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1.
Clin Chim Acta ; 501: 42-47, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31816287

RESUMO

PURPOSE: FIT-DNA test is supposed to be highly sensitive for advanced colorectal neoplasms and is advocated in some developed countries, but lack extensive use in developing countries. METHODS: A case control study on stool DNA test for colorectal neoplasms patients was conducted from March 2016 to October 2017 in China. We recruited CRC, colorectal neoplasms and normal controls from ambulatory patients and screening attendees in communities. The stool DNA was tested by a molecular panel similar as ColoGuard in addition to fecal immunochemical test(FIT) in a blinded manner. A risk scoring system was used to determine the positiveness of tests with histological diagnosis as its reference standard. RESULTS: Eligible subjects included 203 colorectal cancer (CRC), 49 advanced adenoma (AA), 156 non-advanced adenoma(NAA) and 431 normal controls(NC). The FIT-DNA kit detected 97.5% CRC (n = 198, 95% CI = 95.4-99.7) and 53.1% AA (n = 26, 95% CI = 39.1-67.0), with specificity of 89.1% (95% CI = 86.2-92.0) in NC and 88.1% (95% CI = 85.5-90.7) in non-advanced controls. The FIT embedded in the kit alone identified 94.6% (n = 192, 95% CI = 91.5-97.7) CRC and 36.7% AA (n = 18, 95% CI = 23.2-50.2). Consistency of KRAS mutation, BMP3 methylation, NDRG4 methylation in 26 paires stool DNA and CRC tumor DNA were 80.9%, 71.4% and 81.8%, respectively. CONCLUSION: At the sacrifice of significantly decreased specificity, a FIT-DNA kit may has better sensitivity than FIT for predicting advanced colorectal adenoma, but not for predicting colorectal cancer. More evidences are needed for the extensive use of FIT-DNA testing.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31855840

RESUMO

Oxidative RNA damage has been found to be associated with a variety of diseases, and 8-hydroxyguanosine (8-OHG) is a typical marker of oxidative modification of RNA. This guanosine modification is an emerging biomarker for disease detection and determination of 8-OHG in human urine is favored because it is noninvasive to patients. However, due to its poor ionization efficiency in mass spectrometry and trace amount in urine, accurate quantification of this modified nucleoside is still challenging. Herein, a rapid, accurate, sensitive and robust method using solid-phase extraction (SPE) combined with isotope dilution ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for detection of this oxidative RNA modification in human urine. The limit of detection can reach 1.5 fmol and the method exhibits good precision on intra-day (1.8-3.3%) and inter-day (0.6-1.2%) analyses. Satisfactory recovery (87.5-107.2%) at three spiked levels was achieved by using HLB cartridge for urine pretreatment. Using this method, we quantified 8-OHG in urine from 65 colorectal cancer (CRC) patients and 76 healthy volunteers. The measured level of urinary 8-OHG for CRC patients and healthy controls is 1.91 ± 0.63 nmol/mmol creatinine and 1.33 ± 0.35 nmol/mmol creatinine, respectively. We found the content of 8-OHG in urine was raised in CRC patients patients, implying this oxidative RNA modification marker could act as a potential noninvasive indicator for early screening of CRC. In addition, this study will make contributions to the investigations of the influences of oxidative stress on the formation and development of CRC.

