A influência de macrófagos M1, M2 e TAM, e do receptor P2X7 na invasividade e resistência de neuroblastoma / The influence of different macrophages' phenotypes, and of the P2X7 receptor, on the invasiveness and chemoresistance of neuroblastoma

O neuroblastoma é um tumor sólido muito comum em crianças. O estágio mais avançado da doença é altamente agressivo e invasivo, além de pouco responsivo à terapia, que é limitada por mecanismos de resistência e reincidência relacionados à metástase. Muitos estudos tem sido feitos para identificar mecanismos de invasão e quimioresistência de células tumorais, afim de aumentar a sobrevida dos pacientes com câncer. Nesse trabalho, nós estudamos o efeito dos macrófagos, as células imunes mais abundantes no microambiente tumoral, os TAMs (do inglês tumor-associated macrophage) e do receptor P2X7, um purinoreceptor acionado por ATP, nesses processos. Os TAMs respondem e atuam de acordo com a miríade de fatores que encontram, podendo gerar populações heterogêneas e com funções distintas, tanto antitumorais, como pró-tumorais. Altos níveis de ATP extracelular são encontrados no microambiente tumoral, podendo então ativar o receptor P2X7. Este receptor tem sido relacionado tanto a funções inflamatórias como funções na resolução da inflamação de macrófagos. Além disso, o receptor P2X7 está envolvido em uma variedade de eventos celulares, incluindo a secreção de mediadores pró-inflamatórios, a proliferação celular e a apoptose de células tumorais. Primeiramente, foi avaliado o papel do receptor P2X7 na polarização de macrófagos da derivados medula óssea de camundongos wild-type e nocaute para o P2X7 na presença e ausência de fatores secretados por células de neuroblastoma, e então foi estudada a influência desses diferentes macrófagos polarizados em eventos celulares de grande relevância clínica para o neuroblastoma: a invasividade e quimiorresistência. Os resultados demonstraram que, apesar do reconhecido envolvimento do receptor P2X7 na inflamação, a ausência deste receptor não atenua a expressão de marcadores característicos do fenótipo inflamatório, M1. O aumento da expressão do receptor P2Y2, também envolvido na inflamação, nessas células, sugere um mecanismo genético de compensação para não atenuação da inflamação em macrófagos que não expressam o receptor P2X7. Contudo, a ausência do receptor P2X7 levou a alterações no fenótipo alternativo, M2, de modo que a expressão de Tnf, marcador de M2, não foi reprimido. TAMs noucates para P2X7 tiveram a expressão de arg1, marcador de M2, suprimida, reforçando a importância do receptor P2X7 no estabelecimento de fenótipos ativados alternativamente. Nossos dados também sugerem que ausência do receptor P2X7 em TAMs permite a aquisição de um fenótipo capaz de tornar as células de neuroblastoma que expressam P2X7 mais invasivas e mais quimioresistentes à vincristina. Por outro lado, TAMs, independentemente da presença ou ausência do receptor P2X7, induziram a proliferação e quimioresistência das células de neuroblastoma silenciadas para o receptor P2X7, o que nos leva a concluir que o receptor P2X7 em TAMs é desfavorável à progressão de tumores expressando P2X7

Neuroblastoma is a highly common childhood solid tumor. The most advanced stage of the disease is highly aggressive and invasive, besides from being poorly responsive to therapies, which are limited by resistance and recurrence mechanisms related to metastasis. Several studies attempt to identify invasion and resistance mechanisms of the tumor cells in order to increase overall survival of the patients. On the present work, we investigated the effect of macrophages, the most abundant immune cells on the tumor microenvironment, called TAMs (tumor-associated macrophages), and of the P2X7 receptor, an ATP-gated purinoceptor, on these processes. TAMs and cancer cells crosstalk, and behave accordingly to a miriad of factors present at the TME, generating heterogeneous populations with distinct functionalities, either pro- or antitumor. High extracellular levels of ATP are found in the TME, being able to activate the P2X7 receptor. This receptor mediates both pro- and anti-inflammatory functions in macrophages. In addition, it is involved in several cellular events, including the secretion of pro-inflammatory mediators, cell proliferation and tumor cell apoptosis. At first, we evaluated the role of the P2X7 receptor on the polarization of bone marrow-derived macrophages (BMDM), either wild-type or knockout for the P2X7 receptor, in presence or absence or factors secreted by neuroblastoma cells. Next, we investigated the influence of the polarized macrophages in highly relevant cellular events for neuroblastoma, such as invasiveness and chemoresistance. Our results showed that, despite the known involvement of P2X7 receptor on inflammation, its absence did not decrease the expression if inflammatory markers of M1 macrophage populations. An increase in the expression of the P2Y2 receptor, also involved in inflammation, on these cells suggest a genetic compensation mechanism for preventing attenuation of inflammation when P2X7 is lacking. However, P2X7 receptor absence did compromise the M2 phenotype, driving the expression of Tnf. TAMs knockout for the P2X7 receptor were not able to express arg1, also an M2 marker, reinforcing a role of the P2X7 receptor on establishing alternative macrophage phenotypes. Our data also suggest that TAMs lacking the P2X7 receptor acquire a phenotype capable of turning P2X7R-expressing neuroblastoma cells more invasive and chemoresistant to vincristine. On the other hand, TAMs, independently on the presence of the P2X7 receptor, induced proliferation and resistance of neuroblastoma cells silenced for P2X7 receptor expression, leading us to the conclusion that the P2X7 receptor in TAMs is unfavorable for the progression of P2X7R-expressing tumors

