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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 622-629, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699192

RESUMO

Objective To investigate the clinical value of preoperative lymphocyte-to-monocyte ratio(LMR)in evaluating the prognosis of patients with stage T1 non-muscle invasive bladder cancer(NMIBC).Methods A total of 215 patients with stage T1 NMIBC who underwent transurethral resection of bladder tumor were enrolled.Clinical data were collected.Patients were followed up and their disease-free survival(DFS)and overall survival(OS)were recorded.The receiver operating characteristic(ROC)curve of preoperative LMR in detecting patient prognosis was used to determine the optimal cut-off value for LMR.Patients were divided into low LMR group(LMR <3.86,n=77)and high LMR group(LMR ≥ 3.86,n=138).Kaplan-Meier survival curves were explored to compare cumulative DFS and OS rates in patients with different LMR levels,and COX proportional hazards regression model was used to analyze factors associated with DFS and OS.Results All these 215 patients with T1 stage NMIBC were followed up for 2-92 months,and the DFS rate was 59.07% and OS rate was 65.12%.Kaplan-Meier curves showed that the cumulative DFS rate(χ 2=4.784,P=0.029)and cumulative OS rate(χ 2=7.146, P=0.008)in the low LMR group were significantly lower than those in the high LMR group.Tumor size ≥ 3 cm(HR=1.398,95% CI:1.042-1.875,P=0.025),pathological grade G3(HR=1.266,95% CI:1.026-1.563,P=0.028),and LMR ≥ 3.86(HR=2.347,95% CI:1.080-5.101,P=0.031)were independent factors associated with DFS in patients with stage T1 NMIBC.In addition,tumor size ≥ 3 cm(HR=1.228,95% CI:1.015-1.484,P=0.034),pathological grade G3(HR=1.366,95% CI:1.017-1.834,P=0.038),and LMR<3.86(HR=2.008,95% CI:1.052-3.832,P=0.035)were independent factors associated with OS in patients with T1 stage NMIBC. Conclusion Preoperative LMR is an independent factor associated with patients' prognosis in T1 stage NIMBC.Patients with low LMR tend to have higher risk of NMIBC progression and death.


Assuntos
Linfócitos/citologia , Monócitos/citologia , Neoplasias da Bexiga Urinária/diagnóstico , Intervalo Livre de Doença , Humanos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia
2.
Int J Nanomedicine ; 14: 7533-7548, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571862

RESUMO

Background: The influenza A virus (IAV) is known for its high variability and poses a huge threat to the health of humans and animals. Pigs play a central role in the cross-species reassortment of IAV. Ectodomain of matrix protein 2 (M2e) is the most conserved protective antigen in IAV and can be used to develop nanovaccines through nanoparticles displaying to increase its immunogenicity. However, the high immunogenicity of nanoparticles can cause the risk of off-target immune response, and excess unwanted antibodies may interfere with the protective efficacy of M2e-specific antibodies. Therefore, it is necessary to select reasonable nanoparticles to make full use of antibodies against nanoparticles while increasing the level of M2e-specific antibodies. Porcine circovirus type 2 (PCV2) is the most susceptible virus in pigs and can promote IAV infection. It is meaningful to develop a vaccine that can simultaneously control swine influenza virus (SIV) and PCV2. Methods: In the present study, M2e of different copy numbers were inserted into the capsid (Cap) protein of PCV2 and expressed in Escherichia coli to form self-assembled chimeric virus-like particles (VLPs) nanovaccine. BALB/c mice and pigs were immunized with these nanovaccines to explore optimal anti-IAV and anti-PCV2 immunity. Results: Cap is capable of carrying at least 81 amino acid residues (three copies of M2e) at its C-terminal without impairing VLPs formation. Cap-3M2e VLPs induced the highest levels of M2e-specific immune responses, conferring protection against lethal challenge of IAVs from different species and induced specific immune responses consistent with PCV2 commercial vaccines in mice. In addition, Cap-3M2e VLPs induced high levels of M2e-specific antibodies and PCV2-specific neutralizing antibodies in pigs. Conclusion: Cap-3M2e VLP is an economical and promising bivalent nanovaccine, which provides dual protection against IAV and PCV2.


