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1.
Clin Cancer Res ; 27(22): 6222-6234, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34475103

RESUMO

PURPOSE: In this article, we describe a combination chimeric antigen receptor (CAR) T-cell therapy that eradicated the majority of tumors in two immunocompetent murine pancreatic cancer models and a human pancreatic cancer xenograft model. EXPERIMENTAL DESIGN: We used a dual-specific murine CAR T cell that expresses a CAR against the Her2 tumor antigen, and a T-cell receptor (TCR) specific for gp100. As gp100 is also known as pMEL, the dual-specific CAR T cells are thus denoted as CARaMEL cells. A vaccine containing live vaccinia virus coding a gp100 minigene (VV-gp100) was administered to the recipient mice to stimulate CARaMEL cells. The treatment also included the histone deacetylase inhibitor panobinostat (Pano). RESULTS: The combination treatment enabled significant suppression of Her2+ pancreatic cancers leading to the eradication of the majority of the tumors. Besides inducing cancer cell apoptosis, Pano enhanced CAR T-cell gene accessibility and promoted CAR T-cell differentiation into central memory cells. To test the translational potential of this approach, we established a method to transduce human T cells with an anti-Her2 CAR and a gp100-TCR. The exposure of the human T cells to Pano promoted a T-cell central memory phenotype and the combination treatment of human CARaMEL cells and Pano eradicated human pancreatic cancer xenografts in mice. CONCLUSIONS: We propose that patients with pancreatic cancer could be treated using a scheme that contains dual-specific CAR T cells, a vaccine that activates the dual-specific CAR T cells through their TCR, and the administration of Pano.

2.
Nat Immunol ; 22(7): 851-864, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099918

RESUMO

Group 2 innate lymphoid cells (ILC2s) are essential to maintain tissue homeostasis. In cancer, ILC2s can harbor both pro-tumorigenic and anti-tumorigenic functions, but we know little about their underlying mechanisms or whether they could be clinically relevant or targeted to improve patient outcomes. Here, we found that high ILC2 infiltration in human melanoma was associated with a good clinical prognosis. ILC2s are critical producers of the cytokine granulocyte-macrophage colony-stimulating factor, which coordinates the recruitment and activation of eosinophils to enhance antitumor responses. Tumor-infiltrating ILC2s expressed programmed cell death protein-1, which limited their intratumoral accumulation, proliferation and antitumor effector functions. This inhibition could be overcome in vivo by combining interleukin-33-driven ILC2 activation with programmed cell death protein-1 blockade to significantly increase antitumor responses. Together, our results identified ILC2s as a critical immune cell type involved in melanoma immunity and revealed a potential synergistic approach to harness ILC2 function for antitumor immunotherapies.


Assuntos
Anticorpos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Inibidores de Checkpoint Imunológico/farmacologia , Interleucina-33/farmacologia , Linfócitos/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Quimiotaxia de Leucócito/efeitos dos fármacos , Citotoxicidade Imunológica/efeitos dos fármacos , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Eosinófilos/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Melanoma Experimental/genética , Melanoma Experimental/imunologia , Melanoma Experimental/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo
3.
Methods Mol Biol ; 2265: 543-555, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704739

RESUMO

Here we describe the application of mass cytometry to analyze tumor-infiltrating lymphocytes in human melanoma. Mass cytometry is the coupling of flow cytometry and mass spectrometry, which allows for the simultaneous measurement of 40+ cell parameters on a per cell basis. Heavy metal-labeled antibodies can bind to proteins (CD markers, transcription factors, cytokines) on the cell surface and in the cytoplasm/nucleus. As labeled cells pass through the CyTOF, the instrument detects the heavy metals. Combining these signals allows description of melanoma tumor-infiltrating lymphocytes at a greater depth than alternative phenotyping strategies and enables detailed analyses of a variety of cellular parameters, including immune cell lineage, activation status, and functional polarization.


