93 results on '"Jiayun Lu"'
Search Results
52. Distinctive clinicopathological features and disease‑specific survival of adenoid cystic carcinoma and adenoid basal carcinoma in the lower female genital tract
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Deyin Xing and Jiayun Lu
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Adult ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Adenoid cystic carcinoma ,Population ,Uterine Cervical Neoplasms ,Adenoid ,Gastroenterology ,Vulva ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Biomarkers, Tumor ,Carcinoma ,medicine ,Humans ,Stage (cooking) ,education ,Survival rate ,Aged ,Neoplasm Staging ,Aged, 80 and over ,education.field_of_study ,Vulvar Neoplasms ,business.industry ,Age Factors ,Articles ,General Medicine ,Middle Aged ,medicine.disease ,Carcinoma, Adenoid Cystic ,United States ,Survival Rate ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Localized disease ,Female ,business ,SEER Program - Abstract
Adenoid cystic carcinomas (ACCs) and adenoid basal carcinomas (ABCs) in the lower female genital tract are very rare. Data on the clinicopathologic features and survival outcomes of ACCs and ABCs in the lower female genital tract are limited to case reports and small case series studies. The present study systemically analyzed 233 cases, including 84 cervical ACCs, 78 cervical ABCs and 71 vulvar ACCs, to identify clinicopathologic features and survival factors in a population-based Surveillance, Epidemiology and End Results (SEER) study. Whereas cervical ACCs and ABCs tend to occur in the elderly (median, 72 and 69 years, respectively), vulvar ACCs commonly occurred in patients a decade younger (median, 59 years). The majority of patients with cervical ABC had localized disease and almost all received surgery. In contrast, cervical and vulvar ACC patients tended to have higher stage disease, and a significant proportion of these patients received radiotherapy, with or without surgery. The 5-year cause-specific survival (CSS) rates for patients with cervical ACC were 69.3%, vulvar ACC 87.7% and cervical ABC 96.6%. The 5-year overall survival (OS) rate for patients with cervical ACC was 59.2%, significantly worse than that of cervical ABC (88.3%; P=0.002) and vulvar ACC (81.2%; P=0.01). Increased age and high stage were significantly associated with a worse prognosis in patients with cervical and vulvar ACCs by univariate and multivariate analysis (P
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- 2018
53. Observations on Asexual Reproduction by Peronophythora litchii
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Ho, H. H., Jiayun, Lu, and Longyin, Gong
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- 1984
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54. Abstract PO-226: Localization of macrophages and neutrophils in the prostate tumor microenvironment and their association with prostate cancer racial disparities
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Jiayun Lu, Corinne E. Joshu, Angelo M. De Marzo, Igor Vidal, Karen S. Sfanos, and Janielle P. Maynard
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Biochemical recurrence ,Tumor microenvironment ,Tissue microarray ,Epidemiology ,business.industry ,Prostatectomy ,medicine.medical_treatment ,Cancer ,medicine.disease ,Metastasis ,Prostate cancer ,medicine.anatomical_structure ,Oncology ,Prostate ,medicine ,Cancer research ,business - Abstract
African American (AA) men are two to three times more likely to die from prostate cancer (PCa) than European American (EA) men. This disparity may be due in part to socioeconomic status and discrepancies in access to quality care. Studies also suggest that differences in innate immune effector cells and function in the tumor microenvironment of AA men may promote PCa aggressiveness. Increased tumor- associated macrophages are associated with poorer outcomes and a high neutrophil- to-lymphocyte ratio is significantly associated with poorer survival in men with PCa. However, the prevalence of innate immune cells, their spatial localization, and their relationship to PCa racial disparities is largely unknown. We evaluated CD66ce+ neutrophils and CD68+ (pan), CD80+ (M1), and CD163+ (M2) macrophages using RNA in situ hybridization or immunohistochemistry on formalin-fixed paraffin-embedded whole tissue sections from prostate donor tissues with no cancer (n=4) and radical prostatectomy tissues from AA and EA men with low grade (Gleason ≤ 3+4) and higher grade (Gleason ≥ 4+3) PCa (n=38). Tissue microarray (TMA) sets containing radical prostatectomy tissues (n=932) or distant metastatic tissues obtained at autopsy (n=6) were also evaluated. Immune marker expression in TMAs was quantified using TMAJ and FrIDA software. CD66ce+ neutrophils were primarily localized to blood vessels in organ donor prostate specimens as well as normal appearing, non-inflamed regions of radical prostatectomy specimens. Increased CD66ce+ neutrophils were present in inflamed regions of benign tissues from both races. In analysis of TMAs, there was significantly increased CD66ce+ neutrophils in tissues from EA men compared to AA men (p < 0.0001). There was also increased CD66ce expression in cancer compared to benign tissue spots (p There was no association between CD66ce+ neutrophils and risk of metastasis or biochemical recurrence. CD68+ and CD163+ macrophages were abundant in organ donor specimens, while CD80 expression was minimal. Similar expression patterns were observed in benign regions of radical prostatectomy specimens. In analysis of TMAs, CD68, CD80 and CD163 were significantly increased in cancer compared to benign tissues (p < 0.0001). CD163 expression was comparable between races, while CD80 expression was significantly higher in benign tissues from AA men compared to EA men (p = 0.0004). CD68, CD80 and CD163 expression were all significantly increased in benign spots from ERG positive versus ERG negative cases. In conclusion, there is increased infiltration of innate immune cells in the prostate tumor microenvironment of both AA and EA men, however the composition of innate immune cell infiltration varies between races. Our future studies aim to determine the influence of innate immune effector cells on PCa aggressiveness and outcomes. Citation Format: Janielle P. Maynard, Jiayun Lu, Igor Vidal, Corinne E. Joshu, Angelo M. De Marzo, Karen S. Sfanos. Localization of macrophages and neutrophils in the prostate tumor microenvironment and their association with prostate cancer racial disparities [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-226.
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- 2020
55. Abstract C027: Racial variation in umbilical cord blood vitamin D concentrations and telomere length: Implications for cancer risk
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Tanya Agurs-Collins, John R. Barber, Anthony J. Rizzo, Jiayun Lu, Elizabeth A. Platz, Jessica L. Bienstock, Christopher M. Heaphy, Alan K. Meeker, Sabine Rohrmann, and Paige A. Green
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medicine.anatomical_structure ,Variation (linguistics) ,Oncology ,Epidemiology ,business.industry ,Vitamin D and neurology ,Medicine ,Physiology ,business ,Cancer risk ,Umbilical cord ,Telomere - Abstract
Background: Non-Hispanic Blacks (NHBs) experience a markedly higher cancer burden and cancer mortality compared to non-Hispanic Whites (NHWs). Several factors account for this disparity, including suboptimal or deficient vitamin D status. Vitamin D has an important role in cancer risk, disease/cancer progression and telomere biology. Given the documented cancer disparities between these groups, it is important to examine vitamin D concentrations and leukocyte telomere length in utero, a window of susceptibility for disease and cancer risk later in life. We investigated racial differences in neonate umbilical cord blood vitamin D concentrations, and whether differences in vitamin D concentrations are associated with umbilical cord blood telomere length by race and gender. Methods: In 2006-2007, pregnant women were recruited for the Expanded Hormones in Umbilical Cord Blood Study (EHUB) and followed to postpartum. Venous umbilical cord blood samples, along with maternal and birth characteristics, were collected in 39 NHB and 65 NHW full-term neonates. 25(OH)D and 1,25(OH)2D levels were assayed using an equilibrium radioimmunoassay procedure, and relative telomere length was measured by qPCR in leukocyte DNA. Geometric mean plasma concentrations of 25(OH)D and 1,25(OH)2D were calculated. Linear regression analysis was used to examine associations between neonatal cord blood 25(OH)D and 1,25(OH)2D concentrations and leukocyte telomere length by race and gender. Results: Compared to NHW mothers, NHBs were younger, had higher parity, were more likely to be overweight and obese prepregnancy, and more likely to be exposed to secondhand smoke. NHB neonates had lower birth lengths (19.4 versus 20.2 inches; p Conclusion: We did not find an association between umbilical cord blood vitamin D concentrations and telomere length. Instead, our findings suggest an interaction between race and umbilical cord blood vitamin D on telomere length. Further research is warranted to understand whether the effect of in utero exposure to vitamin D concentration on telomere length can inform the underlying mechanisms that are associated with cancer disparities in adulthood. Citation Format: Tanya Agurs-Collins, John Barber, Jessica Bienstock, Paige Green, Christopher Heaphy, Jiayun Lu, Alan Meeker, Anthony Rizzo, Sabine Rohrmann, Elizabeth Platz. Racial variation in umbilical cord blood vitamin D concentrations and telomere length: Implications for cancer risk [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C027.
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- 2020
56. Periodontal Disease Assessed Using Clinical Dental Measurements and Cancer Risk in the ARIC Study
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James D. Beck, Elizabeth A. Platz, Jiayun Lu, Corinne E. Joshu, Steven Offenbacher, Dominique S. Michaud, Alexandra Y Peacock-Villada, Anna E. Prizment, and John R. Barber
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Male ,Cancer Research ,medicine.medical_specialty ,Black People ,Severe periodontitis ,Severity of Illness Index ,White People ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Neoplasms ,medicine ,Humans ,Lung cancer ,Periodontitis ,Periodontal Diseases ,Aged ,Cancer Death Rate ,business.industry ,Diagnosis, Oral ,Age Factors ,Cancer ,Articles ,030206 dentistry ,Middle Aged ,medicine.disease ,Oncology ,Clinical attachment loss ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Cohort study ,Follow-Up Studies - Abstract
Background While evidence is increasingly consistent with a positive association between periodontitis and cancer risk, most studies have relied on self-reported periodontitis. In this study, we prospectively evaluated the association of periodontal disease severity with cancer risk in black and white older adults in a cohort study that included a dental examination. Methods Included were 7466 participants in the Atherosclerosis Risk in Communities study cohort who at visit 4 (1996-1998) reported being edentulous or underwent the dental examination. Probing depth and gingival recession were measured at six sites on all teeth; these measurements were used to define periodontal disease severity. Incident cancers (n = 1648) and cancer deaths (n = 547) were ascertained during a median of 14.7 years of follow-up. All statistical tests were two-sided. Results An increased risk of total cancer (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 1.07 to 1.44, Ptrend = .004) was observed for severe periodontitis (>30% of sites with attachment loss >3 mm) compared with no/mild periodontitis ( 3 mm), adjusting for smoking and other factors. Strong associations were observed for lung cancer (HR = 2.33, 95% CI = 1.51 to 3.60, Ptrend < .001), and elevated risks were noted for colorectal cancer for severe periodontitis, which were significant among never smokers (HR = 2.12, 95% CI = 1.00 to 4.47). Associations were generally weaker, or not apparent among black participants, except for lung and colorectal cancers, where associations were similar by race. No associations were observed for breast, prostate, or hematopoietic and lymphatic cancer risk. Conclusions This study provides additional evidence that cancer risk, especially for lung and colorectal cancer, is elevated in individuals with periodontitis. Additional research is needed to understand cancer site-specific and racial differences in findings.
