Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 28
Filter
1.
PLoS Negl Trop Dis ; 17(6): e0011462, 2023 06.
Article in English | MEDLINE | ID: mdl-37384796

ABSTRACT

Bartonella are generally recognized as zoonotic pathogens of mammals, including many rodent species. However, data on the genetic diversity of Bartonella in some regions are still absent in China. In this study, we collected rodent samples (Meriones unguiculatus, Spermophilus dauricus, Eolagurus luteus, and Cricetulus barabensis) from Inner Mongolia located in Northern China. The Bartonella were detected and identified by sequencing the gltA, ftsZ, ITS, and groEL genes in them. An overall 47.27% (52/110) positive rate was observed. This may be the first report that M. unguiculatus and E. luteus harbor Bartonella. Phylogenetic and genetic analysis on gltA, ftsZ, ITS, and groEL genes indicated that the strains were divided into seven distinct clades, suggesting the diverse genetic genotypes of Bartonella species in this area. Of those, Clade 5 meets the criteria for identification as a novel species based on gene sequence dissimilarity to known Bartonella species and herein we name it "Candidatus Bartonella mongolica".


Subject(s)
Bartonella Infections , Bartonella , Animals , Bartonella/genetics , Bartonella Infections/epidemiology , Bartonella Infections/veterinary , Sciuridae , Phylogeny , Genotype , China/epidemiology , Gerbillinae
2.
J Neurol ; 270(8): 3876-3884, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37106259

ABSTRACT

OBJECTIVES: The clinical value of antiplatelet therapy (APT) for moyamoya disease (MMD) remains controversial. Our study attempts to clarify the value of APT in this disease. METHODS: We collected basic information, treatment strategies, and prognostic information on patients with MMD from 2010 to 2022 at our center. The data were divided into two groups, depending on whether APT was used or not, and compared by Pearson Chi-Square, Fisher's exact test, or Wilcoxon rank-sum test. We used propensity scores or inverse probability of treatment weighting to balance the covariates. Following this, we performed a meta-analysis of APT use in MMD. RESULTS: 177 patients were enrolled, with a median follow-up of 41.1 months. APT did not affect the prognosis of patients with perioperative MMD, ischemic MMD, or asymptomatic MMD (P > 0.05), without increasing cerebral hemorrhagic risk. In contrast, APT was found to reduce mortality among patients with hemorrhagic MMD (P = 0.019), without affecting functional status, increasing stroke risk, or causing intracerebral hemorrhage (P > 0.05). But the small group cannot show the effect of APT. Our meta-analysis included nine articles involving 28,925 patients with MMD. It showed that APT could reduce stroke risk (odds ratio, OR = 0.57, 95% CI 0.49 to 0.65) and the Modified Rankin Scale (mRS) (weighted mean difference, WMD = - 0.07, 95% CI 0.14-0.00) during follow-up. The cohort study has limited weight (1.97% and 19.29%) in the meta-analysis. CONCLUSION: Although the limited number of included documents, APT could be beneficial to the prognosis of MMD.


Subject(s)
Moyamoya Disease , Stroke , Humans , Retrospective Studies , Cohort Studies , Platelet Aggregation Inhibitors/therapeutic use , Treatment Outcome , Moyamoya Disease/complications , Moyamoya Disease/drug therapy , Prognosis , Cerebral Hemorrhage/complications , Stroke/drug therapy , Stroke/etiology
3.
Nanoscale ; 14(26): 9218-9247, 2022 Jul 07.
Article in English | MEDLINE | ID: mdl-35726826

ABSTRACT

Nowadays, the extensive utilization of electronic devices and equipment inevitably leads to severe electromagnetic interference (EMI) issues. Therefore, EMI shielding materials have drawn considerable attention, and great effort has been devoted to the exploration of high-efficiency EMI shielding materials. As a novel kind of 2D transition metal carbide material, MXenes have been widely investigated for EMI shielding in the past few years due to their extraordinary electrical conductivity, large specific surface area, light weight, and easy processability. In view of the great achievements in MXene-based materials for EMI shielding, herein, we reviewed the recent studies on the structural design and evolution of MXenes and their composites for EMI shielding. First, the methods for structural control of MXenes, including HF etching, in situ HF etching, fluorine-free etching, electrochemical etching, and molten salt etching, are systematically summarized. Then we illustrate the fundamental relationship between the microstructure of MXenes and the EMI shielding mechanism. In the following, the effects of different synthesis methods and structures of MXene-based composite materials as well as their EMI shielding performances are comprehensively discussed. Lastly, future prospects for the development of MXene-based composite materials in EMI shielding applications are commented on.

4.
Front Neurol ; 13: 843927, 2022.
Article in English | MEDLINE | ID: mdl-35401401

ABSTRACT

Moyamoya disease (MMD), most often diagnosed in children and adolescents, is a chronic cerebrovascular disease characterized by progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Recently, many investigators show a great interest in MMD with pulmonary arterial hypertension (PAH). Ring finger protein 213 (RNF213) is a major susceptibility gene for MMD and also has strong correlations with PAH. Therefore, this review encapsulates current cases of MMD with PAH and discusses MMD with PAH in the aspects of epidemiology, pathology, possible pathogenesis, clinical manifestations, diagnosis, and treatment.

