38 results on '"Syeling Lai"'
Search Results
2. Association of the HLA-DRB1 with scleroderma in Chinese population.
- Author
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Dongyi He, Jiucun Wang, Lin Yi, Xinjian Guo, Shicheng Guo, Gang Guo, Wenzhen Tu, Wenyu Wu, Li Yang, Rong Xiao, Yuan Li, Haiyan Chu, Syeling Lai, Li Jin, Hejian Zou, John D Reveille, Shervin Assassi, Maureen D Mayes, and Xiaodong Zhou
- Subjects
Medicine ,Science - Abstract
Multiple alleles of the Human leukocyte antigen (HLA) DRB1 have been strongly associated with systemic sclerosis (SSc) and its clinical or serological subsets. However, the associations vary in different ethnic populations. To define SSc-risk and/or -protective alleles of HLA-DRB1 in Chinese population, we studied a Han Chinese cohort containing 585 patients with SSc and 458 gender-matched, unrelated controls. The HLA-DRB1 genotyping was performed with sequence-based typing method. Exact p-values were obtained (Fisher's test) from 2×2 tables of allele frequency and disease status. The major SSc-risk allele subtypes of HLA-DRB1 are the DRB1*15∶02 and *16∶02 in this Chinese cohort. Particularly, DRB1*15∶02 was most significantly associated with anti-centromere autoantibodies (ACA) positive, and DRB1*16∶02 with anti-topoisomerase I autoantibodies (ATA) positive patients. On the other hand, DRB1*01∶01 and *04∶06 were strong SSc-protective alleles in Chinese, especially in patients who were ACA positive and had diffuse cutaneous SSc (dcSSc), respectively. In addition, DRB1*11 and *07∶01 also showed significant association with SSc as a risk for and protection from SSc, respectively, and which is consistent with the studies of Spanish, US Caucasian and Hispanic populations. DRB1*15 was associated with ATA positive Chinese SSc that is consistent with Black South African and Korean SSc. These findings of HLA-DRB1 alleles in association with Chinese SSc provide the growing knowledge of genetics of SSc, and indicate that the genetic heterogeneity among ethnicities may significantly impact the complex trait of SSc.
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- 2014
- Full Text
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3. Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration
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David C. Wilde, Patricia D. Castro, Kaustav Bera, Syeling Lai, Anant Madabhushi, German Corredor, Can Koyuncu, James S. Lewis, Cheng Lu, Mitchell J. Frederick, Allan M. Frederick, Avery E. Haugen, Jose P. Zevallos, Erich M. Sturgis, Justin Shi, Andrew T. Huang, David J. Hernandez, Heath D. Skinner, Jan O. Kemnade, Wendong Yu, Andrew G. Sikora, and Vlad C. Sandulache
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Oropharyngeal Neoplasms ,Head and Neck Neoplasms ,Squamous Cell Carcinoma of Head and Neck ,Papillomavirus Infections ,Humans ,Precision Medicine ,Prognosis ,Papillomaviridae ,Cyclin-Dependent Kinase Inhibitor p16 ,Pathology and Forensic Medicine - Abstract
Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells (MuNI) and targeted transcriptomics. P16 was a dominant determinant of LRC, DFS and OS, but tobacco exposure, OP-TIL and MuNI risk features correlated with clinical outcomes independent of p16 status and the combination of p16, OP-TIL and MuNI generated a better stratification of OPSCC risk compared to individual parameters. Differential gene expression (DEG) analysis demonstrated overlap between MuNI and OP-TIL and identified genes involved in DNA repair, oxidative stress response and tumor immunity as the most prominent correlates with survival. Alteration of inflammatory/immune pathways correlated strongly with all risk features and oncologic outcomes. This suggests that development of OPSCC consists of an intersection between multiple required and permissive oncogenic and immunologic events which may be mechanistically linked. The strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status may provide opportunities for further biomarker development and precision oncology approaches incorporating immune checkpoint inhibitors for maximal anti-tumor efficacy.
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- 2022
4. Secretory Carcinoma with ETV6-NTRK3 Gene Fusion and Lymph Node Metastasis in Maxillary Gingiva: A Case Report with Pathological and Molecular Correlative Studies.