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- 2017
57. Field Experiments of Hyporheic Flow Affected by a Clay Lens
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Jiayun Lu, wei qin, Chengpeng Lu, and Congcong Yao
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clay lens ,lcsh:TD201-500 ,lcsh:Hydraulic engineering ,Field (physics) ,Geography, Planning and Development ,Flow (psychology) ,Lens (geology) ,Sediment ,Flux ,Soil science ,Aquatic Science ,Biochemistry ,heat tracing ,field experiments ,lcsh:Water supply for domestic and industrial purposes ,Flow velocity ,lcsh:TC1-978 ,hyporheic flow ,Surface water ,Groundwater ,Geology ,Water Science and Technology - Abstract
As a typical water exchange of surface water and groundwater, hyporheic flow widely exists in streambeds and is significantly affected by the characteristics of sediment and surface water. In this study, a low-permeability clay lens was chosen to investigate the influence of the streambed heterogeneity on the hyporheic flow at a river section of the Xin&rsquo, an River in Anhui Province, China. A 2D sand tank was constructed to simulate the natural streambed including a clay lens under different velocity of surface water velocity. Heat tracing was used in this study. In particular, six analytical solutions based on the amplitude ratio and phase shift of temperatures were applied to calculate the vertical hyporheic flux. The results of the six methods ranged from &minus, 102.4 to 137.5 m/day and showed significant spatial differences. In view of the robustness of the calculations and the rationality of the results, the amplitude ratio method was much better than the phase shift method. The existence of the clay lens had a significant influence on the hyporheic flow. Results shows that the vertical hyporheic flux in the model containing a clay lens was lower than that for the blank control, and the discrepancy of the hyporheic flow field on both sides of the lens was obvious. Several abnormal flow velocity zones appeared around the clay lens where the local hyporheic flow was suppressed or generally enhanced. The hyporheic flow fields at three test points had mild changes when the lens was placed in a shallow layer of the model, indicating that the surface water velocity only affect the hyporheic flow slightly. With the increasing depth of the clay lens, the patterns of the hyporheic flow fields at all test points were very close to those of the hyporheic flow field without a clay lens, indicating that the influence of surface water velocity on hyporheic flow appeared gradually. A probable maximum depth of the clay lens was 30 to 40 cm, which approached the bottom of the model and a clay lens buried lower than this maximum would not affect the hyporheic flow any more. Influenced by the clay lens, hyporheic flow was hindered or enhanced in different regions of streambed, which was also depended on the depth of lens and surface water velocity. Introducing a two-dimensional sand tank model in a field test is an attempt to simulate a natural streambed and may positively influence research on hyporheic flow.
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- 2019
58. High Extratumoral Mast Cell Counts Are Associated with a Higher Risk of Adverse Prostate Cancer Outcomes.
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Sullivan, Heidi Hempel, Heaphy, Christopher M., Kulac, Ibrahim, Cuka, Nathan, Jiayun Lu, Barber, John R., De Marzo, Angelo M., Lotan, Tamara L., Joshu, Corinne E., and Sfanos, Karen S.
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Background: Given our previous findings that low intratumoral and high extratumoral mast cell numbers are associated with higher risk of biochemical recurrence after radical prostatectomy, we now assessed this relationship with race and the development of metastases. Methods: We stained for mast cell tryptase via IHC and fluorescent immunolabeling in 885 men across multiple tissue microarray sets designed to assess biomarkers in association with race and prostate cancer outcomes (median follow-up, 7.0 years). Results: Intratumoral and extratumoral mast cell counts were significantly lower in tissues from African-American compared with European-American men, but not within strata of cancer grade. There was no association between mast cell counts and ERG positivity, PTEN loss, or TP53 missense mutation. Higher minimum extratumoral mast cells were associated with an increased risk of biochemical recurrence [comparing highest with lowest tertiles: HR, 1.61; 95% confidence interval (CI), 1.12-2.29; P trend = 0.01]; this pattern was similar among European-American and African-American men and by grade of disease. There was no significant association between minimum intratumoral mast cell count and biochemical recurrence, overall or within strata of race and grade. Finally, high minimum number of extratumoral mast cells was associated with prostate cancer metastases (comparing highest with lowest tertiles: HR, 2.12; 95% CI, 1.24-3.63; P trend = 0.01). Conclusions: High extratumoral mast cell numbers are associated with biochemical recurrence and the development of metastases after radical prostatectomy. Impact: Higher numbers of benign tissue mast cells are associated with a higher risk of adverse outcomes after radical prostatectomy, including metastatic prostate cancer. [ABSTRACT FROM AUTHOR]
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- 2020
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59. A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis
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Li Chai, Xiaopan Yao, Ping Tang, Ailing Li, Donna Neuberg, Chong Gao, Gang Huang, Ha-Won Jeong, Youyang Yang, Daniel G. Tenen, Jiayun Lu, and Bee Hui Liu
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Myeloid ,Carcinogenesis ,Gene Expression ,Mice, Transgenic ,Mice, SCID ,Biology ,medicine.disease_cause ,Mice ,Downregulation and upregulation ,Mice, Inbred NOD ,SALL4 ,hemic and lymphatic diseases ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Protein Isoforms ,Promoter Regions, Genetic ,neoplasms ,Homeodomain Proteins ,Binding Sites ,Base Sequence ,Gene Expression Regulation, Leukemic ,HEK 293 cells ,Myeloid leukemia ,Histone-Lysine N-Methyltransferase ,General Medicine ,Hematopoietic Stem Cells ,medicine.disease ,eye diseases ,Up-Regulation ,Leukemia, Myeloid, Acute ,Leukemia ,HEK293 Cells ,medicine.anatomical_structure ,Cancer research ,Myeloid-Lymphoid Leukemia Protein ,Neoplasm Transplantation ,Research Article ,Protein Binding ,Signal Transduction ,Transcription Factors - Abstract
The embryonic self-renewal factor SALL4 has been implicated in the development of human acute myeloid leukemia (AML). Transgenic mice expressing the human SALL4B allele develop AML, which indicates that this molecule contributes to leukemia development and maintenance. However, the underlying mechanism of SALL4-dependent AML progression is unknown. Using SALL4B transgenic mice, we observed that HoxA9 was significantly upregulated in SALL4B leukemic cells compared with wild-type controls. Downregulation of HoxA9 in SALL4B leukemic cells led to decreased replating capacity in vitro and delayed AML development in recipient mice. In primary human AML cells, downregulation of SALL4 led to decreased HOXA9 expression and enhanced apoptosis. We found that SALL4 bound a specific region of the HOXA9 promoter in leukemic cells. SALL4 overexpression led to enhanced binding of histone activation markers at the HOXA9 promoter region, as well as increased HOXA9 expression in these cells. Furthermore, we observed that SALL4 interacted with mixed-lineage leukemia (MLL) and co-occupied the HOXA9 promoter region with MLL in AML leukemic cells, which suggests that a SALL4/MLL pathway may control HOXA9 expression. In summary, our findings revealed a molecular mechanism for SALL4 function in leukemogenesis and suggest that targeting of the SALL4/MLL/HOXA9 pathway would be an innovative approach in treating AML.
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- 2013
60. Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment
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Beatrice Winkel, César Nombela-Arrieta, Gregory Pivarnik, Jiayun Lu, Alexei Protopopov, Kimberly J. Canty, Leslie E. Silberstein, Shin-Young Park, Brendan A.C. Harley, and John E. Mahoney
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Quantitative imaging ,Hematopoietic stem cell niche ,Biology ,Article ,Colony-Forming Units Assay ,Mice ,Bone Marrow ,Image Processing, Computer-Assisted ,medicine ,Animals ,Pimonidazole ,Femur ,Progenitor cell ,Stem Cell Factor ,Cell Cycle ,Cell Biology ,Cell cycle ,Flow Cytometry ,Hematopoietic Stem Cells ,Hypoxia-Inducible Factor 1, alpha Subunit ,Cell Hypoxia ,Cell biology ,Mice, Inbred C57BL ,Haematopoiesis ,Ki-67 Antigen ,medicine.anatomical_structure ,Cellular Microenvironment ,Microscopy, Fluorescence ,Nitroimidazoles ,Bone marrow ,Cytometry ,Spleen - Abstract
The existence of a haematopoietic stem cell niche as a spatially confined regulatory entity relies on the notion that haematopoietic stem and progenitor cells (HSPCs) are strategically positioned in unique bone marrow microenvironments with defined anatomical and functional features. Here, we employ a powerful imaging cytometry platform to perform a comprehensive quantitative analysis of HSPC distribution in bone marrow cavities of femoral bones. We find that HSPCs preferentially localize in endosteal zones, where most closely interact with sinusoidal and non-sinusoidal bone marrow microvessels, which form a distinctive circulatory system. In situ tissue analysis reveals that HSPCs exhibit a hypoxic profile, defined by strong retention of pimonidazole and expression of HIF-1α, regardless of localization throughout the bone marrow, adjacency to vascular structures or cell-cycle status. These studies argue that the characteristic hypoxic state of HSPCs is not solely the result of a minimally oxygenated niche but may be partially regulated by cell-specific mechanisms.