5.
J Neurol ; 269(7): 3470-3481, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35260949

ABSTRACT

BACKGROUND AND PURPOSE: It remains inconclusive whether asymptomatic intracranial hemorrhage (aICH) after acute ischemic stroke is innocuous. We aimed to conduct a meta-analysis assessing the relationship between the aICH and poor neurological outcomes. METHODS: We searched PubMed, EMBASE and Web of Science from their inception to 30 November 2021 and performed a meta-analysis on the association between the aICH and neurological prognosis after acute ischemic stroke at 3 months, including poor outcomes (modified Rankin Scale [mRS] score ≥ 2 or mRS ≥ 3) and mortality. RESULTS: Fourteen studies were included in the analysis, reporting on a total of 10,915 participants after acute ischemic stroke. The risks of poor outcome (mRS ≥ 2 or mRS ≥ 3) in patients with aICH were significantly higher than patients without ICH (OR 1.70, 95% CI 1.33-2.18; OR 1.43, 95% CI 1.20-1.70, respectively), based on adjusted data. The difference between the two groups was not significant for mortality. The results of subgroup analysis showed aICH were associated with higher ratio of mild poor prognosis (mRS ≥ 2) (OR 1.59, 95% CI 1.11-2.27), but it had no association with functional dependence (mRS ≥ 3) after recanalization. No significant influence of aICH on poor outcome (mRS ≥ 3) was found in non-recanalization group. Further stratified analysis revealed that only aICH with patients receiving endovascular therapy (EVT) could increase the risk of mild poor prognosis (mRS ≥ 2) at 3 months. CONCLUSIONS: Our results indicate that compared with patients without ICH, those who developed aICH during the acute stage of ischemic stroke had an increasing risk of worse outcome, especially in patients with endovascular therapy.


Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , Brain Ischemia/drug therapy , Brain Ischemia/therapy , Endovascular Procedures/adverse effects , Humans , Intracranial Hemorrhages/complications , Prognosis , Stroke/drug therapy , Stroke/therapy , Thrombectomy/methods , Thrombolytic Therapy/methods , Treatment Outcome
6.
J Matern Fetal Neonatal Med ; 35(13): 2499-2506, 2022 Jul.
Article in English | MEDLINE | ID: mdl-32698641

ABSTRACT

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common birth defects, and occurs in approximately 1/700 live births worldwide. The correlation between the ABCA4-ARHGAP29 region and NSCL/P was first identified by genome-wide association studies (GWAS), but few reports have examined NSCL/P caused by ARHGAP29 mutations in the Chinese population. METHODS: We performed chromosome microarray analysis (CMA) for two consecutive abnormal fetuses and whole exome sequencing (WES) for the family, including 3 patients and 2 normal family members, Sanger sequencing and RT-PCR were used to confirm the mutation. RESULTS: We identified a novel splice donor mutation (ARHGAP29 c.1920 + 1G > A) in two consecutive NSCL/P fetuses, and the variant was inherited from the mother and grandfather. The mutation caused abnormal skipping of exon 17, and the mRNA level of ARHGAP29 was significantly decreased compared to the wild type. CONCLUSIONS: In this study, we successfully diagnosed the genetic cause of NSCL/P in a family and first report that the c.1920 + 1G > A mutation in ARHGAP29 is associated with NSCL/P. Our study enriches the genetic landscape of NSCL/P, extends the mutation spectrum of ARHGAP29, and provides a new direction for the diagnosis of NSCL/P in patients and its prenatal diagnosis in fetuses.


Subject(s)
Cleft Lip , Cleft Palate , ATP-Binding Cassette Transporters/genetics , Case-Control Studies , Cleft Lip/genetics , Cleft Palate/genetics , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Mutation , Polymorphism, Single Nucleotide
7.
Signal Transduct Target Ther ; 5(1): 3, 2020 01 10.
Article in English | MEDLINE | ID: mdl-32296024

ABSTRACT

The ability to identify a specific type of leukemia using minimally invasive biopsies holds great promise to improve the diagnosis, treatment selection, and prognosis prediction of patients. Using genome-wide methylation profiling and machine learning methods, we investigated the utility of CpG methylation status to differentiate blood from patients with acute lymphocytic leukemia (ALL) or acute myelogenous leukemia (AML) from normal blood. We established a CpG methylation panel that can distinguish ALL and AML blood from normal blood as well as ALL blood from AML blood with high sensitivity and specificity. We then developed a methylation-based survival classifier with 23 CpGs for ALL and 20 CpGs for AML that could successfully divide patients into high-risk and low-risk groups, with significant differences in clinical outcome in each leukemia type. Together, these findings demonstrate that methylation profiles can be highly sensitive and specific in the accurate diagnosis of ALL and AML, with implications for the prediction of prognosis and treatment selection.