Microangiopatía trombótica sistémica asociada a mutaciones del complemento en trasplante renal donante vivo. reporte de caso / Systemic thrombotic microangiopathy associated with complement pathway mutations in living donor kidney transplant. case report

RESUMEN El síndrome urémico hemolítico (SUH) se caracteriza por la presencia de anemia hemolítica, plaquetopenia e insuficiencia renal aguda. Si bien se distingue clásicamente en típico o infeccioso y atípico, es menester reconocer situaciones clínicas en las que se pone de manifiesto, como por ejemplo, embarazo, puerperio inmediato, tumores, trasplante, drogas, etc., condiciones clínicas que han sido denominadas amplificadoras del complemento. La recurrencia postrasplante delsíndrome urémico hemolítico atípico (SUHa) ha sido descrita en porcentajes variables en pacientes con mutaciones del factor H, factor B, factor I y C3, y gen de la trombomodulina, en reportes de casos aislados. Se presenta el caso de una paciente con enfermedad renal crónica (ERC) secundaria a agenesia renal, receptora preemptive de un riñón de donante vivo relacionado que presentó disfunción del injerto renal secundaria a microangiopatía trombótica, asociado a complicación neurológica, hemorragias, disfunción orgánica múltiple y óbito. Se describen los hallazgos del estudio genético y anatomopatológico de necropsia.

ABSTRACT Hemolytic uremic syndrome (HUS) is characterized by the presence of hemolytic anemia, thrombocytopenia and acute kidney injury. Although it is usually distinguished as typical or infectious and atypical, it is necessary to recognize clinical situations in which it is revealed, such as pregnancy, immediate postpartum period, tumors, transplantation, drugs, etc., i.e. clinical conditions that have been called complement-amplifying conditions. Post-transplantation recurrence of atypical hemolytic uremic syndrome (aHUS) has been described in variable percentages in patients with mutations of factor H, factor B, factor I and C3, and thrombomodulin gene, in reports of isolated cases. We present the case of a patient with chronic kidney disease (CKD) secondary to renal agenesis, a preemptive recipient of a related living donor kidney, which presented renal graft dysfunction secondary to thrombotic microangiopathy, associated with neurological complications, hemorrhages, multiple organ dysfunction and death. The findings of the genetic and pathological autopsy study are described.

Impacts of menu information quality and nutrition information quality on technology acceptance characteristics and behaviors toward fast food restaurants' kiosk

BACKGROUND/OBJECTIVES: With the advances in technologies, self-service kiosks at foodservice operations are becoming a new way of service provision. This study examined the relationships among the menu information quality, nutrition information quality, technology acceptance characteristics, and customer behavioral intention toward the kiosks in fast food restaurants.SUBJECTS/METHODS: A survey with a self-administered method was distributed online and offline. The sample consisted of customers who had used the kiosks at fast food restaurants in the last six months prior to the survey. The study hypotheses were tested by applying structural equation modeling.RESULTS: Structural equation modeling revealed the positive impacts of menu information quality and nutrition information quality, technology acceptance characteristics, and behavioral intention toward kiosks at fast food restaurants. On the other hand, one hypothesis (Hypothesis 4) on the impact of nutrition information quality on the perceived usefulness was rejected.CONCLUSION: The study is the first to investigate nutrition and menu information at foodservice kiosks and relate them to technology acceptance. The study is very timely and adequate in the time of the 4th industrial revolution. The critical importance of the presentation of nutrition information and menu information at the kiosks at fast food restaurants was verified. The academic and industrial implications of the study findings were discussed.

