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1.
Rev. ecuat. pediatr ; 23(2): 146-153, 15 de agosto 2022.
Article in Spanish | LILACS | ID: biblio-1397276

ABSTRACT

Introducción: El trasplante de células progenitoras hematopoyéticas (TCPH) es el trata-miento para la leucemia aguda en niños, el tipo de cáncer más común en edad pediátrica. El objetivo del presente estudio fue determinar la supervivencia global y libre de enferme-dad en un grupo de pacientes sometidos a TCPH y explorar los factores de riesgo pacientes pediátricos con leucemia aguda. Metodología: El presente estudio observacional incluye a pacientes pediátricos diagnosticados de leucemia mieloide aguda (LMA) o linfoide (LLA), sometidos a TCPH, de 2011 a 2018 presentados en el Hospital Infantil Federico Gómez. Se construyen curvas de Kaplan Meier para la supervivencia global, por subgrupos según tipo de leucemia y estado libre de enfermedad así como un estudio multivariable para medir factores de riesgo. Resultados: Se incluyeron 53 pacientes en el análisis. 5 pacientes (11%) tuvieron falla primaria del injerto. La supervivencia global fue del 28% a los 24 meses. Fallecieron 30 pacientes (67%). La mediana de supervivencia global fue de 11 meses. Para LMA fue de 8.9 meses y para LLA de 12.4 meses. Uno de los factores de riesgo constituyó la edad >10 años al momento del trasplante OR 5.2 (1.07-25.12), P=0.04 y el número de recaídas previas al trasplante OR 4.3 (1.2-15.07) P=0.025. Conclusión: Los pacientes que sobrevivieron un año libre de la enfermedad tenían un mejor pronóstico en general. En estudios relacionados a TCPH no se ha reportado que exista un rango de edad de los receptores de trasplante que esté relacionado a mayor mortalidad, por lo cual es un dato significativo como un factor de riesgo independiente.


Introduction: Hematopoietic stem cell transplantation (HSCT) is the treatment for acute leukemia in children, the most common type of cancer in children. The objective of the present study was to de-termine the overall and disease-free survival in a group of patients undergoing HSCT and to explore the risk factors for pediatric patients with acute leukemia. Methodology: This observational study includes all pediatric patients diagnosed with acute myeloid leukemia (AML) or lymphoid leukemia (ALL), undergoing HSCT from March 2011 to March 2018, presented at the Federico Gómez Children's Hospital. Kaplan Meier curves are constructed for overall survival by subgroups according to the type of leukemia and disease-free status, as well as a multivaria-ble study to measure risk factors. Results: 53 patients were included in the análisis. 5 patients (11%) had primary graft failure. Overall survival was 28% at 24 months. Thirty patients (67%) died. The median overall survival was 11 months. For AML, it was 8.9 months, and for ALL, it was 12.4 months. One of the risk factors was age >10 years at the time of transplant OR 5.2 (1.07-25.12) P=0.04 and the number of relapses prior to transplant OR 4.3 (1.2-15.07) P=0.025. Conclusión: Patients who survived one year free of the disease had a better prognosis. In studies relat-ed to HSCT, it has not been reported that there is an age range of transplant recipients that is related to higher mortality, which is why it is a significant and independent risk factor.


Subject(s)
Humans , Child, Preschool , Child , Child , Bone Marrow Transplantation , Bone Marrow , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Survivorship
2.
Rev. cuba. hematol. inmunol. hemoter ; 38(2): e1516, abr.-jun. 2022.
Article in Spanish | LILACS, CUMED | ID: biblio-1408444

ABSTRACT

Introducción: Los síndromes mielodisplásicos constituyen un grupo heterogéneo de alteraciones de la célula progenitora hematopoyética. Estos se caracterizan por presentar una médula ósea hipercelular, una hematopoyesis inefectiva, displasia y citopenia periférica y la posibilidad de evolución a leucemia mieloide aguda. Objetivo: Describir las alteraciones citogenéticas y moleculares más frecuentes de los síndromes mielodisplásicos. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados en los últimos cinco años. Se realizó análisis y resumen de la bibliografía. Análisis y síntesis de la información: En los síndromes mielodisplásicos están presentes alteraciones citogenéticas frecuentes como la deleción de los cromosomas 5q, 7q y 20q, la monosomía del cromosoma 7, la trisomía del cromosoma 8 y la presencia de cariotipos complejos, que, unido a mutaciones somáticas en diferentes genes, intervienen en la patogénesis de la enfermedad y su conocimiento permite la estratificación pronóstica de los pacientes. Conclusiones: El diagnóstico a través de los estudios citogenéticos convencionales, la hibridación in situ por fluorescencia y la secuenciación génica permite una mayor comprensión de la biología de la enfermedad, la estratificación del riesgo y la toma de decisiones terapéuticas(AU)