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Fujita, Jun, Krishnan, Bhuvaneswari, Green, Linda K., Sandulache, Vlad C., and Syeling Lai
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- 2023
5. HIV-related Refractory Hodgkin Lymphoma: A Case Report of Complete Response to Nivolumab
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Elizabeth Y. Chiao, Gustavo A. Rivero, John E. Mbue, Syeling Lai, Elaine Chang, Sarvari Venkata Yellapragada, Kelash Bajaj, and Niraj R. Patel
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Immune checkpoint inhibitors ,Treatment outcome ,Human immunodeficiency virus (HIV) ,HIV Infections ,Drug resistance ,medicine.disease_cause ,Article ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Positron Emission Tomography Computed Tomography ,Internal medicine ,medicine ,Refractory Hodgkin Lymphoma ,Humans ,030212 general & internal medicine ,Complete response ,business.industry ,Hematology ,Hodgkin Disease ,Nivolumab ,Treatment Outcome ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Autoimmune diabetes ,business - Published
- 2018
6. Stereotactic Radiosurgery for Carcinoid Brain Metastasis: A Case Report
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David M. Sada, Felicia Cao, Syeling Lai, and Yvonne H. Sada
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carcinoid ,Poor prognosis ,medicine.medical_specialty ,endocrine system ,Rectal Carcinoid ,endocrine system diseases ,medicine.medical_treatment ,stereotactic radiosurgery ,030204 cardiovascular system & hematology ,chemotherapy ,Radiosurgery ,03 medical and health sciences ,0302 clinical medicine ,temozolamide ,Medicine ,brain metastasis ,neoplasms ,Chemotherapy ,Temozolomide ,business.industry ,General Engineering ,Treatment options ,Tumor therapy ,medicine.disease ,digestive system diseases ,3. Good health ,Oncology ,Radiation Oncology ,Radiology ,business ,rectal carcinoid ,030217 neurology & neurosurgery ,Brain metastasis ,medicine.drug - Abstract
Carcinoid brain metastases are extremely rare and are associated with a poor prognosis. Treatment options are variable, ranging from surgery, radiation, or chemotherapy alone or combined. We report on a case of rectal carcinoid metastatic to the cerebellum and review chemotherapeutic regimens for carcinoid tumor treatment, focusing on the potential role of temozolomide or stereotactic radiosurgery.
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- 2019
7. Identification of an Association ofTNFAIP3Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of Systemic Sclerosis-Associated Genetic and Environmental Factors
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Syeling Lai, Shervin Assassi, Xiaodong Zhou, Filemon K. Tan, Xinjian Guo, Yang Yang, Mengyuan Liu, Nainan Hei, and Peng Wei
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0301 basic medicine ,Genetics ,MMP1 ,In silico ,Immunology ,Haplotype ,Biology ,03 medical and health sciences ,030104 developmental biology ,Rheumatology ,Genetic variation ,Gene expression ,Genotype ,Genetic predisposition ,Immunology and Allergy ,Gene - Abstract
Objective Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments. Methods A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis combining the results from Caucasian, African American, and Hispanic subjects. A linear mixed model for longitudinal data analysis was used to identify genetic variants associated with the expression of ECM genes, and the associations were validated by using a haplotype-based longitudinal association test on regions that included the loci identified. Results The single-nucleotide polymorphism rs58905141 in TNFAIP3 was consistently associated with time-course and/or dose-response expression of MMP3 and MMP1 in the fibroblasts stimulated with silica particles in both the analysis of Caucasian subjects only and the meta-analysis. Results of the haplotype-based analysis validated the association signals. Conclusion Our findings indicate that a genetic variant of TNFAIP3 is strongly associated with the silica-induced profibrotic response of fibroblasts. In silico functional analysis based on the ENCODE database revealed that rs58905141 might affect the binding activities of the transcription factors for TNFAIP3. This is the first genome-wide study of interactions between genetic and environmental factors in a complex SSc fibroblast model.
