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1.
Adv Exp Med Biol ; 1224: 1-20, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32036601

RESUMO

Neutrophils are the first responders to inflammation, infection, and injury. As one of the most abundant leukocytes in the immune system, neutrophils play an essential role in cancer progression, through multiple mechanisms, including promoting angiogenesis, immunosuppression, and cancer metastasis. Recent studies demonstrating elevated neutrophil to lymphocyte ratios suggest neutrophil as a potential therapeutic target and biomarker for disease status in cancer. This chapter will discuss the phenotypic and functional changes in the neutrophil in the tumor microenvironment, the underlying mechanism(s) of neutrophil facilitated cancer metastasis, and clinical potential of neutrophils as a prognostic/diagnostic marker and therapeutic target.


Assuntos
Neoplasias/patologia , Neutrófilos/patologia , Microambiente Tumoral , Humanos , Neovascularização Patológica
2.
Medicine (Baltimore) ; 99(2): e18545, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914029

RESUMO

This study aimed to determine the impact of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) on the prognosis of nasopharyngeal carcinoma (NPC) before and after intensity modulated radiotherapy (IMRT).Pre/post-treatment and changes in inflammatory biomarker levels of 207 patients who were diagnosed with NPC and received IMRT between January 2012 and December 2014 were analyzed, and the cellular biomarker analyses were from patient blood. ROC (receiver operating characteristic) analysis was used to decide the optimal cutoff values of NLR and changes in NLR (ΔNLR) and PLR (ΔPLR). The Kaplan-Meier and logarithmic rank methods were used to compare overall survival times between groups. Univariate analysis was used to investigate the effects of age, gender, histology, Karnofsky performance score (KPS), TNM stage, clinical stage, course of disease and lymphocyte, neutrophil and platelet counts as well as alkaline phosphatase (ALP) levels on the prognosis of NPC. The independent predictors of OS were determined by Cox multivariate regression analysis.The optimal cut-off values of NLR, PLR, ΔNLR and ΔPLR were 2.49, 155.82, 1.80, and 100.00, respectively. These were used to classify patients into high (NLR > 2.49) and low NLR groups (NLR < 2.49); high (PLR>155.82) and low (PLR < 155.82) PLR groups; high (ΔNLR>1.80) and low ΔNLR groups (ΔNLR < 1.80); high (ΔPLR > 100.00) and low ΔPLR groups (ΔPLR < 100.00). TNM stage, clinical stage and ALP levels were highly correlated with high NLR and PLR. Cox multivariate regression analysis suggested that the ΔNLR (HR = 2.89, 95% CI: 1.33∼2.78) was independent of the characteristics for NPC.As a novel inflammatory index, ΔNLR appears to have some predictive power for the prognosis of patients with NPC.


Assuntos
Linfócitos/efeitos da radiação , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Neutrófilos/efeitos da radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Contagem de Células Sanguíneas , Plaquetas/patologia , Plaquetas/efeitos da radiação , Feminino , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias/métodos , Neutrófilos/patologia , Valor Preditivo dos Testes , Prognóstico , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
3.
Anticancer Res ; 40(1): 451-458, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892600

RESUMO

BACKGROUND/AIM: We evaluated the clinical implications of pre- and post-treatment hematological parameters as prognostic factors in patients with locally advanced cervical cancer (LACC) who received definitive concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: We retrospectively analyzed 125 patients with LACC (FIGO stage IIB to IIIB) who received definitive CCRT. Clinical factors and hematological parameters, including neutrophil-to-lymphocyte ratio (NLR) were assessed pre- and post-CCRT. Univariate and multivariate analysis for disease-free survival (DFS) and overall survival (OS) were performed using clinicopathological and hematological parameters. RESULTS: Disease recurred in 46 (36.8%) patients, and 24 patients (19.2%) died. On multivariate analysis, post-treatment NLR, ΔNLR (pre-treatment NLR/post-treatment NLR) and ΔPLR (platelet-to-lymphocyte ratio) (pretreatment PLR/post-treatment PLR) were significant prognostic factors for DFS, and only post-treatment NLR was a significant prognostic factor for OS (p<0.001). However, pre-treatment hematological parameters were not associated with prognosis. CONCLUSION: Post-treatment hematological parameters, particularly NLR, may serve as a prognostic indicator in patients with LACC who received definitive CCRT.