Introduction: Myelodysplastic syndromes constitute a heterogeneous group of alterations of the hematopoietic progenitor cell, characterized by hypercellular bone marrow, ineffective hematopoietic, dysplasia and peripheral cytopenia; and the possibility of progressing to acute myeloid leukemia. Objective: To describe the most frequent cytogenetic and molecular alterations of myelodysplastic syndromes. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine Google, for articles published in the last five years. We performed analysis and summary of the reviewed bibliography. Analysis and synthesis of information: In myelodysplastic syndromes, frequent cytogenetic alterations are present such as deletion of chromosomes 5q, 7q and 20q, as well as the monosomy of chromosome 7, trisomy of chromosome 8 and the presence of complex karyotypes, which together with somatic mutations in different genes intervene in the pathogenesis of the disease and allow prognostic stratification of patients. Conclusions: Diagnosis through conventional cytogenetic studies, fluorescence in situ hybridization and gene sequencing allow a better understanding of the biology of the disease, risk stratification and therapeutic decision making(AU)


Subject(s)
Humans , Bone Marrow , Chromosomes, Human, Pair 7 , Chromosomes, Human, Pair 8 , Hematopoietic Stem Cells , Leukemia, Myeloid, Acute , In Situ Hybridization , Cytogenetics , Decision Making
3.
São Paulo; s.n; 20220601. 77 p.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1370995

ABSTRACT

Reabsorções internas das paredes dentinárias levantam dúvidas sobre a origem de células clásticas na polpa dentária em casos idiopáticos. Estudos recentes sugeriram que as células MDPC-23 (odontoblast-like) podem se diferenciar em células clásticas, contrariando estudos anteriores. O presente estudo teve como objetivo observar a influência do calcitriol (1,25-dihidroxivitamina D3) e do lipopolissacarídeo (LPS) na indução da diferenciação de células MDPC-23 (semelhantes a odontoblastos) em células semelhantes a clastos. Como as células MDPC-23 têm origem ectomesenquimal e células clásticas possuem origem hematopoiética, o estudo foi proposto para comparar, in vitro, o potencial clastogênico de dois modelos de origem embrionárias distintas frente a diferentes estímulos. Dois grupos, MDPC-23 e células da medula óssea de camundongos, foram cultivados e tratados com LPS ou 1,25-dihidroxivitamina D3 (calcitriol). No sexto dia, o ensaio de metiltiazolil-tetrazólio (MTT) foi realizado para observar a viabilidade celular diante dos tratamentos. Em seguida, o ensaio citoquímico foi executado para identificar células positivas para TRAP. Adicionalmente foi feito estudo da expressão gênica dos marcadores da clastogênese, OPG, RANK, RANKL, Csf1r, M-Csf1 e catepsina K, através da PCRq. No ensaio de MTT, a viabilidade celular não foi alterada com os tratamentos em comparação com os subgrupos controle. Células TRAP positivas estavam presentes apenas nos subgrupos medula óssea, induzidos com LPS ou calcitriol. O grupo medula óssea apresentou amplificação para todos os genes alvos mencionados. Já para os subgrupos do grupo MDPC-23 apresentaram expressão gênica significativa, diante dos tratamentos, apenas para os genes Csf1r e catepsina K. Concluiu-se, portanto, que embora apresente expressão relativa para os genes Csf1r e catepsina K, sob tratamento, as células MDPC-23 não foram capazes de se diferenciar em células clásticas.


Subject(s)
Bone Marrow , Calcitriol
4.
Notas enferm. (Córdoba) ; 22(39): 23-32, junio 2022.
Article in Spanish | LILACS, BDENF, BINACIS, UNISALUD | ID: biblio-1380255

ABSTRACT

El Trasplante de Médula ósea es actualmente, una alternativa en patologías oncológicas, que busca curación y sobrevida del paciente, los cuidados de enfermería en todas las etapas del tratamiento están encaminados a proporcionar atención oportuna y eficaz, con la finalidad de prevenir, tratar y superar complicaciones propias del proceso. La educación de los pacientes y cuidadores favorece a que el paciente aprenda a autocuidarse, a disminuir su ansiedad, a realizar cambios en su comportamiento y estilo de vida y a prevenir la no adherencia al tratamiento. El objetivo fue diseñar un programa educativo sobre los cuidados que el paciente y su familia debe conocer al ingreso y estadía en el servicio de trasplante de Médula Osea. Diseño Metodológico: la búsqueda se efectuó en bases de datos: Pubmed y Google Académico y Scielo. Se analizaron 13 artículos para el desarrollo del trabajo. Resultados: Educar a los pacientes y sus familias sobre el proceso del trasplante de Medula Osea es un gran desafío que necesita de actualización permanente del personal de enfermería. Brindar conocimientos sobre medidas preventivas y pautas que ayuden a sobrellevar este proceso, permitirá tener al paciente como un miembro activo en sus cuidados, disminuyendo su ansiedad y si es necesario realizando modificaciones en su estilo de vida[AU]