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- 2016
8. Oropharyngeal squamous cell carcinoma in the veteran population: Association with traditional carcinogen exposure and poor clinical outcomes
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Numan A. Khan, John Hamblin, Syeling Lai, Christine Hartman, Todd A. Pezzi, Jennifer R. Kramer, Elizabeth Y. Chiao, Shayan M. Dioun, Vlad C. Sandulache, Xiaodong Zhou, Heath D. Skinner, and Jose P. Zevallos
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Oncology ,medicine.medical_specialty ,education.field_of_study ,business.industry ,medicine.medical_treatment ,Population ,Cancer ,medicine.disease ,Gastrostomy ,Surgery ,Tumor Status ,Otorhinolaryngology ,Internal medicine ,Cohort ,medicine ,Oropharyngeal squamous cell carcinoma ,education ,business ,Veterans Affairs ,Carcinogen - Abstract
Background A significant fraction of oropharyngeal squamous cell carcinoma (SCC) cases is associated with traditional carcinogens; in these patients, treatment response and clinical outcomes remain poor. Methods We evaluated patient, tumor, and treatment characteristics for 200 veterans with oropharyngeal SCC treated at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) between 2000 and 2012. Results Most patients (77%) were white and heavy smokers. Twenty-seven patients required tracheostomy and 63 required gastrostomy placement during treatment. Overall survival (OS) at 5 years was 40%. Survival was impacted by T classification, treatment intensity, completion of treatment, and p16 tumor status. Almost 30% of patients were unable to complete a treatment regimen consistent with National Comprehensive Cancer Network (NCCN) guidelines. Conclusion Oropharyngeal SCC in veterans is associated with traditional carcinogens and poor clinical outcomes. Despite heavy smoking exposure, p16 tumor status significantly impacts survival. Careful consideration must be given to improving treatment paradigms for this cohort given their limited tolerance for treatment escalation. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1246–1253, 2015
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- 2015
9. Impact of race on oropharyngeal squamous cell carcinoma presentation and outcomes among veterans
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Vlad C. Sandulache, Kelsey L. Horter, John Hamblin, Syeling Lai, Xiaodong Zhou, Elizabeth Y. Chiao, Jose P. Zevallos, Jennifer R. Kramer, Heath D. Skinner, and Christine Hartman
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Oncology ,African american ,medicine.medical_specialty ,Multivariate analysis ,Proportional hazards model ,business.industry ,Head neck ,Surgery ,stomatognathic diseases ,03 medical and health sciences ,Race (biology) ,0302 clinical medicine ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,In patient ,Oropharyngeal squamous cell carcinoma ,030223 otorhinolaryngology ,business ,Veterans Affairs - Abstract
Background Racial disparities in oropharyngeal squamous cell carcinoma (SCC) have been demonstrated and attributed to differences in human papillomavirus (HPV) status. The purpose of this study was to examine racial disparities in oropharyngeal SCC among veterans. Methods Retrospective review of patients with oropharyngeal SCC at a tertiary-care Veterans Affairs (VA) hospital. Adjusted Cox proportional hazards models were conducted to examine the effect of race on oropharyngeal SCC outcomes. Results Of 158 patients, 126 (79.7%) were white and 32 (20.3%) were African American. No difference in p16 tumor expression was noted between the groups. Five-year disease-free survival (DFS) was 42.6% and 55.1% for African Americans and whites, respectively (p = .372). Five-year overall survival (OS) for African Americans and whites was 54.6% and 51.8%, respectively (p = .768). On multivariate analysis, there was no significant difference in risk of recurrence or death by race. Conclusion Racial disparities are largely ameliorated in patients with oropharyngeal SCC treated within the VA, there were no racial differences in p16 tumor expression, and outcomes remain poor. © 2015 Wiley Periodicals, Inc. Head Neck, 2015
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- 2015
10. A Case of Unsuspected Peritoneal Mesothelioma Occurring with Colonic Adenocarcinoma Masquerading as Peritoneal Metastases
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Rishi A. Patel, Wei Xie, Linda K. Green, and Syeling Lai
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Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Case Report ,Ileum ,General Medicine ,medicine.disease ,Debulking ,digestive system diseases ,Cecum ,medicine.anatomical_structure ,Ascites ,Biopsy ,lcsh:Pathology ,Peritoneal mesothelioma ,medicine ,Adenocarcinoma ,Mesothelioma ,medicine.symptom ,business ,lcsh:RB1-214 - Abstract
We report a case of synchronous primary colonic adenocarcinoma and malignant mesothelioma. A 61-year-old male presented with a six-month history of fatigue and weight loss. An abdominal computed tomography (CT) scan showed a 5.8 cm partially obstructing mass in the cecum with ascites and peritoneal thickening. A biopsy of the large mass showed an adenocarcinoma. Because the patient was clinically thought to be a T4 colon carcinoma with peritoneal metastatic lesions (M1), prior to initiating chemotherapy, a debulking right hemicolectomy was performed. Resection of the colon and ileum revealed a T3N0 colonic mucinous adenocarcinoma and concurrent diffuse malignant peritoneal mesothelioma. Presenting synchronous colonic and peritoneal mesothelial primary malignancies are exceedingly rare but must be considered to prevent incorrect clinical staging.