Assuntos
Circovirus/imunologia , Vírus da Influenza A/imunologia , Nanopartículas/uso terapêutico , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Formação de Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Aves/virologia , Proteínas do Capsídeo/química , Proliferação de Células , Citocinas/metabolismo , Cães , Feminino , Humanos , Imunidade Humoral , Influenza Aviária/imunologia , Influenza Aviária/prevenção & controle , Influenza Aviária/virologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Linfócitos/citologia , Células Madin Darby de Rim Canino , Camundongos Endogâmicos BALB C , Testes de Neutralização , Proteínas Recombinantes/isolamento & purificação , Suínos , Vírion/imunologia , Vírion/ultraestrutura
3.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 506-511, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642227

RESUMO

OBJECTIVE: To analyse the immunogenicity of a fusion protein containing cell epitopes of Mycobacterium tuberculosis genes Rv2660c, Rv2460c, Rv3875 and Rv3804, and to evaluate the feasibility of using it as a novel target antigen for developing multi-stage TB vaccines. METHODS: Cell epitopes of Rv2660c, Rv2460c, Rv3875 and Rv3804c were fused in series to form a new antigen gene (named msv). Then msv was cloned into the prokaryotic expression vector pEASY-Blunt E1. The fusion protein msv was expressed by pEASY-Blunt E1 under the induction of isopropyl-ß-d-thiogalactoside (IPTG). Purified the protein by affinity chromatography and identified the protein by SDS-PAGE and Western blot. To evaluate the immunogenicity of the protein, the mice were immunized with the purified fusion protein, and the titer of the antibody in mice serum was evaluated by ELISA. Besides, splenocytes of immunized mice were separated and splenocytes proliferation was determined under the stimulation of the protein. RESULTS: The prokaryotic expression plasmid carrying msv gene was constructed successfully and msv protein could be expressed by the plasmid under the induction of IPTG. SDS-PAGE and Western blot results confirmed that a purified protein (relative molecular mass was 41.3×103) was obtained. ELISA result indicated that the titer of the antibody in msv immunized mice serum was about 1:81 920.The spleen lymphocyte proliferation assay showed that after immunization with msv protein, significant proliferation of antigen-sensitized lymphocytes was observed. CONCLUSIONS: The fusion protein msv was successfully expressed and purified, which can induce humoral and cellular immunity in mice. It may be used as an antigen component for the development of TB vaccine in the future.


Assuntos
Proteínas de Bactérias/imunologia , Epitopos/biossíntese , Mycobacterium tuberculosis , Proteínas Recombinantes de Fusão/biossíntese , Animais , Antígenos de Bactérias/imunologia , Western Blotting , Proliferação de Células , Imunidade Celular , Imunidade Humoral , Linfócitos/citologia , Camundongos , Plasmídeos , Proteínas Recombinantes de Fusão/imunologia , Baço/citologia
4.
Klin Lab Diagn ; 64(8): 490-492, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31479605

RESUMO

Lack of clear clinical and laboratory picture of subjective evaluation of bowel viability, the progression of bowel necrosis in the postoperative period with acute mesenteric ischemia (АМI) contributes to the high mortality rate. Earlier experiments we proved that gut necrosis leads to changes in the subpopulation structure of blood lymphocytes. This prompted us to determine the clinical significance of the subpopulation structure of venous blood lymphocytes in patients with acute mesenteric ischemia. The paper is based on a retrospective analysis of the results of a controlled clinical and immunological examination of 18 patients aged 62 to 78 years (control group and a group of АМI). Evaluation lymphocyte subpopulation structure was performed by the standard method of direct immunofluorescence staining of whole blood. The obtained data were processed with nonparametric statistical methods. Study of lymphocyte subpopulation structure in patients with АМI patients showed a decrease in the absolute and relative number of CD8, CD4, B, NK cells on the indicators in the control group. Ischemia and necrosis of the intestinal mucosa accompanied by a massive translocation of intestinal microflora through the impaired intestinal barrier along with the migration of lymphocytes into the lesion and death, which is manifested in a decrease in the number of lymphocytes of the peripheral blood. Comprehensive assessment of venous blood lymphocyte subpopulation structure can be used as an additional diagnostic criterion necrotic step АМI, serve as criteria for selection of patients for immunotherapy.


Assuntos
Intestinos/patologia , Isquemia Mesentérica/diagnóstico , Idoso , Movimento Celular , Humanos , Contagem de Linfócitos , Linfócitos/citologia , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Bratisl Lek Listy ; 120(8): 586-592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379182

RESUMO

OBJECTIVE: In recent years, neutrophil-lymphocyte rate (NLR) and platelet-lymphocyte rate (PLR) are reported to be increasing in plenty of rheumatological diseases and the latter rates to be disease activity indicators. In our study, we aimed to search for the difference in NLR and PLR before and after the treatment, their relationship with the disease activity and their seasonal differences in patients using anti-TNF medication for rheumatoid arthritis (RA) and ankylosing spondylitis (AS) while. METHOD: Sixty-eight RA and 203 AS patients using anti-TNF medication for at least 6 months were included in the study. Patients with acute infection, diabetes, hypertension, cancer, renal failure and liver failure were excluded from the study. NLR, PLR, seasonal differences and the disease activities of the patients were evaluated retrospectively. RESULTS: We determined that NLR and PLR are strongly correlated with disease activity, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP). In addition, we determined that disease activity, thrombocytes and PLR are increased in spring and winter, especially in patients with RA. CONCLUSION: NLR and PLR are simple, cheap, and easily accessible parameters which can be used to evaluate disease activity and treatment response before and after anti-TNF treatment. Further studies are needed to enlighten the effect of seasonal differences on disease activity (Tab. 2, Fig. 2, Ref. 43).