3.
J Cancer ; 10(26): 6594-6598, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777588

RESUMO

Purpose: To investigate the accuracy of magnetic resonance imaging (MRI) in preoperative staging diagnosis for rectal cancer with multidisciplinary team (MDT) discussion. Methods: The retrospective study included 377 patients of rectal cancer with preoperative MRI staging from February 2015 to April 2018, in which 137 patients (36 received MDT discussion) received neoadjuvant therapy, 240 did not (97 received MDT discussion) and direct surgery was given. With postoperative pathological stage as the standard, the accuracy of MRI in preoperative staging for rectal cancer with MDT discussion was compared with non-MDT. Results: For direct surgery group, 21 out 97 (21.6%) patients changed their therapy strategy due to the change of the stage assessment after MDT. The accuracy of MRI for the diagnosis of preoperative N stage with MDT was significantly higher than those without MDT (56.2% vs. 42.1%, P=0.021). And for those without lymph node metastasis, the accuracy of MRI was higher after MDT (61.2% vs. 37.8%, P=0.009). For neoadjuvant therapy group, 7 out of 36 (19.4%) patients altered their therapy after MDT because of the changed stage. MDT improved the accuracy of restaging N stage with MRI (70.0% vs. 33.3%, P=0.003). The accuracy of MRI in staging T stage seemed not improved after MDT in both groups. Conclusions: In conclusion, MDT discussion increased the accuracy of MRI in preoperative staging diagnosis for rectal cancer. This mode could give a more accurate clinical stage of patients, which was in favor of choosing a preferable therapy strategy.

4.
BMJ Open ; 9(10): e028461, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31594871

RESUMO

OBJECTIVES: Disparities in the global burden of breast cancer have been identified. We aimed to investigate recent patterns and trends in the breast cancer incidence and associated mortality. We also assessed breast cancer-related health inequalities according to socioeconomic development factors. DESIGN: An observational study based on the Global Burden of Diseases. METHODS: Estimates of breast cancer incidence and mortality during 1990-2016 were obtained from the Global Health Data Exchange database. Subsequently, data obtained in 2016 were described using the age-standardised and age-specific incidence, mortality and mortality-to-incidence (MI) ratios according to sociodemographic index (SDI) levels. Trends were assessed by measuring the annual percent change using the joinpoint regression. The Gini coefficients and concentration indices were used to identify between-country inequalities. RESULTS: Countries with higher SDI levels had worse disease incidence burdens in 2016, whereas inequalities in the breast cancer incidence had decreased since 1990. Opposite trends were observed in the mortality rates of high and low SDI countries. Moreover, the decreasing concentration indices, some of which became negative, among women aged 15-49 and 50-69 years suggested an increase in the mortality burdens in undeveloped regions. Conversely, inequality related to the MI ratio increased. In 2016, the MI ratios exhibited distinct gradients from high to low SDI regions across all age groups. CONCLUSIONS: The patterns and trends in breast cancer incidence and mortality closely correlated with the SDI levels. Our findings highlighted the primary prevention of breast cancer in high SDI countries with a high disease incidence and the development of cost-effective diagnostic and treatment interventions for low SDI countries with poor MI ratios as the two pressing needs in the next decades.

5.
Front Oncol ; 9: 790, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508359

RESUMO

Aims: PARK2 mutation is originally associated with the progression of Parkinson's disease. In recent years, PARK2 has been reported as a tumor suppressor gene in various cancers, including lung cancer. However, the biological functions and potential molecular mechanisms of PARK2 in non-small cell lung cancer (NSCLC) are still unclear. Methods: The level of PARK2 expression in 32 tissue samples of NSCLC and matched non-tumor lung tissues was detected by Western blot, and 64 specimens of NSCLC tissues were detected by immunohistochemistry. H1299 and H460 cell lines were used to PARK2 overexpression models, and H460 cell line was also used to PARK2 knockdown model. Using cell viability, colony formation, cell cycle, apoptosis, migration, and invasion assay, the biological functions of PARK2 were evaluated and the potential molecular mechanism of PARK2 was investigated in vitro. Meanwhile, 22 nude mice were employed for in vivo studies. Results: Western blot analysis revealed a decrease of PARK2 protein expression in human NSCLC samples. Immunohistochemistry also identified a vastly reduced expression of PARK2 in NSCLC (72%) and low PARK2 expression was significantly associated with tumor histological grade, lymph node metastasis and advanced TNM stage. Overexpression of PARK2 suppressed cell proliferation, colony formation, migration, and invasion, arrested cell cycle progression in the G1 phase, and induced apoptosis in human non-small cell lines H1299 and H460 in vitro. Meanwhile, knockdown of PARK2 had the opposite biological functions. In addition, PARK2 significantly decreased the tumor volumes in subcutaneous xenograft model and reduced the incidence of metastatic tumors in the transfer model. Exploration of the molecular mechanism of PARK2 in NSCLC showed that PARK2 negatively regulated the EGFR/AKT/mTOR signaling pathway. Conclusions: PARK2 was an important tumor suppressor in NSCLC, which might inhibit cancer growth and metastases through the down regulation of the EGFR/AKT/mTOR signaling pathway.