Assuntos
Citometria de Fluxo , Linfócitos do Interstício Tumoral , Espectrometria de Massas , Melanoma , Análise de Célula Única , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Melanoma/metabolismo , Melanoma/patologia
4.
Methods Mol Biol ; 2265: 557-572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704740

RESUMO

Tumor-infiltrating lymphocytes (TILs) are an important prognostic indicator in melanoma and play a key role in the patient's response to immune checkpoint blockade. However, until recently, it was not possible to combine multi-parameter markers to define the TILs and their histological context. Multiplex immunohistochemistry (mIHC) is a new technology which addresses this issue and enables simultaneous detection of melanoma and multiple immune subsets in formalin fixed paraffin embedded tissue. Following antigen retrieval, melanoma tissue sections are stained by OPAL on an autostainer, including serial rounds of epitope labelling with monoclonal antibodies followed by tyramide signal amplification (TSA). The stained tissue sections are then imaged on the Vectra instrument, and digital images are processed by analysis software (inForm and HALO) to derive tissue segmentation and immune subset densities within the tumor and tumor stroma. Spatial relationships between immune cells and tumor cells are then analyzed using a novel R algorithm. Taken together, multiplex IHC describes the histological context of the immune system in melanoma. The data is objective and allows for characterization of individual melanomas as T cell inflamed (hot), immune excluded, or no immune cells (cold).


Assuntos
Biomarcadores Tumorais/metabolismo , Linfócitos do Interstício Tumoral , Melanoma , Microambiente Tumoral , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Melanoma/metabolismo , Melanoma/patologia
5.
Analyst ; 146(5): 1620-1625, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33599635

RESUMO

Nanoparticles are often used to serve as drug delivery systems to improve the therapeutic efficacy of some hydrophobic drugs. In this work, PEG and peptide-modified titanium phosphate nanoparticles (TiP-PEG/peptide) were synthesized to enhance the drug delivery efficacy of tirucalla-8,24-diene-3ß,11ß-diol-7-one (KS-01), a major bioactive and hydrophobic component extracted from Euphorbia kansui. This drug delivery system with a loading efficiency of about 29.8 mg KS-01/1 g TiP-PEG/peptide exerted a significantly lower cell viability rate of MCF-7 than free KS-01, indicating that these carriers can effectively increase the therapeutic efficacy by improving its water solubility. Moreover, according to the fluorescence intensity of FAM which can be generated by caspase-3 cleaving DEVD-embedded peptide, the caspase-3 level could be determined and the therapeutic efficacy could be visualized in real time.


Assuntos
Euphorbia , Nanopartículas , Preparações Farmacêuticas , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Proteínas de Transporte de Fosfato , Polietilenoglicóis , Titânio
7.
J Immunother Cancer ; 8(1)2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32581061

RESUMO

BACKGROUND: Prostate cancer (PCa) has a profoundly immunosuppressive microenvironment and is commonly immune excluded with few infiltrative lymphocytes and low levels of immune activation. High-dose radiation has been demonstrated to stimulate the immune system in various human solid tumors. We hypothesized that localized radiation therapy, in the form of high dose-rate brachytherapy (HDRBT), would overcome immune suppression in PCa. METHODS: To investigate whether HDRBT altered prostate immune context, we analyzed preradiation versus postradiation human tissue from a cohort of 24 patients with localized PCa that received HDRBT as primary treatment (RadBank cohort). We performed Nanostring immune gene expression profiling, digital spatial profiling, and high-throughput immune cell multiplex immunohistochemistry analysis. We also resolved tumor and nontumor zones in spatial and bioinformatic analyses to explore the immunological response. RESULTS: Nanostring immune profiling revealed numerous immune checkpoint molecules (eg, B7-H3, CTLA4, PDL1, and PDL2) and TGFß levels were increased in response to HDRBT. We used a published 16-gene tumor inflammation signature (TIS) to divide tumors into distinct immune activation states (high:hot, intermediate and low:cold) and showed that most localized PCa are cold tumors pre-HDRBT. Crucially, HDRBT converted 80% of these 'cold'-phenotype tumors into an 'intermediate' or 'hot' class. We used digital spatial profiling to show these HDRBT-induced changes in prostate TIS scores were derived from the nontumor regions. Furthermore, these changes in TIS were also associated with pervasive changes in immune cell density and spatial relationships-in particular, between T cell subsets and antigen presenting cells. We identified an increased density of CD4+ FOXP3+ T cells, CD68+ macrophages and CD68+ CD11c+ dendritic cells in response to HDRBT. The only subset change specific to tumor zones was PDL1- macrophages. While these immune responses were heterogeneous, HDRBT induced significant changes in immune cell associations, including a gained T cell and HMWCK+ PDL1+ interaction in tumor zones. CONCLUSION: In conclusion, we showed HDRBT converted "cold" prostate tumors into more immunologically activated "hot" tissues, with accompanying spatially organized immune infiltrates and signaling changes. Understanding and potentially harnessing these changes will have widespread implications for the future treatment of localized PCa, including rational use of combination radio-immunotherapy.