Subject(s)
Biomarkers, Tumor/genetics , DNA Methylation/genetics , Leukemia/genetics , Prognosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , CpG Islands/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Infant , Leukemia/classification , Leukemia/diagnosis , Leukemia/pathology , Machine Learning , Male , Middle Aged , Promoter Regions, Genetic/genetics , Young Adult
8.
Mol Genet Genomics ; 295(3): 635-643, 2020 May.
Article in English | MEDLINE | ID: mdl-32020275

ABSTRACT

The ring finger protein 213 gene (RNF213) rs112735431 was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. We conducted a case-control study to examine the prevalence and correlates of the RNF213 rare variants in Chinese patients with symptomatic ICASO. A total of 503 cases including 390 ischemic stroke patients (ICASO-IS), 113 intracranial hemorrhage patients (ICASO-ICH) and 227 control subjects were recruited. The snapshot technique was used for RNF213 rare variants analysis, including rs112735431, rs148731719, rs37144111 and rs138130613. Moreover, a meta-analysis was performed to explore the relationship between RNF213 variants and ICASO in Asian. In our case-control study, we found that the rs138130613 variant was significantly associated with ICASO-IS (OR = 9.92, 95% CI 1.24-79.19, p = 0.03). The mean age of first ischemic stroke onset of variant carriers was earlier than the noncarriers (51.3 ± 18.0 versus 66.0 ± 12.9 years old, p = 0.02), but the conventional atherosclerotic risk factors and the characteristics of artery stenosis did not differ between them. In addition, the meta-analysis showed significant association between the rs112735431 polymorphism and the ICASO or ICASO-IS, and this variant was found more often in women and young-onset patients in Asia. This study suggests that the RNF213 rs112735431 and rs138130613 are genetic risk variants for ischemic stroke with intracranial artery stenosis/occlusion in China and rs112735431 is also associated with the high risk of ICASO in Asia. Further large-scale investigation of the RNF213 gene will provide new insights into pathogenetic mechanisms of symptomatic ICASO.


Subject(s)
Adenosine Triphosphatases/genetics , Asian People/genetics , Constriction, Pathologic/genetics , Genetic Predisposition to Disease , Moyamoya Disease/genetics , Polymorphism, Single Nucleotide , Ubiquitin-Protein Ligases/genetics , Aged , Case-Control Studies , China/epidemiology , Constriction, Pathologic/epidemiology , Constriction, Pathologic/pathology , Female , Humans , Male , Meta-Analysis as Topic , Middle Aged , Moyamoya Disease/epidemiology , Moyamoya Disease/pathology , Prevalence
9.
J Clin Lab Anal ; 33(3): e22825, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30485544

ABSTRACT

BACKGROUND: Hypoxic preconditioning alters the biological properties of mesenchymal stem cells (MSCs). It is not known whether this process has an effect on circular RNAs (circRNAs) in MSCs. METHODS: Human placental chorionic plate-derived MSCs (hpcpMSCs) isolated from the same placentae were classed into two groups: hypoxic pretreated (hypoxia) group and normally cultured (normoxia) group. The comparative circRNA microarray analysis was used to determine circRNAs expression and verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in the two groups. RESULTS: One hundred and two differentially expressed circRNAs in the hypoxia group were found compared to that in the normoxia group (fold change >1.5-fold and P < 0.05). The expression levels of circRNAs by qRT-PCR were consistent with those evaluated by microarray analysis. Gene ontology (GO) analysis showed that the putative function of their target genes for those differentially expressed circRNAs was primarily involved in cell development and its differentiation and regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that transcriptional misregulation in cancer and mitogen-activated protein kinase (MAPK) signaling pathway were the most significant. MAPK signaling pathway was found to be the core regulatory pathway triggered by hypoxia. CONCLUSIONS: The results indicate that the altered expression of specific circRNAs in MSCs is associated with hypoxic preconditioning. This finding provides further exploration of underlying mechanisms of the characteristic changes of MSCs with hypoxic preconditioning.


Subject(s)
Cell Hypoxia/genetics , Mesenchymal Stem Cells/metabolism , Placenta/cytology , RNA/metabolism , Cells, Cultured , Female , Humans , Placenta/metabolism , Placenta/physiology , Polymerase Chain Reaction , Pregnancy , RNA/analysis , RNA/genetics , RNA, Circular , Transcriptome/genetics
10.
Oncol Lett ; 11(5): 3111-3116, 2016 May.
Article in English | MEDLINE | ID: mdl-27123073