7.
Front Oncol ; 9: 407, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214490

RESUMO

Breast cancer (BC) remains the most frequently diagnosed cancer worldwide. Among breast cancer patients, distant metastasis and invasion is the leading cause of BC related death. Recently, long non-coding RNAs (lncRNAs), which used to be considered a genetic byproduct (owing to their unknown biological function), have been reported to be highly implicated in the development and progression of BC. In this review, we produce a summary of the functions and mechanisms of lncRNAs implicated in the different distant metastases of BC. The functions of lncRNAs have been divided into two types: oncogenic type and tumor suppressor. Furthermore, the majority of them exert their roles through the regulation of invasion, migration, epithelial-mesenchymal transition (EMT), and the metastasis process. In the final part, we briefly addressed future research prospects of lncRNAs, especially the testing methods through which to detect lncRNAs in the clinical work, and introduced several different tools with which to detect lncRNAs more conveniently. Although lncRNA research is still in the initial stages, it is a promising prognosticator and a novel therapeutic target for BC metastasis, which requires more research in the future.

8.
Cancer Cell Int ; 19: 162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31210753

RESUMO

Background: AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of the mammary SWI/SNF chromatin remodeling complex and a tumor suppressor protein. The loss of ARID1A been observed in several types of human cancers and associated with poor patient prognosis. Previously, we have reported that ARID1A protein was rapidly ubiquitinated and destructed in gastric cancer cells during DNA damage response. However, the ubiquitin e3 ligase that mediated this process remains unclear. Materials and methods: The interaction between ARID1A and ß-TRCP was verified by co-immunoprecipitation (Co-IP) assay. The degron site of ARID1A protein was analyzed by bioinformatics assay. Short hairpin RNAs (shRNAs) were used to knockdown (KD) gene expression. Results: Here we show that DNA damage promotes ARID1A ubiquitination and subsequent destruction via the ubiquitin E3 ligase complex SCFß-TRCP. ß-TRCP recognizes ARID1A through a canonical degron site (DSGXXS) after its phosphorylation in response to DNA damage. Notably, genetic inactivation of the Ataxia Telangiectasia Mutated (ATM) kinase impaired DNA damage-induced ARID1A destruction. Conclusions: Our studies provide a novel molecular mechanism for the negative regulation of ARID1A by ß-TRCP and ATM in DNA damaged gastric cancer cells.

9.
Cancer Biol Med ; 16(1): 189-204, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31119060

RESUMO

Next-generation sequencing (NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously. Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology (CSCO) and the China Actionable Genome Consortium (CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians, pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure (SOP), data analysis, report, and NGS platform certification and validation.