Assuntos
Artrite Reumatoide/tratamento farmacológico , Estações do Ano , Espondilite Anquilosante/tratamento farmacológico , Artrite Reumatoide/patologia , Plaquetas/citologia , Contagem de Células , Humanos , Linfócitos/citologia , Neutrófilos/citologia , Estudos Retrospectivos , Espondilite Anquilosante/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
7.
Lancet Haematol ; 6(10): e521-e529, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31378662

RESUMO

BACKGROUND: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy has been shown to have activity in patients with relapsed or refractory multiple myeloma. Reports have suggested that a small subgroup of less differentiated myeloma clones express CD19 and anti-CD19 CAR T-cell therapy has shown activity in some of these patients. We aimed to assess the activity and safety of a combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma. METHODS: We did a single-centre, single-arm, phase 2 trial at the Affiliated Hospital of Xuzhou Medical University in China. Patients were eligible if they were aged 18-69 years, had histologically confirmed multiple myeloma, a Karnofsky Performance Score of 50 points or more, and met the International Myeloma Working Group diagnostic criteria for relapsed or refractory disease. Fludarabine (three daily doses of 30mg/m2) and cyclophosphamide (one daily dose of 750 mg/m2) were used to deplete lymphocytes before infusion of humanised anti-CD19 CAR T cells (1 × 106 cells per kg) and murine anti-BCMA CAR T cells (1 × 106 cells per kg). The primary outcome was the proportion of patients who achieved an overall response. Responses were assessed according to the International Myeloma Working Group criteria. This study is registered with the Chinese Clinical Trial Registration Center, number ChiCTR-OIC-17011272. FINDINGS: From May 1, 2017, to Jan 20, 2019, 22 patients were enrolled and 21 received an infusion of CAR T cells and were evaluable for safety and activity analyses. At a median follow-up of 179 days (IQR 72-295), 20 (95%) of 21 patients had an overall response, including nine (43%) stringent complete responses, three (14%) complete responses, five (24%) very good partial responses, and three (14%) partial responses. The most common adverse events included cytokine release syndrome (19 [90%] of 21), including 18 patients (86%) with grade 1-2 cytokine release syndrome. The most common serious adverse events were haematological toxicities, which occurred in 20 (95%) of 21 patients. Common grade 3 or higher adverse events included neutropenia (18 [86%]), anaemia (13 [62%]), and thrombocytopenia (13 [62%]). One patient died due to cerebral hemorrhage, which was considered related to sustained thrombocytopenia. No deaths were judged to be treatment-related. INTERPRETATION: Our results confirm that combined infusion of humanised anti-CD19 and anti-BCMA CAR T cells is feasible in patients with relapsed or refractory multiple myeloma, and the preliminary activity observed warrants further investigation in randomised trials. This dual CAR-T cell combinations might be a promising treatment option for relapsed or refractory multiple myeloma. FUNDING: National Natural Science Foundation of China, Natural Science Foundation, Key Research and Development Plan of Jiangsu.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD19/imunologia , Antígeno de Maturação de Linfócitos B/imunologia , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Ciclofosfamida/farmacologia , Feminino , Doenças Hematológicas/etiologia , Humanos , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/farmacologia , Adulto Jovem
8.
Nord J Psychiatry ; 73(6): 372-379, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31304832

RESUMO

Background: Currently, increasing evidence supports the hypothesis that alterations in the immune-inflammatory system are critical for the pathophysiology of bipolar disorder (BD). Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and mean platelet volume (MPV) have recently been investigated as inexpensive and simple inflammatory markers. Aims: The aim of this study is to compare NLR, PLR, MLR, and MPV in depressive, manic, and euthymic patients with BD and healthy controls, and to evaluate whether values of NLR, PLR, MLR, and MPV are possible state or trait biomarkers in BD. Methods: This retrospective study was conducted with 341 patients with BD (100 patients in a depressive state, 141 patients in a manic state, and 100 patients in a euthymic state) and 114 healthy controls. Results: We found that patients with BD in manic states had higher levels of MPV, NLR, and MLR, and patients with BD in depressive states had higher levels of MPV than the controls. Moreover, MPV predicted all states of BD, while NLR and MLR predicted the manic state of BD. Conclusions: NLR, MLR, and MPV obtained from simple and inexpensive blood tests were significantly higher in patients with BD than in healthy controls, which each imply low-grade inflammation. MPV may serve as a possible trait biomarker of BD, while NLR and MLR may both serve as possible state biomarkers of the manic state.


