurrence (HR = 0.47, p = 0.002) and predictive scores for early recurrence (HR = 1.39, p = 0.004) were independent factors for survival in patients with recurrence. In patients with early recurrence, bilobar distribution of metastases (HR = 2.05, p = 0.025) and salvage treatment for recurrence (HR = 0.46, p = 0.019) were independent factors for survival. In conclusion, we developed a predictive model that is a very useful tool for determining both the likelihood of early recurrence and the necessity for salvage treatment.

18.
Oncotarget ; 8(43): 75151-75161, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088853

RESUMO

The long-term outcome of 228 patients with colorectal liver metastases (CRLM) who underwent preoperative chemotherapy followed by hepatectomy ± RFA were retrospectively analyzed. Stratified by chemotherapy response, patients were divided into responding (n=129) and non-responding groups (n=99). Patients who underwent hepatectomy-RFA had a greater number of metastases (median of 4 vs. 2, p=0.000), a higher incidence of bilobar involvement (66.7% vs. 49.1%, p=0.014) and longer chemotherapy cycles (median of 6 vs. 4, p=0.000). In the responding group, the median overall survival (OS) and recurrence free survival (RFS) of hepatectomy-RFA and the hepatectomy alone subgroups were comparable (38.6 months vs. 43.2 months, p=0.824; 8.2 months vs. 11.4 months, p=0.623). In the non-responding group, the median OS and RFS of patients treated with hepatectomy-RFA were significantly shorter (18.5 months vs. 34.2 months, p=0.000; 5.1 months vs. 5.9 months, p=0.002). RFA was identified as the unfavorable independent factor for both OS (HR=3.60, 95%CI=1.81-7.16, p=0.039) and RFS (HR=1.70, 95%CI=1.00-2.86, p=0.048) in non-responsive patients. Local recurrence rate after hepatectomy-RFA was higher in the non-responding group (48.1% vs. 23.6%, p=0.018). Non-response to preoperative chemotherapy may be a contraindication to hepatectomy-RFA in patients with CRLM.

19.
Chin Med J (Engl) ; 130(11): 1283-1289, 2017 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-28524826

RESUMO

BACKGROUND: The liver is the most common site for colorectal cancer (CRC) metastases. Their removal is a critical and challenging aspect of CRC treatment. We investigated the prognosis and risk factors of patients with CRC and liver metastases (CRCLM) who underwent simultaneous resections for both lesions. METHODS: From January 2009 to August 2016, 102 patients with CRCLM received simultaneous resections of CRCLM at our hospital. We retrospectively analyzed their clinical data and analyzed their outcomes. Overall survival (OS) and disease-free survival (DFS) were examined by Kaplan-Meier and log-rank methods. RESULTS: Median follow-up time was 22.7 months; no perioperative death or serious complications were observed. Median OS was 55.5 months; postoperative OS rates were 1-year: 93.8%, 3-year: 60.7%, and 5-year: 46.4%. Median DFS was 9.0 months; postoperative DFS rates were 1-year: 43.1%, 3-year: 23.0%, and 5-year 21.1%. Independent risk factors found in multivariate analysis included carcinoembryonic antigen ≥100 ng/ml, no adjuvant chemotherapy, tumor thrombus in liver metastases, and bilobar liver metastases for OS; age ≥60 years, no adjuvant chemotherapy, multiple metastases, and largest diameter ≥3 cm for DFS. CONCLUSIONS: Simultaneous surgical resection is a safe and effective treatment for patients with synchronous CRCLM. The main prognostic factors are pathological characteristics of liver metastases and whether standard adjuvant chemotherapy is performed.


Assuntos
Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
20.
Hepatol Res ; 47(8): 731-741, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27558521

RESUMO

AIM: The prognostic value of the newly raised objective liver function assessment tool, the albumin-bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child-Pugh (C-P) score in predicting prognosis in this study. METHODS: The clinical data of 491 C-P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C-P score in predicting the short- and long-term clinical outcomes were compared. RESULTS: The ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C-P score. With a median follow-up of 57 months, the 1-year, 3-year, and 5-year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C-P score in terms of both the Akaike information criterion value and χ2 value of likelihood ratio test. CONCLUSIONS: The ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C-P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well-designed studies with larger sample sizes are warranted.

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