10.
BMC Cancer ; 19(1): 47, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630450

RESUMO

BACKGROUND: To date, no single colorectal cancer (CRC) screening strategy has been determined to be applicable worldwide. In China, a CRC screening protocol that combines double fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) as the first stage of screening and colonoscopy as the second stage of screening (scenario A) was adapted by the Chinese Ministry of Health in 2006. However, applying this CRC screening protocol nationally remains difficult because its effectiveness and convenience are controversial. This study evaluated the effects of subitems of the CRC screening protocol in China. METHODS: CRC screening results (scenario A) from Jiashan County, China, (2007-2009) were used to analyze the detection rates of CRC and advanced neoplasms as well as the cost-effectiveness of the protocol. Scenario A was divided into scenarios B-G (by selecting some items at the first stage of screening) for analysis. RESULTS: Compared with scenario A, removing the whole HRFQ (scenario F) reduced advanced neoplasm and adenoma detections by 29.8 and 41.2%, respectively, whereas the whole HRFQ accounted for 10.1% of the total screening cost. Removing FITs (scenario G) reduced CRC, advanced neoplasm and adenoma detections by 71.8, 56.9 and 47.7%, respectively, and the costs per case of CRC and advanced neoplasm were 82.0 and 19.1% higher, respectively, than those in scenario A. In scenarios B-E (deleting some high-risk factor questions on the HRFQ), the odds ratios (ORs) of the detection rates and costs per CRC, advanced neoplasm, adenoma, and neoplasm case were near 1.00. Scenarios C and D reduced the high-risk population and total screening costs by less than 6.0 and 4.1%, respectively. Scenarios E and B (FITs and a personal history of cancer or colorectal adenoma were reserved) reduced the high-risk population by 17.6 and 24.2% and the total screening costs by 11.2 and 15.4%, respectively, while the numbers of CRC cases were not missed, and advanced neoplasms detected decreased by only 5 and 11%, respectively. CONCLUSION: The results of this study demonstrate that FITs and a personal history of colorectal adenoma are the most effective items in the Chinese CRC screening protocol.


Assuntos
Neoplasias Colorretais/epidemiologia , China/epidemiologia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Programas de Rastreamento , Razão de Chances , Vigilância em Saúde Pública , Fatores de Risco
11.
J Cancer Res Clin Oncol ; 145(3): 725-736, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30542791

RESUMO

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer, and colorectal liver metastases is one of the most difficult and challenging points in the treatment of colorectal cancer. To improve the diagnosis and comprehensive treatment in China, the Guidelines have been edited and revised several times since 2008, including the overall evaluation, personalized treatment goals and comprehensive treatments, to prevent the occurrence of liver metastases, improve the resection rate of liver metastases and survival. The revised Guideline includes the diagnosis and follow-up, prevention, MDT effect, surgery and local ablative treatment, neoadjuvant and adjuvant therapy, and comprehensive treatment, and with advanced experience, latest results, detailed content, and strong operability.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/terapia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino
12.
Future Oncol ; 14(20): 2031-2044, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30117334

RESUMO

AIM: To investigate whether the benefit of combining aflibercept with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) chemotherapy could be confirmed in patients from the Asia-Pacific region (ClinicalTrials.gov: NCT01661270). Patients & methods: Asian patients with oxaliplatin-pretreated metastatic colorectal cancer were randomized to receive aflibercept or placebo, followed by FOLFIRI. The primary end point was progression-free survival. RESULTS: The intention-to-treat population comprised 332 patients. A clinical supply misallocation resulted in 198/332 (60%) patients receiving at least one cycle of misallocated treatment. Nevertheless, the addition of aflibercept to FOLFIRI was shown to improve progression-free survival (hazard ratio: 0.629; 95% CI: 0.488-0.812). Adverse events were in line with expectations. CONCLUSION: The beneficial treatment effect associated with the addition of aflibercept to FOLFIRI was confirmed in Asian patients with pretreated metastatic colorectal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Retratamento , Resultado do Tratamento
13.
PLoS Pathog ; 14(8): e1007202, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30075008