Assuntos
Quimiorradioterapia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/terapia , Intervalo Livre de Doença , Feminino , Humanos , Linfócitos/patologia , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neutrófilos/patologia , Prognóstico , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia
4.
Medicine (Baltimore) ; 99(4): e18887, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977897

RESUMO

INTRODUCTION: MYH9-related disease (MYH9-RD) is a rare autosomal dominant disorder caused by mutations in MYH9, which is responsible for encoding nonmuscle myosin heavy chains IIA (NMMHCIIA). MYH9-RD is clinically characterized by congenital macrothrombocytopenia, granulocyte inclusions variably associated with the risk of developing progressive sensorineural deafness, cataracts and nephropathy. PATIENT CONCERNS: A 5-year-old boy had a history of a mild bleeding tendency and chronic thrombocytopenia, first identified at four months of age. No other family members were noted to have similar clinical features or hematologic disorders. DIAGNOSES: The boy was diagnosed with MYH9-RD. Light microscopic examination of peripheral blood films (Wright-Giemsa stain) showed marked platelet macrocytosis with giant platelets and basophilic Döhle-like inclusions in 83% of the neutrophils. Immunofluorescence analysis disclosed a type II pattern, manifested by neutrophils which contained several circle-to-oval shaped cytoplasmic NMMMHCA-positive granules. Sequencing analysis of MYH9-RD genes was carried out and revealed a novel missense mutation of c.97T>G (p.W33G) in the patient but not in his parents. INTERVENTION: No treatment is necessary. Recognition of MYH9-RD is important to Avoiding unnecessary and potentially harmful treatments. OUTCOMES: The patient's condition remained stable during the follow-up. CONCLUSIONS: As a result of identifying this missense mutation in this particular case, we have added c.97T>G (p.W33G) to the broad spectrum of potential MYH9 mutations.


Assuntos
Perda Auditiva Neurossensorial/genética , Trombocitopenia/congênito , Pré-Escolar , Imunofluorescência , Perda Auditiva Neurossensorial/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação de Sentido Incorreto , Neutrófilos/patologia , Trombocitopenia/diagnóstico , Trombocitopenia/genética
5.
J Cancer Res Clin Oncol ; 146(1): 53-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31741042

RESUMO

PURPOSE: Tumor-associated neutrophils (TANs) are part of the tumor immune microenvironment (TIME) and may contribute to gastric cancer (GC) biology. We hypothesized that TAN are enriched in the TIME, show sex-specific differences, and correlate with patient outcome. METHODS: We analyzed the distribution and putative tumor biological significance of TANs in a well-characterized, therapy-naïve, European GC cohort using immunohistochemical staining of myeloperoxidase (MPO), and digital image analysis using Definiens Tissue Studio®. RESULTS: Different tumor compartments were examined, and TAN densities were correlated with various clinicopathological patient characteristics. TAN density showed a large interindividual variability ranging from 0 to 6711.0 TANs/mm2. Intratumoral distribution patterns were inhomogeneous (tumor surface vs. tumor center vs. invasion front) and correlated significantly with Laurén phenotype, tumor grade, and microsatellite status in the tumor center and invasion front. In the multivariate analysis, TAN density in the invasion front was an independent predictor of tumor-specific survival only for women (HR = 2.77, p < 0.001). In men, no correlation was found between TAN density and survival. CONCLUSION: With regard to TANs, our study independently validates sexual dimorphism in GC biology.


Assuntos
Neutrófilos/imunologia , Neutrófilos/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Caracteres Sexuais , Fatores Sexuais , Microambiente Tumoral/imunologia
6.
Int J Gynaecol Obstet ; 148(1): 102-106, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31571212