Chidamide enhances inhibitory effect on colon cancer cells by modulating tumorassociated macrophage / 中国肿瘤生物治疗杂志

@# Objective: To investigate the effect of tumor-associated macrophage (TAM) on the anti-tumor function of chidamide and to explore the mechanism. Methods: Mouse macrophage cell linesAna1 and Raw264.7 were cultured in vitro and induced into TAM with tumor supernatant. HDAC enzyme activity was detected after TAM treated with chidamide. The mRNA expressions of cytokines, such as IL-6, IL-12,TNF and IL-1β, in TAM were detected by qPCR. The protein expression of NF-κB and STAT3 in TAM treated with chidamide were detected by Wb. The mixture of TAM and colon cancer CT26 cells was inoculated into nude mice to construct the subcutaneous xenograft model; and the efficacy of chidamide (3.87 mg/kg) on the growth of CT26 xenograft tumors was observed. The protein expressions of PCNA, F4/80, Arg1 and iNos were detected by immunohistochemistry. Results: Chidamide inhibited the proliferation of CT26 cells. In the in vivo experiment, the inhibition rate of chidamide alone on CT26 xenograft was about 18.7%; however, the inhibition rate was up to 57.2% with the presence of TAM. Chidamide could inhibit the activity of HDAC enzyme in TAM, and further increase the Histone acetylation level. Chidamide could affect the expression of nuclear transcription factor NF-κB, inhibit the expressions of Arg1, IL-6 and IL-12, but up-regulate the expressions of iNOS, TNF and IL-1β in TAM. Conclusion: Chidamide can enhance its inhibitory effect on colon cancer CT26 cells via regulating the expression of cytokines and inhibiting the activity of HDAC in TAM.

Activation of phagocytosis by immune checkpoint blockade / 医学前沿

Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. One mechanism inhibiting the innate response is the presence of the macrophage inhibitory molecule, signal regulatory protein-α (SIRPα), on tumor-associated macrophages (TAMs) and its cognate ligand cluster of differentiation 47 (CD47) on tumor cells in the tumor microenvironment. On the basis of a recently discovered programmed death protein 1 (PD-1) in TAMs, we discuss the potential inhibitory receptors that possess new functions beyond T cell exhaustion in this review. As more and more immune receptors are found to be expressed on TAMs, the corresponding therapies may also stimulate macrophages for phagocytosis and thereby provide extra anti-tumor benefits in cancer therapy. Therefore, identification of biomarkers and combinatorial therapeutic strategies, have the potential to improve the efficacy and safety profiles of current immunotherapies.

Public Acceptance of a Health Information Exchange in Korea / 대한의료정보학회지

OBJECTIVES: We assessed the public acceptance of a health information exchange (HIE) and examined factors that influenced the acceptance and associations among constructs of the Technology Acceptance Model (TAM). METHODS: We collected data from a survey of 1,000 individuals in Korea, which was administered through a structured questionnaire. We assessed the validity and reliability of the survey instrument with exploratory factor analysis and Cronbach's alpha coefficients. We computed descriptive statistics to assess the acceptance and performed regression analyses with a structural equation model to estimate the magnitude and significance of influences among constructs of TAM. RESULTS: Eighty-seven percent of the respondents were willing to use the technology, and the average level of agreement with the need for the technology was 4.16 on a 5-point Likert scale. The perception of ease of use of the technology significantly influenced perceptions of usefulness and attitudes about the need for HIE. Perceptions of usefulness influenced attitude and behavioral intention to use HIE, and attitude influenced intention. Age showed a wide range of influences throughout the model, and experience with offline-based information exchange and health status also showed noteworthy influences. CONCLUSIONS: The public acceptance of HIE was high, and influences posited by TAM were mostly confirmed by the study results. The study findings indicated a need for an education and communication strategy tailored by population age, health status, and prior experience with offline-based exchange to gain public buy-in for a successful introduction of the technology.

Correlation between tumor-associated macrophages and the occurrence and development of Kazakh esophageal squamous cell carcinoma in Xinjiang / 西安交通大学学报(医学版)

Objective To investigate the correlation between tumor-associated macrophages(TAMs)and the occurrence and progression of Kazakh esophageal squamous cell carcinoma.Methods We collected 200 cases of esophageal squamous cell carcinoma(ESCC),cancer adjacent normal(CAN)tissues and clinical pathological data of the specimens.CD68 was used as the TAM marker,and immunohistochemistry(IHC)counts were used to detect the distribution of TAMs and quantify the density of TAMs in tumor nest/epithelial and surrounding stroma.At the same time,by combining with clinical pathological data and the patients' prognosis,we analyzed whether the high density of TAMs distribution was associated with the occurrence and development of Kazakh ESCC and the patients' poor prognosis.Results ① The density of TAMs in the tumor nests and stroma was significantly higher than that in CAN tissues(P＜0.05).② The density of TAMs in tumor nest had a significant positive correlation with lymph node metastasis and clinical pathological stage(advanced)in Kazakh ESCC(P＜ 0.05),and this correlation was more evident between the density of TAMs in tumor stroma and lymph node metastasis and clinical pathological stage (advanced)(P＜0.001).③ The survival analysis found that the high density of CD 68-positive TAMs in cancer nest showed a positive correlation with poor prognosis of ESCC(P＜0.05).Conclusion High density of TAMs can promote the occurrence and development of Kazakh ESCC in Xinjiang and can be used as a poor prognostic factor for ESCC in Kazakh population.