RESUMO

Gamma interferon (IFN-γ) is known to negatively regulate murine gammaherpesvirus-68 (MHV-68 or γHV-68) replication. This process involves the suppression of the viral gene replication and transcription activator (RTA) promoter, as well as activation of signal transducers and activators of transcription (STAT1). Notably, this effect is gradually attenuated during MHV-68 infection of bone marrow-derived macrophages (BMMs), which raised the possibility that the virus may utilize a mechanism that counteracts the antiviral effect of IFN-γ. By identifying the cellular factors that negatively regulate JAK-STAT1 signaling, we revealed that the infection of BMMs by MHV-68 induces the expression of suppressor of cytokine signaling 1 (SOCS1) and that depletion of SOCS1 restores the inhibitory effect of IFN-γ on virus replication. Moreover, we demonstrated that the expression of SOCS1 was induced as a result of the Toll-like receptor 3 (TLR3) mediated activation of the NF-κB signaling cascade. In conclusion, we report that TLR3-TRAF-NF-κB signaling pathway play a role in the induction of SOCS1 that counteracts the antiviral effect of IFN-γ during MHV-68 infection. This process is cell type-specific: it is functional in macrophages, but not in epithelial cells or fibroblasts. Our study reveals a mechanism that balances the immune responses and the escape of a gamma-herpesvirus in some antigen-presenting cells.


Assuntos
Infecções por Herpesviridae/imunologia , Interferon gama/metabolismo , Macrófagos/virologia , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Replicação Viral/fisiologia , Animais , Infecções por Herpesviridae/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Evasão da Resposta Imune/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Rhadinovirus/fisiologia , Proteína 1 Supressora da Sinalização de Citocina/imunologia , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/metabolismo
14.
Cell Death Dis ; 9(3): 375, 2018 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-29515107

RESUMO

Osteosarcoma (OS) is the most common primary malignant bone tumor mainly occurring in children and adolescents. In past decades, studies revealed that PARK2 was a vital tumor suppressor gene in many malignant solid tumors. However, the role of PARK2 in OS remains largely unclear. Therefore, we assessed PARK2 expression in OS tissue and adjacent non-tumor tissues by immunohistochemical (IHC) analysis, and evaluated PARK2 mRNA expression in OS cell lines by real-time PCR analysis. The HOS and U2OS cell lines were employed to establish a PARK2 overexpression model. Using this model, we investigated the potential role of PARK2 in OS and explored the underlying molecular mechanisms. Our study showed PARK2 was downregulated in OS tissue and cell lines, which was significantly associated with higher tumor stage (P < 0.05). Overexpression of PARK2 arrested the cell cycle, inhibited cell proliferation, migration, and invasion, induced cell apoptosis, and reduced tube formation in vitro. Moreover, overexpression of PARK2 significantly suppressed tumor growth and angiogenesis in vivo. Additionally, PARK2 negatively regulated OS development through the JAK2/STAT3/VEGF pathway. Our findings demonstrate that PARK2 is a tumor suppressor gene that may negatively affect OS growth and angiogenesis via partly inhibiting the JAK2/STAT3/VEGF signaling pathway.


Assuntos
Janus Quinase 2/metabolismo , Osteossarcoma/metabolismo , Fator de Transcrição STAT3/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Janus Quinase 2/genética , Masculino , Camundongos , Osteossarcoma/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Ubiquitina-Proteína Ligases/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto Jovem
15.
Mol Cancer Res ; 16(3): 476-485, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29187560

RESUMO

Increasing evidence suggests that left-sided colon cancer (LCC) and right-sided colon cancer (RCC) are emerging as two different colorectal cancer types with distinct clinical characteristics. However, the discrepancy in the underlying molecular event between these types of cancer has not been thoroughly elucidated to date and warrants comprehensive investigation. To this end, an integrated dataset from The Cancer Genome Atlas was used to compare and contrast LCC and RCC, covering mutation, DNA methylation, gene expression, and miRNA. Briefly, the signaling pathway cross-talk is more prevalent in RCC than LCC, such as RCC-specific PI3K pathway, which often exhibits cross-talk with the RAS and P53 pathways. Meanwhile, methylation signatures revealed that RCC was hypermethylated relative to LCC. In addition, differentially expressed genes (n = 253) and differentially expressed miRNAs (n = 16) were determined between LCC and RCC. Especially for Prostate Cancer Susceptibility Candidate 1 (PRAC1), a gene that was closely associated with hypermethylation, was the top significantly downregulated gene in RCC. Multi-omics comparison of LCC and RCC suggests that there are more aggressive markers in RCC and that tumor heterogeneity occurs within the location-based subtypes of colon cancer. These results clarify the debate regarding the conflicting prognosis between LCC and RCC, as proposed by different studies.Implications: The underlying molecular features present in LCC and RCC identified in this study are beneficial for adopting reasonable therapeutic approaches to prolong overall survival and progression-free survival in colorectal cancer patients. Mol Cancer Res; 16(3); 476-85. ©2017 AACR.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Masculino , Prognóstico
16.
Chin J Integr Med ; 24(3): 200-206, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28432529