RESUMO

OBJECTIVES: To evaluate the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) upon diagnosis, and its impact on surgical outcome, among patients with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy (NACT). METHODS: A retrospective cohort study included all women with stage IIIC and IV ovarian carcinoma receiving NACT in Rabin Medical Center, Petah-Tikva, Israel; January 1, 2005, to June 30, 2017. Demographics and treatment outcome were compared between patients with NLR at diagnosis ≥6.0 and those with NLR <6.0. Primary outcome was optimal debulking (<1 cm largest residual disease). Overall survival was compared between groups using Kaplan-Meier survival analysis. RESULTS: Of 111 patients, 33 (29.7%) had NLR ≥6.0 at diagnosis, and 78 (70.3%) had NLR <6.0. No difference was found in rates of optimal debulking between the group with NLR ≥6.0 and that with NLR <6.0 (78.9% vs 84.7%, respectively, P=0.555). Using Kaplan-Meier survival analysis, NLR ≥6.0 was associated with significantly worse overall survival (P<0.05). In a multivariate Cox proportional hazard model, elevated NLR was not statistically associated with poor overall survival (P=0.080). CONCLUSIONS: In advanced stage ovarian carcinoma, NLR ≥6.0 at diagnosis did not predict surgical outcome, however it was a predictive factor for poor overall survival.


Assuntos
Carcinoma Epitelial do Ovário/sangue , Linfócitos/patologia , Neutrófilos/patologia , Neoplasias Ovarianas/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/terapia , Feminino , Humanos , Israel , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
7.
Medicine (Baltimore) ; 98(50): e18306, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852112

RESUMO

This retrospective analysis of patients aims to show the blood levels of preoperative inflammatory markers in patients with glioblastoma and brain metastasis and to provide the diagnostic accuracy of the neutrophil-lymphocyte (NLR), lymphocyte-monocyte (LMR), and platelet-lymphocyte (PLR) ratios between the 2 groups of patients.The retrospective reviews of the neutrophil, lymphocyte, monocyte, and platelet counts were analyzed in 80 patients with newly diagnosed glioblastoma and 70 patients with brain metastasis. The NLR, LMR, and PLR were calculated in each group. The differences in all the parameters were compared between the 2 groups.Although the neutrophil, monocyte, and platelet counts were higher and the lymphocyte count was lower in patients with metastasis, the difference was not significant. A significantly higher PLR (P = .004) and a lower LMR (P = .01) were found in patients with brain metastasis. Although both PLR and LMR had diagnostic accuracy in differentiating glioblastoma from brain metastasis, LMR showed the highest diagnostic accuracy. NLR showed no diagnostic accuracy.Systemic inflammation is more severe in glioblastoma than in brain metastasis, and LMR is more sensitive and/or specific than PLR in differentiating glioblastoma from brain metastasis. Therefore, LMR (less likely PLR) can be used as an index for differentiating between glioblastoma and brain metastasis before surgery.


Assuntos
Plaquetas/patologia , Neoplasias Encefálicas/secundário , Glioblastoma/diagnóstico , Linfócitos/patologia , Monócitos/patologia , Procedimentos Neurocirúrgicos , Neutrófilos/patologia , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/diagnóstico , Diagnóstico Diferencial , Feminino , Seguimentos , Glioblastoma/cirurgia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Contagem de Plaquetas , Período Pré-Operatório , Estudos Retrospectivos
8.
Zhonghua Nei Ke Za Zhi ; 58(12): 933-936, 2019 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-31775462

RESUMO

A 54-year-old man was admitted to respiratory department with chief complaints of recurrent cough and dyspnea. Chest imaging showed multiple patchy shadows and interstitial changes. Evidence of infectious diseases was not definite, and antibiotic treatments were not effective. In the meantime, myelodysplasia syndrome was diagnosed with pancytopenia. The pathologic findings of transbronchoscopic lung biopsyshowed chronic inflammatory interstitial changes, suggesting a clinical diagnosis of organizing pneumonia. After glucocorticoids treatment, his condition aggravated. The second percutaneous lung biopsy showed the infiltration of a large number of neutrophils. Therefore, the final diagnosis of myelodysplasia syndrome with Sweet syndrome was made. Then glucocorticoids and supportive treatment were given This case may improve physicians' understanding of myelodysplasia syndrome complicated with Sweet syndrome.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Pulmão/patologia , Síndromes Mielodisplásicas/diagnóstico , Neutrófilos/patologia , Síndrome de Sweet/diagnóstico , Broncoscopia , Tosse/etiologia , Dispneia/etiologia , Glucocorticoides/uso terapêutico , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , Pancitopenia/diagnóstico , Pneumonia , Síndrome de Sweet/complicações , Síndrome de Sweet/tratamento farmacológico , Resultado do Tratamento
9.
Actas urol. esp ; 43(9): 503-508, nov. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-185252