Effects of estrogen receptor antagonist on the expressions of Erα, Erβ and p57kip2 in JEC cells of human endometrial carcinoma / 临床与实验病理学杂志

Purpose To explore the effects of estrogen receptor antagonist on the expression of estrogen receptor subtype (ERα, ERβ), and p57kip2 protein in human endometrioid carcinoma cells named JEC. Methods The JEC cells (moderately differentiated EC cells) cultured in vitro were treated with β-Estradiol (E2) (10～6 mol/L) and two types of estrogen receptor antagonists, tamoxifen (TAM) and fulvestrant (ICI182780) (10-6 mol/L). After 24, 48, 72 h, MTT was used to detect the growth condition of JEC cells, and the light microscopy and electron microscopy were used to observe the growth condition and morphological changes of cells, Western blot was used to detect the expression of ERα, ERβ, PR-A, PR-B and P57kip2 protein in JEC cells. Results MTT results: Compared with the control group, E2 could promote the proliferation of JEC cells significantly (P＜0.05), and ICI182780 could inhibit the proliferation of JEC cells obviously (P＜0.05). Compared with the E2 group, the proliferation ability of JEC cells in E2 + ICI182780 group were lower(P＜0.05). Morphological change: Compared with the control group, the cells density of E2 group increased obviously, and the pathologic mitosis was easy to seen in some cells. The cells density decreased obviously in ICI182780 group. Compared with E2 group, the cells density of E2 + TAM group and E2 + ICI182780 group were decreased, and pathological mitotic figures were difficult to seen. Western blot results: Compared with the control group, the expression of ERβ protein increased, and the expression of p57kip2 protein decreased in E2 group (P＜0.05). The expression of ERβ protein decreased, and the expression of p57kip2 protein increased in ICI182780 group and TAM group, and the difference was statistically significant between ICI182780 group and control group (P＜0.05). Compared with the E2 group, the expression of ERβ protein decreased, and the expression of p57kip2 protein increased in E2 + ICI182780 group and E2 + TAM group, and the difference was statistically significant between E2 + ICI182780 group and E2 group (P＜0.05). ERa protein of JEC cells did not expressed in experimental group or control group. Conclusion ERa protein are not expressed in JEC cells. ICI182780 have a stronger role in antagonizing estrogen, and may induce the expression of p57kip2 protein by down-regulating the expression of ERβ protein in JEC cells, block the cell cycle progression and inhibit the growth of tumor cells. TAM has a weaker estrogen like effect on the growth of JEC cells. It is possible that combined detection of the expression of ERa and p57kip2 protein in EC has an important reference value for individualized selection of endocrine therapy for EC patients.

The Effect of Oxaliplatin Injection Combined with S-1 on Levels of CEA, CA199,TAM and the Quality of Life of Patients with Advanced Gastric Cancer / 昆明医科大学学报

Objective To investigate the effect of oxaliplatin injection combined with S-1 on levels of carcinoembryonic antigen (CEA), cancer antigen 199 (CA199) and tumor associated materials (TAM) and the quality of life of patients with advanced gastric cancer. Methods The clinical data of 70 patients with advanced gastric cancer treated in our hospital from January 2013 to June 2016 were retrospectively analyzed. According to different chemotherapy regimens, the patients were divided into the study group (n=35, treated with oxaliplatin injection combined with S-1) and the control group (n=35, treated with S-1) . The short-term curative effect in the two groups was evaluated, and levels of serum tumor markers were detected before and after the treatment. The toxicity and quality of life were evaluated. Results The total effective rate of treatment and disease control rate in the study group were significantly higher than those in the control group (45.71％ and 88.57％ vs 2.86％ vs 71.43％) ( <0.05) . There were no significant differences in levels of serum CEA, CA199 and TAM between the two groups before the treatment ( >0.05) . After the treatment, levels of serum CEA, CA199 and CEA were significantly decreased ( <0.05), and the decrease was significantly greater in the study group than in the control group ( <0.05) . During and after the treatment, nausea and vomiting was more severe in the study group than in the control group ( <0.05), while the incidence rates of neutropenia, thrombocytopenia, peripheral neuritis and liver or kidney function damage showed no statistically significant difference ( > 0.05) . After the treatment, the improvement rate of KPS score in the study group was significantly higher than that in the control group (60％VS 31.42％),and the overall improvement of the quality of life was significantly better than that in the control group ( < 0.05) . Conclusion Oxaliplatin injection combined with S-1 can effectively inhibit the growth and metastasis of tumor cells, remit the condition and improve the clinical efficacy with high safety in patients with advanced gastric cancer. It also can improve the quality of life of patients.