ABSTRACT

Breast cancer remains a major public health problem worldwide. Chemotherapy serves an important role in the treatment of breast cancer. However, resistance to chemotherapeutic agents, in particular, multi-drug resistance (MDR), is a major cause of treatment failure in cancer. Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance are urgently needed for the treatment of breast cancer. Pristimerin, a quinonemethide triterpenoid compound isolated from Celastraceae and Hippocrateaceae, has been shown to possess antitumor, anti-inflammatory, antioxidant and insecticidal properties. The aim of the present study was to investigate whether pristimerin can override chemoresistance in MCF-7/adriamycin (ADR)-resistant human breast cancer cells. The results demonstrated that pristimerin indeed displayed potent cytocidal effect on multidrug-resistant MCF-7/ADR breast cancer cells, and that these effects occurred through the suppression of Akt signaling, which in turn led to the downregulation of antiapoptotic effectors and increased apoptosis. These findings indicate that use of pristimerin may represent a potentially promising approach for the treatment of ADR-resistant breast cancer.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(4): 1112-9, 2015 Aug.
Article in Chinese | MEDLINE | ID: mdl-26314456

ABSTRACT

OBJECTIVE: To investigate the feasibility of umbilical cord blood plasma (UCP) as a replacement for fetal bovine serum (FBS) for culturing mesenchymal stem cells (MSC) derived from umbilical cord, and to observe the supporting effects of these cells (served as a feeder layer) on ex vivo expanding of human umbilical cord blood CD34(+) cells. METHODS: Umbilical cord blood (UCB) units were suitable if the Guangzhou cord blood bank donor selection criteria strictly were fulfilled. UCP were ready to use after the collection from the plasma depletion/reduction during the processing and pooling of suitable UCB units (at least 30 units were screened for pathogens and microorganisms, and qualified). Umbilical cord mesenchymal stem cells (UCMSC) were harvested from the umbilical cord tissue of health full-term newborns after delivery by enzyme digestion and divided into 3 groups: group 1 and 2 were cultured in the presence of DMEM/F12 containing either FBS or UCP; and group 3 was cultured in serum-free medium (StemPro® MSC SFM CTS™). Morphology, proliferation and surface marker expression were examined by flow cytometry, and the differentiation toward adipogenic and osteogenic lineages was used for investigating the effect of media on UCMSC after 3-5 passages. Next, the cells cultured in the three different media were cryopreserved and thawed, then prepared as feeder layers with the name of UCMSC(FBS), UCMSC(UCP), and UCMSC(SFM), respectively. The CD34⁺ cells were separated from UCB by magnetic activated cell sorting (MACS) and divided into 4 groups cultured in StemPro(-34) SFM medium added with hematopoietic cytokine combination (StemSpan® CC100). The control group included only CD34⁺ cells as group A (blank control) and experimental groups included UCMSC(FBS) + CD34⁺ cells as group B, UCMSC(UCP) + CD34⁺ cells as group C, UCMSC(SFM) + CD34⁺ cells as group D, and cells in all groups were cultured ex vivo for 7 days. The nucleated cell (NC) number was counted by cell counter, CD34⁺ cells were measured by flow cytometry, and clonogenic assay was conducted at day 0 and 7 of culture. The expansion efficiency was assessed. RESULTS: The morphology (spindle-shaped and plastic-adherent), the immunophenotype (high positive percentage of CD73, CD90, CD105 and CD166) and the differentiation potential (osteogenic and adipogenic) were almost indistinguishable among the cells cultured in any of these three media except for the expression of CD105 in group 3 (serum-free medium) was lower than that in other 2 groups (P < 0.05). UCMSC grown in UCP medium demonstrated significantly higher proliferation rates than that in media containing FBS or commercial serum-free supplement (P < 0.05). After co-culture for 7 days, the CD34⁺ cell percentage decreased in all the groups, while NC were amplified effectively and the CD34⁺ cell number increased with the same order as group C or D group B or A (control group) (P < 0.05). As compared with the colony-forming unit (CFU) number at day 0, there was no significant difference in the expansion multiple between group C and D, while the expansion of CFU in group C were higher than that in group B and A. CONCLUSION: The UCP can be used as a better animal-free serum supplement for growth, maintenance and differentiation of UCMSC, thus would be a safe choice for clinical-scale production of human MSC.


Subject(s)
Fetal Blood , Mesenchymal Stem Cells , Antigens, CD34 , Biomarkers , Cell Culture Techniques , Cell Differentiation , Cell Separation , Cells, Cultured , Coculture Techniques , Flow Cytometry , Humans , Immunophenotyping , Umbilical Cord
12.
Transfusion ; 55(9): 2158-67, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25994982