RESUMO

Objetivos: El objetivo del presente estudio es evaluar la correlación entre la puntuación de riesgo de la Organización Europea para la Investigación y Tratamiento del Cáncer (EORTC, por sus siglas en inglés) y el índice neutrófilo/linfocito (INL) en pacientes con cáncer de vejiga no músculo-invasivo, y la relación entre el INL y los grupos de riesgo. Métodos: Se revisaron retrospectivamente los datos de 212 pacientes con cáncer de vejiga no músculo-invasivo incluidos en el estudio. Los tumores se clasificaron de acuerdo con el sistema de la Organización Mundial de la Salud de 1973 y el sistema TNM de estadificación (tumor, ganglio y metástasis) de 2002. Siguiendo las directrices de la Asociación Europea de Urología, se llevó a cabo la estratificación de los pacientes en grupos de bajo, intermedio y alto riesgo para recidiva y progresión. El día previo a la operación se midieron y analizaron los valores séricos del INL para determinar el valor basal de neutrófilos y linfocitos. Resultados: De los 212 pacientes, 193 eran hombres y 19 mujeres. La media de edad fue 66,7. La puntuación media de INL fue de 3,04 ± 2,11. Se encontró una mayoría de tumores T1, tumores G3, tumores múltiples y tumores > 3 cm en pacientes con INL > 2,41. Tras comparar los 3 grupos de riesgo, se obtuvieron tasas de INL significativamente mayores en los pacientes del grupo de alto riesgo (p < 0,001). Al evaluar la correlación entre las puntuaciones de recidiva y progresión del INL y la EORTC, se observó que un valor elevado del INL se asocia a un aumento significativo en la puntuación de recidiva (r = 0,252; p < 0,001) y progresión (r = 0,145; p = 0,034). Conclusiones: Este estudio demostró la asociación entre un INL alto con los tumores T1, de grado alto, tumores múltiples, tumores > 3 cm y con el grupo de alto riesgo EORTC en pacientes con cáncer de vejiga no músculo-invasivo. También hubo una correlación positiva de la recidiva y progresión entre INL y EORTC


Objectives: Aim of this study is to evaluate the correlation between European Organization for Research and Treatment of Cancer (EORTC) risk score and neutrophil-lymphocyte ratio (NLR) in patients with non-muscle invasive bladder cancer and the relationship between NLR and risk groups. Methods: We retrospectively reviewed data of 212 patients with non-muscle invasive bladder cancer were included in the study. The tumors were graded according to the 1973 World Health Organization grading system and the tumor node metastasis (TNM) 2012 staging system. Patients were categorized low, intermediate and high risk for recurrence and progression, according to European Association of Urology guidelines. Serum values for the NLR were measured on the day before the operation to ascertain the baseline value for neutrophil and lymphocyte counts and statistically analyzed. Results: Of the 212 patients, 193 were male and 19 were female. Mean age was 66.7. Mean NLR score was 3.04 ± 2.11. T1 tumors, G3 tumors, multiple tumors and > 3 cm tumors seen mostly in patients with NLR > 2.41. Low, intermediate and high risk groups compared and NLR rates were significantly higher in high risk group patients (P < .001). When the correlation between NLR and EORTC recurrence and progression scores was evaluated, it was observed that as NLR value increased, recurrence (r = 0.252, P < .001) and progression (r = 0.145, P = .034) scores increased significantly. Conclusions: This study demonstrated the association of high NLR value with T1 tumor, high grade, multiple tumor, > 3 cm tumor and EORTC high risk group in non-muscle invasive bladder cancer patients. There was also a positive correlation between NLR and EORTC recurrence and progression scores


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/diagnóstico , Neutrófilos/patologia , Linfócitos/patologia , Fatores de Risco , Neoplasias da Bexiga Urinária/patologia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Grupos de Risco , Estudos Retrospectivos , Classificações em Saúde , Razão de Chances , Intervalos de Confiança
10.
Yonsei Med J ; 60(11): 1021-1027, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31637883

