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1.
Postgrad Med J ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767468

RESUMO

For metastatic prostate cancer, androgen deprivation therapy (ADT) is the key strategy to control the disease. However, after 18-24 months of treatment, most patients will progress from metastatic hormone-sensitive prostate cancer (mHSPC) to metastatic castration-resistant prostate cancer (mCRPC) even with ADT. Once patients enter into mCRPC, they face with significant declines in quality of life and a dramatically reduced survival period. Thus, doublet therapy, which combines ADT with new hormone therapy (NHT) or ADT with docetaxel chemotherapy, substitutes ADT alone and has become the "gold standard" for the treatment of mHSPC. In recent years, triplet therapy, which combines ADT with NHT and docetaxel chemotherapy, has also achieved impressive effects in mHSPC. This article provides a comprehensive review of the recent applications of the triplet therapy in the field of mHSPC.

2.
Comput Biol Med ; 160: 106985, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37178604

RESUMO

Accurate segmentation of medical images is an important step during radiotherapy planning and clinical diagnosis. However, manually marking organ or lesion boundaries is tedious, time-consuming, and prone to error due to subjective variability of radiologist. Automatic segmentation remains a challenging task owing to the variation (in shape and size) across subjects. Moreover, existing convolutional neural networks based methods perform poorly in small medical objects segmentation due to class imbalance and boundary ambiguity. In this paper, we propose a dual feature fusion attention network (DFF-Net) to improve the segmentation accuracy of small objects. It mainly includes two core modules: the dual-branch feature fusion module (DFFM) and the reverse attention context module (RACM). We first extract multi-resolution features by multi-scale feature extractor, then construct DFFM to aggregate the global and local contextual information to achieve information complementarity among features, which provides sufficient guidance for accurate small objects segmentation. Moreover, to alleviate the degradation of segmentation accuracy caused by blurred medical image boundaries, we propose RACM to enhance the edge texture of features. Experimental results on datasets NPC, ACDC, and Polyp demonstrate that our proposed method has fewer parameters, faster inference, and lower model complexity, and achieves better accuracy than more state-of-the-art methods.


Assuntos
Redes Neurais de Computação , Radiologistas , Humanos , Processamento de Imagem Assistida por Computador
3.
J Clin Nurs ; 32(13-14): 3852-3862, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36081313

RESUMO

AIMS AND OBJECTIVES: To investigate, for the first time, aberrant time-varying local brain activity in nurses following night shift-related sleep deprivation (SD) and its association with memory decline. BACKGROUND: Prior studies have elucidated alterations in static local brain activity resulting from SD in the occupations outside medical profession. DESIGN: A longitudinal study followed the STROBE recommendations. METHODS: Twenty female nurses underwent resting-state functional magnetic resonance imaging and memory function assessment (by Complex Figure Test (CFT) and the California Verbal Learning Test, Second Edition (CVLT-II)) twice, once in a rested wakefulness (RW) state and another after SD. By combining the sliding-window approach and amplitude of low-frequency fluctuation (ALFF) analysis, the dynamic ALFF (dALFF) variability was calculated to reflect the characteristics of dynamic local brain activity. RESULTS: Poor performance on the CFT and CVLT-II was observed in nurses with night shift-related SD. Reduced dALFF variability was found in a set of cognition-related brain regions (including the medial/middle/superior frontal gyrus, anterior/posterior cingulate gyrus, precuneus, angular gyrus, orbitofrontal and subgenual areas, and posterior cerebellum lobe), while increased dALFF variability was observed in the somatosensory-related, visual and auditory regions. SD-related dALFF variability alterations correlated with changes in subjects' performance on the CFT and CVLT-II. CONCLUSIONS: Night shift-related SD disturbed dynamic brain activity in high cognitive regions and induced compensatory reactions in primary perceptual cortex. Identifying dALFF variability abnormalities may broaden our understanding of neural substrates underlying SD-related cognitive alterations, especially memory dysfunction. RELEVANCE TO CLINICAL PRACTICE: Night shift-related SD is as an important occupational hazard affecting brain function in nurses. The effective countermeasure addressing the adverse outcomes of SD should be advocated for nurses. PATIENT OR PUBLIC CONTRIBUTION: Patients or public were not involved in the design and implementation of the study or the analysis and interpretation of the data.