Assuntos
Transtorno Bipolar/sangue , Inflamação/sangue , Linfócitos/citologia , Volume Plaquetário Médio , Monócitos/citologia , Neutrófilos/citologia , Adulto , Biomarcadores/sangue , Plaquetas/citologia , Plaquetas/fisiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos
9.
Pan Afr Med J ; 32: 154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303925

RESUMO

Introduction: the aim of this study was to investigate the possible relationship of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) and routine hematological parameters with recurrent epistaxis in children. Methods: In this retrospective case-controlled study, 294 patients aged between 2 and 18 years who applied to the Tokat State Hopital Ear Nose Throat Clinic due to recurrent epistaxis between January 1st 2013 and December 31st December 2017 and 329 sex-and age-matched controls were investigated. Results: NLR was 1.45±0.75 in the study group and the 1.35±0.7 in the control group. There was no significant difference between the groups (p>0.05). PLR values were found significantly (p<0.05) higher in the study group than in the control group (103,21±29.57 vs. 97,3±30.38). Red Blood Cell Distribution Width (RDW) values were found significantly (p<0.05) lower in the study group than in the control group (39,56±2,87 and 38,92±2,46). Conclusion: the increase of PLR, an inflammatory marker, in epistaxis supports the effect of inflammatory factors in the etiology of epistaxis. However, more study in future is needed to support this.


Assuntos
Plaquetas/citologia , Epistaxe/sangue , Linfócitos/citologia , Neutrófilos/citologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Contagem de Linfócitos , Masculino , Contagem de Plaquetas , Recidiva , Estudos Retrospectivos
10.
Nat Immunol ; 20(8): 992-1003, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31263279

RESUMO

Here we identify a group 2 innate lymphoid cell (ILC2) subpopulation that can convert into interleukin-17 (IL-17)-producing NKp44- ILC3-like cells. c-Kit and CCR6 define this ILC2 subpopulation that exhibits ILC3 features, including RORγt, enabling the conversion into IL-17-producing cells in response to IL-1ß and IL-23. We also report a role for transforming growth factor-ß in promoting the conversion of c-Kit- ILC2s into RORγt-expressing cells by inducing the upregulation of IL23R, CCR6 and KIT messenger RNA in these cells. This switch was dependent on RORγt and the downregulation of GATA-3. IL-4 was able to reverse this event, supporting a role for this cytokine in maintaining ILC2 identity. Notably, this plasticity has physiological relevance because a subset of RORγt+ ILC2s express the skin-homing receptor CCR10, and the frequencies of IL-17-producing ILC3s are increased at the expense of ILC2s within the lesional skin of patients with psoriasis.


Assuntos
Interleucina-17/imunologia , Linfócitos/imunologia , Psoríase/patologia , Pele/patologia , Células Cultivadas , Humanos , Interleucina-1beta/imunologia , Subunidade p19 da Interleucina-23/imunologia , Interleucina-4/imunologia , Linfócitos/citologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Psoríase/imunologia , Receptores CCR10/metabolismo , Pele/imunologia , Fator de Crescimento Transformador beta/metabolismo
11.
Nat Immunol ; 20(8): 980-991, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31209406

RESUMO

Innate lymphoid cells (ILCs) are tissue-resident lymphocytes categorized on the basis of their core regulatory programs and the expression of signature cytokines. Human ILC3s that produce the cytokine interleukin-22 convert into ILC1-like cells that produce interferon-γ in vitro, but whether this conversion occurs in vivo remains unclear. In the present study we found that ILC3s and ILC1s in human tonsils represented the ends of a spectrum that included additional discrete subsets. RNA velocity analysis identified an intermediate ILC3-ILC1 cluster, which had strong directionality toward ILC1s. In humanized mice, the acquisition of ILC1 features by ILC3s showed tissue dependency. Chromatin studies indicated that the transcription factors Aiolos and T-bet cooperated to repress regulatory elements active in ILC3s. A transitional ILC3-ILC1 population was also detected in the human intestine. We conclude that ILC3s undergo conversion into ILC1-like cells in human tissues in vivo, and that tissue factors and Aiolos were required for this process.