Bone Marrow Transplantation is currently an alternative in oncological pathologies, which seeks healing and patient survival, here nursing care at all stages of treatment is aimed at providing timely and effective care, in order to prevent, treat and overcome complications of the process. The education of patients and caregivers favors the patient learning to care for himself, to reduce his anxiety, to make changes in his behavior and lifestyle and to prevent non-adherence to treatment. The objective was to design an educational program on the care that the patient and his family should know during their admission and stay in the Bone Marrow Transplant Service. Methodological design: the search was carried out in the database: Pubmed and Google Scholar and Scielo. 13 articles were analyzed for the development of the work. Results: Educating patients and their families about the bone marrow transplant process is a great challenge that requires permanent updating of the nursing staff. Providing knowledge about preventive measures and guidelines to help cope with this process will allow us to have the patient as an active member in their care, reducing their anxiety and, if necessary, making changes to their lifestyle[AU]


O Transplante de Medula Óssea é atualmente uma alternativa nas patologias oncológicas, que busca a cura e a sobrevivência do paciente, aqui a assistência de enfermagem em todas as etapas do tratamento visa proporcionar uma assistência oportuna e eficaz, | 24a fim de prevenir, tratar e superar complicações do processo. A educação de pacientes e cuidadores favorece que o paciente aprenda a cuidar de si mesmo, a diminuir sua ansiedade, a realizar mudanças em seu comportamento e estilo de vida e a prevenir a não adesão ao tratamento. O objetivo foi elaborar um programa educativo sobre os cuidados que o paciente e sua família devem conhecer durante sua admissão e permanência no serviço de transplante de medula óssea. Desenho metodológico: a busca foi realizada nas bases de dados: Pubmed e Google Acadêmico e Scielo. 13 artigos foram analisados para o desenvolvimento do trabalho. Resultados: Educar os pacientes e seus familiares sobre o processo de transplante de medula óssea é um grande desafio que exige atualização permanente da equipe de enfermagem. Fornecer conhecimento sobre medidas preventivas e orientações para auxiliar no enfrentamento desse processo nos permitirá ter o paciente como um membro ativo em seu cuidado, reduzindo sua ansiedade e, se necessário, realizando mudanças em seu estilo de vida[AU]


Subject(s)
Humans , Anxiety , Bone Marrow , Patient Education as Topic , Bone Marrow Transplantation , Life Style , Nursing Care
5.
Article in Spanish | LILACS-Express | LILACS, CUMED | ID: biblio-1408441

ABSTRACT

Introducción: La circulación de células tumorales en la sangre periférica, conocido como carcinocitemia, es un fenómeno raro y muy poco comunicado en la literatura científica y su diagnóstico diferencial puede constituir un desafío en la práctica clínica. Objetivos: Describir las causas más frecuentes de carcinocitemia, los retos diagnósticos que representa y contribuir a elevar el índice de sospecha de esta entidad. Presentación del caso: Paciente femenina de 71 años de edad que acude por dolores óseos y palidez cutánea. En el examen de sangre periférica se observa células de gran tamaño que recordaron células plasmáticas. El inmunofenotipo por citometría de flujo fue sugestivo de mieloma múltiple isotipo IgM. El ultrasonido de mamas y la tomografía de tórax mostraron lesión tumoral en la mama izquierda. El estudio inmunohistoquímico de la biopsia de médula ósea fue compatible con adenocarcinoma de mamas. La paciente falleció sin haber comenzado tratamiento específico. Conclusiones: Se presenta paciente con células circulantes tumorales secundaria a adenocarcinoma de la mama donde la inmunohistoquímica de la biopsia de médula ósea descartó el diagnóstico de mieloma múltiple sospechado clínica, radiológicamente, por la morfología celular y el inmunofenotipo(AU)


Introduction: The circulating tumor cells in peripheral blood, known as carcinocythemia is a rare and poorly documented phenomenon, that can be a challenge diagnosis. Objectives: To describe the most frequents causes of carcinocythemia, the diagnosis challenges that it represents and to contribute raising awareness of this entity. Case presentation: Female patient, 71-year-old who complained bone pain and skin pale. The peripheral blood smear showed big size cells mimicking plasma cells. The immunophenotype by flow cytometry suggested IgM isotype multiple myeloma. Breast ultrasound and thorax tomography showed a tumor in the left breast. The bone marrow biopsy immunohistochemical was compatible with adenocarcinoma of breast. The patient died short after before receive specific treatment. Conclusions: We present a patient with circulating tumor cells secondary to breast adenocarcinoma where the bone marrow biopsy immunohistochemical ruled out multiple myeloma diagnosis suspected by clinical, image studies, cell morphology and immunophenotype(AU)


Subject(s)
Humans , Female , Aged , Bone Marrow , Immunoglobulin M , Adenocarcinoma , Multiple Myeloma , Neoplastic Cells, Circulating , Diagnosis, Differential , Flow Cytometry
6.
Fisioter. Bras ; 23(1): 73-79, Fev 11, 2022.
Article in Portuguese | LILACS | ID: biblio-1358411