Roles of human leukocyte antigen-G ( HLA-G) in MDSC proliferation, M1/M2 macrophage differ-entiation and tumor immune evasion / 中华微生物学和免疫学杂志

Objective To investigate the roles of human leukocyte antigen-G ( HLA-G) in mye-loid-derived suppressor cell (MDSC) proliferation and M1/M2 macrophage differentiation in C57BL/6-NCI-H446-G tumor-bearing mice for better understanding the mechanisms of HLA-G involved in tumor immune evasion. Methods NCI-H446 ( human small cell lung cancer cells) and NCI-H446-G ( NCI-H446 cells ex-pressing HLA-G) cells were labeled with CFSE at a final concentration of 1μmol/L. CFSE fluorescence lev-els were measured by flow cytometry at different time points. Mouse tumor models were established by subcu-taneous injection of C57BL/6 mice with NCI-H446 and NCI-H446-G cells, respectively. PBS was used to set up negative control group. The mice in each group were sacrificed to collect tissue samples on 5 d, 10 d, 15 d and 20 d after injection. The percentages of splenic CD11b+Gr1+MDSCs, F4/80+CD80+M1 and F4/80+CD206+M2 macrophages were analyzed by flow cytometry. Results Steady expression of HLA-G in NCI-H446-G cells was confirmed by Western blot and flow cytometry. HLA-G enhanced the proliferation of NCI-H446 cells. Tumor size increased dramatically in tumor-bearing mice in the first five days and then de-creased over time. The tumor-bearing mice in the NCI-H446-G group had larger tumor than those in the NCI-H446 group in every time point (P<0. 05) and required longer time to fully reject the tumor. Compared with the PBS and NCI-H446 groups, the percentage of splenic MDSCs in tumor-bearing mice was significantly in-creased in the NCI-H446-G group (P<0. 05). Moreover, the ratio of M1/M2 in NCI-H446-G tumor-bearing mice was much lower than that in the other two groups (P<0. 05). Conclusion This study indicated that HLA-G could increase the percentage of MDSCs and decrease the ratio of M1/M2, which might illustrate the role of HLA-G in tumor immune evasion and its potential clinical significance in cancer immunotherapy.

Technology acceptance model & realidad aumentada: estudio en desarrollo

Introducción. Este artículo presenta el proyecto de investigación I+D, financiado por el Ministerio de Economía y Competitividad de España (EDU5746-P-Proyecto Rafodiun), para conocer el nivel de adopción de una tecnología o modelo TAM, formulado por Davies (1989). Se presentan las características del modelo, se formula uno para el análisis de la RA, así como el instrumento para su diagnóstico. Objetivo. Establecer el grado de motivación y nivel de satisfacción que despierta en los estudiantes universitarios el hecho de participar en experiencias formativas apoyadas en RA, e indagar sobre las dificultades técnicas, curriculares y organizativas que pudiera tener la RA para ser aplicada a los contextos de formación universitaria. Materiales y métodos. Se utilizó el Modelo de Aceptación de la Tecnología (TAM), formulado inicialmente por Davies(1989). Resultados. La investigación se llevó a cabo mediante estudios experimentales realizados con estudiantes de diferentes estudios universitarios, que interaccionen con diferentes objetos de aprendizaje producidos bajo la arquitectura de la RA, algunos de los cuales pueden observarse en el sitio web del RA del "Secretariado de Recursos Audiovisuales y Nuevas Tecnologías" de la Universidad de Sevilla (http://ra.sav.us.es/). Conclusiones. La RAes una tecnología que se está presentando como de verdadera utilidad y con diferentes posibilidades para facilitar el aprendizaje por parte de los estudiantes en diferentes áreas curriculares, pero sobre la que se debe reconocer que se están efectuando más análisis tecnológicos que investigaciones sobre su aplicación en el terreno educativo.

Introduction. This article introduces a R+D Project funded by Ministerio de Economía y Competitividad de España (EDU-5746-P-Proyecto Rafodiun) to get to know the degree of adoption of a TAM model or technology formulated by Davis (1989). The characteristics of the model are introduced and one is formulated for the RA analysis, along with the instrument for its diagnosis. Objective. Establish the motivation and satisfaction degrees the fact of participating in experiences supported by RAproduce among university students, and delve into the technical, curricular and organizational difficulties RA could have for being applied in university formation contexts. Materials and methods. The Technology Acceptance Model (TAM), initially formulated by Davis (1989) was used. Results. The research work was performed by means of experimental studies made with students from several university areas, who interact with different learning objects produced under RA´s architecture, some of which can be seen at RA´s website of "Secretariado de Recursos Audiovisuales y Nuevas Tecnologías", Universidad de Sevilla (http://ra.sav.us.es/). Conclusions. RA is a really useful technology, with several possibilities to make learning easier for students from different curricular areas, but it is also necessary to recognize that more technological analysis than research on its application in the education field are being made.