Assuntos
Imunidade Inata/imunologia , Interferon gama/metabolismo , Interleucinas/metabolismo , Mucosa Intestinal/imunologia , Linfócitos/imunologia , Tonsila Palatina/imunologia , Animais , Diferenciação Celular/imunologia , Células Cultivadas , Criança , Pré-Escolar , Humanos , Fator de Transcrição Ikaros/metabolismo , Mucosa Intestinal/citologia , Linfócitos/classificação , Linfócitos/citologia , Camundongos , Proteínas com Domínio T/metabolismo
12.
BMC Cancer ; 19(1): 524, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151428

RESUMO

BACKGROUND: Abiraterone is an important agent in the treatment of advanced prostate cancer. Early changes in prostate-specific antigen while on abiraterone in patients with metastatic castrate-resistant prostate cancer potentially have financial and health implications for patients. Limited data is available on early prostate-specific antigen change and subsequent survival given phase III trials did not measure prostate-specific antigen changes before 12 weeks. METHODS: A single-center retrospective study was performed. Metastatic castrate-resistant prostate cancer patients treated with abiraterone (without prior enzalutamide) at Tulane Cancer Center were reviewed with a focus on early prostate-specific antigen decline and relationship to overall survival. RESULTS: A total of 110 patients were analyzed for prostate-specific antigen response of ≥ 30 and > 50% at 4, 8, and 12 weeks. A prostate-specific antigen response of either > 30% or > 50% at 4, 8, or 12 weeks was associated with improved overall survival at all time points except > 50% decline at 8 weeks. Multivariate analysis indicated, for all time points, that early prostate-specific antigen declines were predictive of overall survival. The neutrophil to lymphocyte ratio and docetaxel pretreatment also were predictive in many, but not all, of the multivariate analyses. CONCLUSIONS: A > 30% or > 50% prostate-specific antigen decline at 4, 8, or 12 weeks provides important information regarding subsequent overall survival for patients with metastatic castrate-resistant prostate cancer. While these data require validation with a large, multi-institutional trial, they can provide physicians with information regarding prognosis and the timing of expected outcomes. These data affirms the notion that prostate-specific antigen responses as early as 4 weeks after abiraterone initiation can be used to inform both patients and physicians about metastatic castrate-resistant prostate cancer outcomes after initiating treatment with this important but costly therapeutic choice.


Assuntos
Androstenos/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Docetaxel/uso terapêutico , Humanos , Contagem de Leucócitos , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/secundário , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
13.
J Ovarian Res ; 12(1): 51, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151469

RESUMO

INTRODUCTION: Prognostic biomarkers are highly needed to properly manage patients with cancer and improve their clinical courses. The relationship between lymphocyte-to-monocyte ratio (LMR) at diagnosis and ovarian cancer prognosis has been extensively studied, but little consensus has been reached regarding its utility as a biomarker of poor outcome. Thus, this study aimed to investigate the potential prognostic value of pretreatment LMR in such patients to shed light on this issue. METHODS: We searched the scientific databases of MEDLINE, Embase, Cochrane Library, and WangFang for relevant studies about the inflammatory prognostic factor LMR in ovarian cancer, based on specific inclusion and exclusion criteria. The following parameters were analyzed among others: LMR values and respective cut-offs, patient's overall survival (OS) and progression-free survival (PFS), and clinicopathological features. RESULTS: Eight studies, including 2259 patients, were eligible for inclusion in this meta-analysis. We found that low LMR was associated with both poor OS [Hazard ratio (HR): 1.92; 95% confidence interval (CI): 1.58-2.34; p < 0.001] and PFS (HR: 1.70; 95% CI: 1.54-1.88; p < 0.001). Moreover, our findings revealed that low LMR was correlated with high G2/G3 histological grade (OR: 1.67; 95% CI: 1.26-2.20; p < 0.001) and late III-IV FIGO stage tumors (OR: 3.55; 95% CI: 2.68-4.70; p < 0.001), high serum CA-125 level (OR: 2.18; 95% CI: 1.71-2.77; p < 0.001), and presence of malignant ascites (OR: 1.87; 95% CI: 1.11-3.14; p = 0.02) and lymph node metastases (OR: 1.70; 95% CI: 1.13-2.54; p = 0.01). CONCLUSION: Pretreatment LMR is a potential prognostic marker of poor outcome in ovarian cancer patients and may thus be important in clinical care and disease control.