RESUMO

PURPOSE: Computed tomography (CT) is the most useful diagnostic modality for staging renal cell carcinoma (RCC). However, CT is limited in its ability to predict renal sinus fat invasion (SFI). Here, we aimed to evaluate whether preoperative neutrophil-to-lymphocyte ratio (NLR) could predict pathological SFI in patients with RCC of ≤7 cm for whom preoperative imaging reveals potential renal SFI. MATERIALS AND METHODS: We reviewed the medical records of 1311 patients who underwent extirpative renal surgery for non-metastatic RCC of ≤7 cm between November 2005 and December 2014. After excluding patients with no SFI in preoperative imaging, unavailable preoperative data, and morbidity affecting inflammatory markers, a total of 476 patients were included in this study. Multivariate logistic regression analysis was used to evaluate predictors of pathological SFI. RESULTS: We implemented a cut-off value of 1.98, which was calculated by ROC analysis to obtain high (≥1.98) and low (<1.98) NLR groups. A total of 93 patients with pathological SFI had larger clinical tumor size, higher preoperative NLR, larger pathological tumor size, more frequent renal vein involvement, and higher Fuhrman nuclear grade. Multivariate analysis indicated that high NLR [odds ratio (OR) 2.032, p=0.004], clinical tumor size (OR 1.586, p<0.001), and collecting system involvement on preoperative imaging (OR 3.957, p=0.011) were significantly associated with pathological SFI in these tumors. CONCLUSION: Preoperative high NLR was associated with pathological SFI in patients with RCC of ≤7 cm and presumed SFI on preoperative imaging. Greater surgical attention is needed to obtain negative margins during partial nephrectomy in these patients.


Assuntos
Adiposidade , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Rim/patologia , Linfócitos/patologia , Neutrófilos/patologia , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Rim/cirurgia , Neoplasias Renais/cirurgia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prognóstico , Curva ROC , Estudos Retrospectivos
11.
J Surg Oncol ; 120(7): 1102-1111, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31598983

RESUMO

BACKGROUND AND OBJECTIVES: To assess the prognostic significance of postoperative changes in immune status represented by total lymphocyte count (TLC) and neutrophil-to-lymphocyte ratio (NLR) in resectable pancreatic cancer. METHODS: Patients who underwent curative pancreatectomy for pancreatic adenocarcinoma were divided into high and low groups according to cut-off values of TLC, and NLR measured preoperatively, immediately after surgery, and 1 or 6 months after surgery. Oncologic outcomes were compared between the two groups at different times, and prognostic roles of TLC and NLR were evaluated. RESULTS: Of 193 patients, the median follow-up time was 22 months, and median survival was 18 months. Their immunologic status deteriorated within 3 to 4 days after the operation and recovered after that. At 1 and 6 months postoperatively, overall survival rates were significantly lower in the group with high NLR (>2.535 and >3.21, respectively) and low TLC (<1.66 × 109 and <1.62 × 109 /L, respectively). In multiple regression analyses, elevated NLR at postoperative 1 and 6 months and decreased TLC at postoperative 1 month were significant prognosis predictors. CONCLUSIONS: Changes in immune status such as decreased TLC and elevated NLR at postoperative 1 and 6 months are effective prognostic predictors after curative pancreatectomy in patients with pancreatic adenocarcinoma.


Assuntos
Adenocarcinoma/patologia , Linfócitos/patologia , Neutrófilos/patologia , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/patologia , Adenocarcinoma/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Contagem de Linfócitos , Masculino , Neoplasias Pancreáticas/cirurgia , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
12.
Anticancer Res ; 39(10): 5581-5588, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570453

RESUMO

BACKGROUND/AIM: The utility of peripheral blood neutrophil-to-lymphocyte ratios (NLRs) and platelet-to-lymphocyte ratios (PLRs) as prognostic predictors of surgery and chemotherapy in breast cancer has been reported. In this study, NLRs and PLRs were calculated before treatment and during cancer progression in primary hormone receptor-positive breast cancer (HRBC) patients who chose endocrine therapy (ET) as the primary treatment, and prognostic prediction and factor analysis were performed. PATIENTS AND METHODS: A total of 55 patients diagnosed with stage IIIB, IIIC, or IV HRBC who received ET as the primary treatment were included. RESULTS: Increased NLRs were found to significantly contribute to a shorter overall survival from cancer progression (OS-CP) (p=0.040, log-rank). Increased PLRs were similarly associated with a shorter OS-CP (p=0.036, log-rank). In multivariate analysis, an increased NLR was an independent prognostic factor (p=0.035, hazard ratio(HR)=5.221). CONCLUSION: Changes in NLRs and PLRs become prognostic indicators when the therapeutic effect of ET is limited.