Introdução. Este artigo apresenta o projeto de investigação I+D, financiado pelo Ministério de Economia e Competitividade da Espanha (EDU5746-P-Projeto Rafodiun), para conhecer o nível de adoção de uma tecnologia ou modelo TAM, formulado por Davies (1989). Se apresentam as características do modelo, se formula um para a análise da RA, assim como o instrumento para seu diagnóstico. Objetivo. Estabelecer o grau de motivação e nível de satisfação que desperta nos estudantes universitários o fato de participar em experiências formativas apoiadas em RA, e indagar sobre as dificuldades técnicas, curriculares e organizativas que pudesse ter a RApara ser aplicada aos contextos de formação universitária. Materiais e métodos. Se utilizou o Modelo de Aceitação da Tecnologia (TAM), formulado inicialmente por Davies (1989). Resultados. A investigação se levou a cabo mediante estudos experimentais realizados com estudantes de diferentes estudos universitários, que interagem com diferentes objetos de aprendizagem produzidos sob a arquitetura da RA, alguns dos quais podem observar-se na página web do RA do "Secretariado de Recursos Audiovisuais e Novas Tecnologias" da Universidade de Sevilla (http://ra.sav.us.es/). Conclusões. A RA é uma tecnologia que se está apresentando como de verdadeira utilidade e com diferentes possibilidades para facilitar a aprendizagem por parte dos estudantes em diferentes áreas curriculares, mas sobre a que se deve reconhecer que se estão efetuando mais análise tecnológicos que investigações sobre sua aplicação no terreno educativo.

Expression and correlation of tumor-associated macrophages and CCL5 in ganstric cancer / 中国免疫学杂志

Objective:To study the expression and correlation of tumor-associated macrophages(TAM) and CCL5 in ganstric cancer.Methods:48 cases patients with completed clinical and pathological data of gastric cancer paraffin block specimens were select-ed.Cancer tissues and adjacent tissues were used as control,using SP immunohistochemical method to detect CD68 and CCL5 in gastric cancer tissues and adjacent tissues,and using the Spearman correlation statistics statistical methods for the correlation.Results:CD68 and CCL5 showed positive expression in gastric cancer tissue,significantly higher than those in the adjacent tissues(P<0.01),CD68 and CCL5 were related with gastric cancer invasion depth, lymph node metastasis, TNM stage and tumor differentiation ( P<0.001 ) . There was positive relation between the expression of CD68 and CCL5 in gastric cancer(P<0.01,r=0.759).Conclusion: CD68 and CCL5 played a driving role to the invasion and metastasis of gastric cancer occurrence,suggesting that the secretion CCL5 by TAM may promote the invasion and metastasis of gastric cancer.

GATA1 mutations in a cohort of Malaysian children with Down syndrome-associated myeloid disorder

<p><b>INTRODUCTION</b>Children with Down syndrome (DS) are at increased risk of developing distinctive clonal myeloid disorders, including transient abnormal myelopoiesis (TAM) and myeloid leukaemia of DS (ML-DS). TAM connotes a spontaneously resolving congenital myeloproliferative state observed in 10%-20% of DS newborns. Following varying intervals of apparent remission, a proportion of children with TAM progress to develop ML-DS in early childhood. Therefore, TAM and ML-DS represent a biological continuum. Both disorders are characterised by recurring truncating somatic mutations of the GATA1 gene, which are considered key pathogenetic events.</p><p><b>METHODS</b>We herein report, to our knowledge, the first observation on the frequency and nature of GATA1 gene mutations in a cohort of Malaysian children with DS-associated TAM (n = 9) and ML-DS (n = 24) encountered successively over a period of five years at a national referral centre.</p><p><b>RESULTS</b>Of the 29 patients who underwent GATA1 analysis, GATA1 mutations were observed in 15 (51.7%) patients, including 6 (75.0%) out of 8 patients with TAM, and 9 (42.9%) of 21 patients with ML-DS. All identified mutations were located in exon 2 and the majority were sequence-terminating insertions or deletions (66.7%), including several hitherto unreported mutations (12 out of 15).</p><p><b>CONCLUSION</b>The low frequency of GATA1 mutations in ML-DS patients is unusual and potentially indicates distinctive genomic events in our patient cohort.</p>

Value of Detecting Serum TAM and Cyfra21-1 Levels in the Diagnosis and Chemotherapeutic Efficacy of Esophageal Cancer / 现代检验医学杂志