ABSTRACT

BACKGROUND: The operation of cord blood banks (CBBs) requires immense labor, material, and financial resources. Thus, increasing the ratio of high-quality cord blood units (HQCBUs) in storage that are qualified for clinical use is critical for the efficient use of limited resources. Understanding the factors that contribute to HQCBUs, including maternal, fetal, and processing conditions, may improve the number of HQCBUs in storage. STUDY DESIGN AND METHODS: The maternal, fetal, and processing conditions of 4613 CBUs at the Guangzhou Cord Blood Bank were analyzed retrospectively to determine their effect on HQCBUs. All CBUs were obtained following strict standard operation procedures. RESULTS: Several factors may contribute to HQCBUs: fetal age older than 37 gestational weeks, female fetus, large cord blood (CB) volume (>80 mL), high birthweight (>3500 g), vaginal delivery, and a shorter amount of time between CB collection and processing (12 hr). We report for the first time that α-thalassemia carriers exhibit a postprocessing total nucleated cell count (p-TNCC) increase to at least 1.25 × 10(9) and an increase of the CD34+ cell count to at least 6.01 × 10(6) . Meconium-stained amniotic fluid and mothers younger than 25 years of age exhibited increased p-TNCC to at least 1.25 × 10(9) , and colony-forming units increased to at least 23.24 × 10(5) . CONCLUSIONS: We identified several factors that affect HQCBUs. These results may be used as a reference for updating CB collection strategies, with priority given to collecting CBUs from female fetuses older than 37 gestational weeks, at high birthweight, and born by vaginal delivery from mothers younger than 25 years of age, especially newborns with one parent carrying the trait or with meconium-stained amniotic fluid. The collected CBUs should be sent to the laboratory as soon as possible for priority processing, which will help to increase the number and ratio of HQCBUs and the effective use of CBB resources.


Subject(s)
Blood Banks , Donor Selection/methods , Fetal Blood , Adolescent , Adult , Female , Humans , Infant, Newborn , Leukocyte Count , Retrospective Studies , alpha-Thalassemia/blood
13.
Oncol Rep ; 33(5): 2285-90, 2015 May.
Article in English | MEDLINE | ID: mdl-25738752

ABSTRACT

Lipid rafts, specialized domains in cell membranes, function as physical platforms for various molecules to coordinate a variety of signal transduction processes. Flotillin-2 (FLOT2), a marker of lipid rafts, is involved in the progression of cancer, yet the precise mechanism remains unclear. In the present study, we examined the effect of FLOT2 on cell proliferation and found that silencing endogenous FLOT2 with shRNAs inhibited proliferation of breast cancer cells. Furthermore, the antiproliferative effect of silencing FLOT2 on breast cancer cells was associated with upregulation of cyclin-dependent kinase (CDK) inhibitors p21Cip1 and p27Kip1. Moreover, we further demonstrated that the silencing of FLOT2 enhanced the transcriptional activity of FOXO factors by decreasing its phosphorylation through inhibiting the PI3K/Akt signaling pathway. Taken together, our results provide the first demonstration of a novel mechanism by which FLOT2 induces proliferation of breast cancer cells, and our findings suggest that FLOT2 plays an important role in oncogenesis of breast cancer and thereby may be a potential target for human breast cancer treatment.


Subject(s)
Adenocarcinoma/genetics , Breast Neoplasms/genetics , Cell Proliferation/genetics , Forkhead Transcription Factors/genetics , Membrane Proteins/genetics , Proto-Oncogene Proteins c-akt/metabolism , Cell Cycle Proteins , Cell Line, Tumor , Forkhead Box Protein O1 , Forkhead Box Protein O3 , Gene Knockdown Techniques , Humans , MCF-7 Cells , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Signal Transduction , Transcription Factors/genetics
14.
Int J Oncol ; 45(2): 804-12, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24865236

ABSTRACT

Inhibitors of cyclin-dependent kinases (Cdks) have been reported to have activities in many types of cancer cells by inhibiting Cdk7 and Cdk9, which control transcription. SNS-032 is a potent and selective inhibitor of Cdk2, Cdk7 and Cdk9 and has emerged in clinical trials. Here, we examined the viability of MCF-7 and MDA-MB-435 breast cancer cells in the presence of SNS-032 and observed a dose-dependent inhibition of cellular proliferation in both cell lines. SNS-032 had a direct apoptosis-inducing effect through both the extrinsic and intrinsic apoptotic pathways in breast cancer cells as shown by a dose-dependent increase in Annexin V-positive cells and terminal deoxynucleotidyl transferase-mediated dUTP nick?end labeling (TUNEL)-positive cells, as well as activation of caspase-8, -9 and poly(ADP-ribose) polymerase (PARP). At the molecular level, SNS-032 induced a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and blocked RNA synthesis. Consistent with the inherently rapid turnover rates of their transcripts and proteins, the anti-apoptotic proteins Mcl-1 and X-linked inhibitor of apoptosis protein (XIAP) were rapidly reduced on exposure to SNS-032. Our results also indicated that SNS-032 suppressed the growth of breast cancer xenografts in mice. These data demonstrate that the use of SNS-032 may be a rational and novel therapeutic strategy for human breast cancer and warrants further clinical investigation.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Breast Neoplasms/metabolism , Oxazoles/pharmacology , Thiazoles/pharmacology , Animals , Blotting, Western , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Survival/drug effects , Cyclin-Dependent Kinase 2 , Female , Heterografts , Humans , In Situ Nick-End Labeling , Mice , Mice, Inbred BALB C , Mice, Nude , Myeloid Cell Leukemia Sequence 1 Protein , Real-Time Polymerase Chain Reaction , X-Linked Inhibitor of Apoptosis Protein
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(3): 754-8, 2011 Jun.
Article in Chinese | MEDLINE | ID: mdl-21729565