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- 2013
61. Abstract 3620: Histopathological associations with PTEN and ERG status in prostate biopsies from men treated with radiation
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Phuoc T. Tran, Jessica L. Hicks, Danny Y. Song, Elizabeth A. Platz, Onur Ertunc, Amol Narang, Angelo M. De Marzo, Mark C. Markowski, Jiayun Lu, and T.L. DeWeese
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Cancer Research ,Pathology ,medicine.medical_specialty ,medicine.anatomical_structure ,Oncology ,biology ,business.industry ,Prostate ,biology.protein ,Medicine ,PTEN ,business ,Erg - Abstract
Loss of the PTEN tumor suppressor gene in prostate cancer, which usually occurs by genomic deletion, is associated with adverse outcome. Recent work (PMID:23888040) suggested that PTEN activity is also required for maintaining genomic integrity and its loss may be associated with resistance to DNA damaging agents, such as ionizing radiation. We assembled a series of patients with intermediate to high grade clinically localized prostate cancer who underwent external beam radiation as their primary treatment. We obtained and regraded all positive biopsy cores according the the new Grade Grouping system for Gleason scores (PMID: 26492179) and performed analytically and clinically validated IHC assays for PTEN (associated with PTEN genomic alterations) and ERG (associated with the TMPRSS2-ERG gene fusion) on all positive tissue cores from a given biopsy that were contained in up to 5 separate FFPE blocks (n=589 positive cores, n positive cores ranged from 1 to 13, with median of 2 and mean of 3) from 193 patients. PTEN and ERG status were correlated with the new Grade Groups as well as other histopathological features, including the presence of cribriform architecture and intraductal carcinoma. Patients were 66% White, and 27% African American, and median age was 68.5. Grade Group designations (taken as the highest Grade group in the case) were as follows (Group 1 = 27%, Group 2 = 30%, Group 3= 15%, Group 4 = 18%, Group 5 = 11%). Overall there was at least some PTEN loss in 36% of cases. The presence of any PTEN loss in a given case was strongly associated with Grade Group (P Citation Format: Onur Ertunc, Mark Markowski, Phuoc T. Tran, Amol Narang, Jessica Hicks, Daniel Song, Jiayun Lu, Elizabeth A. Platz, Theodore Deweese, Angelo M. De Marzo. Histopathological associations with PTEN and ERG status in prostate biopsies from men treated with radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3620.
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- 2018
62. Adapter Protein SH2B1β Cross-Links Actin Filaments and Regulates Actin Cytoskeleton
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Leah Rider, Jiayun Lu, Brittany Brinley, Maria Diakonova, Jing Tao, and Stacy Snyder
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Arp2/3 complex ,macromolecular substances ,Biology ,Article ,Mice ,Actin remodeling of neurons ,Endocrinology ,Cell Movement ,Animals ,Humans ,Protein Isoforms ,Pseudopodia ,Actin-binding protein ,Molecular Biology ,Cells, Cultured ,Cytoskeleton ,Adaptor Proteins, Signal Transducing ,Mice, Knockout ,Microvilli ,Microfilament Proteins ,Actin remodeling ,General Medicine ,Janus Kinase 2 ,Phosphoproteins ,Actin cytoskeleton ,Actins ,Cell biology ,biology.protein ,Mutant Proteins ,MDia1 ,Protein Multimerization ,Lamellipodium ,Cell Adhesion Molecules ,Filopodia ,Protein Binding - Abstract
The Src homology 2 (SH2) domain-containing adapter protein SH2B1beta plays a role in severe obesity, leptin and insulin resistance, and infertility. SH2B1beta was initially identified as a Janus tyrosine kinase 2 (JAK2) substrate, and it has been implicated in cell motility and regulation of the actin rearrangement in response to GH and platelet-derived growth factor. SH2B1beta is also required for maximal actin-based motility of Listeria. Here we have used a low-speed pelleting assay and electron microscopy to demonstrate that SH2B1beta has two actin-binding sites and that it cross-links actin filaments in vitro. Wild-type SH2B1beta localized to cell ruffles and along filopodia, but deletion of amino acids 150-200 (the first actin-binding site) led to mislocalization of the protein to filopodia tip complexes where it colocalized with vasodilator-stimulated phosphoprotein (VASP). Based on studies performed in VASP-deficient MVD7(-/-) cells, with or without green fluorescent protein-VASP reconstitution, we concluded that the proper intracellular localization of native SH2B1beta required the presence of the first SH2B1beta actin-binding site and VASP. Finally, we found that both SH2B1beta actin-binding domains were required for maximal GH- and prolactin-induced cell ruffling. Together, these results suggest that SH2B1beta functions as an adapter protein that cross-links actin filaments, leading to modulation of cellular responses in response to JAK2 activation.
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- 2009
63. Leukemic survival factor SALL4 contributes to defective DNA damage repair
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Lars U Müller, Fei Wang, Chong Gao, Hiro Tatetsu, David A. Williams, Wei Cui, Li Chai, and Jiayun Lu
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0301 basic medicine ,Male ,Cancer Research ,DNA End-Joining Repair ,DNA Repair ,Fancl ,Gene Expression ,Mice ,Fanconi anemia ,hemic and lymphatic diseases ,Cluster Analysis ,FANCL ,Homologous Recombination ,Bone Marrow Transplantation ,SALL4 ,Fanconi Anemia Complementation Group D2 Protein ,Cell cycle ,3. Good health ,DNA-Binding Proteins ,Leukemia, Myeloid, Acute ,Female ,Bcl2 ,DNA repair ,DNA damage ,Mitomycin ,Karyotype ,Fanconi Anemia Complementation Group L Protein ,Bone Marrow Cells ,Mice, Transgenic ,Biology ,Article ,03 medical and health sciences ,Chromosomal Instability ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Myelodysplastic syndromes ,Gene Expression Profiling ,medicine.disease ,Hematopoietic Stem Cells ,Molecular biology ,eye diseases ,Genes, bcl-2 ,Disease Models, Animal ,030104 developmental biology ,Gene Expression Regulation ,Myelodysplastic Syndromes ,Homologous recombination ,DNA Damage ,Transcription Factors - Abstract
SALL4 is aberrantly expressed in human myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We have generated a SALL4 transgenic (SALL4B Tg) mouse model with pre-leukemic MDS-like symptoms that transform to AML over time. This makes our mouse model applicable for studying human MDS/AML diseases. Characterization of the leukemic initiation population in this model leads to the discovery that Fancl (Fanconi anemia, complementation group L) is down-regulated in SALL4B Tg leukemic and pre-leukemic cells. Similar to the reported Fanconi anemia (FA) mouse model, chromosomal instability with radial changes that can be detected in pre-leukemic SALL4B Tg bone marrow (BM) cells after DNA damage challenge. Results from additional studies using DNA damage repair reporter assays support a role of SALL4 in inhibiting the homologous recombination pathway. Intriguingly, unlike the FA mouse model, after DNA damage challenge, SALL4B Tg BM cells can survive and generate hematopoietic colonies. We further elucidated that the mechanism by which SALL4 promotes cell survival is through Bcl2 activation. Overall, our studies demonstrate for the first time that SALL4 has a negative impact in DNA damage repair, and support the model of dual functional properties of SALL4 in leukemogenesis through inhibiting DNA damage repair and promoting cell survival.
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- 2015
64. CASK and its target gene Reelin were co-upregulated in human esophageal carcinoma
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Jiayun Lu, Yuntian Sun, Lu Cheng, Gengxi Hu, Min Wu, Xiuqin Wang, Qun Wang, Zhihua Liu, Cuihong Yang, and Xun Zhang
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Cancer Research ,Esophageal Neoplasms ,Cell Adhesion Molecules, Neuronal ,Blotting, Western ,Nerve Tissue Proteins ,Immunoenzyme Techniques ,Stomach Neoplasms ,Gene expression ,Carcinoma ,medicine ,Humans ,RNA, Messenger ,Reelin ,CASK ,Extracellular Matrix Proteins ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Serine Endopeptidases ,medicine.disease ,Molecular biology ,Up-Regulation ,Blot ,Reverse transcription polymerase chain reaction ,Reelin Protein ,nervous system ,Oncology ,Suppression subtractive hybridization ,Calcium-Calmodulin-Dependent Protein Kinases ,Colonic Neoplasms ,Carcinoma, Squamous Cell ,Cancer research ,biology.protein ,Immunohistochemistry ,Nucleoside-Phosphate Kinase ,Guanylate Kinases - Abstract
Calcium/calmodulin-dependent serine protein kinase (CASK) showed overexpression in human esophageal carcinoma by suppression subtractive hybridization. The upregulation of CASK gene and its target gene Reelin in human esophageal carcinoma tissues versus corresponding normal tissues was revealed by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry or Western blot. Moreover, RT-PCR results indicated that the expression patterns of CASK and Reelin in human gastric carcinoma and colon carcinoma were different with those in esophageal carcinoma. Therefore, it suggested that CASK and Reelin were associated with tumorigenesis of esophagus and they were co-upregulated in human esophageal carcinoma.