Assuntos
Biomarcadores/análise , Braquiterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/radioterapia , Linfócitos T/imunologia , Microambiente Tumoral/imunologia , Idoso , Humanos , Linfócitos do Interstício Tumoral/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Linfócitos T/efeitos da radiação , Microambiente Tumoral/efeitos da radiação
8.
Clin Transl Immunology ; 9(5): e1127, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32377339

RESUMO

Objectives: To facilitate disease prognosis and improve precise immunotherapy of gastric cancer (GC) patients, a comprehensive study integrating immune cellular and molecular analyses on tumor tissues and peripheral blood was performed. Methods: The association of GC patients' outcomes and the immune context of their tumors was explored using multiplex immunohistochemistry (mIHC) and transcriptome profiling. Potential immune dysfunction mechanism/s in the tumors on the systemic level was further examined using mass cytometry (CyTOF) in complementary peripheral blood from selected patients. GC cohorts with mIHC and gene expression profiling data were also used as validation cohorts. Results: Increased CD4+FOXP3+ T-cell density in the GC tumor correlated with prolonged survival. Interestingly, CD4+FOXP3+ T cells had a close interaction with CD8+ T cells rather than tumor cells. High densities of CD4+FOXP3+ T cells and CD8+ T cells (High-High) independently predicted prolonged patient survival. Furthermore, the interferon-gamma (IFN-γ) gene signature and PDL1 expression were up-regulated in this group. Importantly, a subgroup of genomically stable (GS) tumors and tumors with chromosomal instability (CIN) within this High-High group also had excellent survival. The High-High GS/CIN tumors were coupled with increased frequencies of Tbet+CD4+ T cells and central memory CD4+ T cells in the peripheral blood. Conclusion: These novel findings identify the combination of CD8+ T cells and FOXP3+CD4+ T cells as a significant prognostic marker for GC patients, which also could potentially be targeted and applied in the combination therapy with immune checkpoint blockades in precision medicine.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32092913

RESUMO

BACKGROUND: This study aims (1) to assess socioeconomic disparities in healthcare use and catastrophic health expenditure (CHE) among cancer patients in China, which is defined as the point at which annual household health payments exceeded 40% of non-food household consumption expenditure, and (2) to examine the association of different treatments for cancers with health service utilization and CHE. METHODS: We used nationally representative data from the China Health and Retirement Longitudinal Study in 2015 with 17,018 participants in which 381 with doctor-diagnosed cancer. The main treatments for cancer included the Chinese traditional medicine (TCM), western modern medicine (refers to taking western modern medications excluding TCM and other treatments for cancers), surgery, and radiation/chemotherapy. Concentration curve was used to assess economic-related disparities in healthcare and CHE. Multivariate regression models were used to examine the impact of the cancer treatment on health service use and incidence of CHE. RESULTS: The main cancer treatments and health service use were more concentrated among the rich patients than among the poor patients in 2015. There was a positive association between the treatment of cancer and outpatient visit (Adjusted Odds Ratio (AOR) = 2.492, 95% CI = 1.506, 4.125), inpatient visit (AOR = 1.817, 95% CI = 1.098, 3.007), as well as CHE (AOR = 2.744, 95% CI = 1.578, 4.772). All cancer therapies except for medication treatments were associated with a higher incidence of CHE, particularly the surgery therapy (AOR = 6.05, 95% CI = 3.393, 27.866) in urban areas. CONCLUSION: Disparities in treatment and health service utilization among Chinese cancer patients was largely determined by financial capability. The current insurance schemes are insufficient to address these disparities. A comprehensive health insurance policy of expanding the current benefits packages and strengthening the Public Medical Assistance System, are essential for Chinese adults with cancer.