ABSTRACT

This study was purposed to investigate the role of post-thaw infused donor cells for predicting engraftment and hematopoietic reconstitution after unrelated cord blood transplantation (UCBT). The retrospective analysis was performed on clinical data of 97 children with malignant or non-malignant diseases received single unit UCBT from August 1999 to April 2010. The impact of pre-freezing and post-thaw cell dose of total nucleated cells (TNC), CD34(+) cells and colony-forming units-granulocyte/macrophage (CFU-GM) on engraftment and hematological recovery after UCBT was analyzed. Unrelated donors were from Guangzhou cord blood bank (GZCBB) entirely. The results indicated that the pre-freezing TNC (/kg) (mean ± SD: 7.65 × 107 ± 4.26 × 107; median: 6.34 × 107), CD34(+)cells (/kg) (mean ± SD: 4.64 × 10(5) ± 4.47 × 105; median: 3.03 × 105) and CFU-GM (/kg) (mean ± SD: 0.79 × 105 ± 1.09 × 105; median: 0.57 × 105) showed a good correlation with their post-thaw counterparts including TNC(/kg) (mean ± SD: 6.98 × 107 ± 4.12 × 107; median: 6.00 × 107), CD34(+)cells (/kg)(Mean ± SD: 6.86 × 105 ± 8.56 × 105; Median: 4.17 × 105), and CFU-GM (/kg) (mean ± SD: 0.52 × 105 ± 0.52 × 105; median: 0.39 × 105) (r = 0.952, p < 0.001; r = 0.794, p < 0.001; r = 0.478, p < 0.001). Either the pre-freezing or post-thaw number of infused CFU-GM was significant higher in patients who achieved engraftment (n = 70) than those who suffered graft failure (n = 22) (p = 0.023 and 0.011, respectively), but no significant difference of TNC and CD34(+) cells dose (pre-freezing or post-thaw) were found between these two groups. Pre-freezing CFU-GM, TNC, CD34(+) cell dose negatively correlated with the time of neutrophil engraftment (r = -0.285, p = 0.018; r = -0.396, p = 0.002; r = -0.373, p = 0.002), as well as the post-thaw number of TNC and CD34(+) cells (r = -0.260, p = 0.031; r = -0.483, p < 0.001), whereas only pre-freezing CD34(+) cells showed a significant correlation with platelet engraftment time (r = -0.352, p = 0.013). It is concluded that the CFU-GM amount is useful for predicting engraftment of UCBT, while pre-freezing hematopoietic cell doses show superior correlation with the speed of engraftment and hematopoietic reconstitution than their post-thaw counterparts in pediatric recipients, suggesting that it is essential to perform hematopoietic potency assay on each cord blood unit prior to listing or release for administration.


Subject(s)
Cord Blood Stem Cell Transplantation/methods , Granulocyte-Macrophage Progenitor Cells , Adolescent , Antigens, CD34/blood , Blood Banks , Child , Child, Preschool , Female , Fetal Blood/cytology , Graft Survival , Humans , Infant , Male , Retrospective Studies , Tissue Donors
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 18(6): 1535-41, 2010 Dec.
Article in Chinese | MEDLINE | ID: mdl-21176366

ABSTRACT

Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for transplantation with success being associated with the total nucleated cell (TNC) count, CD34(+) cells and colony-forming unit-granulocyte-macrophage (CFU-GM) content infused. This study was purposed to clarify the impact of maternal and neonatal factors on hematopoietic potential of UCB product. UCB samples were screened, processed, tested and cryopreserved according to the Standard Operation Procedure (SOP) of Guangzhou cord blood bank (GZCBB). Relationship of hematopoietic cell parameters with maternal and neonatal characteristics for 4615 UCB units was analyzed retrospectively. The results showed that both collected volume (Mean ± SD: 95.23 ± 22.42 ml; Median: 91.85 ml) and initial TNC [Mean ± SD: (1.34 ± 0.49) × 10(9); Median: 1.25 × 10(9)] correlated well with postprocessed TNC [Mean ± SD: (1.21 ± 0.42) × 10(9); Median: 1.14 × 10(9); p < 0.001], CD34(+)count [Mean ± SD: (5.14 ± 4.55) × 10(6); Median: 4.08 × 10(6); p < 0.001] and CFU-GM content [Mean ± SD: (9.72 ± 8.66) × 10(5); Median: 7.53 × 10(5); p < 0.001]. As for donor factors, only infant birth weight correlated strongly with volume collected and all hematopoietic cell parameters (p < 0.001). UCB samples from bigger babies had higher collected volume, TNC, CD34(+) count and CFU-GM content (p < 0.001). Mother's age had no correlation with all the above parameters. Gestational age correlated positively with initial/postprocessed TNC (p < 0.001) and negatively with CD34(+) count (p = 0.04), but no relation with collected volume and CFU-GM content. Cesarean section produced superior volume (Mean ± SD: 97.05 ± 22.23 ml vs 92.53 ± 22.43 ml; Median: 94.08 ml vs 88.82 ml; p < 0.001), but inferior cell count than vaginal delivery (p < 0.001). Male infants had more initial volume and CD34(+) count (Mean ± SD: 96.41 ± 22.31 ml vs 93.95 ± 22.47 ml; Median: 93.27 ml vs 90.14 ml; p < 0.001); [Mean ± SD: (5.28 ± 5.04) × 10(6) vs (5.00 ± 3.94) × 10(6); Median: 4.18 × 10(6) vs 3.94 × 10(6); p < = 0.042], but lower initial and postprocessed TNC than female ones [Mean ± SD: (1.31 ± 0.50) × 10(9) vs (1.37 ± 0.47) × 10(9); Median: 1.22 × 10(9) vs 1.28 × 10(9); p < 0.001]; [Mean ± SD: (1.18 ± 0.42) × 10(9) vs (1.24 ± 0.41) × 10(9); Median: 1.10 × 10(9) vs 1.17 × 10(9); p < 0.001], while no significant difference of CFU-GM were found between male and female infants. It is concluded that these data may be helpful to optimize the UCB donor selection and improve cost efficiency of UCB bank resource. The heavier infants after vaginal delivery should be selected and large-volume units with higher TNC should be chosen at first.