Assuntos
Enfermeiras e Enfermeiros , Privação do Sono , Humanos , Feminino , Estudos Longitudinais , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Transtornos da Memória
4.
Zhonghua Nan Ke Xue ; 29(6): 498-504, 2023 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38602721

RESUMO

OBJECTIVE: To explore the value of systematic male reproductive system ultrasonography in the diagnosis of azoospermia etiology. METHODS: Retrospective analysis and classification statistics were conducted on the data of azoospermia cases who underwent systematic male reproductive system ultrasound examination at the First Affiliated Hospital of Ningbo University from January 2013 to January 2023. RESULTS: A total of 375 cases were included in the group, of which 303 cases could be diagnosed by ultrasound, including 161 cases of obstructive causes, 110 cases of non obstructive causes, and 32 cases of mixed causes. Obstructive causes mainly include bilateral absence or underdevelopment of the seminal vesicles and vas deferens, non obstructive causes mainly include bilateral simple testicular dysplasia, and the most common combined causes are bilateral absence or underdevelopment of the seminal vesicles and vas deferens combined with bilateral testicular dysplasia. The main causes involved a single organ in 174 cases, with 82 cases, 43 cases, and 4 cases involving 2-4 organs, respectively. In addition, there are multiple accompanying ultrasound manifestations of non primary causes. CONCLUSION: Systematic ultrasound examination can comprehensively evaluate the male reproductive system, effectively diagnose the causes of most azoospermia, and provide valuable imaging evidence for clinical treatment.


Assuntos
Azoospermia , Masculino , Humanos , Azoospermia/diagnóstico por imagem , Azoospermia/etiologia , Estudos Retrospectivos , Ultrassonografia , Glândulas Seminais , Testículo/diagnóstico por imagem
5.
Dev Cogn Neurosci ; 56: 101126, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35751993

RESUMO

Adverse early life experiences, such as maternal separation, are associated with an increased risk for several mental health problems. Symptoms induced by maternal separation that mirror clinically relevant aspects of mental problems, such as cognitive inflexibility, open the possibility of testing putative therapeutics prior to clinical development. Although several animal (e.g., rodent) studies have evaluated the effects of early maternal separation on cognitive flexibility, no consistent conclusions have been drawn. To clarify this issue, in this study, a meta-analysis method was used to systematically explore the relationship between early maternal separation and cognitive flexibility in rodent offspring. Results indicate that early maternal separation could significantly impair cognitive flexibility in rodent offspring. Moderator analyses further showed that the relationship between early maternal separation and cognitive flexibility was not consistent in any case, but was moderated by variations in the experimental procedures, such as the deprivation levels, task characteristics, and rodent strains. These clarify the inconsistent effects of maternal separation on cognitive flexibility in rodents and help us better understand the association between early life adversity and cognitive development.


Assuntos
Privação Materna , Roedores , Animais , Cognição
6.
Front Zool ; 16: 43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31788010

RESUMO

BACKGROUND: Social isolation, i.e., the deprivation of social contact, is a highly stressful circumstance that affects behavioral and functional brain development in social animals. Cognitive flexibility, one of the essential executive brain function that facilitates survival problem solving, was reported to be impaired after social isolation rearing. However, most of the previous studies have focused on the constrained aspect of flexibility and little is known about the unconstrained aspect. In the present study, the unconstrained cognitive flexibility of Kunming mice (Mus musculus, Km) reared in isolation was examined by a novel digging task. The exploratory behavior of the mice was also tested utilizing the hole-board and elevated plus maze tests to explain the differences in cognitive flexibility between the mice reared socially and in isolation. RESULTS: The results demonstrated that the isolated mice had a higher success rate in solving the novel digging problem and showed a higher rate of exploratory behavior compared with the controls. Linear regression analysis revealed that the time it took the mice to solve the digging problem was negatively associated with exploratory behavior. CONCLUSIONS: The data suggest that social isolation rearing improves unconstrained cognitive flexibility in mice, which is probably related to an increase in their exploratory behavior. Such effects may reflect the behavioral and cognitive evolutionary adaptations of rodents to survive under complex and stressful conditions.