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- 2002
65. Dissecting the role of SALL4, a newly identified stem cell factor, in chronic myelogenous leukemia
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Daniela S. Krause, Nikki R. Kong, Leslie E. Silberstein, Jiayun Lu, Yupo Ma, Zaida Alipio, Li Chai, and Chong Gao
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Cancer Research ,Myeloid ,Myeloid leukemia ,Stem cell factor ,Hematology ,CD38 ,Biology ,medicine.disease ,eye diseases ,Leukemia ,medicine.anatomical_structure ,Oncology ,hemic and lymphatic diseases ,Immunology ,medicine ,Cancer research ,Bone marrow ,Progenitor cell ,Chronic myelogenous leukemia - Abstract
Chronic myelogenous leukemia (CML) is a hematological malignancy that expresses the BCR-ABL fusion oncogene. It has three distinct clinicopathological phases: chronic and accelerated phase and blast crisis. Tyrosine kinase inhibitors, which target the BCR-ABL fusion protein, can induce complete cytogenic remission (CCR) in more than 70% of newly diagnosed chronic CML patients. However, complete molecular response is a rare event in these CML patients with CCR, suggesting that they are not effective in eliminating CML leukemia initiating cells (LIC), although there are differences between the trosine kinase inhibitors. Once CML progresses to blast crisis, it becomes resistant to most treatment approaches, and survival rapidly declines. The exact underlying mechanism of transformation of chronic phase CML to blast crisis is still unclear; however, it is thought to be supported by self-renewing LIC. Therefore, identifying genes or signaling pathways involved in the self-renewal of LIC may promote more effective leukemia treatments. So far, two key regulators in self-renewal of LIC have been linked to CML progression, Wnt/β-catenin and Bmi-1(1–4). Recently, several research groups, including ours, have demonstrated that SALL4 plays an essential role in the maintenance of pluripotent and self-renewal properties of embryonic stem cells (ESC) by interacting with Nanog and Oct4 (5). In addition, our group has shown that constitutive expression of SALL4 contributes to leukemogenesis in adult mice by interacting with two other key regulators in LIC, Wnt/β-catenin and Bmi-1 (6, 7). It appears that SALL4 is a unique gene involved in self-renewal in ESC and LIC. Therefore, we examined SALL4 expression in CML to determine whether it could be involved in the pathogenesis of this disease. Using immunohistochemistry staining, we observed that SALL4 expression was present in blast-crisis CML (9/12, 75%) but not in chronic phase (0/11, 10%). In accelerated phase (1/6, 16.7%), wherein the blast count was 10–19%, immature blasts expressing SALL4 were observed in a background of negative, more mature myeloid cells (Figure 1A). Similar results were observed when we performed FACS analysis on whole bone marrow cells from normal human and CML samples at different disease phases using a conjugated SALL4 antibody (Figure 1B). No SALL4 positive population was detectable in normal whole bone marrow or chronic phase CML samples. A distinct SALL4 positive population was present in accelerated phase and blast crisis CML marrows, which correlated well with the blast count and overlapped with the CD34+ population. The CD34+CD38+ cells had the highest SALL4 RNA expression when tested by qRT-PCR (Figure 1C and Supplemental Table 1). This finding is of particular interest since Granulocyte-Macrophage Progenitors, which are CD34+CD38+, have been proposed as candidate LIC in CML, that transforms to acute myeloid leukemia (AML)(1). Figure 1 SALL4 expression correlates with disease progression of human CML To explore the role of SALL4 in CML, we first tested whether overexpression of SALL4B could block myeloid differentiation and cooperate with BCR-ABL in, consequently, promoting blastic transformation of chronic phase CML. For induction of CML-like leukemia, we harvested bone marrow cells from SALL4B transgenic and wild-type donor mice 4 days post intravenous administration of 200 mg per kg (body weight) 5-fluorouracil (5-FU), transduced with BCR-ABL-GFP retrovirus as described (8), and injected 4×105 cells intravenously into sublethally irradiated (750cGy) C57BL/6 recipients. Slightly sublethal irradiation in this mouse model has been shown not to inhibit induction of CML-like disease. Both, recipients of BCR-ABL induced SALL4B transgenic and wild-type bone marrow, succumbed to fatal CML-like leukemia within 3–6 weeks with increased WBC counts (Supplemental Table 2). Flow cytometry analysis demonstrated that 80% of BCR-ABL-positive bone marrow cells from both groups were Mac1+and Gr-1+ neutrophils (Supplemental Figure 1A). In addition, the percentage of CD34+ or c-Kit BCR-ABL-positive cells from bone marrow and spleen increased about 2- and 3-fold in leukemic SALL4B transgenic recipients compared to wild-type counterparts (Supplemental Figure 1B and 1C and data not shown). This suggests that BCR-ABL- transduced SALL4B leukemic cells were more immature and less differentiated. We next investigated the functional role of SALL4 in CML progression using a loss-of-function approach by knocking down SALL4 expression in the human CML cell line KBM5. Two shRNA retroviral constructs targeting different regions of the SALL4 mRNA as we previously reported (6), were shown by qRT-PCR to reduce SALL4 and Bmi-1 mRNA level in KBM5 cells (Figure. 2A). Figure 2 SALL4 expression is essential for CML cell survival The KBM5 cells expressing reduced levels of SALL4 grew slowly. To better explain this phenomenon, we measured the level of caspase-3, which is a marker for the apoptosis signaling pathway. In KBM5 cells that retained 50% of the wild–type (WT) levels of SALL4, there was a 3-fold increase of caspase-3 activity from 27.9 % in WT cells to 93.6% in cells with reduced SALL4 levels as measured by FACS (Figure 2B). We have previously shown that Bmi-1 is a major downstream target of SALL4 in leukemic cells (6). To determine if overexpression of Bmi-1 could rescue SALL4-induced apoptosis, we transfected SALL4 shRNA treated KBM5 cells with an expression vector containing Bmi-1. As shown in figure 2B, SALL4-induced caspase-3 activity (Fig. 2B-ii) was restored to a near normal level by overexpression of Bmi-1 (Fig. 2B-iii). To further study the role of SALL4 in cell growth in a leukemic cell line, we monitored cell-cycle changes and cellular DNA synthesis in SALL4-reduced and WT KBM5 cells using the BrdU incorporation assay by FACS. A 50% reduction of SALL4 expression level in KBM5 cells resulted in G0/G1 phase (37.8%) and G2 phase (21.7%) arrests (Fig 2C-ii). A more than two-fold decrease in S phase cells was also observed, paralleling the drop in DNA synthesis measured by the level of BrdU incorporation. In contrast, no significant change in the cell-cycle profile was observed when WT- KBM5 cells were infected with control viruses (Fig. 2C-i). Reintroduction of Bmi-1 in SALL4-reduced KBM5 cells can rescue this phenotype (Fig. 2C-iii). Our data suggest that the stem cell factor SALL4 plays an important role in the proliferation and survival of CML cells, and its expression is associated with an advanced stage of CML disease. The mechanism of SALL4-mediated proliferation and survival of CML cells, at least in part, is mediated by the Bmi-1 pathway. In support of this concept, downregulation of SALL4 leads to apoptosis and cell cycle arrest in CML cells, which is rescued by restoring its downstream target gene Bmi-1. This finding suggests that targeting SALL4 may provide a novel therapeutic modality for advanced-stage CML disease.
- Published
- 2011
66. Aberrant expression of SALL4 in acute B cell lymphoblastic leukemia: Mechanism, function, and implication for a potential novel therapeutic target
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XiaoXian Zhang, Jiayun Lu, Ailing Li, Li Chai, Jerome Ritz, Jie He, Leslie E. Silberstein, and Shikiko Ueno
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Male ,Cancer Research ,Cell Survival ,Cellular differentiation ,Stem cell factor ,Biology ,Article ,RNA interference ,Cell Line, Tumor ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Gene expression ,Genetics ,Humans ,Molecular Biology ,Gene knockdown ,Cell growth ,Gene Expression Regulation, Leukemic ,Cell Biology ,Hematology ,DNA, Neoplasm ,DNA Methylation ,eye diseases ,Neoplasm Proteins ,Cell culture ,Caspases ,Gene Knockdown Techniques ,DNA methylation ,Cancer research ,Female ,Transcription Factors - Abstract
Treatment for high-risk pediatric and adult acute B cell lymphoblastic leukemia (B-ALL) remains challenging. Exploring novel pathways in B-ALL could lead to new therapy. Our previous study has shown that stem cell factor SALL4 is aberrantly expressed in B-ALL, but its functional roles and the mechanism that accounts for its upregulation in B-ALL remain unexplored. To address this question, we first surveyed the existing B-ALL cell lines and primary patient samples for SALL4 expression. We then selected the B-ALL cell lines with the highest SALL4 expression for functional studies. RNA interference was used to downregulate SALL4 expression in these cell lines. When compared with control cells, SALL4 knockdown cells exhibited decreased cell proliferation, increased apoptosis in vitro, and decreased engraftment in a xenotransplant model in vivo. Gene expression analysis showed that in SALL4 knockdown B-ALL cells, multiple caspase members involved in cell apoptosis pathway were upregulated. Next, we explored the mechanisms of aberrant SALL4 expression in B-ALL. We found that hypomethylation of the SALL4 CpG islands was correlated with its high expression. Furthermore, treatment of low SALL4-expressing B-ALL cell lines with DNA methylation inhibitor led to demethylation of the SALL4 CpG and increased SALL4 expression. In summary, to our knowledge, we are the first to show that the aberrant expression of SALL4 in B-ALL is associated with hypomethylation, and that SALL4 plays a key role in B-ALL cell survival and could be a potential novel target in B-ALL treatment.
- Published
- 2014
67. Gene expression profile changes in initiation and progression of squamous cell carcinoma of esophagus
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Momiao Xiong, Qun Wang, Chuannong Zhou, Xiuqin Wang, Zhihua Liu, Min Wu, Zongliang Qiu, Jiayun Lu, Guanrui Yang, and Liqun Zhao
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Mild Dysplasia ,Cancer Research ,Pathology ,medicine.medical_specialty ,Esophageal Neoplasms ,Carcinoma in situ ,Biology ,medicine.disease_cause ,medicine.disease ,Immunohistochemistry ,Polymerase Chain Reaction ,Gene Expression Regulation, Neoplastic ,Oncology ,Epidermoid carcinoma ,Dysplasia ,Tumor progression ,Carcinoma, Squamous Cell ,medicine ,Gene chip analysis ,Humans ,Carcinogenesis ,Precancerous Conditions ,Carcinoma in Situ ,Moderate Dysplasia - Abstract
Tumorigenesis is a complex process involving multiple genes. As a step toward understanding the complicated changes between normal and malignant cells, this report focused on gene expression profile variations among normal and abnormal esophageal epithelium tissues. The cDNA microarray approach was used to investigate gene expression profiles of 5 different stages during initiation and progression of esophageal cancer. According to pathological characteristics, these 5 stages were normal, dysplasia I (mild dysplasia), dysplasia II (moderate dysplasia), carcinoma in situ (CIS) and squamous cell carcinoma of esophagus (SCC). Comparing and analyzing those gene expression profiles, we observed that the expression levels of many genes changed in dysplasia I and some known tumor-related genes were over-expressed or under-expressed in all 4 abnormal stages. Using principle component analysis we identified a set of genes that may play an important role in tumor development. Hybridization data were confirmed by semi-quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. These results suggest that cDNA microarray technology is a useful tool to discover genes frequently involved in esophageal neoplasia and provides novel clues to diagnosis, early detection and intervention of SCC.