ABSTRACT

Introdução: A anemia aplásica (AA) é uma condição clínica considerada rara que se desenvolve a partir da disfunção hematopoiética da medula óssea. O tratamento indicado é o transplante de células tronco hematopoiéticas (TCHP). Objetivo: Descrever o caso clínico e as estratégias utilizadas pela fisioterapia durante o processo de reabilitação física. Métodos: Trata-se de estudo de caso, realizado com paciente do sexo feminino, 34 anos de idade e diagnóstico de AA severa. Após avaliação clínica foi indicado o TCHP alogênico de um doador aparentado que apresentou compatibilidade histo-imunológica. O tempo total de internação hospitalar foi de 35 dias. Os objetivos da reabilitação física foram o de manter a ventilação pulmonar, prevenir o acúmulo de secreção, minimizar a progressão da fadiga, perda de força e resistência muscular. Resultados: A estratégia utilizada para contornar a extrema fragilidade hematológica e as implicações clínicas decorrentes evitou perda expressiva no desempenho no teste de caminhada de seis minutos (-10%) ao final da internação. Conclusão: Foi um verdadeiro desafio a implementação da reabilitação física durante o TCHP para o tratamento da AA, mas a estratégia adotada demonstrou-se segura, bem tolerada e suficiente para evitar maiores prejuízos no estado funcional. (AU)


Subject(s)
Female , Adult , Therapeutics , Bone Marrow , Physical Therapy Modalities , Health Strategies , Cell Transplantation , Fatigue , Walk Test , Frailty , Anemia, Aplastic
8.
Acta sci., Health sci ; 44: e56546, Jan. 14, 2022.
Article in English | LILACS | ID: biblio-1367534

ABSTRACT

The aim of the study is to determine the psychological well-being of patients who underwent stem cell transplantation. This cross-sectional study was conducted with 100 patients. Data were collected face-to-face using an introductory information form and the Brief Symptom Inventory.When the results of the patients were examined, the interpersonal sensitivity of the sub-dimensions of the scale was found to be 5.0 ± 4.06, depression 7.60 ± 5.37, and anxiety disorder 7.90 ± 5.34. There was a significant difference between the diagnosistime of the patients and all sub-factors of the scale, except phobic anxiety. It was found that the psychological state of the patients was directly related to the time of first diagnosis. As a result, the importance of following the psychological processof the patients during the treatment process was revealed when planning nursing care.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Patients/psychology , Stem Cell Transplantation/nursing , Emotional Adjustment/ethics , Nursing Care/ethics , Anxiety Disorders/diagnosis , Anxiety Disorders/nursing , Anxiety Disorders/rehabilitation , Paranoid Disorders/diagnosis , Paranoid Disorders/nursing , Paranoid Disorders/therapy , Psychotic Disorders/diagnosis , Psychotic Disorders/nursing , Psychotic Disorders/therapy , Somatoform Disorders/diagnosis , Somatoform Disorders/nursing , Somatoform Disorders/therapy , Bone Marrow , Demography/statistics & numerical data , Cross-Sectional Studies , Depression/diagnosis , Depression/nursing , Hostility , Neoplasms/diagnosis , Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/nursing , Obsessive-Compulsive Disorder/therapy
9.
Artrosc. (B. Aires) ; 29(4): 155-162, 2022.
Article in Spanish | LILACS, BINACIS | ID: biblio-1411045

ABSTRACT

Descripta por Ahlbäck en 1968, la osteonecrosis de rodilla es una patología con un gran potencial de morbilidad. Está dividida en tres grandes grupos: primaria/espontánea, postoperatoria y secundaria/atraumática. Esta última podría estar directamente relacionada con el consumo prolongado de corticoides. Su tratamiento constituye un desafío para el cirujano ortopedista. Va a depender del estadio de la enfermedad y del colapso articular, y se intentará siempre preservar la superficie articular nativa. Dentro de las distintas opciones terapéuticas, las terapias biológicas constituyen una herramienta potencialmente valiosa como complemento al tratamiento quirúrgico, y muestran resultados clínicos esperanzadores. Presentamos el caso de una paciente con una osteonecrosis de rodilla bilateral, secundaria al consumo crónico de corticoides, tratada con una artroscopía bilateral asociada a perforaciones subcondrales descompresivas y aplicación subcondral de concentrado de médula ósea (CMO), con evolución satisfactoria de los síntomas a los treinta meses de seguimiento en la rodilla derecha, mientras que en la rodilla izquierda presentó una evolución tórpida de los síntomas a partir de los veinticuatro meses, por lo que está en plan de reemplazo articular.


Described by Ahlbäck in 1968, osteonecrosis of the knee is a pathology with great potential for morbidity. It is divided into three large groups: primary/spontaneous, postoperative, and secondary/atraumatic. The latter might be directly related to prolonged consumption of steroids. Its treatment is a challenge for the orthopedist. It will depend on the disease stage and articular collapse, always trying to preserve the native articular surface. Within the different therapeutic options, biological therapies are a potentially valuable tool as a complement to surgical treatment, showing encouraging clinical results. We present the case of a female patient with bilateral osteonecrosis of the knee, secondary to chronic consumption of steroids, treated with bilateral arthroscopy associated with decompressive subchondral perforations and subchondral application of bone marrow concentrate (BMC), with a satisfactory evolution of symptoms after thirty months of follow-up in the right knee. However, the left knee showed a torpid evolution of symptoms after twenty-four months of follow-up, so she is on a joint replacement plan