Assuntos
Doença Catastrófica , Características da Família , Gastos em Saúde , Neoplasias , Fatores Socioeconômicos , Doença Catastrófica/economia , China , Estudos Transversais , Feminino , Humanos , Seguro Saúde , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/terapia
10.
J Invest Dermatol ; 140(4): 869-877.e16, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31580843

RESUMO

Lentigo maligna (LM) is a common subtype of in situ melanoma on chronically sun-exposed skin, particularly the head and neck of older patients. Although surgery is the standard treatment, there is associated morbidity, and options such as imiquimod cream or radiotherapy may be used if surgery is refused or inappropriate. Complete response rates following imiquimod treatment are variable in the literature. The aim of this study was to evaluate the host immune response both before and following treatment with imiquimod to better identify likely responders. Paired pre- and post-imiquimod treatment specimens were available for 27 patients. Patients were treated with imiquimod 5 days per week for 12 weeks; at 16 weeks, lesions were excised for histological assessment. Of the 27 patients, 16 were responders and 11 failed to clear the disease. PDL1 protein expression was increased, accompanied by a unique gene signature in lesions from patients that subsequently histologically cleared LM by 16 weeks. This comprised 57 upregulated immune genes in signaling networks for antigen presentation, type I interferon signaling, and T-cell activation. This may represent an early responder group to imiquimod, and this unique gene signature potentially can be used as a biomarker of LM response to imiquimod.


Assuntos
Antígeno B7-H1/genética , Regulação Neoplásica da Expressão Gênica , Sarda Melanótica de Hutchinson/tratamento farmacológico , Imiquimode/administração & dosagem , Imunidade Celular/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Administração Tópica , Antígeno B7-H1/biossíntese , Biópsia , DNA de Neoplasias/genética , Humanos , Sarda Melanótica de Hutchinson/genética , Sarda Melanótica de Hutchinson/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo
11.
Proc Natl Acad Sci U S A ; 116(50): 25229-25235, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31767744

RESUMO

Responses of solid tumors to chimeric antigen receptor (CAR) T cell therapy are often minimal. This is potentially due to a lack of sustained activation and proliferation of CAR T cells when encountering antigen in a profoundly immunosuppressive tumor microenvironment. In this study, we investigate if inducing an interaction between CAR T cells and antigen-presenting cells (APCs) in lymphoid tissue, away from an immunosuppressive microenvironment, could enhance solid-tumor responses. We combined CAR T cell transfer with the bacterial enterotoxin staphylococcal enterotoxin-B (SEB), which naturally links a proportion of T cell receptor (TCR) Vß subtypes to MHC-II, present on APCs. CAR T cell proliferation and function was significantly enhanced by SEB. Solid tumor-growth inhibition in mice was increased when CAR T cells were administered in combination with SEB. CAR T cell expansion in lymphoid tissue was demonstrated, and inhibition of lymphocyte egress from lymph nodes using FTY720 abrogated the benefit of SEB. We also demonstrate that a bispecific antibody, targeting a c-Myc tag on CAR T cells and cluster of differentiation 40 (CD40), could also enhance CAR T cell activity and mediate increased antitumor activity of CAR T cells. These model systems serve as proof-of-principle that facilitating the interaction of CAR T cells with APCs can enhance their ability to mediate antitumor activity.


Assuntos
Enterotoxinas/farmacologia , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Antígenos CD40/imunologia , Proliferação de Células/efeitos dos fármacos , Humanos , Imunoterapia Adotiva , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/genética , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/citologia
12.
Nat Commun ; 10(1): 3928, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477692

RESUMO

Tumor-associated macrophages (TAMs), one of the most abundant immune components in gastric cancer (GC), are difficult to characterize due to their heterogeneity. Multiple approaches have been used to elucidate the issue, however, due to the tissue-destructive nature of most of these methods, the spatial distribution of TAMs in situ remains unclear. Here we probe the relationship between tumor context and TAM heterogeneity by multiplex immunohistochemistry of 56 human GC cases. Using distinct expression marker profiles on TAMs, we report seven predominant populations distributed between tumor and non-tumor tissue. TAM population-associated gene signatures reflect their heterogeneity and polarization in situ. Increased density of CD163+ (CD206-) TAMs with concurrent high CD68 expression is associated with upregulated immune-signaling and improved patient survival by univariate, but not multivariate analysis. CD68-only and CD206+ TAMs are correlated with high PDL1 expression.