Objective To evaluate the levels of serum TAM and Cyfra21-1 in diagnosis and chemotherapeutic efficacy assess-ment of patients with esophageal cancer.Methods The serum TAM and Cyfra21-1 levels were measured in 92 patients with initially diagnosed esophageal cancer or postoperative recurrence of esophageal cancer from September 2012 to September 2013 and 50 cases of healthy people in the same periods as control.The sensitivity and specificity of TAM and Cyfra21-1 were analyzed.Moreover,60 patients with high TAM and Cyfra21-1 levels before chemotherapy from September 2012 to A-pril 2014 were detected TAM and Cyfra21-1 levels after two cycles of chemotherapy.Relation between changes of TAM or Cyfra21-1 and chemotherapeutic efficacy were investigated.Results The diagnostic sensitivity of TAM for esophageal canc-er was 71.7%,which was higher than that of Cyfra21-1 (51.1%,P = 0.004).The diagnostic specificity of TAM and Cy-fra21-1 for esophageal cancer was 94.0% and 92.0% respectively.There were no significantly different between TAM and Cyfra21-1 (P =0.695).Of patients undergoing chemotherapy,the overall response was 25 cases,progress was 11 cases. There was no statistically significant difference in the coincidence rate of TAM and Cyfra21-1 (77.8% vs 75.0%,P =0.781).Conclusion Detection of serum TAM and CYFRA21-1 was valuable in the diagnosis and assessment of the thera-peutic efficacy of chemotherapy in patients with esophageal carcinoma.TAM was better than Cyfra21-1 in the diagnosis of e-sophageal carcinoma.

Impact of tumor-associate macrophages(TAMs) to imbalance ofT reg/Th17 in Eoc microenvironment / 中国免疫学杂志

Objective:To investigate the impact and mechanisms of TAM to the imbalance of Treg /Th17 in the Eoc microenvi-ronment.Mte hods:Build the in vitro M2 macrophage model ,which was like TAMs .Use flow cytometry to detect the difference of the Treg/Th17 before and after the co-culture of M2 macrophage and CD 4+T cells.Use Western bolt to detect the change of T cell transcription factor and ELISA to detect the IL-10 levels in the supernatant after co-culture.Use crystal violet methods to detect the influence to the ovarian tumor cell proliferation between the different co-culture supernatants and the Transwell to detect the influence to the ovarian tumor cell migration.Thus to analysis the how TAMs influence the imbalance of Treg/Th17 in Eoc microenvironments.R esults:①After coc-ultured with M2 macrophage ,the ratio of Treg/Th17 was( 0.76 ±0.33 ) significant increased compared with control (0.41±0.25) ,M0( 0.40±0.32) and M1(0.31±0.16) (P<0.05).②After co-cultured,the supernatant of M2 group has a significant ability to promote the proliferation of Skov-3 cells.After co-cultured for 1 day, the Skov-3 cell number of M2 group was 14 942.43 ±434.19 , which was significantly higher than the control group ( 12 445.57 ±179.34 ) and CD3/28 group (12 470.32±434.18)(P<0.001).After co-cultured for 2 days,the Skov-3 cell number of M2 group was 30 129.09±520.53 ,which was significantly higher than the control group (25 622.81±897.07) and CD3/28 group(25 721.62±1 808.60) (P<0.05).③After co -cultured with M2 macrophage , the Treg-specific transcription factor Foxp 3 increased ( P=0.047 ) compared with control and M 1 group .④After co-cultured with M2 macrophage for 3 days,the concentration of IL1-0 in the supernatant was(264.04±75.9)pg/ml, which was significantly higher than CD 3/28 group ( 60.89 ±46.54 ) pg/ml,M 0 group ( 44.81 ±32.93 ) pg/ml, M1 group ( 42.71 ± 26.09)pg/ml(P=0.001).Conclusion: M2 macrophage induces the increase of the radio of Treg /Th17 as well as the increase of Treg-specific transcription factor Foxp 3 and the decrease of Th17 -specific transcription factor ROR-γt.Meanwhile , the co-culture supernatant of M2 macrophage and CD4+T cell have the ability to promote the proliferation and migration of ovarian cancer cell ,the mechanism which ,may related to the IL -10 in the supernatant .

Interactions between Immune Cells and Tumor Cells / 대한갑상선학회지

Tumor microenvironment is defined as a heterogeneous complex composed of cancer cells, vascular endothelial cells, fibroblasts, and diverse immune cells. Cancer immunology is the study of interactions between the immune system and cancer cells which is applied to develop therapeutic strategies for human cancers. This review focused on tumor promoting myeloid derived cells such as tumor associated macrophages (TAM) and myeloid derived suppressor cells (MDSC) and their therapeutic applications.

Los estudiantes de medicina como parte del equipo de salud / Medical students as members of the health care team

Background: Teaching hospitals include both undergraduate and postgraduate students, but the role of medical students in the health care team has not been clearly established. Aim: To know the opinion of different professionals about the role of medical students and how this opinion may have an influence in medical education. Material and Methods: A qualitative method was used, asking open questions to focus groups of physicians, nurses and midwives, technicians and undergraduate medical students of 4th and 5th grade. Results: Physicians believe that medical students have no special role in the health care team, nurses think that they may help in commu-nication with patients, and technicians (nurses’s aids) value their companionship and closeness with patients. Medical students recognize that their main function is to learn but they are aware that they do help patients. They suggest increasing their integration with other students of other health related careers. Conclusions: Although medical students are usually not seen as part of the health care team, they may fulfll a role with patients during their clinical learning practice. This would improve the quality of their training and the multidisciplinary work of the health care team.