Subject(s)
Osteonecrosis , Bone Marrow , Decompression, Surgical , Knee
10.
São Paulo; s.n; s.n; 2022. 74 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-1378473

ABSTRACT

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


Subject(s)
Animals , Male , Female , Mice , Receptors, Purinergic P2X7/analysis , Receptors, Purinergic P2Y2/analysis , Tumor-Associated Macrophages/pathology , Macrophages/drug effects , Neuroblastoma/pathology , Training Support/classification , Bone Marrow , Cells/chemistry , Inflammation
11.
Article in Chinese | WPRIM | ID: wpr-939682

ABSTRACT

OBJECTIVE@#To explore the expression of cellular apoptosis susceptibility protein (CAS) in acute myeloid leukemia (AML) and its correlation with clinical characteristics.@*METHODS@#The expression of CAS in bone marrow tissue of 54 patients with AML and 24 patients with non-hematological malignant diseases was detected by Western blot and immune-histochemical method, and compared between AML group and control group. Also the relationship of CAS expression in AML and sex, age, WBC count, Hb, platelet count, bone marrow blast cell ratio, ki-67 index, cytogenetic and molecular biological prognostic risk stratification, extramedullary infiltration and other clinical characteristics was analyzed.@*RESULTS@#Western blot showed that the expression of CAS protein in bone marrow biopsies of AML patients was significantly higher than that in control group (P<0.05). Immune-histochemical method revealed that CAS was mainly located in the cytoplasm in both AML group and control group. Among 54 AML patients, 14 patients (25.9%) showed high expression of CAS, while all the 24 patients in the control group showed low expression of CAS. The high expression rate of CAS in AML patients was significantly higher than that in the control group (P<0.05). There were statistically significant differences in prognostic risk stratification and the remission rate of the first chemotherapy between CAS high expression group and CAS low expression group in AML (P<0.05). The proportion of high risk patients and unremission patients after the first chemotherapy in CAS high expression group were significantly higher than those in CAS low expression group (57.1% vs 27.5%, 30.8% vs 7.9%), while the proportion of low risk patients and complete remission patients after the first chemotherapy were significantly lower than those in CAS low expression group (14.3% vs 37.5%, 53.8% vs 84.2%). In AML patients, the ki-67 index of bone marrow tissue in CAS high expression group was higher than that in CAS low expression group (60% vs 50%) (P<0.05).@*CONCLUSION@#CAS is localized in cytoplasm in both AML and non-hematological malignant diseases, and its expression increases in AML. CAS is related to the risk stratification of cytogenetics and molecular biology, the remission rate after the first chemotherapy and ki-67 index in AML, which suggests that CAS may be involved in the occurrence and development of AML.


Subject(s)
Bone Marrow/metabolism , Cellular Apoptosis Susceptibility Protein/metabolism , Humans , Ki-67 Antigen/metabolism , Leukemia, Myeloid, Acute/drug therapy , Prognosis , Remission Induction
12.
Chinese Journal of Burns ; (6): 422-433, 2022.
Article in Chinese | WPRIM | ID: wpr-936029