7.
Hear Res ; 381: 107777, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31430633

RESUMO

The integration of visual and auditory information is important for humans or animals to build an accurate and coherent perception of the external world. Although some evidence has shown some principles of the audiovisual integration, little insight has been gained into its functional purpose. In this study, we investigated the functional influence of dynamic visual input on auditory frequency processing by recording single unit activity in the central nucleus of the inferior colliculus (ICc). Results showed that the auditory responses of ICc neurons to sound frequencies could be enhanced or suppressed by visual stimuli even though the same visual stimuli induced no neural responses when presented alone. For each ICc neuron, the most effective visual stimuli were located in the same azimuth as for auditory stimuli and preceded for ∼20 ms. Additionally, visual stimuli could steepen or flatten the frequency tuning curves (FTCs) of ICc neurons by various visual effects at each responsive frequency. The modulation degree of auditory FTCs was dependent on the minimal thresholds (MTs) of ICc neurons, i.e., with MTs increasing, the modulation degree decreased. Due to the non-homogeneous distribution of MTs which was lowest at 10 kHz, visual modulation of auditory FTCs exhibited a frequency-specific manner, the closer it reached the characteristic frequency (CF) of 10 kHz, the greater modulation. Thus, visual modulation of auditory frequency responses in ICc is dependent not only on the visual stimulus but also on the auditory characteristics of ICc neurons. These results suggest a moment-to-moment visual modulation of auditory frequency responses that in real time increase auditory frequency sensitivity to audiovisual stimuli. Furthermore, in the long term such modulation could serve to instruct auditory adaptive plasticity to maintain necessary and accurate auditory detection and perceptual behavior.


Assuntos
Vias Auditivas/fisiologia , Percepção Auditiva , Potenciais Evocados Auditivos do Tronco Encefálico , Colículos Inferiores/fisiologia , Vias Visuais/fisiologia , Percepção Visual , Estimulação Acústica , Animais , Feminino , Masculino , Camundongos , Plasticidade Neuronal , Estimulação Luminosa , Tempo de Reação , Fatores de Tempo
8.
Journal of Medical Postgraduates ; (12): 206-210, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-818213

RESUMO

Neutrophil is an important part of innate immune system, and plays a key role in resisting pathogen invasion and tumor immune surveillance. Meanwhile, neutrophil could produce reactive oxygen species , which are side products of cell metabolism. It is closely related to tumor development and progression. On the one hand, neutrophil could produce ROS to promote tumor growth and metastasis. On the other hand, it could also induce tumor cell death through different mechanisms. In this review, we summarize the roles of neutrophil- derived ROS in tumor development and discuss its prospects in cancer treatment.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1515-1522, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30295277

RESUMO

OBJECTIVE: To investigate the efficiency and safety of treating Epstein-Barr virus (EBV) infection of acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) by EBV specific cytotoxic T lymphocytes (EBV-CTL). METHODS: The Clinical characteristics, therapeutic efficacy and safety of 12 patients with EBV infection treated by EBV-CTL infusion after allo-HSCT in Department of Hemahlogy of Aero Space Center Hospital between Jan 2015 and May 2017 were analyzed retrospectioely. RESULTS: Our of 12 cases received EBV-CTL infusion after transplantation, 9 did not received Rituximab therapy due to the active infection, 4 cases including 3 received Ritaximab progressed into posttransplantation lymphoroliferetive disease (PTLD). The median time of EBV infection was 47 (22-71) days, median time of antivirus therapy before tramplantation was 10 (8-33) days, median time of first CTL infusion was 59(34-86) days after transplatation. The 43 cases-time CTL infusion was performed smoothly, no related harmful evnts occoured, no progression of GVHD was observed. After the first course of infusion, complete remission (CR), Partial remssion (PR) and no remssion (NR) were obtained in 9, 1 and 2 patients respectively, the relapse was observed in 4 patients who then received the socond course of infusion and all reached CR, the patient in PR did not reathed CR finally and died of GVGD at 5 months after transpplantation . Only 1 out of 2 cases of NR obtained CR, another 1 still was in NR, and died of transplantation related infection at 5 months after transplantation. 4 cases of PTLD were all cared. CONCLUSION: Preliminary results of this study suggest that EBV-CTL infusion is safe for the EBV infection combined with acute GVHD after all-HSCT. However, a further larger scale clinical studies are needed to prove the efficiency.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Herpesvirus Humano 4 , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfócitos T Citotóxicos
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-698478