Assuntos
Linfócitos/citologia , Monócitos/citologia , Neoplasias Ovarianas/sangue , Biomarcadores Tumorais/sangue , Feminino , Humanos , Contagem de Leucócitos , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Intervalo Livre de Progressão , Taxa de Sobrevida
14.
Ulus Travma Acil Cerrahi Derg ; 25(3): 222-228, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31135939

RESUMO

BACKGROUND: The objective of this research was to evaluate the potential clinical utility of baseline hematological parameters measured on admission as adjuncts in the identification of complicated and uncomplicated appendicitis in children. METHODS: The records of a total of 334 pediatric patients who underwent curative surgery for acute appendicitis (AA) between 2015 and 2016 were retrospectively investigated. The patients were categorized as complicated or uncomplicated appendicitis based on the histopathological reports. The clinical features and baseline hematological parameters of leukocyte count, neutrophil percentage, thrombocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width (RDW), and platelet distribution width (PDW) of the groups were compared. RESULTS: Complicated AA was determined in 36 (10.8%) patients. The white blood cell count (WBC) (p<.001), neutrophil percentage (p<.001), NLR (p<.001), and PLR (p=.004) were higher in the complicated appendicitis group compared with the uncomplicated group, while the RDW, MPV, and PDW levels were uninformative. Analysis of receiver operating characteristic curves yielded the cut-off values of 14.870 cell/mm3 for WBC (area under the curve [AUC]: 0.675; sensitivity: 86.1%; specificity: 41.6%), 10.4 for NLR (AUC: 0.717; sensitivity: 61.1%; specificity: 73.2%), and 284 for PLR (AUC: 0.647; sensitivity: 42%; specificity: 86%) were found to be the best predictive values for the determination of complicated acute appendicitis. CONCLUSION: The present study demonstrated that AA patients with higher NLR and PLR levels might be more likely to develop a complication. The NLR and PLR values combined with a physical examination, imaging studies, and other laboratory tests may help clinicians to identify high-risk AA patients in the emergency department.


Assuntos
Apendicite , Contagem de Leucócitos/estatística & dados numéricos , Apendicite/diagnóstico , Apendicite/epidemiologia , Criança , Serviço Hospitalar de Emergência , Humanos , Linfócitos/citologia , Volume Plaquetário Médio/estatística & dados numéricos , Neutrófilos/citologia , Estudos Retrospectivos , Sensibilidade e Especificidade
15.
J Nanobiotechnology ; 17(1): 69, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113488

RESUMO

BACKGROUND: The major obstacle impeding human immunodeficiency virus-1 (HIV-1) eradication in antiretroviral treatment (ART) treated HIV-1 subjects is the establishment of long-lived latently infected resting CD4+ T cells. Due to the fact that no drug has been effective, the search for new drugs and combinations are a priority in the HIV cure. Treatments based on nanotechnology have emerged as an innovative and promising alternative to current and conventional therapies. In this respect, nanotechnology opens up a new door for eliminating latent HIV infection. We studied the role of G1-S4, G2-S16 and G3-S16 polyanionic carbosilane dendrimers in the context of latent HIV-1 persistence. Moreover, we study the efficiency of these dendrimers in combination with latency reversal agents (LRAs) against HIV-1 infection. METHODS: J89GFP lymphocyte and THP89GFP monocyte derived cell lines latently infected with HIV-1 p89GFP were used as an in vitro model of latency for our study. Viability assays by 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) were performed to determine the working concentrations of dendrimers and LRAs. Both cell lines were treated with G1-S4, G2-S16 and G3-S16 either alone or in combination with bryostatin (BRY), romidepsin (RMD) or panobinostat (PNB) for 24 and 48 h. The expression pattern of GFP was measured by flow cytometry and referred as measure of viral reactivation. RESULTS AND DISCUSSION: The combination treatment of the dendrimers with the protein kinase C (PKC) agonist did not modify the antilatency activity in J89GFP lymphocyte cell line. Interestingly enough, G3-S16 dendrimer alone and its combination with BRY, RMD or PNB showed a significant increased expression of GFP in the THP89GFP monocyte cell line. CONCLUSION: We showed for the first time that nanoparticles, in this case, G3-S16 anionic carbosilan dendrimer may play an important role in new treatments against HIV-1 infection.