ABSTRACT

Objective: To investigate the effects of non-muscle myosin Ⅱ (NMⅡ) gene silenced bone marrow-derived mesenchymal stem cells (BMMSCs) on pulmonary extracellular matrix (ECM) and fibrosis in rats with acute lung injury (ALI) induced by endotoxin/lipopolysaccharide (LPS). Methods: The experimental research methods were adopted. Cells from femur and tibial bone marrow cavity of four one-week-old male Sprague-Dawley rats were identified as BMMSCs by flow cytometry, and the third passage of BMMSCs were used in the following experiments. The cells were divided into NMⅡ silenced group transfected with pHBLV-U6-ZsGreen-Puro plasmid containing small interference RNA sequence of NMⅡ gene, vector group transfected with empty plasmid, and blank control group without any treatment, and the protein expression of NMⅡ at 72 h after intervention was detected by Western blotting (n=3). The morphology of cells was observed by an inverted phase contrast microscope and cells labeled with chloromethylbenzoine (CM-DiⅠ) in vitro were observed by an inverted fluorescence microscope. Twenty 4-week-old male Sprague-Dawley rats were divided into blank control group, ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group according to the random number table, with 5 rats in each group. Rats in blank control group were not treated, and rats in the other 3 groups were given LPS to induce ALI. Immediately after modeling, rats in ALI alone group were injected with 1 mL normal saline via tail vein, rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were injected with 1×107/mL BMMSCs and NMⅡ gene silenced BMMSCs of 1 mL labelled with CM-DiⅠ via tail vein, and rats in blank control group were injected with 1 mL normal saline via tail vein at the same time point, respectively. At 24 h after intervention, the lung tissue was collected to observe intrapulmonary homing of the BMMSCs by an inverted fluorescence microscope. Lung tissue was collected at 24 h, in 1 week, and in 2 weeks after intervention to observe pulmonary inflammation by hematoxylin eosin staining and to observe pulmonary fibrosis by Masson staining, and the pulmonary fibrosis in 2 weeks after intervention was scored by modified Ashcroft score (n=5). The content of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected by immunohistochemistry in 2 weeks after intervention (n=3), the activity of superoxide dismutase (SOD), malondialdehyde, myeloperoxidase (MPO) was detected by enzyme-linked immunosorbent assay at 24 h after intervention (n=3), and the protein expressions of CD11b and epidermal growth factor like module containing mucin like hormone receptor 1 (EMR1) in 1 week after intervention were detected by immunofluorescence staining (n=3). Data were statistically analyzed with one-way analysis of variance, Bonferroni method, and Kruskal-Wallis H test. Results: At 72 h after intervention, the NMⅡprotein expression of cells in NMⅡ silenced group was significantly lower than those in blank control group and vector group (with P values <0.01). BMMSCs were in long spindle shape and grew in cluster shaped like vortexes, which were labelled with CM-DiⅠ successfully in vitro. At 24 h after intervention, cell homing in lung of rats in ALI+NMⅡ silenced BMMSC group was more pronounced than that in ALI+BMMSC group, while no CM-DiⅠ-labelled BMMSCs were observed in lung of rats in blank control group and ALI alone group. There was no obvious inflammatory cell infiltration in lung tissue of rats in blank control group at all time points, while inflammatory cell infiltration in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly less than that in ALI alone group at 24 h after intervention, and alveolar wall turned to be thinner and a small amount of congestion in local lung tissue appeared in rats of the two groups in 1 week and 2 weeks after intervention. In 1 week and 2 weeks after intervention, collagen fiber deposition in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group was significantly aggravated compared with that in blank control group, while collagen fiber deposition in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly improved compared with that in ALI alone group. In 2 weeks after intervention, modified Ashcroft scores for pulmonary fibrosis of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were 2.36±0.22, 1.62±0.16, 1.06±0.26, respectively, significantly higher than 0.30±0.21 in blank control group (P<0.01). Modified Ashcroft scores for pulmonary fibrosis of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly lower than that in ALI alone group (P<0.01), and modified Ashcroft score for pulmonary fibrosis of rats in ALI+NMⅡ silenced BMMSC group was significantly lower than that in ALI+BMMSC group (P<0.01). In 2 weeks after intervention, the content of α-SMA in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly decreased compared with that in ALI alone group (P<0.05 or P<0.01). The content of MMP-2 in lung tissue of rats in the 4 groups was similar (P>0.05). The content of MMP-9 in lung tissue of rats in ALI alone group was significantly increased compared with that in blank control group (P<0.01), and the content of MMP-9 in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01). At 24 h after intervention, the activity of malondialdehyde, SOD, and MPO in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in blank control group (P<0.01), the activity of malondialdehyde in lung tissue of rats in ALI+NMⅡ silenced BMMSC group and the activity of SOD in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in ALI alone group (P<0.05 or P<0.01), and the activity of SOD in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). The activity of MPO in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01), and the activity of MPO in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). In 1 week after intervention, the protein expression of CD11b in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly increased compared with those in the other three groups (P<0.05 or P<0.01), while the protein expressions of EMR1 in lung tissue of rats in the four groups were similar (P>0.05). Conclusions: Transplantation of NMⅡ gene silenced BMMSCs can significantly improve the activity of ECM components in the lung tissue in LPS-induced ALI rats, remodel its integrity, and enhance its antioxidant capacity, and alleviate lung injury and pulmonary fibrosis.


Subject(s)
Acute Lung Injury/therapy , Animals , Bone Marrow , Collagen/metabolism , Endotoxins , Extracellular Matrix , Lipopolysaccharides/adverse effects , Lung , Male , Malondialdehyde/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mesenchymal Stem Cells/metabolism , Myosin Type II/metabolism , Pulmonary Fibrosis , Rats , Rats, Sprague-Dawley , Saline Solution/metabolism , Superoxide Dismutase/metabolism
13.
Chinese Journal of Hematology ; (12): 272-278, 2022.
Article in Chinese | WPRIM | ID: wpr-929635

ABSTRACT

Objective: To establish an intramedullary transplantation model of primary megakaryocytes to evaluate the platelet-producing capacity of megakaryocytes and explore the underlying regulatory mechanisms. Methods: Donor megakaryocytes from GFP-transgenic mice bone marrow were enriched by magnetic beads. The platelet-producing model was established by intramedullary injection to recipient mice that underwent half-lethal dose irradiation 1 week in advance. Donor-derived megakaryocytes and platelets were detected by immunofluorescence staining and flow cytometry. Results: The proportion of megakaryocytes in the enriched sample for transplantation was 40 to 50 times higher than that in conventional bone marrow. After intramedullary transplantation, donor-derived megakaryocytes successfully implanted in the medullary cavity of the recipient and produce platelets, which showed similar expression of surface markers and morphology to recipient-derived platelets. Conclusion: We successfully established an in vivo platelet-producing model of primary megakaryocytes using magnetic-bead enrichment and intramedullary injection, which objectively reflects the platelet-producing capacity of megakaryocytes in the bone marrow.