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- 2001
68. Studying the micromechanism of water injection to suppress coal and gas protrusion
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Jiayun Lun, Haoliang Han, Xinliang Fang, Junling Ding, and Nan Jia
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Physics ,QC1-999 - Abstract
To explore the adsorption mechanism of CH4 and H2O molecules on the surface of low-rank coal (LRC) from the microscopic point of view, the electrostatic potential and frontier orbitals of each oxygen-containing functional group (OFGs) in LRC and adsorbent molecule, the adsorption energy, and Mulliken charge layout of CH4 molecules and H2O molecules with OFGs in LRC were investigated by density functional theory (DFT) simulation method. The results of DFT calculations showed that the order of adsorption strength of CH4 molecules on different OFGs was OCH3–LRC (-9.643 kJ/mol) > C=O–LRC (−8.625 kJ/mol) > OH–LRC (−7.241 kJ/mol) > COOH–LRC (−6.194 kJ/mol), which were all smaller than that of the C–LRC model without functionalization (−10.749 kJ/mol). The presence of OFGs reduces the adsorption strength of CH4 molecules on the surface of LRC. The order of strength of adsorption of H2O molecules on different OFGs was COOH–LRC (−69.836 kJ/mol) > OH−LRC (−46.442 kJ/mol) > C=O–LRC (−42.848 kJ/mol) > OCH3–LRC (−33.079 kJ/mol), and they were all greater than that of the C–LRC model without functionalization (−32.572 kJ/mol). The presence of OFGs improves the adsorption strength of H2O molecules on the surface of LRC. Both the LRC model modified with OFGs and the non-functionalized C–LRC model showed stronger adsorption of H2O molecules compared to that of CH4 molecules. Therefore, coal seam water injection can reduce the amount of gas gushing and mitigate coal seam gas protrusion.
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- 2022
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69. Phytophthora spp. associated with the decline of Cedrus deodara in Nanjing, China
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Ho, H. H., Jiayun, Lu, and Longyin, Gong
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- 1984
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70. Fak depletion in both hematopoietic and nonhematopoietic niche cells leads to hematopoietic stem cell expansion
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Yan Sun, Shin-Young Park, Jiayun Lu, Hongbo R. Luo, Carl R. Walkley, Leslie E. Silberstein, Karrie P. Du, Li Chai, and César Nombela-Arrieta
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Cancer Research ,Cell type ,Stromal cell ,Cell Communication ,Cell Separation ,Biology ,Article ,Colony-Forming Units Assay ,Mice ,Animals, Congenic ,Genes, Reporter ,Genetics ,medicine ,Animals ,Homeostasis ,Cell Lineage ,Progenitor cell ,Stem Cell Niche ,Molecular Biology ,Bone Marrow Transplantation ,Mice, Knockout ,Cell Cycle ,Hematopoietic stem cell ,Cell Biology ,Hematology ,Flow Cytometry ,Hematopoietic Stem Cells ,Antigens, Differentiation ,Cell biology ,Hematopoiesis ,Transplantation ,Mice, Inbred C57BL ,Haematopoiesis ,medicine.anatomical_structure ,Focal Adhesion Kinase 1 ,Radiation Chimera ,Bone marrow ,Stem cell ,Stromal Cells - Abstract
Hematopoietic stem cells (HSCs) reside in complex bone marrow microenvironments, where niche-induced signals regulate hematopoiesis. Focal adhesion kinase (Fak) is a nonreceptor protein tyrosine kinase that plays an essential role in many cell types, where its activation controls adhesion, motility, and survival. Fak expression is relatively increased in HSCs compared to progenitors and mature blood cells. Therefore, we explored its role in HSC homeostasis. We have used the Mx1-Cre-inducible conditional knockout mouse model to investigate the effects of Fak deletion in bone marrow compartments. The total number as well as the fraction of cycling Lin(-)Sca-1(+)c-kit(+) (LSK) cells is increased in Fak(-/-) mice compared to controls, while hematopoietic progenitors and mature blood cells are unaffected. Bone marrow cells from Fak(-/-) mice exhibit enhanced, long-term (i.e., 20-week duration) engraftment in competitive transplantation assays. Intrinsic Fak function was assessed in serial transplantation assays, which showed that HSCs (Lin(-)Sca-1(+)c-kit(+)CD34(-)Flk-2(-) cells) sorted from Fak(-/-) mice have similar self-renewal and engraftment ability on a per-cell basis as wild-type HSCs. When Fak deletion is induced after engraftment of Fak(fl/fl)Mx1-Cre(+) bone marrow cells into wild-type recipient mice, the number of LSKs is unchanged. In conclusion, Fak inactivation does not intrinsically regulate HSC behavior and is not essential for steady-state hematopoiesis. However, widespread Fak inactivation in the hematopoietic system induces an increased and activated HSC pool size, potentially as a result of altered reciprocal interactions between HSCs and their microenvironment.
- Published
- 2012
71. Influence of nano zinc oxide treated by HMDS in humidity detection
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Quansheng Jiang, Jiayun Lu, and Jian Zhang
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Reproducibility ,Materials science ,technology, industry, and agriculture ,food and beverages ,Humidity ,chemistry.chemical_element ,Quartz crystal microbalance ,Zinc ,humanities ,chemistry ,Chemical engineering ,Electrode ,Relative humidity ,Selectivity ,Absorption (electromagnetic radiation) - Abstract
QCM-based gas sensors are potential for applications due to its simple structure and high sensitivity. But the low selectivity attributed to the environment factors need to be concerned such as the variations of humidity and volatile organic vapors. In this paper, humidity sensitive properties of HMDS treated nano zinc oxide was researched. The work can be divided into two sections: First, the sensing properties of nano zinc oxide were studied by quartz crystal microbalance (QCM) in relative humidity detection. The results showed that the nano zinc oxide film had high humidity sensitivity and well reproducibility. Second, the humidity sensing properties of nano zinc oxide treated by Hexamethyldisilazane (HMDS) were also investigated. It is found that the humidity sensitivity of nano zinc oxide treated by HMDS was much lower than untreated ZnO, especially in high relative humidity environment. The experiment results indicate that the HMDS treated by nano zinc oxide can be used to detect the ethanol in high humidity environment.
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- 2009
72. FAK silencing inhibits leukemogenesis in BCR/ABL-transformed hematopoietic cells
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Li Chai, Lu-Hong Xu, Jian-Pei Fang, Yi Le, Jiayun Lu, Valentina Nardi, and Leslie E. Silberstein
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Fusion Proteins, bcr-abl ,Apoptosis ,Biology ,Philadelphia chromosome ,medicine.disease_cause ,Small hairpin RNA ,Focal adhesion ,Mice ,hemic and lymphatic diseases ,medicine ,Biomarkers, Tumor ,STAT5 Transcription Factor ,Gene silencing ,Animals ,Humans ,Phosphorylation ,Cell Line, Transformed ,Cell Proliferation ,ABL ,Leukemia ,Cell growth ,breakpoint cluster region ,Hematology ,medicine.disease ,Focal Adhesion Protein-Tyrosine Kinases ,Cancer research ,RNA Interference ,biological phenomena, cell phenomena, and immunity ,Carcinogenesis - Abstract
Focal adhesion kinase (FAK) is constitutively activated and tyrosine phosphorylated in BCR/ABL-transformed hematopoietic cells, but the role it plays during leukemogenesis remains unclear. Here, we examined the effects of RNA interference-mediated FAK silencing on leukemogenesis induced by a BCR/ABL-transformed cell line. Transduction of BCR/ABL-BaF3 cells with FAK shRNA inhibited FAK expression and reduced STAT5 phosphorylation, but induced caspase-3 activation. In vitro studies showed that treatment with FAK shRNA resulted in impaired cell proliferation and colony formation, while increasing cell apoptosis. Mice that received transplants of BCR/ABL-BaF3 cells with FAK shRNA displayed significantly prolonged survival time and diminished leukemia progression. In addition, FAK silencing enhanced in vitro and in vivo efficacy of ABL tyrosine kinase inhibitor imatinib in BCR/ABL-BaF3 cells. Our results suggest that FAK is critical for leukemogenesis and might be a potential target for leukemia therapy.
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- 2009
73. Graph Neural Network for Traffic Forecasting: The Research Progress
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Weiwei Jiang, Jiayun Luo, Miao He, and Weixi Gu
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traffic forecasting ,graph neural network ,graph convolutional network ,graph attention network ,Geography (General) ,G1-922 - Abstract
Traffic forecasting has been regarded as the basis for many intelligent transportation system (ITS) applications, including but not limited to trip planning, road traffic control, and vehicle routing. Various forecasting methods have been proposed in the literature, including statistical models, shallow machine learning models, and deep learning models. Recently, graph neural networks (GNNs) have emerged as state-of-the-art traffic forecasting solutions because they are well suited for traffic systems with graph structures. This survey aims to introduce the research progress on graph neural networks for traffic forecasting and the research trends observed from the most recent studies. Furthermore, this survey summarizes the latest open-source datasets and code resources for sharing with the research community. Finally, research challenges and opportunities are proposed to inspire follow-up research.
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- 2023
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74. Transformation, genomic instability and senescence mediated by platelet/megakaryocyte glycoprotein Ibalpha
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D Cohen, Edward V. Prochownik, Youjun Li, and Jiayun Lu
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Senescence ,Genome instability ,Male ,Cancer Research ,Mice, Nude ,Mitosis ,Biology ,medicine.disease_cause ,Retinoblastoma Protein ,Proto-Oncogene Proteins c-myc ,Mice ,Megakaryocyte ,Chromosomal Instability ,Neoplasms ,Genetics ,medicine ,Animals ,Humans ,Platelet ,Molecular Biology ,Cells, Cultured ,Cellular Senescence ,chemistry.chemical_classification ,Cell Cycle ,Megacaryocyte ,Fibroblasts ,Molecular biology ,Cell biology ,Rats ,Transformation (genetics) ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,chemistry ,Platelet Glycoprotein GPIb-IX Complex ,Female ,Glycoprotein ,Carcinogenesis - Abstract
GpIbalpha, a subunit of the von Willebrand factor receptor, functions during blood clotting to promote platelet adhesion and activation. GpIbalpha is widely expressed, is positively regulated by c-Myc and is essential for the promotion of c-Myc-mediated chromosomal instability. We now show that GpIbalpha is also a classical oncoprotein in which its deregulated expression leads to transformation, reduced growth factor requirements, increased resistance to apoptosis, and, in primary cells, p53-dependent senescence. Finally, GpIbalpha also promotes double-stranded DNA breaks, and induces profound nuclear dysmorphology, indicating that, in addition to its direct transforming function, it displays genotoxicity at several distinct levels. These findings identify novel functions for GpIbalpha and pathways through which c-Myc mediates transformation and global genomic destabilization.