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- 2014
11. Inflammatory Cells in Tissues of Gout Patients and Their Correlations with Comorbidities
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Xiaodong Zhou and Syeling Lai
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Pathology ,medicine.medical_specialty ,Cell type ,Gout ,Cell ,B-cells ,Article ,chemistry.chemical_compound ,Immune system ,Rheumatology ,uric acid ,Diabetes mellitus ,Hyperlipidemia ,Medicine ,mononucleated macrophages ,comorbidities ,business.industry ,T-cells ,nutritional and metabolic diseases ,medicine.disease ,medicine.anatomical_structure ,chemistry ,Giant cell ,Uric acid ,multinucleated giant cells ,business - Abstract
Background: The major pathological finding of gout is the deposition of monosodium urate monohydrate (MSU) crystals with inflammatory infiltrate in the tissue. There have been many reports of in vitro analysis of inflammatory mechanism and comorbidities in gout. However, the associations of immune response cells and comorbidities of gout have not been well documented. Our studies aimed to examine the immune cell types and quantity in gout tissues, and to define the association of individual cell type with comorbidities. Methods: Surgically resected or biopsied tissues from 48 patients diagnosed as gout were used for this study. Cell count was performed on Hemotoxylin and Eosin stained sections for macrophages, plasma cells, neutrophils and on immunostained slides for T and B lymphocytes. Results: Hyperlipidemia, hypertension and diabetes mellitus were seen in 70.8%, 87.5% and 37.5% of patients, respectively. There were 35.6% and 37.8% of patients who admitted history of smoking and alcohol intake, respectively. Mean serum uric acid level was 8.5 mg/dl. The average body mass index was 30.1 kg/m2. H&E stained tissue sections demonstrated the crystalline deposits rimmed by palisading multinucleated giant cells, macrophages, neutrophils, plasma cells, T and B cells. Significant correlations between the clinical features and tissue inflammatory cells were observed in hyperlipidemia with number of T cells (p = 0.0363), hypertension with number of T cells and B cells (p = 0.0138 and 0.0033, respectively), diabetes mellitus with macrophages (p = 0.0016), and uric acid level with giant cells (p = 0.0088). Conclusion: Comorbidity factors including hyperlipidemia, hypertension and diabetes are significantly associated with the inflammatory cells in the tissues.