Subject(s)
Blood Banking/methods , Donor Selection , Fetal Blood , Adult , Birth Weight , Cord Blood Stem Cell Transplantation/methods , Delivery, Obstetric , Female , Fetal Blood/cytology , Fetal Blood/immunology , Gestational Age , Hematopoietic Stem Cells , Humans , Infant, Newborn , Male , Maternal Age , Pregnancy , Young Adult
17.
Zhonghua Fu Chan Ke Za Zhi ; 43(5): 321-4, 2008 May.
Article in Chinese | MEDLINE | ID: mdl-18953861

ABSTRACT

OBJECTIVE: To determine the value of spectral karyotyping(SKY) in identification of the marker chromosome. METHODS: Selected six cases that could not be identified in clinic were studied, using samples of peripheral blood from four cases, and samples of amonic fluid and fetal cord blood for prenatal diagnosis in two cases were investigated. All cases were analyzed with the routine SKY method, and the results with the SKY View software. The SKY results were identified by using fluorescence in situ hybridization (FISH). And C-banding technique was used to help diagnose the heterochromatin. RESULTS: SKY was successfully performed on all of 6 cases. The origin of all marker chromosomes was identified by SKY. Except case No. 4, the others were confirmed by FISH. It helped determine the pregnancy outcome in two cases of prenatal diagnosis: one case of genetic marker chromosome continued the pregnancy, and another case of de novo marker chromosome was terminated of the pregnancy. CONCLUSION: SKY may be a valuable tool to diagnose the marker chromosome with rapidness,direct-viewing and sensitiveness. It can be used to assess the prognosis and the pregnancy outcome.


Subject(s)
Chromosome Aberrations , Chromosomes, Human/genetics , Prenatal Diagnosis/methods , Spectral Karyotyping/methods , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Chromosomes, Human, Pair 15/genetics , Chromosomes, Human, Pair 22/genetics , Female , Genetic Markers , Humans , In Situ Hybridization, Fluorescence/methods , Pregnancy , Pregnancy Outcome , Sensitivity and Specificity
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 14(5): 941-4, 2006 Oct.
Article in Chinese | MEDLINE | ID: mdl-17096893

ABSTRACT

From June 1998 to July 2004, Guangzhou umbilical cord blood bank provided unrelated umbilical cord blood for 54 patients to more than 21 transplantation centers. HLA sequencing-based typing (SBT) was used to re-analyze the results of HLA antigens and alleles so as to investigate the relationship between HLA alleles and GVHD. The information about 48 out of 54 patients was obtained after 6 months of follow up. SBT was used to identify HLA-A, B, DRB1 alleles in 48 patients received the unrelated umbilical cord blood units, and the obtained results were compared with the results of HLA-SSP Low Resolution Typing. The results showed that the difference of GVHD incidence between less than 2 mismatched HLA sites and less than 3 sites was statistically significant (P < 0.05). In the results from single factor analysis and high-resolution typing of HLA-A, B and DRB1 alleles, the mismatch between HLA-B and HLA-DRB1 alleles was found to be a significant factor for the occurence of GVHD. It is concluded that SBT plays an important role in umbilical cord blood transplantation, and the incidence of GVHD is higher in the transplantation with HLA-DRB1 alleles mismatching.