Subject(s)
Animals , Blood Platelets , Bone Marrow , Bone Marrow Cells , Bone Marrow Transplantation , Humans , Megakaryocytes/metabolism , Mice
14.
Chinese Journal of Hematology ; (12): 115-119, 2022.
Article in Chinese | WPRIM | ID: wpr-929542

ABSTRACT

Objective: To reveal the compensatory features of bone marrow (BM) erythropoiesis in hereditary spherocytosis (HS) and to explore the effect of diferent hemoglobin levels on this compensation. Methods: Clinical and laboratory data of patients with HS were collected, and the peripheral blood absolute reticulocytes counts value was taken as the surrogate parameter to evaluate the ability of erythropoiesis compensation. BM erythropoiesis compensation in HS with diferent degrees of anemia were evaluated. Results: ①Three hundred and two patients were enrolled, including 115 with compensated hemolytic disease, 74 with mild anemia, 90 with moderate anemia, and 23 with severe anemia. ②Hemoglobin (HGB) was negatively correlated with serum erythropoietin in the decompensated hemolytic anemia group (EPO; rs=-0.585, P<0.001) . ③The median absolute reticulocyte count (ARC) of HS patients was 0.34 (0.27, 0.44) ×10(12)/L, up to 4.25 times that of normal people. The maximum ARC was 0.81×10(12)/L, about 10 times that of normal people. The median ARC of patients with compensated hemolytic disease was 0.29 (0.22, 0.38) ×10(12)/L, up to 3.63 times that of normal people. The median ARC of patients with hemolytic anemia was 0.38 (0.30, 0.46) ×10(12)/L, which was significantly higher than the patients with compensated hemolytic disease, up to 4.75 times that of normal people (z=4.999, P=0.003) . ④ ARC was negatively correlated with HGB in the compensated hemolytic disease group (rs=-0.177, P=0.002) and positively correlated with HGB in the decompensated hemolytic anemia group (rs=0.191, P=0.009) . There was no significant difference in the ARC among patients with mild, moderate, and severe anemia (χ(2)=4.588, P=0.101) . ⑤The median immature reticulocyte production index of the mild, moderate, and severe anemia groups was 13.1% (9.1%, 18.4%) , 17.0% (13.4%, 20.8%) , and 17.8% (14.6%, 21.8%) , respectively; the mild anemia group had lower index values than the moderate and severe anemia groups (P(adj) values were both<0.05) , but there was no significant difference between the latter groups (P(adj)=1.000) . The median immature reticulocyte count of patients in the mild, moderate, and severe groups was 5.09 (2.60, 7.74) ×10(10)/L, 6.24 (4.34, 8.83) ×10(10)/L, and 7.00 (3.07, 8.22) ×10(10)/L, respectively; there was no significant difference among the groups (χ(2)=3.081, P=0.214) . Conclusion: HGB can be maintained at a normal level through bone marrow erythropoiesis, while red blood cells are reduced in HS. However, once anemia develops, the bone marrow exerts its maximum erythropoiesis capacity and does not increase, regardless of anemia aggravation or serum EPO increase.


Subject(s)
Bone Marrow , Erythropoiesis , Humans , Reticulocyte Count , Reticulocytes , Spherocytosis, Hereditary
15.
Chinese Journal of Hematology ; (12): 107-114, 2022.
Article in Chinese | WPRIM | ID: wpr-929541

ABSTRACT

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.


Subject(s)
Adult , Aged , Aged, 80 and over , Bone Marrow/pathology , Exons , Humans , Janus Kinase 2/genetics , Middle Aged , Mutation , Mutation, Missense , Polycythemia Vera/genetics , Young Adult
16.
Article in Chinese | WPRIM | ID: wpr-928861

ABSTRACT

Advances in digital pathology technology have enabled pathologists and laboratory physicians to perform quick, easy, accurate and reproducible analysis of digital images of tissues and cells with the aid of electronic screens and software tools, rather than relying solely on traditional optical microscopy observations. The conventional clinical cytology testing practice is to be replaced by a digital workflow, which includes both digital imaging and image analysis. This article provides an overview of the basic principles of digital pathology techniques, the advances of development of device in cytology digital pathology, and their clinical applications in bone marrow morphology, and existing problems and prospects of digital pathology application in hematology.


Subject(s)
Bone Marrow , Image Processing, Computer-Assisted , Microscopy , Software , Technology
17.
Article in Chinese | WPRIM | ID: wpr-928744