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- 2013
12. Hemophagocytic lymphohistiocytosis associated with influenza A (H1N1) infection in a patient with chronic lymphocytic leukemia: an autopsy case report and review of the literature
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Syeling Lai, Linda K. Green, Lei Chen, Xiaodong Zhou, and Brian Y. Merritt
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Male ,Secondary Hemophagocytic Lymphohistiocytosis ,Pathology ,medicine.medical_specialty ,Chronic lymphocytic leukemia ,Lymphohistiocytosis, Hemophagocytic ,Pathology and Forensic Medicine ,Fatal Outcome ,Influenza A Virus, H1N1 Subtype ,Leukocytopenia ,Influenza, Human ,Humans ,Medicine ,Diffuse alveolar damage ,Lung ,Pneumonitis ,Hemophagocytic lymphohistiocytosis ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Leukemia ,Immunology ,Pulmonary hemorrhage ,Tomography, X-Ray Computed ,business - Abstract
H1N1 influenza A virus can trigger fatal hemophagocytic lymphohistiocytosis in immunocompromised patients and in immunocompetent hosts, usually children. We present a case of a 50-year-old man with low-burden chronic lymphocytic leukemia who had sudden reactivation of his leukemia triggered by influenza A (H1N1) infection with hemophagocytic lymphohistiocytosis during the 2009 H1N1 pandemic. His rapid course was complicated by acute respiratory distress syndrome with diffuse alveolar damage, a 6-fold rise in lymphocyte count, disseminated intravascular coagulation, and, ultimately, cardiac arrest. Major findings at autopsy included: bilateral H1N1 pneumonitis with diffuse alveolar damage, intra-alveolar pulmonary hemorrhage, pulmonary microthromboemboli, pulmonary hemorrhagic infarction, hemophagocytic lymphohistiocytosis in multiple locations, and diffuse chronic lymphocytic leukemia. Hemophagocytic lymphohistiocytosis is a serious and often fatal condition, which may be primary or secondary. It may be associated with high-grade lymphoproliferative malignancies, especially in patients with therapy-related leukocytopenia, but only rarely is it seen in uncomplicated chronic lymphocytic leukemia. Hemophagocytic lymphohistiocytosis may be triggered by a variety of infections (viral, fungal, bacterial and parasitic), but H1N1 influenza A-associated hemophagocytic lymphohistiocytosis is often rapidly fatal, especially in children. This adult patient's clinical presentation with low tumor burden and leukocytosis is thus unique. We review the recently published autopsy findings in fatal influenza A (H1N1) infection and the association with resultant secondary hemophagocytic lymphohistiocytosis.
- Published
- 2012
13. Overexpression of Semaphorin-3E enhances pancreatic cancer cell growth and associates with poor patient survival
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Lin-Kin Yong, George Van Buren, William E. Fisher, Ethan Poteet, Changyi Chen, Qianxing Mo, Fengju Chen, Syeling Lai, Qizhi Yao, and Zhengdong Liang
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,MAP Kinase Signaling System ,pancreatic cancer ,Semaphorins ,Metastasis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Semaphorin ,Cell Movement ,Pancreatic cancer ,Internal medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Extracellular Signal-Regulated MAP Kinases ,Cell Proliferation ,Cell growth ,business.industry ,semaphorin 3E ,Cancer ,Patient survival ,medicine.disease ,Molecular medicine ,3. Good health ,Surgery ,Pancreatic Neoplasms ,030104 developmental biology ,Tumor progression ,030220 oncology & carcinogenesis ,Female ,business ,Research Paper - Abstract
// Lin-Kin Yong 1, 2 , Syeling Lai 3 , Zhengdong Liang 1 , Ethan Poteet 1 , Fengju Chen 4,5 , George van Buren 4,6 , William Fisher 4,6 , Qianxing Mo 4,5 , Changyi Chen 1,4 , Qizhi Yao 1, 4,7 1 Michael E. DeBakey Department of Surgery, Division of Surgical Research, Baylor College of Medicine, Houston, TX, USA 2 Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA 3 Department of Pathology, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX, USA 4 Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA 5 Department of Medicine, Baylor College of Medicine, Houston, TX, USA 6 Michael E. DeBakey Department of Surgery, Division of General Surgery, Baylor College of Medicine, Houston, TX, USA 7 Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX, USA Correspondence to: Qizhi Yao, email: qizhiyao@bcm.edu Keywords: semaphorin 3E, pancreatic cancer Received: July 05, 2016 Accepted: October 17, 2016 Published: November 29, 2016 ABSTRACT Semaphorin-3E (Sema3E) is a member of an axon guidance gene family, and has recently been reported to contribute to tumor progression and metastasis. However, its role in pancreatic cancer is yet unknown and uncharacterized. In this study, we showed that Sema3E is overexpressed in human pancreatic cancer, and that high Sema3E levels are associated with tumor progression and poor survival. Interestingly, we also observed Sema3E expression in the nucleus, even though Sema3E is reported to be a secreted protein. Overexpression of Sema3E in pancreatic cancer cells promoted cell proliferation and migration in vitro , and increased tumor incidence and growth in vivo . Conversely, knockout of Sema3E suppressed cancer cell proliferation and migration in vitro, and reduced tumor incidence and size in vivo . Moreover, Sema3E induced cell proliferation via acting through the MAPK/ERK pathway. Collectively, these results reveal an undiscovered role of Sema3E in promoting pancreatic cancer pathogenesis, suggesting that Sema3E may be a suitable prognostic marker and therapeutic target for pancreatic cancer.