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- 2007
75. Simulation study on adsorption characteristics of lignite to mine gas
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Jiayun Lun, Yinghao Sun, Junling Ding, Huijie Song, and Zhaohong Zhang
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Physics ,QC1-999 - Abstract
This study aims at investigating the adsorption mechanism of CO2, CH4, CO, and N2 mine gases and oxygen-containing functional groups in lignite. Thus, density functional theory and grand canonical Monte Carlo simulation methods were used to determine the adsorption energy, configuration, isotherm, and isosteric heat as well as the diffusion coefficient of gas in lignite. The results showed that the adsorption capacity of CO2 molecules and oxygen-containing functional groups was greater than that of CH4, CO, and N2. The order of the absolute value of the adsorption energy of each oxygen-containing functional group of each gas molecule on the lignite surface model was as follows: carboxyl > hydroxyl > carbonyl > ether bond. The adsorption isotherms of the four gases (CO2, CH4, CO, and N2) in the lignite molecular structure model were consistent with the Langmuir adsorption isotherm model. The relationship between the adsorption amount of the four gases in the lignite structure model was CO2 > CH4 > CO > N2. In addition, the adsorption capacity of the four gases decreased as the temperature increased. The CO2 isosteric heat of adsorption was considerably greater than that of CH4, CO, and N2, indicating that the adsorption capacity of the lignite molecular structure model for CO2 was considerably stronger than that of CH4, CO, and N2. The CO2 diffusion coefficient showed the slowest change with the temperature increase, whereas the N2 self-diffusion coefficient showed the fastest change. The following diffusion activation energy sequence was obtained: CO2 < CH4 < CO < N2.
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- 2022
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76. Sustained reduction of central line–associated bloodstream infections in an intensive care unit using a top-down and bottom-up approach
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Julie E. Mangino, Jiayun Lu, Justin Smyer, Lisa Fawley, Mark E. Lustberg, Elliott D. Crouser, Sheila Chucta, and Madhuri Sopirala
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Infection Control ,medicine.medical_specialty ,Central line ,Epidemiology ,business.industry ,Incidence ,Health Policy ,Public Health, Environmental and Occupational Health ,Intensive care unit ,law.invention ,Hospitals, University ,Reduction (complexity) ,Intensive Care Units ,Infectious Diseases ,law ,Catheter-Related Infections ,Sepsis ,Humans ,Medicine ,Guideline Adherence ,business ,Intensive care medicine - Published
- 2013
77. [Construction and expression of basic fibroblast growth factor mammalian expression vector]
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Qixu, Zhang, Gang, Zhou, Jiayun, Lu, and Zhihua, Liu
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DNA, Complementary ,Eukaryotic Cells ,Tissue Engineering ,Genetic Vectors ,Escherichia coli ,Animals ,Humans ,Fibroblast Growth Factor 2 ,Genetic Therapy ,Transfection ,Recombinant Proteins ,Plasmids - Abstract
To construct a mammalian expression vector of basic fibroblast growth factor (bFGF) and to investigate the expression of bFGF in vitro and in vivo.A mammalian expression vector pcDNA3. 1/ myc-His(-)C-bFGF was constructed with gene cloning technique. The mammalian expression system was prepared and purified. The expression of bFGF cDNA in cultured transfected cells was examined by RT-PCR and cell immunohistochemistry. The recombinant plasmids, pcDNA3. 1/myc-His(-)C-bFGF and pCD2-VEGF121, were transferred into rabbit cervical muscle by direct injection of plasmid following electric pulses in vivo. The transferred gene expression and the biological effect were measured by use of histochemistry and immunohistochemistry analysis.The eukaryon expression system pcDNA3. 1/myc-His (-)C-bFGF could express the target protein bFGF in vitro. The recombinant plasmids, pcDNA3. 1/myc-His(-)C-bFGF and pCD2-VEGF121 were transferred into muscles flap in vivo successfully. The active proteins bFGF and VEGF121 were expressed at high levels. Blood vessels increased significantly in the muscles, and blood circulation was improved by local angiogenesis.The eukaryon expression vector of bFGF is constructed and can be expressed successfully in vitro and in vivo. That is a primary preparation for the research on tissue transplantation and tissue engineering with bFGF gene therapy.
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- 2004
78. The deregulation of arachidonic acid metabolism-related genes in human esophageal squamous cell carcinoma
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Huiying Zhi, Chuannong Zhou, Zhihua Liu, Min Wu, Gengxi Hu, Xiuqin Wang, Jiayun Lu, and Jian Zhang
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Cancer Research ,Esophageal Neoplasms ,Cell ,Blotting, Western ,Down-Regulation ,Biology ,medicine.disease_cause ,Isozyme ,Immunoenzyme Techniques ,Gene expression ,medicine ,Humans ,RNA, Messenger ,RNA, Neoplasm ,DNA Primers ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Arachidonic Acid ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Neoplasm Proteins ,Up-Regulation ,Blot ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Oncology ,Biochemistry ,Epidermoid carcinoma ,Case-Control Studies ,Cancer research ,Carcinoma, Squamous Cell ,Carcinogenesis - Abstract
Esophageal squamous cell carcinoma (ESCC) is 1 of the most common cancers worldwide. In our study, cDNA microarray comprising 14,803 genes was employed to identify gene-specific expression profile in 6 paired samples of ESCC. Nine genes identified were commonly upregulated and 36 downregulated in tumors, as compared to normal esophageal squamous epithelia. Among these genes, we found that 9 of the altered expression genes were related to arachidonic acid (AA) metabolism, such as annexin-I, annexin-II, S100A8, S100A10, S100P, glutathione peroxidase-3, phosphatidylcholine transfer protein, aldo-keto reductase family 1 and cyclooxygenase-2 (COX-2). To gain insights into the regulation of the AA metabolism pathway involved in the carcinogenesis of ESCC, we investigated the expression of 8 genes related to the AA metabolism by semiquantitative reverse transcript (RT)-PCR and/or Western blot and immunohistochemistry. These genes include annexin-I, annexin-II, COX-2, cyclooxygenase-1 (COX-1) and cytosolic phospholipase A(2) (cPLA(2)), 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP) and 12-lipoxygenase (12-LOX) (not included in the array data). The expression level of annexin-I, annexin-II was downregulated in esophageal cancer, whereas cPLA(2), FLAP, COX-2, 5-LOX and 12-LOX were upregulated. These data suggested that AA metabolism pathway and its altered expression may contribute to esophageal squamous cell carcinogenesis.
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- 2003
79. Cloning and characterization of a novel gene EC97 associated with human esophageal squamous cell carcinoma
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Gengxi Hu, Min Wu, Zhihua Liu, Xiuqin Wang, and Jiayun Lu
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Male ,Esophageal Neoplasms ,Sequence analysis ,Molecular Sequence Data ,Vesicular Transport Proteins ,Biology ,law.invention ,law ,Complementary DNA ,Genetics ,Humans ,Amino Acid Sequence ,Northern blot ,Cloning, Molecular ,Gene ,Polymerase chain reaction ,Aged ,Aged, 80 and over ,Expressed sequence tag ,Base Sequence ,DNA, Neoplasm ,Sequence Analysis, DNA ,General Medicine ,Middle Aged ,Molecular biology ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Reverse transcription polymerase chain reaction ,genomic DNA ,Carcinoma, Squamous Cell ,Female - Abstract
We report on the cloning and characterization of a novel gene EC97 which is associated with human esophageal squamous cell carcinoma (ESCC). A fragment of expressed sequence tag (EST) (aa700351) was overexpressed in ESCC tissues compared with the normal tissues in cDNA microarray data. Based on the sequence of aa700351, the full-length cDNA was acquired by polymerase chain reaction (PCR) amplification and named EC97. EC97 was 3353 bp long and its encoding protein contained 813 amino acid residues. Northern blot and reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that EC97 had a transcript of 3.4 kb in most human normal tissues we checked and its expression level was increased in 60% (12/20) of tested ESCC tissues versus the normal counterparts. EC97 was mapped to human chromosome 16p12-16p13.1 using radiation hybridization (RH) and predicted to include 25 exons and disseminated over 100 kb of genomic DNA.
- Published
- 2003
80. Three‐dimensional characterization of open and closed coal nanopores based on a multi‐scale analysis including CO2 adsorption, mercury intrusion, low‐temperature nitrogen adsorption, and small‐angle X‐ray scattering
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Baisheng Nie, Jiayun Lun, Kedi Wang, and Jiesheng Shen
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3D reconstruction ,degree of coal metamorphism ,multi‐scale analysis ,pore structure ,Technology ,Science - Abstract
Abstract Coal seams in China have poor permeability and a complex pore structure, leading to a low gas extraction efficiency. Studying the pore structure of different metamorphic degrees of coal by using modern technological methods and employing appropriate pumping measures for different pore structures can improve the gas extraction efficiency. In this study, the pore sizes of three coal samples with different metamorphic grades were measured at different pore scales through CO2 adsorption, nitrogen adsorption, small‐angle X‐ray scattering, and mercury pressure methods. The pore structure was three‐dimensionally reconstructed using the lattice Boltzmann method‐based quartet structure generation set algorithm. The optimum pore size measurements performed using the CO2 adsorption, nitrogen adsorption, small‐angle X‐ray scattering, and mercury pressure methods were in the ranges of 0.3‐2, 1.7‐300, 1‐50, and 7.5‐11 000 nm, respectively; this demonstrates that the structure of a full‐scale coal model cannot be accurately tested using a single technique. The pore structure varies depending on the metamorphic degree of the coal; therefore, coal metamorphism should be considered for effective gas extraction.