Assuntos
Adjuvantes Imunológicos/farmacologia , Fármacos Anti-HIV/farmacologia , Dendrímeros/química , Infecções por HIV/tratamento farmacológico , Polímeros/química , Silanos/química , Briostatinas/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Depsipeptídeos/farmacologia , Liberação Controlada de Fármacos , Quimioterapia Combinada/métodos , HIV-1/efeitos dos fármacos , Humanos , Linfócitos/citologia , Monócitos/citologia , Panobinostat/farmacologia , Tamanho da Partícula , Propriedades de Superfície
16.
Medicine (Baltimore) ; 98(20): e15702, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096516

RESUMO

This study aimed to investigate the prognostic predictive value of the platelet-lymphocyte ratio (PLR) in patients with acute paraquat (PQ) intoxication.A total of 107 patients with acute PQ intoxication via oral ingestion were admitted in Cangzhou Central Hospital from May 2012 to September 2018. Valuable detection indices were screened out by using Cox proportional hazard regression and receiver operating characteristic (ROC) curve analyses, and their diagnostic efficiency was evaluated by using Kaplan-Meier curve.The 90-day mortality was 58.9% (63/107). The Kaplan-Meier curve showed that PLR was not associated with 90-day survival (log-rank test; P = .661). In Cox proportional hazard regression analyses, PLR was not an independent risk factor. Meanwhile, the ROC curves showed that PLR had an AUC value of 0.569 (95% confidence interval: 0.459-0.679, P = .227) in predicting 90-day survival.PLR is not a prognostic predictor for patients with acute PQ intoxication.


Assuntos
Plaquetas/citologia , Linfócitos/citologia , Intoxicação por Organofosfatos/sangue , Paraquat/envenenamento , Adulto , China/epidemiologia , Serviço Hospitalar de Emergência , Feminino , Lavagem Gástrica/métodos , Herbicidas/efeitos adversos , Herbicidas/envenenamento , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Intoxicação por Organofosfatos/complicações , Intoxicação por Organofosfatos/diagnóstico , Intoxicação por Organofosfatos/mortalidade , Paraquat/efeitos adversos , Contagem de Plaquetas/métodos , Estudos Retrospectivos , Tempo para o Tratamento/estatística & dados numéricos , Tempo para o Tratamento/tendências
17.
Zhongguo Fei Ai Za Zhi ; 22(5): 289-298, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31109438

RESUMO

BACKGROUND: Current research shows that platelet to lymphocyte ratio (PLR) has important prognostic value in renal cell carcinoma, esophageal cancer, gastric cancer, liver cancer and colon cancer. The aim of the study is to evaluate the prognostic value of PLR in non-small cell lung cancer (NSCLC) through meta-analysis. METHODS: Literature search for PubMed, EMBASE, Web of Science, Medline, Cochrane Library, China National Knowledge Internet (CNKI), China Biomedical Medicine disc (CBMdisc), VIP, Wanfang Database using computer electronic system to study the association between PLR and overall survival (OS) and disease-free survival (DFS). Each eligible study data is extracted and a meta-analysis is performed using the hazard risk (HR) and 95% confidence interval (95%CI) to assess the prognostic value of PLR, the time limit for the search is to build the library until November 2018. RESULTS: We include a total of 15 research literatures involving 5,524 patients for meta-analysis. According to the results of the meta-analysis: The OS of the higher PLR group is significantly lower than that of the lower PLR group (HR=1.69, 95%CI: 1.45-1.97, P<0.000,01, I²=46.2%, Pheterogeneity=0.026); the DFS of the higher PLR group is significantly lower than that of the lower PLR group (HR=1.41, 95%CI: 1.14-1.74, P=0.001, I²=46.2%, Pheterogeneity=0.026). Subgroup analysis show that the OS of the higher PLR group is still significantly lower than the lower PLR group (P<0.05) after grouping by ethnicity, sample size, PLR cutoff value and treatment. CONCLUSIONS: Increased PLR is associated with poor prognosis in NSCLC, so PLR may be an important biological predictive marker for NSCLC patients, however, its clinical application still needs to be verified through more research in the future.


Assuntos
Plaquetas/citologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Linfócitos/citologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Contagem de Plaquetas , Prognóstico
18.
J Photochem Photobiol B ; 196: 111496, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129507

RESUMO

Surgical resection is one of the most common radical treatments for cancers. However, tumors may be compressed or the local intravascular pressure may be increased during surgical manipulation, causing the shedding and entry of tumor cells into the blood circulation and hence distant recurrence and metastasis of tumors. We have preliminarily established a method of riboflavin photosensitization treatment (RPT) for inactivation of circulating tumor cells. This technology promises to solve the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. In the present study, apoptosis detection and tumorigenicity experiment in immunodeficient mice were conducted to evaluate the effect of RPT for inactivation of circulating tumor cells respectively. Next, functional evaluation was carried out for the immune cells through detecting apoptosis rate and cytokine secretion of lymphocyte. Finally, thromboelastography (TEG) and free hemoglobin were detected to assess peripheral blood coagulation and red blood cell damage. The results showed that RPT (50 µmol/L riboflavin, 10.8 J/cm2 UV) could effectively make tumor cell lose the ability of proliferation in the peripheral blood. In the meantime, the damage caused to peripheral blood coagulation, immune cell function and red blood cells was generally acceptable. The results of the study showed that RPT had huge potential in addressing the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. This therapy is expected to be an auxiliary and supportive method to reduce the risk of hematogenous metastasis and recurrence of cancers, and to increase the surgical success rate of malignant solid tumors.