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- 2016
14. Prognostic Significance of p16 Cellular Localization in Oropharyngeal Squamous Cell Carcinoma
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Syeling, Lai, Ashley E, Wenaas, Vlad C, Sandulache, Christine, Hartman, Elizabeth, Chiao, Jennifer, Kramer, and Jose P, Zevallos
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Adult ,Male ,Middle Aged ,Prognosis ,Disease-Free Survival ,Oropharyngeal Neoplasms ,Protein Transport ,Risk Factors ,Multivariate Analysis ,Humans ,Female ,Neoplasm Recurrence, Local ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Demography ,Neoplasm Staging ,Proportional Hazards Models - Abstract
p16 immunohistochemical expression serves as a surrogate for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). While HPV-positive OPSCC commonly demonstrates prominent nuclear expression, aberrant cytoplasmic expression has been demonstrated in tobacco-related head and neck cancers. The purpose of this study is to investigate the prognostic significance of p16 cellular localization in OPSCC.Retrospective cohort study and immunohistochemical expression analysis of 159 OPSCC patients treated at a tertiary-care Veterans Affairs Medical Center.All patients included in this study were male and the majority had significant tobacco (91%) and alcohol (88%) exposure. Overall, 57% of tumors were p16-positive, 32 (20%) subjects have tumors demonstrating low nuclear/low cytoplasmic (LN/LC) p16 expression, 29 (18%) high nuclear/high cytoplasmic (HN/HC) expression, 25 (16%) high nuclear/low cytoplasmic (HN/LC) expression, and 5 (3%) low nuclear/high cytoplasmic (LN/HC) expression. The 5-year disease-free survival (DFS) for the p16-negative group was 13.7%, compared to p16-positive LN/LC 28.4%, LN/HC 0%, HN/LC 74.7%, and HN/HC 93.1% (p0.0001). Overall survival for the p16-negative group was 24.2%, compared to p16-positive LN/LC 23.5%, LN/HC 0%, HN/LC 74.2%, and HN/HC 88.7% (p0.0001). On multivariable analysis, HN/HC and HN/LC expression patterns were associated with a statistically significant decreased risk of recurrence and death compared to p16-negative tumors.P16 localization has prognostic significance in OPSCC, with high nuclear expression associated with significantly better oncologic outcomes compared to low nuclear expression with high or low cytoplasmic p16 expression. P16 localization may provide additional insight into OPSCC carcinogenesis, particularly in patients with heavy tobacco exposure.
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- 2016
15. Lack of Association of the CD247 SNP rs2056626 with Systemic Sclerosis in Han Chinese
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Xiaodong Zhou, Shervin Assassi, Dongyi He, Yi Wang, Yuanhui Gu, Lin Yi, Xinjian Guo, Hejian Zou, Jiucun Wang, Gang Guo, Syeling Lai, Wenzhen Tu, Hongyi Li, Rong Xiao, Maureen D. Mayes, Li Yang, and Wenyu Wu
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Oncology ,polymorphism/SNP ,Han chinese ,medicine.medical_specialty ,Disease status ,integumentary system ,Traditional medicine ,Genetic heterogeneity ,business.industry ,CD247 ,Genome-wide association study ,Article ,Rheumatology ,Internal medicine ,Cohort ,medicine ,SNP ,genetics ,Chinese population ,scleroderma systemic sclerosis/SSc ,Allele ,skin and connective tissue diseases ,business - Abstract
Systemic sclerosis (SSc) is a complex disease involving multiple genetic factors. A recent genome-wide association study (GWAS) indicated that CD247 was strongly associated with SSc, which was subsequently confirmed in a SSc cohort of European population. However, genetic heterogeneity in different ethnic populations may significantly impact the complex trait of SSc. The studies herein aimed to examine whether the SSc-associated SNP rs2056626 of CD247 identified in Caucasian is also associated with Han Chinese SSc. A Han Chinese cohort consisting of 387 SSc patients and 523 healthy controls were examined in the studies. TaqMan assays were performed to examine the SNP. Exact p-values were obtained (Fisher’s test) from 2x2 tables of allele counts and disease status. The results showed that there was no association between rs2056626 of CD247 and SSc or any SSc subtypes of Han Chinese. The negative results are important in understanding genetics of SSc in different ethnic populations, which further suggest complex nature of genetics of SSc.