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- 2020
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81. Designing better online teaching material
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Jiayun Lu and Judy Brown
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Multimedia ,Process (engineering) ,business.industry ,Computer science ,Usability ,computer.software_genre ,Data warehouse ,Test (assessment) ,Synchronous learning ,Learning theory ,Online teaching ,Software engineering ,business ,computer - Abstract
The creation of excellent online teaching material is challenging because it requires that designers are able to apply learning theories and usability principles. In this paper we describe a web-based tutorial we developed to teach database students about SQL-like operators that can be used to access data in data warehouses (very large collections of data used by analysts). This paper describes the processes and methods used to develop the tutorial and the techniques we used to test prototypes of our tutorial. We show how ideas from user-centered design and learning theory can be usefully combined to create a new process for developing online teaching material that meets learning and usability aims.
- Published
- 2001
82. Filling characteristics of the micropores in coals with different metamorphic degrees
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Wenjing Wang, Lin Hong, Dameng Gao, and Jiayun Lun
- Subjects
Physics ,QC1-999 - Abstract
To explore the occurrence state of coalbed methane (CBM) in coals of different metamorphic degrees and accurately predict CBM, we studied the micromechanism of coal and gas outbursts in a bid to avoid or reduce personnel injuries or property losses in such underground accidents. Low-temperature N2 adsorption experiments were conducted on three coal samples of different metamorphism degrees. We explored the critical filling characteristics of the packed N2 molecules in the coal. The Dubinin–Astakhov equation in the micropore filling theory and the density functional theory method were applied to obtain the critical filling pressure and critical filling aperture range for the N2 molecules to complete the micropore filling in the coal. The results showed that in the low-temperature nitrogen adsorption experiment, the pore structure of lignite was uniform, and the adsorption of N2 molecules was better. The ratio of nitrogen molecules in the adsorbed form was higher than those found in bituminous coal and anthracite. The initial filling of the micropores in coal started when the relative pressure was P/P0 ≈ 10−6–10−4 and completed when P/P0 ≈ 10−2. The order of completion was anthracite, bituminous coal, and lignite. The slit-type channel was more conducive to microhole filling than the ink bottle channel. The critical filling pore size of the coal samples with different levels of metamorphism was in the range of 1.7–2.2 nm. Finally, the critical filling pore size was divided into a primary filling stage with the range being 0.36–1.7 nm and a secondary filling stage with the range being 1.7–2.2 nm.
- Published
- 2021
- Full Text
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83. Erratum: Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment
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Brendan A.C. Harley, César Nombela-Arrieta, Beatrice Winkel, John E. Mahoney, Kimberly J. Canty, Jiayun Lu, Shin-Young Park, Gregory Pivarnik, Leslie E. Silberstein, and Alexei Protopopov
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Haematopoiesis ,Quantitative imaging ,medicine.anatomical_structure ,medicine ,Cell Biology ,Bone marrow ,Progenitor cell ,Biology ,Cell biology - Published
- 2013
84. SALL4 Is a Key Survival Factor in Acute B-Cell Lymphoblastic Leukemia
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Li Chai, XiaoXian Zhang, Jiayun Lu, He Jie, Shikiko Ueno, Leslie E. Silberstein, Jerome Ritz, and Ailing Li
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Homeobox protein NANOG ,Gene knockdown ,Immunology ,CD34 ,Stem cell factor ,Cell Biology ,Hematology ,Biology ,Caspase 8 ,medicine.disease ,Biochemistry ,Molecular biology ,eye diseases ,Leukemia ,Apoptosis ,Cell culture ,Cancer research ,medicine - Abstract
Abstract 2428 SALL4 is a zinc-finger transcriptional factor and a member of the SALL gene family. It plays an essential role in the maintenance of ESC pluripotent and self-renewal properties by interacting with other two key regulators in ESCs, Nanog and Oct4. We previously have shown that stem cell factor SALL4 is aberrantly expressed in 75% of acute B-cell lymphoblastic leukemia (B-ALL). We have also shown that SALL4 is aberrantly expressed in AML, and down-regulation of SALL4 in AML leads to significant cell death. In this study, we focused on investigating the functional role of SALL4 in human B-ALL leukemogenesis. We first assessed the SALL4 mRNA level in four B-ALL cell lines (REH, Nalm6, 697, Blin-1) and five primary patient samples by qRT-PCR. We observed SALL4 mRNA in these four cell lines increased when compared to normal human CD34 negative BM cells. Moreover 4 of 5 primary samples showed high level expression of SALL4, suggesting that SALL4 might play a role in B-ALL pathogenesis. Then, we selected a SALL4 expressing B-ALL cell line (REH and Nalm6) and attenuated SALL4 expression through GFP-labeled shRNA approach in these cell lines. We monitored the growth of SALL4 knockdown and control REH and Nalm6 cells through MTS assay. SALL4 knockdown cells had a decreased growth rate compared to that of the control cells. We also stained SALL4 knockdown and control cells with Annexin V and 7-AAD by flow cytometric quantitation of apoptotic cells. The percentages of apopotic cells in SALL4 knockdown cells were much higher than these in controls. These data demonstrated that inhibition of SALL4 in REH cells and Nalm6 cells led to reduced proliferation and increased apoptosis. We then examined the oncogenesis ability of SALL4 knockdown REH cells in a mouse xenotransplantation model. SALL4 knockdown or control REH cells were injected intravenously into immunodeficient mice. All the recipients succumbed to fatal leukemia within 4 to 6 weeks post transplantation. In both BM and spleen of SALL4 knockdown recipients the engrafted proportion of GFP+ cells was significantly decreased compared to the initial donor cells. Whereas, in both BM and spleen control recipients the percentage of GFP+ REH cells engrafted was similar to that of initial donor cells. This suggests that down-regulation of SALL4 is essential for B-ALL engraftment. To rule out the observed engraftment defect was due to homing, we next performed homing assay. SALL4 knockdown or control cells were injected intravenously into immunodeficient mice as well. Three hours of the injection, mice were sacrificed and analyzed the percentage of GFP+ cells in BM and spleen by flow cytometry. There was no difference among SALL4 knockdown and the control. Furthermore, we performed gene expression profiling on apoptosis-related genes in SALL4 knockdown and control REH cells. The result showed that in SALL4-knockdown REH, TNF mediated cell apoptosis pathways was up-regulated as well as multiple caspase members. The expression of Caspase 3, Caspase 8, FADD was up-regulated in both SALL4 knockdown REH and Nalm6 when compared to these controls, and was verified by real time RT-PCR. This suggests that SALL4 could repress apoptosis through the TNF signal pathway. In summary, we report a novel SALL4/TNF pathway in maintaining cell survival in B-ALL. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2011
85. Down-Regulation of Homeobox Gene Ventx Promotes Expansion of Human Bone Marrow Hematopoietic Stem Cells (HSC)
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Jiayun Lu, Yan Sun, Zhenglun Zhu, Hong Gao, Xiaoming Wu, and Leslie E. Silberstein
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Gene knockdown ,Immunology ,Wnt signaling pathway ,Cell Biology ,Hematology ,Cell cycle ,Biology ,Cell fate determination ,Biochemistry ,Molecular biology ,Cell biology ,Transplantation ,Haematopoiesis ,BMI1 ,Stem cell - Abstract
Abstract 1272 Hematopoietic stem cells (HSC) give rise to mature cells of all lineages of blood and immune systems. HSC transplantation has shown great promise in the treatment of malignancies, reconstitution of hematopoietic systems and HSC-based gene therapy. Cell intrinsic factors/pathways have been the targets of intensive investigation for its potential application in HSC expansion. Over the past decades, several critical cell fate determination pathways, such as the Wnt signaling pathways and senescence pathways have been implicated in the proliferation and differentiation of HSC. Moreover, overexpression of HoxB4 and BMI1 was found to be able to expand human HSC 2∼3 folds. Nevertheless, the regulatory mechanisms of HSC proliferation and differentiation remain incompletely understood and safe and efficacious expansion of human HSC remains as a fundamental challenge that limits the clinical application of HSC-based therapy. VentX is a human homologue of the Xenopus homeobox protein Xom of the BMP4 signaling pathway. Using Xenopus model and methods of reverse genetics, our recent work showed that VentX is a LEF/TCF associated Wnt repressor and an activator of senescence pathways. VentX expression is highly regulated and restricted in hematopoietic cells and serves a major regulator of hematopoietic cell differentiation. To explore the potential role of VentX in proliferation and differentiation of HSC during hematopoiesis, we quantified VentX expression during hematopoiesis, using qRT-PCR methods and examined the effects of altered VentX expression on HSC properties in vitro and in vivo. Our data showed that VentX expression is significantly up-regulated during oncogenesis of hematopioetic cells. We demonstrated that lentiviral knockdown of VentX allowed for more than 5 fold ex vivo expansion of human HSC with balanced lineage development. Importantly, transient knockdown of VentX by siRNA also led to expansion of HSC. The effect of VentX down-regulation on the expansion of human HSC was also demonstrated by enhanced engraftment in the SCID/NODγ2null mouse model. Consistent with its role as a novel regulator of HSC, overexpression of VentX significantly inhibited clonal genesis of HSC. Mechanistically, we demonstrated that VentX controls the expression of cell cycle regulators downstream of the Wnt and senescence pathways, such as the C-myc, CyclinD1 and p21. In summary, using methods of reverse genetic and developmental modeling, we identified VentX as a novel regulator for expansion of human BM HSC. The results of our investigations provide novel insight in regulating HSC proliferation and differentiation. In addition, the findings that transient down-regulation of VentX by SiRNA lead to efficient expansion of bone marrow HSC suggests that VentX may serve as a novel target for safe expansion of HSC for its potential clinical applications. Disclosures: No relevant conflicts of interest to declare.
- Published
- 2011
86. Hypoxic Hematopoietic Stem and Progenitor Cells Reside in Structurally Diverse Perivascular Niches in the Bone Marrow
- Author
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John E. Mahoney, Brendan A.C. Harley, Beatrice Winkel, Leslie E. Silberstein, Jiayun Lu, Alexei Protopopov, Gregory Pivarnik, and César Nombela-Arrieta
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Pathology ,medicine.medical_specialty ,Immunology ,Niche ,Endogeny ,Cell Biology ,Hematology ,Hypoxia (medical) ,Biology ,Biochemistry ,Cell biology ,Endothelial stem cell ,Haematopoiesis ,medicine.anatomical_structure ,medicine ,Bone marrow ,medicine.symptom ,Progenitor cell ,Intracellular - Abstract
Abstract 3417 The identification of specific microenvironments, in which Hematopoietic Stem and Progenitor Cells (HSPCs), reside within the BM is a major challenge in stem cell biology. Yet the extreme rarity of HSCs, their dynamic nature, and the lack of unique specific markers to identify them, have precluded an accurate definition of HSC niches to date. Using Laser Scanning Cytometry, a powerful emerging quantitative imaging technology that enables analysis of whole femoral sections at the single cell level, we have mapped the global distribution of hematopoietic stem and progenitor cells within femoral bone marrow cavities, and analyzed their inmediate surrounding microenvironment. Systematic mapping of the global distribution of endogenous HSPC-enriched populations in the BM, revealed an accumulation of these cells inside endosteal regions (ER Disclosures: No relevant conflicts of interest to declare.