RESUMO

BACKGROUND:Due to limited sources,poor hemocompatibility and poor anticoagulation performance,small-diameter tissue-engineered blood vessels cannot be applied in clinical practice.OBJECTIVE:To explore the physicochemical and mechanical properties of sheep carotid arteries after the decellularization in order to find appropriate materials for the preparation of tissue-engineered blood vessels.METHODS:Fresh carotid arteries from sheep were randomly divided into two groups:control group,in which,the sheep carotid arteries were cryopreserved for use after trimming and cleaning;experimental group,in which,after trimming and cleaning,the carotid arteries were decallularized by Triton X-100.sodium deoxycholate and EDTA for 24 hours,rinsed for 72 hours,digested with RNA/DNA enzymes for 24 hours,rinsed for 24 hours and reserved for later use.In both groups,blood samples were subjected to hematoxylin-eosin staining,collagen fiber staining,elastic fiber dyeing,and electron microscopy observation.The physical and chemical properties of the blood vessels are tested by tensile strength,wall tension and thickness.RESULTS AND CONCLUSION:(1) The collagen fibers in both two groups were neat and compact in alignment,with no obvious fracture.(2) Hematoxylin-eosin staining showed that:in the control group,the nuclei were distributed in the inner membrane,middle lamella and outer membrane of the vessels,and the fibers ran regularly;in the experimental group,the fibers ran in order but loosely,and there were no nuclei in the inner membrane,middle lamella and outer membrane of the vessels.(3) Elastic fibers in the control group were regular in alignment and mainly distributed in the middle lamella and outer membrane of the vessels,while in the experimental group,the elastic fibers ran regularly but loosely,and mainly distributed in the middle lamella and outer membrane of the vessels.(4) Under the scanning electron microscope,the originally formed vessels were observed in the experimental group,with no cell residues,and the collagen fibers ran orderly with no fracture and with uniform pore structure.(5) The vessel thickness was lower in the experimental group than the control group (P < 0.01),but the tensile strength showed no difference between the two groups,which was 46.55 kPa in the two groups.To conclude,the decelluarized sheep carotid artery can retain the necessary mechanical properties of the blood vessels after achieving the maximum removal of antigenicity.

11.
Sci Rep ; 7(1): 14666, 2017 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-29116193

RESUMO

Quantum random number generation attracts considerable attention, since its randomness inherently originates in quantum mechanics, but not mathematical assumptions. Randomness certification, e.g. entropy estimation, becomes a key issue in the context of quantum random number generation protocol. We study a self-testing protocol based on dimension witness, with the assumption of independent devices. It addresses the random number extraction problem in a practical prepare-and-measure scenario with uncharacterized devices. However, the lower bound of min-entropy as a function of dimension witness is not tight in existing works. We present a tighter bound of analytic form, by introducing the Lagrangian multiplier method to closely analyze the optimization problem on average guessing probability. Through simulation, it turns out that a significantly higher random number generation rate can be achieved in practice.

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-705215

RESUMO

Doxorubicin (Dox) is an effective wide-spectrum antitumor drug. However, its clinical application may be hampered by dose-dependent cardiotoxicity. The mechanisms of cardiotoxicity have not been clearly elucidated, but are known to involve oxidative stress, mitochondrial dysfunction and apoptosis. Autophagy is a lysosome-dependent protein degradation pathway. More recently, many studies have suggested that autophagy plays an important role in Dox-induced cardiotoxicity. This paper gives a systematic review of the role of autophagy in Dox-induced cardiotoxicity.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-349648

RESUMO

This study was aimed to investigate the inducing-apoptosis effect of brucine on human monocytic leukemia cell line THP-1 cells and its possible mechanism. The inhibition effect of brucine on growth of THP-1 cells was measured by CCK-8 method. Morphological changes of THP-1 cells treated with brucine was detected by acridine orange/ethidium bromide (AO/EB)double staining. Annexin-V/PI double labeling method was used to assay the apoptosis rate of THP-1 cells. The effect of brucine on THP-1 cell cycle distribution was detected by PI single staining. RT-PCR was used to detect the expression of BCL-2 and BAX. The results showed that the brucine could inhibit the THP-1 cell growth in concentration and time-dependent manners at the range of 50 to 400 µg/ml. The cells stained with AO/EB revealed that the brucine induced the nuclear chromatin condensation. After the THP-1 cells were treated with brucine of 400µg/ml for 48 hours, most nucleic were stained as orange-red, and condensed, displaying the late apoptotic cell morphology. Annexin-V/PI detection showed that brucine could induce apoptosis of THP-1 cells in a concentration-dependent manner. Compared with the control group, more cells in brucine-treated group were arrested at G0/G1 phase in a concentration-dependent manner. RT-PCR detection revealed that the expression of BCL-2 was down-regulated strikingly and BAX was up-regulated. It is concluded that brucine can efficiently inhibit cell growth and block THP-1 cells in G0/G1 phase. The mechanism of THP-1 cell apoptosis induced by brucine may be related to the inhibition of BCL-2 and activation of BAX.