Assuntos
Células Neoplásicas Circulantes/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Coagulação Sanguínea/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Células HCT116 , Hemólise/efeitos dos fármacos , Humanos , Luz , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias/tratamento farmacológico , Células Neoplásicas Circulantes/metabolismo , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico
19.
Radiat Res ; 191(6): 545-555, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30995164

RESUMO

In advanced radiotherapy, treatment of the tumor with high-intensity modulated fields is balanced with normal tissue sparing. However, the non-target dose delivered to surrounding healthy tissue within the irradiated volume is a potential cause for concern. Whether the effects observed are caused after exposure to out-of-field radiation or bystander effects through neighboring irradiated cells is not fully understood. The goal of this study was to determine the effect of exposure to out-of-field radiation in lymphocyte cell lines and primary blood cells. The role of cellular radiosensitivity in altering bystander responses in out-of-field exposed cells was also investigated. Target cells were positioned in a phantom in the center of the radiation field (in-field dose) and exposed to 2 Gy irradiation. Lymphocyte cell lines (C1, AT3ABR, Jurkat, THP-1, AT2Bi and AT3Bi) and peripheral blood were placed 1 cm away from the radiation field edge (out-of-field dose) and received an average dose of 10.8 ± 4.2 cGy. Double-stranded DNA damage, cell growth and gene expression were measured in the out-of-field cells. Radiosensitive AT3ABR and primary blood cells demonstrated the largest increase in γ-H2AX foci after irradiation. Exposure of normal cells to bystander factors from irradiated radiosensitive cell lines also increased DNA damage. Expression of IL-1, IL-6, TNFα and TGFß after addition of bystander factors from radiosensitive cells showed differential effects in normally responding cells, with some evidence of an adaptive response observed. Exposure to out-of-field radiation induces DNA damage and reduces growth in radiosensitive cells. Bystander factors produced by directly irradiated cells in combination with out-of-field exposure may upregulate pro- and anti-inflammatory genes in responding cells of different radiosensitivities, with the potential of affecting the tumor microenvironment. A greater understanding of the radio-biological response in normal cells outside the primary treatment field would assist in radiation treatment planning and in reducing early and late toxicities.


Assuntos
Efeito Espectador/genética , Efeito Espectador/efeitos da radiação , Citocinas/biossíntese , Dano ao DNA , Linfócitos/metabolismo , Linfócitos/efeitos da radiação , Proliferação de Células/efeitos da radiação , Citocinas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Histonas/metabolismo , Humanos , Células Jurkat , Linfócitos/citologia , Tolerância a Radiação , Microambiente Tumoral/efeitos da radiação
20.
Int J Mol Sci ; 20(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999563

RESUMO

The presence of microgravity conditions deeply affects the human body functions at the systemic, organ and cellular levels. This study aimed to investigate the effects induced by simulated-microgravity on non-stimulated Jurkat lymphocytes, an immune cell phenotype considered as a biosensor of the body responses, in order to depict at the cellular level the effects of such a peculiar condition. Jurkat cells were grown at 1 g or on random positioning machine simulating microgravity. On these cells we performed: morphological, cell cycle and proliferation analyses using cytofluorimetric and staining protocols-intracellular Ca2+, reactive oxygen species (ROS), mitochondria membrane potential and O2- measurements using fluorescent probes-aconitase and mitochondria activity, glucose and lactate content using colorimetric assays. After the first exposure days, the cells showed a more homogeneous roundish shape, an increased proliferation rate, metabolic and detoxifying activity resulted in decreased intracellular Ca2+ and ROS. In the late exposure time, the cells adapted to the new environmental condition. Our non-activated proliferating Jurkat cells, even if responsive to altered external forces, adapted to the new environmental condition showing a healthy status. In order to define the cellular mechanism(s) triggered by microgravity, developing standardized experimental approaches and controlled cell culture and simulator conditions is strongly recommended.


Assuntos
Linfócitos/citologia , Simulação de Ausência de Peso , Cálcio/metabolismo , Forma Celular , Glucose/metabolismo , Humanos , Células Jurkat , Linfócitos/metabolismo , Potencial da Membrana Mitocondrial , Estresse Oxidativo , Oxigênio/metabolismo
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