Aromatase inhibitors and TAM in the treatment of post-menopausal Luminal B breast cancer patients / 中华普通外科杂志

Objective To evaluate a therapeutic strategy using aromatase inhibitors and TAM in postmenopausal Luminal B breast cancer patients. Methods The clinical data of 733 primary breast cancer cases receiving postoperative endocrine thempy from July 2002 to Mar 2005 in Tianjin Cancer Hospital were retrospectively analyzed.Diagnosis was confirmed by pathology in all the cases.All patients were post-menopausal and ER-positive.501 patients were given tamoxifen(TAM 2.5 mg qd,po),232 patients were given aromatase inhibitors(Letrozole 10 mg bid,po).The follow-up time ranged from 36 to 90 months.Median follow-up time was 46 months.Results The disease-free-survival(DFS)rate of Luminal B breast cancer patients in aromatase inhibitors(AIS)group was higherthan that in TAM group(90.6% vs.88.6%,P=0.038).In TAM group,subgroup analysis showed 3-year DFS of node-positive with HER2(+)is lower than that of node-positive with Her-2-negative(88.2% vs.90.4%,P=0.037);3-year DFS of ER+/PR+ group in HER2(+) patients was higher than that of ER+/PR-group(90.8% vs.89.5%.P=0.032).In AIs group,in spite of the axillary lymph node status,there was no significant difference of 3-year DFS between HER2(+)patients and HER2(-)ones(P>0.05).3-year DFS of ER+/PR+with HER2(+) patients was higher than that of ER+/PR-ones with HER2(+)(91.9% vs.90.5%,P=0.029).Hot flush,vaginal bleeding and thromboembolics in AIS group is less frequent,but muscle pain and bone fracture is more common than that in TAM group(P<0.05).Conclusion Compared to TAM, AIs is more effective and safer with postmenopausal Luminal B patients,and the effect is independent on node stams.

The effect of TCM method of regulating liver Qi and tonifying kidney Yin on plasma concentration of E2, P and FAS of post-surgery breast-cancer patients received endocrine therapy (Tamoxifen) / 国际中医中药杂志

Objective The prospective study was trying to explore the altering tendency of plasma concentration of E2, P and PAS after TCM intervention for post-surgery breast cancer patient who received endocrine therapy (tamoxifen).Methods By randomization, parallel, coincidence measures and the lab. technologies of AXSYM registered at Abbott lab. in the USA, plasma concentration of E2, P and FAS were tested before and after treatment. Results The results of biochemical test of plasma E2, P and FAS concentration of the two arms showed no significance difference before and after the intervention,indicating the side effects relating to TAM had nothing to do with plasma E2, P and FAS level. Conclusion It could be predicable that there must be some other by-pass ways initiating breast cancer rather than the way directly altering the level of plasma concentration of E2, P and FAS.

Autologous Stem Cell Transplantation using a Modified TAM Conditioning Regimen for Clinically Aggressive Non-Hodgkin's Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: High-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) have been used for the treatment of clinically aggressive non-Hodgkin's lymphoma (NHL). However, the superiority of specific conditioning regimens has not yet been established. The present study evaluated the efficacy and toxicity of a conditioning regimen involving fractionated total body irradiation (TBI), and the use of Ara-C and melphalan (TAM) for clinically aggressive NHL. MATERIALS AND METHODS: Between March 2002 and December 2004, 31 patients with aggressive NHL received fractionated TBI with a dose of 12 Gy over 3 days, and were administered 9 g/m2 Ara-C and 100 mg/m2 melphalan followed by autologous peripheral blood stem Cell Transplantation at the Catholic Hematopoietic Stem cell transplantation Center Korea. Patients that responded to first line chemotherapy and achieved complete remission (CR), or were in a first sensitive relapse were defined as having less advanced disease, while the other patients were defined as having more advanced disease. RESULTS: Objective responses were obtained in 24 of 31 patients (77.4%), comprising complete remission in 19 patients (61.3%) and partial remission in 5 (16.1%) patients. The median follow-up time was 28 months (range 1~62 months). At 3 years, the overall survival and event-free survival (EFS) rates were 62.3% and 47.3%, respectively. Patients with less advanced disease and more advanced disease showed 3-year EFS rates of 73.3% and 22.5 %, respectively (p=0.006). Early (within the first 100 days) treatment-related mortality occurred in 3 (9.7%) patients. Of the 31 total patients, 15 (48.4%) developed grade 3 mucositis, 22 (70.9%) developed neutropenic fever, and two (6.5%) developed interstitial pneumonia syndrome >grade 3. CONCLUSION: The modified TAM conditioning regimen and ASCT appear to be a feasible treatment regimen for clinically aggressive NHL, particularly for patients with less advanced disease.