RESUMO

OBJECTIVE: To investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX). METHODS: Mice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot. RESULTS: In response to PDS-C therapy, the peripheral WBC, NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner. Similarly, bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells (P<0.01). PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice, as evidenced by significantly increase in colony formation units-granulocytes/monocytes and -megakaryocytes (P<0.01). The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway, this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase (p-MEK) and extracellular signal-regulated kinases (p-ERK), and receptor tyrosine kinase (C-kit) and globin transcription factor 1 (GATA-1) in hematopoietic cells of CTX-treated mice (P<0.05). CONCLUSIONS: PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice, probably mediated by a mechanism involving MEK and ERK protein kinases, and C-kit and GATA-1 transcription factors. PDS-C may potentially be a novel treatment of myelosuppression and pancytopenia caused by chemotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Ciclofosfamida/efeitos adversos , Ginsenosídeos/uso terapêutico , Hematopoese/efeitos dos fármacos , Células Mieloides/patologia , Panax/química , Pancitopenia/tratamento farmacológico , Saponinas/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator de Transcrição GATA1/metabolismo , Ginsenosídeos/farmacologia , Camundongos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Células Mieloides/efeitos dos fármacos , Pancitopenia/induzido quimicamente , Pancitopenia/patologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Regulação para Cima/efeitos dos fármacos
17.
Front Psychiatry ; 9: 682, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30618863

RESUMO

The relationship between depression and intracerebral hemorrhage (ICH) is complicated. One of the most common neuropsychiatric comorbidities of hemorrhagic stroke is Post-ICH depression. Depression, as a neuropsychiatric symptom, also negatively impacts the outcome of ICH by enhancing morbidity, disability, and mortality. However, the ICH outcome can be improved by antidepressants such as the frequently-used selective serotonin reuptake inhibitors. This review therefore presents the mechanisms of post-ICH depression, we grouped the mechanisms according to inflammation, oxidative stress (OS), apoptosis and autophagy, and explained them through their several associated signaling pathways. Inflammation is mainly related to Toll-like receptors (TLRs), the NF-kB mediated signal pathway, the PPAR-γ-dependent pathway, as well as other signaling pathways. OS is associated to nuclear factor erythroid-2 related factor 2 (Nrf2), the PI3K/Akt pathway and the MAPK/P38 pathway. Moreover, autophagy is associated with the mTOR signaling cascade and the NF-kB mediated signal pathway, while apoptosis is correlated with the death receptor-mediated apoptosis pathway, mitochondrial apoptosis pathway, caspase-independent pathways and others. Furthermore, we found that neuroinflammation, oxidative stress, autophagy, and apoptosis experience interactions with one another. Additionally, it may provide several potential therapeutic targets for patients that might suffer from depression after ICH.