Assuntos
Imuno-Histoquímica/métodos , Macrófagos/metabolismo , Neoplasias Gástricas/metabolismo , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
14.
Neuroreport ; 30(5): 363-368, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30762615

RESUMO

Neuroimaging studies have manifested functional abnormalities in pain-related brain regions in patients with primary dysmenorrhea (PDM). However, as the key region in brain pain matrix, whether and how the amygdala functional network alteration in PDM is unclear. In this study, we aimed to investigate the intrinsic amygdala functional connectivity (AFC) network alteration in patients with PDM during ovulatory period. Thirty-six PDM patients and 35 matched healthy controls were enrolled in this study. The AFC was constructed using amygdala-based functional connectivity using resting-state functional MRI data. The plasma prostaglandin E2 level was measured during ovulatory period. The group difference on AFC network was conducted and further explored the clinical significant of the abnormal AFC network in PDM patients. Compared to the healthy control group, PDM patients showed increased left AFC in default mode network, including medial prefrontal cortex, posterior cingulate cortex/precuneus, angular gyrus, and inferior temporal gyrus, while, decreased left AFC at bilateral nucleus accumbens/orbital frontal cortex, and decreased right AFC network in right orbital frontal cortex and insula, ventral tegmental area (VTA), left hippocampal, and insula. In addition, the decreased right AFC in VTA was associated with higher plasma prostaglandin E2 level in the PDM group. The AFC network was disrupted in PDM patients, mainly in default mode network and reward system. The disrupted connectivity between amygdala and VTA might contribute to the prostaglandins associated pathological mechanism of PDM.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Dismenorreia/fisiopatologia , Vias Neurais/fisiopatologia , Mapeamento Encefálico , Feminino , Humanos , Adulto Jovem
15.
BMC Infect Dis ; 18(1): 271, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29890956

RESUMO

BACKGROUND: Invasive pulmonary aspergillosis (IPA) has been increasingly reported in patients with underlying respiratory diseases (URD). Early diagnosis of IPA is crucial for mortality reduction and improved prognosis, yet remains difficult. Existing diagnostic tools for IPA largely rely on the detection of biomarkers based on serum or bronchoalveolar lavage fluid (BALF), both of which have their limitations. The use of sputum sample is non-invasive, and Aspergillus detection is feasible; however, the usefulness of sputum biomarkers for the diagnosis of IPA, especially in patients with URD, has not been systematically studied. METHODS: This is a prospective diagnostic trial. At least 118 participants will be recruited from respiratory wards and intensive care units. IPA is defined according to the EORTC/MSG criteria modified for patients with URD. Induced sputum and blood will be collected, and BALF will be obtained by bronchoscopy. Sputum biomarkers, including galactomannan, Aspergillus DNA, triacetylfusarinine and bis(methylthio)gliotoxin will be determined, and the presence of a JF5 antigen will be examined with a lateral fluid device. The sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratio will be computed for different biomarkers and compared using the McNemar χ2 test. Receiver operating characteristic analyses will be performed, and the cut-off values will be established. Participants will receive follow-up evaluations at 3 months and 6 months after recruitment. The difference in hospital stay and survival will be analysed, and the relationships between the levels of biomarkers and hospital stay and survival will be analysed via regression models. DISCUSSION: We have developed and verified the feasibility of Aspergillus-related biomarker assays for sputum. The study findings will contribute to a novel look at the diagnostic performance of sputum biomarkers in IPA and provide important insight into the improvement of the early diagnosis of IPA, particularly in patients with URD. TRIAL REGISTRATION: This study has been registered with the Chinese Clinical Trial Registry ( ChiCTR-DPD-16009070 ) on 24th of August 2016.


Assuntos
Aspergilose Pulmonar Invasiva/diagnóstico , Transtornos Respiratórios/microbiologia , Escarro/microbiologia , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar , Broncoscopia , Protocolos Clínicos , Diagnóstico Precoce , Humanos , Unidades de Terapia Intensiva , Aspergilose Pulmonar Invasiva/complicações , Tempo de Internação , Mananas/análise , Estudos Prospectivos , Curva ROC , Transtornos Respiratórios/complicações , Sensibilidade e Especificidade , Análise de Sobrevida
16.
World J Gastroenterol ; 22(28): 6373-84, 2016 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-27605873

RESUMO

Like the wars predating the First World War where human foot soldiers were deemed tools in the battlefield against an enemy, so too are the host immune cells of a patient battling a malignant gastric cancer. Indeed, the tumour microenvironment resembles a battlefield, where the patient's immune cells are the defence against invading tumour cells. However, the relationship between different immune components of the host response to cancer is more complex than an "us against them" model. Components of the immune system inadvertently work against the interests of the host and become pro-tumourigenic while other components soldier on against the common enemy - the tumour cell.