Assuntos
Plaquetas/patologia , Neoplasias da Mama/patologia , Células Endócrinas/patologia , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Leucócitos/métodos , Contagem de Linfócitos/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Prognóstico , Estudos Retrospectivos
13.
Anticancer Res ; 39(10): 5675-5682, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570466

RESUMO

BACKGROUND/AIM: This study explored the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) and use of antibiotics in advanced esophageal squamous cell carcinoma (ESCC) patients receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: Patients were enrolled from two referral centers in Taiwan. Clinical benefit was defined as complete response, partial response, or a stable disease for ≥6 months via Response Evaluation Criteria In Solid Tumors 1.1. Clinicopathological factors' impact on overall survival (OS) and progression-free survival (PFS) was analyzed via Cox proportional hazards model. RESULTS: Forty-nine patients were enrolled. The median PFS and OS were 1.8 and 6.1 months, respectively. The median NLR at baseline was 6.40, and 21 patients received antibiotics. Both high NLR and use of antibiotics were associated with inferior PFS (p=0.028 and p<0.001, respectively) and OS (p<0.001 and p<0.001, respectively) in multivariate analysis. CONCLUSION: High NLR and use of antibiotics were associated with inferior survival in advanced ESCC patients receiving ICIs.


Assuntos
Antibacterianos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Taiwan
14.
Lancet Haematol ; 6(12): e630-e637, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31537486

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis is a cytokine-driven inflammatory syndrome that is associated with substantial morbidity and mortality. Overall survival in adult patients with secondary haemophagocytic lymphohistiocytosis remains suboptimal, and novel therapeutic strategies are needed. The phosphorylation-dependent activation of the Janus family kinases JAK1 and JAK2 are hallmarks of the final common pathway in this disease. We therefore aimed to determine the activity and safety of ruxolitinib, a JAK inhibitor, in adults with secondary haemophagocytic lymphohistiocytosis. METHODS: We performed an open-label, single-centre, pilot study of ruxolitinib in adults with secondary haemophagocytic lymphohistiocytosis at the University of Michigan Rogel Cancer Center (Ann Arbor, MI, USA). We included patients aged 18 years or more who fulfilled at least five of the eight HLH-2004 criteria for hemophagocytic lymphohistiocytosis. Discontinuation of corticosteroids was not required for enrolment in this study. Patients received oral ruxolitinib (15 mg twice a day) on a continuous 28-day cycle, or until disease progression or unacceptable toxicity. The primary endpoint was overall survival at 2 months from the first dose of ruxolitinib. Secondary endpoints included the assessment of adverse events, response (defined as the assessment of all quantifiable signs and laboratory abnormalities included in the diagnostic criteria for haemophagocytic lymphohistiocytosis), and pharmacodynamic biomarkers. Analyses were done in all treated patients with available data. This study is registered with ClinicalTrials.gov, number NCT02400463, and is still recruiting. FINDINGS: As of Feb 7, 2019, five patients had been enrolled. The first patient was enrolled in February, 2016. No deaths were recorded, with a median follow-up of 490 days (IQR 190-1075). 2-month overall survival was 100% (95% CI 57-100). Regarding response, resolution of symptoms (either partial or complete) and disease-associated laboratory abnormalities was observed in all five patients. Cytopenias improved in all patients within the first week of treatment, leading to relatively rapid transfusion independence, discontinuation of corticosteroids, and hospital discharge. A single serious adverse event (ie, grade 4 febrile neutropenia) was reported. One patient discontinued treatment because of grade 2 extremity pain and no treatment-related deaths were observed. Improvements in inflammatory markers (eg, ferritin, soluble IL-2 receptor) and T cells and monocytes activation (ie, decreased STAT1 phosphorylation) were observed following treatment. INTERPRETATION: These preliminary data suggest that ruxolitinib is active, well tolerated, and manageable in the outpatient setting in patients with secondary haemophagocytic lymphohistiocytosis. Given the paucity of effective, non-myelosuppressive therapies, these preliminary findings have important therapeutic implications for patients with haemophagocytic lymphohistiocytosis and other cytokine-release syndromes and warrant further investigation. FUNDING: National Cancer Institute, the University of Michigan Rogel Cancer Center, and Incyte Corporation.