Assuntos
Humanos , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Proto-Oncogênicas c-bcl-2 , Metabolismo , Estricnina , Farmacologia , Proteína X Associada a bcl-2 , Metabolismo
14.
Journal of Experimental Hematology ; (6): 1780-1784, 2014.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-259652

RESUMO

Caspase independent cell death (CICD) is defined as death that ensues when a signal that normally induces apoptosis fails to activate caspases,it can be activated by PARP-1, Calpains, Bax and AIF, possessing distinctive biologic characteristic differed from apoptosis and necrosis. Recent researchs have found that the molecular mechanisms governing CICD of K562 is opposite from that of the traditional medicine killing leukemia cells, which may have the potential pharmaceutical point for new drugs. This article reviews the newly acquaintance of molecular mechanisms for CICD and recent studies concerning the induction death of K562 cells via CICD, so as to provide some reference for the research of new drug point.


Assuntos
Humanos , Apoptose , Calpaína , Caspases , Células K562 , Necrose , Poli(ADP-Ribose) Polimerases , Proteína X Associada a bcl-2
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(3): 545-8, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22739152

RESUMO

This study was purposed to analyze the characteristics of morphology, immunology, cytogenetic and molecular biology of leukemia cells in 12 AML patients with Ph(+) and their correlation with survival of patients. 12 patients with Ph(+) AML were diagnosed according to diagnostic criteria of WHO and existence of t(9;22) (q34;q11) or t(9;22) abnormality, meanwhile no evidence of CML chronic phase was observed. The results showed that 8 out of 12 cases were confirmedly diagnosed to be AML by morphologic and immunophenotypic examination, 4 cases were diagnosed as myeloid and B lymphocytic mixed acute leukemia. The Ph chromosome was detected in 10 cases by chromosome analysis at the first time of diagnosis, and some of the cases had coexistence of complex chromosome and/or normal karyotype. BCR-ABL transcript was detected in all 12 cases, including 7 cases with b3a2, 1 case with b2a2, 1 case with b2a2 variants, 2 cases with e1a2 and 1 case with e18a2. The 12 cases all got complete remission after chemotherapy and/or gleevec treatment, out of them 3 cases received chemotherapy and gleevec treatment, but 2 cases died; 9 cases received allogeneic hematopoietic stem-cell transplantation (allo-HSCT), 1 case died from relapse, among them 1 case died from transplant complications. The median survival was 24 (8 - 80) months, the overall survival of 3 years was (51.4 ± 17.7)%. It is concluded that the Ph(+) AML is a acute myelogenous leukemia with poor prognosis, but long-term survival may be achieved with HSCT as quick as after complete remission from gleevec and chemotherapy treatment. Meanwhile, the detection of BCR-ABL gene and it variants may be give more opportunity for diagnose and treatment, which can be used as routine screening for newly diagnosed leukemia.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Criança , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Prognóstico
16.
Zhonghua Nei Ke Za Zhi ; 50(4): 280-3, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21600143