18.
Oncotarget ; 8(43): 75767-75777, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088908

RESUMO

Reactive oxygen species (ROS) are generated after exposure to harmful environmental factors and during normal cellular metabolic processes. The balance of the generating and scavenging of ROS plays a significant role in living cells. The accumulation of ROS will lead to oxidative damage to biomolecules including nucleic acid. Although many types of oxidative nucleic acid damage products have been identified, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoG) has been commonly chosen as the biomarkers of oxidative damage to DNA and RNA, respectively. It has been demonstrated that oxidative damage to nucleic acid is an initiator in pathogenesis of numerous diseases. Thus, oxidative nucleic acid damage biomarkers have the potential to be utilized for detection of diseases. Herein, we reviewed the relationship of oxidative nucleic acid damage and development of various diseases including cancers (colorectal cancer, gastrointestinal cancer, breast cancer, lung cancer, epithelial ovarian carcinoma, esophageal squamous cell carcinoma), neurodegenerative disorders and chronic diseases (diabetes and its complications, cardiovascular diseases). The potential of oxidative nucleic acid damage biomarkers for detection of diseases and drug development were described. Moreover, the approaches for detection of these biomarkers were also summarized.

19.
Open Biol ; 7(11)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29118272

RESUMO

Colorectal cancer (CRC) has complex pathological features that defy the linear-additive reasoning prevailing in current biomedicine studies. In pursuing a mechanistic understanding behind such complexity, we constructed a core molecular-cellular interaction network underlying CRC and investigated its nonlinear dynamical properties. The hypothesis and modelling method has been developed previously and tested in various cancer studies. The network dynamics reveal a landscape of several attractive basins corresponding to both normal intestinal phenotype and robust tumour subtypes, identified by their different molecular signatures. Comparison between the modelling results and gene expression profiles from patients collected at the second affiliated hospital of Zhejiang University is presented as validation. The numerical 'driving' experiment suggests that CRC pathogenesis may depend on pathways involved in gastrointestinal track development and molecules associated with mesenchymal lineage differentiation, such as Stat5, BMP, retinoic acid signalling pathways, Runx and Hox transcription families. We show that the multi-faceted response to immune stimulation and therapies, as well as different carcinogenesis and metastasis routes, can be straightforwardly understood and analysed under such a framework.


Assuntos
Neoplasias Colorretais/genética , Modelos Teóricos , Biologia de Sistemas , Estudos de Casos e Controles , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Dinâmica não Linear , Processos Estocásticos
20.
Oncotarget ; 8(37): 62358-62370, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28977951

RESUMO

Non-Hodgkin lymphoma is a heterogeneous group of lympho-proliferative disorders. We performed a meta-analysis to summarize the available evidence from case-control studies and cohort study on the inconsistent association between occupational sun exposure and the risk of non-Hodgkin lymphoma. We searched PubMed, ISI web of science, the Cochrane Library, EMBASE and reference lists for relevant articles. Study specific odds ratios or relative risk and 95% confidence intervals were pooled by using fixed-effects or random-effects models. Ten case-control studies and one cohort study were included in the meta-analysis. Overall, the pooled odds ratios for occupational ultraviolet exposure and non-Hodgkin lymphoma risk was 1.15(95% confidence intervals: 0.99, 1.32; I2 = 44.4%). Occupational sun exposure was positively associated with the risk of NHL 1.14 (95% confidence intervals: 1.05, 1.23; I2=25.4% p for heterogeneity =0.202) in Caucasian population. Common subtypes of non-Hodgkin lymphoma and ultraviolet exposure had the negative results. The pooled odds ratios was 1.16, (95%confidence intervals: 0.90, 1.50) for T-cell non-Hodgkin lymphoma; 0.79, (95%confidence intervals: 0.61, 1.02) for B-cell non-Hodgkin lymphoma; 1.13, (95%confidence intervals: 0.96, 1.34) for chronic lymphocytic leukemia; 1.25, (95%confidence intervals: 0.95, 1.64) for males; 1.49, (95%confidence intervals: 0.99, 2.25) for females. Data suggested that occupational ultraviolet exposure was a risk factor for non-Hodgkin lymphoma in Caucasian population. While, there had no relationship between occupational ultraviolet exposure and risk of non-Hodgkin lymphoma in general population as well as non-Hodgkin lymphoma common subtypes. Besides, gender specific occupational sun exposure also indicated no association on risk of non-Hodgkin lymphoma.

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