- Published
- 2011
87. Sall4, a Stem Cell Factor, Promotes Chemoresistance by Regulates the Side Population Cell Phenotype
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Ha-Won Jeong, Ye Guo, Li Chai, Jiayun Lu, Youyang Yang, Wei Cui, and Chong Gao
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education.field_of_study ,Immunology ,Population ,Stem cell factor ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Embryonic stem cell ,Molecular biology ,eye diseases ,Leukemia ,Side population ,Cell culture ,Cancer stem cell ,medicine ,Stem cell ,education - Abstract
Abstract 3093 Poster Board III-30 The side population (SP) phenotype, defined as the verapamil-blockable ability to efflux the nucleic acid dye Hoechst 33342, has been used to enrich for stem cells in several human normal tissues, cancers, and multiple cell lines including blood cells, and thus may be useful for the identification and isolation of cancer stem cells, which has emerged as a new therapeutic target for cancer treatment. However, the molecular mechanism(s) operating in SP cells remain unclear. Previous studies show that the stem cell factor, SALL4 plays a central role in the self-renewal of embryonic and leukemic stem cells. In this study, we determined the role of SALL4 in side population (SP). Using FACS sorting, we found the presence of SP fractions in four leukemic cell lines: HL-60, NB-4, RPMI8226 and KG1a. SALL4 expression was more abundant in SP cells compared with non-SP cells by 2- 4 fold in these leukemic cell lines. Knockdown of SALL4 in purified SP cells resulted in a reduction of SP population, indicating that SALL4 is required for the self-renewal of SP cells in this culture system. Since the side population phenotype is known to be mediated by the ATP-binding cassette proteins, we further investigated whether SALL4 could regulate the ATP transporters in SP cells. Chromatin immunoprecipitation (ChIP), luciferase assays and real-time PCR analysis demonstrated that SALL4 could bind to the promoter region of ABCA3, one of the ABC transporters, and activated its expression. In addition, while overexpression of SALL4 led to drug resistance in cell lines, SALL4-knockdown cells displayed more sensitive to drug treatments than the control cells. Further more, SALL4 expression was associated with primary AML treatment status (N= 64 cases), with higher SALL4 mRNA expression seen in drug resistance and partial remission patients than that from complete remission cases. Taken together, our results suggest that SALL4 plays an important in the sensitivity to drug treatment, at least in part, through the maintenance of SP cells, and is responsible for drug-resistance in leukemia. Disclosures No relevant conflicts of interest to declare.
- Published
- 2009
88. Deletion of Fak in Hematopoietic Stem Cells Leads to Enhanced Engraftment
- Author
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Jiayun Lu, Leslie E. Silberstein, Yi Le, Li Chai, César Nombela-Arrieta, and Shin-Young Park
- Subjects
Immunology ,CD34 ,Hematopoietic stem cell ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Embryonic stem cell ,Cell biology ,Transplantation ,Haematopoiesis ,medicine.anatomical_structure ,Megakaryocyte ,medicine ,Progenitor cell ,Stem cell - Abstract
Hematopoietic stem and progenitor cells (HSPC) can be induced to leave the bone marrow (BM) and such mobilized hematopoietic stem cell (HSC) enriched cell populations when infused intravenously rapidly home back to the marrow and transmigrate into the extravascular compartment where they lodge in specialized niches. Niche induced signals coupled to intrinsic factors, promote HSC maintenance and regulate HSC localization, migration and/or differentiation. A better understanding of molecular pathways governing these HSC fate decisions could identify new targets for ex vivo HSC expansion and improvement of transplantation. Focal adhesion kinase (Fak) is a non-receptor protein tyrosine kinase, whose function has been well studied in fibroblasts, where it plays an important role in cell adhesion, survival and motility. Fak is also differentially expressed in HSPC, with highest expression in long-term HSCs (LT-HSCs, Lin-Sca-1+c-Kit +CD34-). Its functional role in hematopoiesis has not been well studied due to early embryonic lethality (E.8) of Fak−/− mice. We have generated conditional Fak deleted mice (Fakfl/flMx1-Cre+) to define how Fak signaling contributes to different components of HSC transplantation. We observed that the total cellularity in BM was comparable between Fak knockout (Fak−/−Mx1-Cre+) and control (Fakfl/fl) mice. The frequencies of both Lin-Sca-1+c-Kit + cells (LSKs) and short-term HSCs (ST-HSCs, Lin-Sca-1+c-Kit +CD34+) increased 2-fold in BM of Fak knockout mice compared to WT controls (n=5; p
- Published
- 2008
89. New method of fault feature extraction based on supervised LLE.
- Author
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Quansheng Jiang, Jiayun Lu, and Minping Jia
- Published
- 2010
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90. Influence of nano zinc oxide treated by HMDS in humidity detection.
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Jiayun Lu, Quansheng Jiang, and Jian Zhang
- Published
- 2009
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91. Big Data for Traffic Estimation and Prediction: A Survey of Data and Tools
- Author
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Weiwei Jiang and Jiayun Luo
- Subjects
big data ,call detail records ,census data ,GPS trajectory data ,location-based service data ,open data ,Technology ,Applied mathematics. Quantitative methods ,T57-57.97 - Abstract
Big data have been used widely in many areas, including the transportation industry. Using various data sources, traffic states can be well estimated and further predicted to improve the overall operation efficiency. Combined with this trend, this study presents an up-to-date survey of open data and big data tools used for traffic estimation and prediction. Different data types are categorized, and off-the-shelf tools are introduced. To further promote the use of big data for traffic estimation and prediction tasks, challenges and future directions are given for future studies.
- Published
- 2022
- Full Text
- View/download PDF
92. Deficiency of Lipid Phosphatase SHIP Enables Long-Term Reconstitution of Hematopoietic Inductive Bone Marrow Microenvironment
- Author
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Leslie E. Silberstein, Subhanjan Mondal, Li Chai, Hongbo R. Luo, Jia Zhong, Gregory Pivarnik, César Nombela-Arrieta, Li Zhao, Olin Dehui Liang, and Jiayun Lu
- Subjects
Stromal cell ,Population ,Apoptosis ,Bone Marrow Cells ,Spleen ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Cell Lineage ,Myeloid Cells ,Femur ,education ,Lung ,Molecular Biology ,Bone Marrow Transplantation ,030304 developmental biology ,Mice, Knockout ,B-Lymphocytes ,0303 health sciences ,education.field_of_study ,Adipogenesis ,Inositol Polyphosphate 5-Phosphatases ,Mesenchymal Stem Cells ,Cell Biology ,Phosphoric Monoester Hydrolases ,Hematopoiesis ,Laser Scanning Cytometry ,Mice, Inbred C57BL ,Transplantation ,Haematopoiesis ,medicine.anatomical_structure ,Cellular Microenvironment ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Leukocyte Common Antigens ,Bone marrow ,Developmental Biology - Abstract
SummaryA dysfunctional bone marrow (BM) microenvironment is thought to contribute to the development of hematologic diseases. However, functional replacement of pathologic BM microenvironment through BM transplantation has not been possible. Furthermore, the study of hematopoietic inductive BM microenvironment is hampered by the lack of a functional nonhematopoietic reconstitution system. Here, we show that a deficiency of SH2-containing inositol-5′-phosphatase-1 (SHIP) in a nonhematopoietic host microenvironment enables its functional reconstitution by wild-type donor cells. This microenvironment reconstitution normalizes hematopoiesis in peripheral blood and BM and alleviates pathology of spleen and lung in the SHIP-deficient recipients. SHIP-deficient BM contains a significantly smaller population of multipotent stromal cells with distinct properties, which may contribute to the reconstitution by wild-type cells. We further demonstrate that it is the nonhematopoietic donor cells that are responsible for the reconstitution. Thus, we have established a nonhematopoietic BM microenvironment reconstitution system to functionally study specific cell types in hematopoietic niches.
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93. A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis.
- Author
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Ailing Li, Youyang Yang, Chong Gao, Jiayun Lu, Ha-Won Jeong, Bee H. Liu, Ping Tang, Xiaopan Yao, Neuberg, Donna, Gang Huang, Tenen, Daniel G., and Li Chai
- Subjects
- *
EMBRYOLOGY , *ACUTE myeloid leukemia , *PROTEIN binding , *LEUKEMIA , *APOPTOSIS - Abstract
The embryonic self-renewal factor SALL4 has been implicated in the development of human acute myeloid leukemia (AML). Transgenic mice expressing the human SALL4B allele develop AML, which indicates that this molecule contributes to leukemia development and maintenance. However, the underlying mechanism of SALL4-dependent AML progression is unknown. Using SALL4B transgenic mice, we observed that HoxA9 was significantly upregulated in SALL4B leukemic cells compared with wild-type controls. Downregulation of HoxA9 in SALL4B leukemic cells led to decreased replating capacity in vitro and delayed AML development in recipient mice. In primary human AML cells, downregulation of SALL4 led to decreased HOXA9 expression and enhanced apoptosis. We found that SALL4 bound a specific region of the HOXA9 promoter in leukemic cells. SALL4 overexpression led to enhanced binding of histone activation markers at the HOXA9 promoter region, as well as increased HOXA9 expression in these cells. Furthermore, we observed that SALL4 interacted with mixed-lineage leukemia (MLL) and co-occupied the HOXA9 promoter region with MLL in AML leukemic cells, which suggests that a SALL4/MLL pathway may control HOXA9 expression. In summary, our findings revealed a molecular mechanism for SALL4 function in leukemogenesis and suggest that targeting of the SALL4/MLL/HOXA9 pathway would be an innovative approach in treating AML. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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