RESUMO

OBJECTIVE: To study the type and corresponding clinical characteristics of primary hemophagocytic lymphohistiocytosis (HLH) associated immune gene mutations in the refractory virus infection or HLH of unknown causes. METHODS: From December 2009 to July 2010, the patients with refractory virus infection or HLH of unknown causes were screened for the primary HLH associated immune genes mutations by DNA sequence analysis, including PRF1, UNC13D, STX11, STXBP2, SH2D1A and XIAP. The clinical characteristics and outcomes were followed up. RESULTS: Totally 25 patients with refractory virus infection or HLH of unknown causes were investigated for the 6 genes and 13 cases were found carrying gene mutations, composing of 6 of PRF1 mutation, 3 of UNC13D, and each one of STX11, XIAP, SH2D1A and STXBP2, respectively. Among the 13 cases with gene mutations, 5 suffered from Epstein-Barr virus associated HLH (EBV-HLH), 1 human herpes virus 7 associated HLH (HHV7-HLH), 1 HLH without causes, 4 chronic activated EB virus infection (CAEBV) with 1 progressing to Hodgkin's lymphoma carrying abnormal chromosome of t(15;17) (q22;q25) and hyperdiploid, 2 EBV associated lymphoma. Among the other 12 patients without gene mutation, 4 suffered from EBV-HLH with 1 progressing to peripheral T lymphoma, 8 suffered from CAEBV. CONCLUSIONS: Primary HLH associated immune gene mutations are critical causes of refractory virus infection of unknown causes, most patients manifest as HLH, some cases appear in CAEBV and EBV associated lymphoma. DNA sequence analysis is helpful to early diagnosis and correct decision-making for treatment.


Assuntos
Infecções por Vírus Epstein-Barr/genética , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/virologia , Adolescente , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Herpesvirus Humano 4 , Humanos , Lactente , Masculino , Proteínas de Membrana/genética , Proteínas Munc18/genética , Mutação , Perforina , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Qa-SNARE/genética
17.
Cell Signal ; 23(8): 1273-80, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21514376

RESUMO

The DNA-dependent protein kinase (DNA-PK) is a DNA-activated serine/threonine protein kinase, and abundantly expressed in almost all mammalian cells. The roles of DNA-PK in DNA-damage repair pathways, including non-homologous end-joining (NHEJ) repair and homologous recombinant (HR) repair, have been studied intensively. However, the high levels of DNA-PK in human cells are somewhat paradoxical in that it does not impart any increased ability to repair DNA damage. If DNA-PK essentially exceeds the demand for DNA damage repair, why do human cells universally express such high levels of this huge complex? DNA-PK has been recently reported to be involved in metabolic gene regulation in response to feeding/insulin stimulation; our studies have also suggested a role of DNA-PK in the regulation of the homeostasis of cell proliferation. These novel findings expand our horizons about the importance of DNA-PK.


Assuntos
Reparo do DNA , Proteína Quinase Ativada por DNA/metabolismo , Proliferação de Células , Proteína Quinase Ativada por DNA/química , Proteína Quinase Ativada por DNA/fisiologia , Regulação da Expressão Gênica , Humanos
18.
Zhonghua Xue Ye Xue Za Zhi ; 32(11): 748-51, 2011 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-22339910

RESUMO

OBJECTIVE: To study the predictable value of monitoring minimal residual disease (MRD) regularly by flow cytometry (FCM) in patients with acute leukemia (AL) in the first complete remission (CR(1)). METHODS: From April 2005 to July 2009, AL patients who had got CR(1) after chemotherapy were regularly monitored for MRD in bone marrow by FCM to relapse or to July 2010 in Beijing Daopei Hospital (not including those received stem cell transplantation). The special antibody combinations were employed for each patient according to aberrant expression of leukemia cells. MRD(+) was defined as the aberrant cells more than 0.01%. The probability of continuous CR (CCR) was calculated by Kaplan-Meier formula, and the statistical difference between two CCR probabilities was evaluated by log-rank test. RESULTS: A total of 163 AL patients in CR(1) were monitored to relapse or to July 2010. Among 89 AML patients referred to our hospital within 1 year after diagnosis, 30 cases were in MRD(+) and 59 cases MRD(-) till 12 months following chemotherapy, 3/30 patients in MRD(+) and 47/59 remained in CCR to July 2010. The probability of CCR at 24, 36 months was 13%, 13%in MRD(+) group, 94%, 78% in MRD(-) group respectively, the difference between them was statistically significant (P < 0.01). Among 35 ALL referred to our hospital within 5 months after diagnosis, 13 cases were MRD(+) and 22 cases MRD(-) till 5 months following chemotherapy, 0/13 patients in MRD(+) and 20/22 patients in MRD(-) remained in CCR to July 2010. The probability of CCR at 24, 36 months was 0% in MRD(+) group, 96%, 96% in MRD(-) group respectively, the difference between them was statistically significant (P < 0.01). Over the time point above, all patients with MRD(+) or their MRD from negative to positive relapsed finally, and most patients with MRD(-) remained CCR to July 2010. CONCLUSION: It had a clinical prognostic value to monitor MRD regularly by FCM in the patients with AL after CR(1).