Assuntos
Adenocarcinoma/imunologia , Imunoterapia , Neoplasias Gástricas/imunologia , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia , Adenocarcinoma/terapia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Humanos , Neoplasias Gástricas/terapia
17.
Artigo em Inglês | MEDLINE | ID: mdl-26294922

RESUMO

The prevalence of vascular dementia (VaD) is high among the elderly. Acupuncture, a popular therapeutic method in China, can improve memory, orientation, calculation, and self-managing ability in VaD patients. However, in clinical acupuncture and acupuncture research, the selection of acupoints to treat VaD remains challenging. This study aimed to discover acupoints and acupoint combinations with potential for VaD based on data mining. After database searching and screening for articles on clinical trials evaluating the effects of acupuncture on VaD, 238 acupuncture prescriptions were included for further analysis. Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Shuigou (GV 26), and Shenting (GV 24) appeared most frequently in the modern literature and are potential acupoints for VaD. Combinations between Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Shenting (GV 24), Shuigou (GV 26), and Zusanli (ST 36) were most frequent and represent potential combinations for VaD treatment. These results provide a reference for the selection and combination of acupoints to treat VaD in clinical acupuncture and acupuncture research.

18.
Trials ; 15: 418, 2014 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-25352050

RESUMO

BACKGROUND: Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP. METHODS/DESIGN: The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire. DISCUSSION: The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov of the National Institute of Health on 22 October 2013 (http://NCT01973010).


Assuntos
Dor Crônica/terapia , Dor Lombar/terapia , Massagem , Medicina Tradicional Chinesa/métodos , Projetos de Pesquisa , Adulto , China , Dor Crônica/fisiopatologia , Dor Crônica/psicologia , Protocolos Clínicos , Avaliação da Deficiência , Feminino , Humanos , Dor Lombar/diagnóstico , Dor Lombar/fisiopatologia , Dor Lombar/psicologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Percepção da Dor , Limiar da Dor , Valor Preditivo dos Testes , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Sci Rep ; 4: 6145, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-25174450

RESUMO

In this study we investigated the biological role and mechanism of miR-198 in colorectal carcinoma (CRC). MiR-198 expression was shown to exhibit a strongly negative correlation with lymph node invasion, distant metastasis and patient survival in examinations of colorectal cancer tissues and paired normal colorectal mucosa tissues. fucosyl transferase 8 (FUT8) was identified as a potential target of miR-198 in bioinformatics analysis and luciferase reporter assays. Overexpression of miR-198 in CRC cell lines decreased FUT8 levels as shown by immunofluorescence analysis, and inhibited cell proliferation, migration, and invasion. These anti-tumor phenotypes were rescued by reconstitution of FUT8 expression. Furthermore, miR-198 was shown to target the 3'UTR of FUT8 directly to downregulate FUT8 expression at both mRNA and protein levels in qRT-PCR and Western blot analyses, respectively. In vivo, restoration of miR-198 significantly inhibited xenograft growth and invasion of CRC tumors in nude mice. Therefore, it could be concluded that miR-198 suppresses the proliferation and invasion of CRC by directly targeting FUT8.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , Fucosiltransferases/genética , MicroRNAs/genética , Metástase Neoplásica/genética , Regiões 3' não Traduzidas/genética , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Metástase Neoplásica/patologia
20.
Zhongguo Zhen Jiu ; 34(12): 1225-7, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25876360

RESUMO

Professor LUO Cai-gui's experience of acupuncture at acupoint "Baliao" with twisting manipulation for treatment of low back pain is introduced. This method has significant efficacy on improving low back pain and numbness of lower extremities, which is characterized with short-time manipulation, quick de-qi and long effective time. The acupuncture methods, manipulations, precautions, etc. are elaborated in details. A typical case is added.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Dor Lombar/terapia , Terapia por Acupuntura/instrumentação , Terapia por Acupuntura/métodos , Humanos , Masculino , Pessoa de Meia-Idade
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