Assuntos
Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Pirazóis/uso terapêutico , Adulto , Feminino , Estudo Historicamente Controlado , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Projetos Piloto , Contagem de Plaquetas , Esplenomegalia/sangue , Esplenomegalia/tratamento farmacológico , Esplenomegalia/etiologia , Esplenomegalia/mortalidade , Análise de Sobrevida
16.
DNA Cell Biol ; 38(10): 1025-1029, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31532239

RESUMO

Neutrophil trafficking into damaged or infected tissues is essential for the initiation of inflammation, clearance of pathogens and damaged cells, and ultimately tissue repair. Neutrophil recruitment is highly dependent on the stepwise induction of adhesion molecules and promigratory chemokines and cytokines. A number of studies in animal models have shown the efficacy of cannabinoid receptor 2 (CB2) agonists in limiting inflammation in a range of preclinical models of inflammation, including colitis, atherosclerosis, multiple sclerosis, and ischemia-reperfusion injury. Recent work in preclinical models of inflammation raises two questions: by what mechanisms do CB2 agonists provide anti-inflammatory effects during acute inflammation and what challenges exist in the translation of CB2 modulating therapeutics into the clinic.


Assuntos
Aterosclerose/genética , Colite/genética , Esclerose Múltipla/genética , Neutrófilos/metabolismo , Receptor CB2 de Canabinoide/genética , Traumatismo por Reperfusão/genética , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/patologia , Agonistas de Receptores de Canabinoides/uso terapêutico , Antagonistas de Receptores de Canabinoides/uso terapêutico , Colite/tratamento farmacológico , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Citocinas/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Inflamação , Ligantes , Camundongos , Camundongos Knockout , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Infiltração de Neutrófilos , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/deficiência , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
18.
Chemosphere ; 236: 124423, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31545209

RESUMO

Glufosinate-ammonium (Gla) is a broad-spectrum and non-selective herbicide that widely used in many countries worldwide, but the biological safety including potentially negative effects on aquatic organisms remains largely unknown. In this study, we investigated the immunotoxic effects of Gla exposure on zebrafish embryos. Firstly, Gla markedly decreased the survival rate and caused a series of morphological malformations in a dose-dependent manner. Meanwhile, the number of macrophages and neutrophils was substantially reduced upon Gla exposure. In addition, the levels of oxidative stress were changed and the antioxidant enzyme activities such as CAT and SOD were elevated with the increase of Gla concentrations. Secondly, comparative transcriptome analysis identified 1, 366 differentially expressed genes (DEGs) including 789 up-regulated and 577 down-regulated in zebrafish embryos after Gla exposure. KEGG pathway analysis revealed that metabolic pathways such as drug metabolism-cytochrome P450 was markedly regulated and proteolysis, oxidation-reduction process, and peptidase activity were significantly enriched by the GO analysis. Besides, 55 immunity-related genes were identified in the DEGs, and we found that the genes in the metabolism, redox and immunity display an unique expression profilings by clustering analysis. Finally, 8 inflammatory cytokines and chemokines were further confirmed and they were differentially regulated after Gla exposure. In summary, a global survey of zebrafish defense against glufosinate was performed, and a large number of gene expression levels regarding metabolism, redox, and immunity-related genes were acquired from RNA-Seq. This study provides valuable informations for future elucidating the molecular mechanism of herbicide induced immunotoxicity in aquatic ecosystems.