ABSTRACT

OBJECTIVE@#To analyze the change of serum C1q in the course of multiple myeloma (MM) and its correlation with clinical characteristics.@*METHODS@#A total of 138 newly diagnosed MM patients in Zhongnan Hospital of Wuhan University from June 2016 to December 2019 were selected as research objects, during the same period 50 age-matched anemia patients, 50 lymphoma patients, 50 leukemia patients, and 50 myelodysplastic syndrome (MDS) patients were selected as control groups. All the patients met WHO disease classification, and were definitely diagnosed by pathology or bone marrow smear/biopsy. The changes of C1q between MM patients and control group, as well as in different therapeutic responses of MM patients before and after treatment were compared, also the difference of clinical characteristics among MM patients with different C1q level, so as to analyze risk factors which led to C1q decline.@*RESULTS@#The average value of C1q in MM patients was (128.18±51.24) mg/L, which was significantly lower than control group (P<0.01). The levels of white blood cell, platelet (PLT), hemoglobin (Hb), serum calcium, albumin, lactate dehydrogenase (LDH) in newly diagnosed high C1q group were significantly higher than those in low C1q group (P<0.05). Logistic analysis showed that the levels of PLT, Hb, albumin, and LDH in newly diagnosed high C1q group were higher than those in low C1q group (r=0.248, r=0.394, r=0.405, r=0.295). After treatment, the levels of C1q in MM patients with complete remission and very good partial remission were significantly higher than before treatment (P<0.05), while those with partial remission and stable disease also increased but not significantly (P>0.05).@*CONCLUSION@#The C1q level in MM patients is significantly lower than that in patients with other hematologic system diseases, and it increases with the remission of the disease after treatment.


Subject(s)
Albumins , Bone Marrow , Complement C1q , Humans , Multiple Myeloma , Risk Factors
18.
Article in Chinese | WPRIM | ID: wpr-928732

ABSTRACT

OBJECTIVE@#To investigate the effect of acute myeloid leukemia cells in leukemia-microenvironment on proliferation and apoptosis of bone marrow-derived mesenchymal stromal cells (BM-MSC).@*METHODS@#Acute myeloid leukemia (AML) murine models overexpressing MLL-AF9 were established. The number of BM-MSC of wild type (WT) and AML-derived mice were analyzed by flow cytometry. Morphology and growth differences between WT and AML-derived BM-MSC were analyzed by inverted fluorescence microscope. Proliferation and apoptosis of BM-MSC between these two groups were detected by Brdu and Annexin V/PI.@*RESULTS@#Compared with WT-derived BM-MSC, the number and proliferation rate of AML-derived BM-MSC significantly increased (P<0.01, P<0.001), while apoptosis rate decreased (P<0.05). When cultured in vitro, BM-MSC grew faster under conditional medium.@*CONCLUSION@#AML cells can promote proliferation and inhibit apoptosis of BM-MSC.


Subject(s)
Animals , Apoptosis , Bone Marrow , Bone Marrow Cells , Cell Proliferation , Humans , Leukemia, Myeloid, Acute , Mesenchymal Stem Cells , Mice , Tumor Microenvironment
19.
Article in Chinese | WPRIM | ID: wpr-928717

ABSTRACT

OBJECTIVE@#To establish 10-color fluorescent antibody combination panels for the detection of minimal residual disease (MRD) of acute myeloid leukemia (AML) in our laboratory and discuss the value of clinical application.@*METHODS@#According to the antigen expression characteristics of leukemia cells of incipient AML patients, MRD in bone marrow were detected by multiparameter flow cytometry, and the test results were compared with both bone marrow cell morphology and PCR results, then 10-color fluorescent antibody combination panels in our lab for MRD detection was determined.@*RESULTS@#The immunophenotypic characteristics of 392 incipient patients with AML in the First Affiliated Hospital of Zhengzhou University were analyzed, among them 357 (91.07%) cases showed abnormal immunophenotypes, which mainly included cross-lineage expression, cross-stage expression, deficiency of antigen expression or abnormal antigen intensity and other abnormal expression. The 10-color fluorescent antibody combination panels established according to abnormal immunophenotypic characteristics of leukemia cells were applied for detecting MRD in 156 patients with AML, the positive rate (43.6%) was higher than 26.8% of morphology, and the results were highly consistent with PCR detection results (96.49%), moreover, the recurrence rate of MRD positive patients (86.96%) was significantly higher than 5.75% of MRD negative patients. Therefore, this method could truly reflect the load of leukemia cells and prompt change of disease condition.@*CONCLUSION@#Multiparameter flow cytometry can detect various abnormal immunophenotypes of AML. The 10-color fluorescent antibody combination panels in our lab based on the characteristics of antigens expression in leukemia cells can well detect MRD of leukemia cells, so as to predict relapse and provide basis for clinical treatment.


Subject(s)
Bone Marrow , Flow Cytometry/methods , Humans , Immunophenotyping , Leukemia, Myeloid, Acute/diagnosis , Neoplasm, Residual/diagnosis
20.
Article in Chinese | WPRIM | ID: wpr-928713

ABSTRACT

Acute lymphoblastic leukemia (ALL) is a kind of the most common hematopoietic malignancy, its recurrence and drug resistance are closely related to the bone marrow microenvironment. Bone marrow stromal cell (BMSC) is an important part of the bone marrow microenvironment and their interaction with leukemia cells cannot be ignored. BMSC participates in and regulate signaling pathways related to proliferation or apoptosis of ALL cells by secretes cytokines or extracellular matrix proteins, thus affecting the survival of ALL cells. In this review, the research advance of several signaling pathways of the interaction between BMSC and ALL cells was summarized briefly.


Subject(s)
Apoptosis , Bone Marrow , Bone Marrow Cells , Humans , Mesenchymal Stem Cells , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Stromal Cells , Tumor Microenvironment
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