Subject(s)
Cord Blood Stem Cell Transplantation , Fetal Blood/immunology , Graft vs Host Disease/prevention & control , Adolescent , Adult , Aged , Alleles , Child , Child, Preschool , Cord Blood Stem Cell Transplantation/adverse effects , Female , Fetal Blood/cytology , HLA-A Antigens/genetics , HLA-A Antigens/immunology , HLA-B Antigens/genetics , HLA-B Antigens/immunology , HLA-DR Antigens/genetics , HLA-DR Antigens/immunology , HLA-DRB1 Chains , Histocompatibility Testing/methods , Humans , Leukemia/therapy , Male , Middle Aged , Sequence Analysis
19.
Hemoglobin ; 30(3): 365-70, 2006.
Article in English | MEDLINE | ID: mdl-16840227

ABSTRACT

Beta-thalassemia (thal) is the most common genetic disease and is widely distributed in southern China. Prenatal diagnosis is needed to prevent the birth of thalassemic offspring in couples at-risk. This can be performed in the first or second trimester of pregnancy by DNA analysis using polymerase chain reaction (PCR). As there are more than 30 mutations causing beta-thal in Chinese, the point mutation detection by reverse dot-blot for common mutations together with direct DNA sequencing was developed for prenatal diagnosis. Using reverse dot-blot, we were able to offer complete diagnosis in 315 (99.4%) of 317 pregnancies. Only two fetuses needed the DNA sequencing technique for diagnosis. Of the 319 at-risk fetuses, 82 (25.7%) were found to be normal, 143 (44.8%) to be heterozygous for beta-thal and 94 (29.5%) to be affected with beta-thal. Therefore, the combination of reverse dot-blot with direct DNA sequencing can perform prenatal diagnosis by DNA analysis in almost all cases at- risk of beta-thal in southern China.


Subject(s)
Fetal Diseases/diagnosis , Genetic Testing/methods , Prenatal Diagnosis/methods , beta-Thalassemia/diagnosis , China , Chorionic Villi Sampling , Female , Fetal Diseases/genetics , Humans , Immunoblotting/methods , Point Mutation/genetics , Pregnancy , Sequence Analysis, DNA/methods , beta-Thalassemia/genetics
20.
Zhonghua Er Ke Za Zhi ; 44(3): 220-3, 2006 Mar.
Article in Chinese | MEDLINE | ID: mdl-16624064

ABSTRACT

OBJECTIVE: From December 1998 to April 2004, 3960 umbilical cord blood units were stored in Guangzhou cord blood bank, which provided 100 umbilical cord blood units to 25 transplant center for 83 patients with malignant or non-malignant diseases. To study the related factors affecting unrelated umbilical cord blood stem cell transplantation, the authors analyzed retrospectively the results of transplantation of unrelated umbilical cord blood stem cells for 65 patients. METHODS: ALL (acute lymphocytic leukemia) cord blood units were obtained from full term normal vaginal and cesarean deliveries in Guangzhou Women and Infants Hospital. The fractionation, cryopreservation and thawing of the cord blood were performed according to the regulations of New York umbilical cord blood bank and pertinent literature. The selection of cord blood was based on HLA typing and the number of nucleated cells. The sex and HLA antigens of donors were defined as the evidence of engraftment. Time to engraftment was recorded when the absolute number of neutrophil ANC (absolute neutrophil count) was higher than 5.0 x 10(8) for three days. Event-free survival and graft versus host disease (GVHD) were provided by transplant centers. RESULTS: Out of 65 patients who received unrelated cord blood stem cell transplant, 49 patients were diagnosed as having malignant diseases [including 23 with ALL, 16 with AML (acute myeloid leukemia), 7 with CML (chronic myelogenous leukemia), 3 with lymphoma and one with MDS (myelodysplastic syndrome)], 16 patients had non-malignant disease. The 65 transplanted patients (42 male, 23 female) had a median age of 10 years (range 1 - 33 years) and a median body weight of 27 kg (range 10 - 67 kg). The patients received cord blood stem cells from unrelated 0-locus (n = 9) or 1-locus (n = 43) or 2-locus (n = 13) HLA mismatched donor. The median dose of infused cells was: total neutrophil count (TNC) 5.7 x 10(7), CD(34)(+) 5.1 x 10(5), CFU-GM 3.8 x 10(4). Fifty of 65 (77%) patients had engraftment. GVHD occurred in 41 patients (63%), including acute grade I - II GVHD in 31 patients (76%), acute grade III - IV GVHD in 8 patients (20%) and chronic GVHD in 2 patients (5%). Fifty patients had engraftment (ANC > 5.0 x 10(8)) after a median time of 17 (range 7 to 44) days after transplant, while an autologous hematopoietic reconstitution was observed in 6 patients; 24 patients died of severe pneumonia (n = 8), acute GVHD (n = 4), or sepsis (n = 12) and the disease-free survival probability was 61%. CONCLUSIONS: Unrelated allogeneic umbilical cord blood transplantation may be a good substitution for unrelated allogeneic bone marrow transplantation with a good prospect.


Subject(s)
Cord Blood Stem Cell Transplantation/methods , Leukemia/therapy , Adolescent , Adult , Child , Child, Preschool , China , Cord Blood Stem Cell Transplantation/adverse effects , Disease-Free Survival , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Humans , Infant , Leukemia/mortality , Male , Retrospective Studies , Survival Rate , Transplantation, Homologous , Treatment Outcome , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...