Assuntos
Aminobutiratos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Perfilação da Expressão Gênica , Imunotoxinas/toxicidade , Peixe-Zebra/metabolismo , Animais , Contagem de Células , Regulação da Expressão Gênica/efeitos dos fármacos , Herbicidas/toxicidade , Imunidade Inata/genética , Macrófagos/patologia , Neutrófilos/patologia , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Peixe-Zebra/embriologia , Peixe-Zebra/imunologia
19.
PLoS Negl Trop Dis ; 13(9): e0007368, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31504035

RESUMO

Up to 50% of patients with the multibacillary form of leprosy are expected to develop acute systemic inflammatory episodes known as type 2 reactions (T2R), thus aggravating their clinical status. Thalidomide rapidly improves T2R symptoms. But, due to its restricted use worldwide, novel alternative therapies are urgently needed. The T2R triggering mechanisms and immune-inflammatory pathways involved in its pathology remain ill defined. In a recent report, we defined the recognition of nucleic acids by TLR9 as a major innate immunity pathway that is activated during T2R. DNA recognition has been described as a major inflammatory pathway in several autoimmune diseases, and neutrophil DNA extracellular traps (NETs) have been shown to be a prime source of endogenous DNA. Considering that neutrophil abundance is a marked characteristic of T2R lesions, the objective of this study was to investigate NETs production in T2R patients based on the hypothesis that the excessive NETs formation would play a major role in T2R pathogenesis. Abundant NETs were found in T2R skin lesions, and increased spontaneous NETs formation was observed in T2R peripheral neutrophils. Both the M. leprae whole-cell sonicate and the CpG-Hlp complex, mimicking a mycobacterial TLR9 ligand, were able to induce NETs production in vitro. Moreover, TLR9 expression was shown to be higher in T2R neutrophils, suggesting that DNA recognition via TLR9 may be one of the pathways triggering this process during T2R. Finally, treatment of T2R patients with thalidomide for 7 consecutive days resulted in a decrease in all of the evaluated in vivo and ex vivo NETosis parameters. Altogether, our findings shed light on the pathogenesis of T2R, which, it is hoped, will contribute to the emergence of novel alternative therapies and the identification of prognostic reactional markers in the near future.


Assuntos
Armadilhas Extracelulares/imunologia , Imunidade Inata , Hanseníase/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/patologia , Hanseníase/tratamento farmacológico , Hanseníase/patologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Mycobacterium leprae/patogenicidade , Neutrófilos/patologia , Talidomida/administração & dosagem , Talidomida/uso terapêutico
20.
BMC Cancer ; 19(1): 805, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412814

RESUMO

BACKGROUND: Clinical features of Asian melanoma patients are distinct from those of Western patients. This study was designed to determine the molecular and clinical characteristics of Asian melanoma patients treated with anti-PD-1 antibody. METHODS: Patients with recurrent or metastatic melanoma who began anti-PD-1 antibody therapy between January 2015 and April 2018 were retrospectively reviewed. Patients who underwent next-generation sequencing were also analyzed. RESULTS: A total of 152 patients were included. The median age was 61 years, and 53% of patients were female. A total of 56 patients (37%) received immunotherapy as second-line or greater chemotherapy. Primary sites were acral (38%), mucosal (31%), cutaneous (24%), uveal (2%), and unknown (5%). The overall response rate was 17% (95% CI, 11-22%), and disease control rate was 60% (95% CI, 52-68%). The median progression-free survival (PFS) was 4.2 months (95% CI, 1.8-6.6 months), and median overall survival (OS) was 32.9 months (95% CI, 20.0-45.7 months). However, BRAFV600 and KIT mutational statuses were not associated with response or survival. High neutrophil-lymphocyte ratio (NLR) was associated with poor PFS (median PFS 6.9 vs. 2.4 months, p = 0.015) and OS (median OS NR vs. 10.4 months, p < 0.001). In multivariate analysis, high NLR independently predicted poor survival. CONCLUSION: This study includes the largest set of integrated genomic data analyzing Asian patients with melanoma treated with immunotherapy. BRAF V600 and KIT mutational statuses were not associated with response or survival, and high NLR was a strong predictor of poor response to and survival with anti-PD-1 therapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/terapia , Receptor de Morte Celular Programada 1/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Imunoterapia , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Melanoma/patologia , Melanoma/secundário , Pessoa de Meia-Idade , Mutação , Neutrófilos/metabolismo , Neutrófilos/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
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