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , Neoplasia Residual/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva , Adulto Jovem
19.
Zhonghua Xue Ye Xue Za Zhi ; 32(7): 445-9, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-22213862

RESUMO

OBJECTIVE: To analyze the clinical and laboratory features of 9 cases of gammadeltaT cell lymphoma or leukemia. METHODS: From 2007 to 2011, 9 patients with gammadeltaT-cell lymphoma/leukemia were diagnosed in our hospital. The immunophenotype of the abnormal cells were detected by flow cytometry, clonal gene rearrangement of IgH, TCRgamma, TCRdelta by PCR, chromosome karyotype analysis by G banding, acute leukemia gene and the DNA of type 1 - 8 human herpes virus by multiple nested PCR, The gammadeltaT cells were determined by T cell with TCR gammadelta chain, the malignant gammadelta T cells by the abnormal expression of T cell antigens and the precursor malignant gammadelta T cells by the expression of CD34, TDT, CD99, CD1 a or acute leukemia genes. RESULTS: In the 9 patients with gammadeltaT cell lymphoma leukemia, significant malignant gammadeltaT cells infiltration of bone marrow were found in 8 with blast morphology. 5 were diagnosed as T-ALL/LBL (gammadeltaT type) and 4 HSgammadelta TCL. The clonal gene rearrangement of TCRgamma and/or TCRB were detected in 6/6 patients. Patients either did not achieve complete remission(CR) after induction therapy or relapsed quickly after CR. Only 4/5 patients remained continuous CR(CCR) at 2, 2, 3,12 months respectively, after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the fifth T-ALL (gammadeltaT) relapsed 1 month after allo-HSCT. CONCLUSIONS: The incidence of gammadelta T cell lymphoma or leukemia may be higher than reported, part of them were T-ALL/LBL with poor prognoses. FCM and clonal gene rearrangement of TCRgamma and/or TCRdelta are helpful to diagnosis. Allo-HSCT may be the only curative approach.


Assuntos
Leucemia de Células T/genética , Linfoma de Células T/genética , Receptores de Antígenos de Linfócitos T gama-delta/genética , Adolescente , Adulto , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Cariótipo , Leucemia de Células T/diagnóstico , Linfoma de Células T/diagnóstico , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 18(6): 1381-5, 2010 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-21176334

RESUMO

This study was aimed to analyze the clinical and cytogenetic characteristics of acute leukemia with 11q23/mll rearrangement and explore the reasonable therapeutic principles. Characteristics in general situation, morphology, immunology, molecular biology, cytogenetics, treatment and overall survival of 36 cases of acute leukemias with mll gene rearrangement were studied and analyzed. The results showed that 36 cases with mll gene rearrangement were found positive (7.2%) in 494 patients with acute leukemia. Among the 36 cases of mll rearrangement positive, 32 cases were diagnosed as acute myeloid leukemia (AML) with myeloid antigen expression, of which 5 cases expressed lymphoblastic differentiation antigen; 4 cases were classified as B-lineage acute lymphoblastic leukemia (ALL), of which non-lineage myeloid expression pattern were found in 3 cases. In 29 out of 36 cases (80%) the clonal chromosomal aberration were detected, of which chromosome 11 aberration were observed in 22 cases. All patients received chemotherapy with a total response rate of 47.2%. Of the responded patients, 10 cases relapsed within 6 months, with a recurrence rate of 40%; 9 cases received hematopoietic stem cell transplantation (HSCT), 7 cases of which survived after transplantation. The median survival time of 36 cases was 16 months (range 2 - 46) and their 2-year overall survival rate was 41.4%. The 2-year overall survival rate of 9 patients who received HSCT was 87.5%. It is concluded that acute leukemia patients with mll gene rearrangement show poor response to chemotherapy, high recurrence rate and poor prognosis. Hematopoietic stem cell transplantation may be a reasonable treatment principle to improve these patients' survival situation.


Assuntos
Leucemia/genética , Proteína de Leucina Linfoide-Mieloide/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Leucemia/classificação , Leucemia/diagnóstico , Leucemia/terapia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
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