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- 2014
16. Identification of an Association of TNFAIP3 Polymorphisms With Matrix Metalloproteinase Expression in Fibroblasts in an Integrative Study of Systemic Sclerosis-Associated Genetic and Environmental Factors
- Author
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Peng, Wei, Yang, Yang, Xinjian, Guo, Nainan, Hei, Syeling, Lai, Shervin, Assassi, Mengyuan, Liu, Filemon, Tan, and Xiaodong, Zhou
- Subjects
Adult ,Male ,Polymorphism, Genetic ,Scleroderma, Systemic ,Genotype ,Dose-Response Relationship, Immunologic ,Intracellular Signaling Peptides and Proteins ,Gene Expression ,Genetic Variation ,Nuclear Proteins ,Hispanic or Latino ,Fibroblasts ,Middle Aged ,Silicon Dioxide ,Polymorphism, Single Nucleotide ,White People ,Article ,Extracellular Matrix ,Black or African American ,DNA-Binding Proteins ,Humans ,Female ,Matrix Metalloproteinase 3 ,Matrix Metalloproteinase 1 ,Tumor Necrosis Factor alpha-Induced Protein 3 - Abstract
Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments.A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis combining the results from Caucasian, African American, and Hispanic subjects. A linear mixed model for longitudinal data analysis was used to identify genetic variants associated with the expression of ECM genes, and the associations were validated by using a haplotype-based longitudinal association test on regions that included the loci identified.The single-nucleotide polymorphism rs58905141 in TNFAIP3 was consistently associated with time-course and/or dose-response expression of MMP3 and MMP1 in the fibroblasts stimulated with silica particles in both the analysis of Caucasian subjects only and the meta-analysis. Results of the haplotype-based analysis validated the association signals.Our findings indicate that a genetic variant of TNFAIP3 is strongly associated with the silica-induced profibrotic response of fibroblasts. In silico functional analysis based on the ENCODE database revealed that rs58905141 might affect the binding activities of the transcription factors for TNFAIP3. This is the first genome-wide study of interactions between genetic and environmental factors in a complex SSc fibroblast model.
- Published
- 2015
17. Catastrophic antiphospholipid syndrome: A rare cause of disseminated microvascular thrombotic injury - a case report with pathological and molecular correlative studies
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Syeling Lai, M. Tarek Elghetany, and David H. Walker
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Adult ,Pathology ,medicine.medical_specialty ,Multiple Organ Failure ,medicine.medical_treatment ,Autopsy ,Gene mutation ,Catastrophic antiphospholipid syndrome ,Thrombophilia ,Pathology and Forensic Medicine ,Fatal Outcome ,Antiphospholipid syndrome ,Skin Ulcer ,medicine ,Factor V Leiden ,Humans ,cardiovascular diseases ,Catastrophic Illness ,Skin ,Gangrene ,business.industry ,Microcirculation ,Thrombosis ,General Medicine ,Antiphospholipid Syndrome ,medicine.disease ,Antibodies, Antiphospholipid ,Female ,Plasmapheresis ,business - Abstract
Catastrophic antiphospholipid syndrome (CAPS) is a severe and rare variant of antiphospholipid syndrome (APS) characterized by acute multiorgan failure due to small vessel thrombi in patients with positive antiphospholipid antibodies. We report a fatal case of catastrophic antiphospholipid syndrome in a young woman with a history of polymyositis and Hodgkin lymphoma. The patient was admitted to hospital because of severe foot pain following several weeks of skin ulcerations. Doppler ultrasonography showed evidence of arterial ischemia of the both lower extremities. Despite anticoagulation, immunosuppression, plasmapheresis and antibiotic therapy, she developed cutaneous gangrene, retroperitoneal hematoma, ileus, and acute respiratory and renal failure that resulted in death. Autopsy showed multifocal vascular injury and microthrombi with associated hemorrhages and infarcts in multiple organs. The patient had normal levels of functional protein C and protein S and a normal level of plasma homocysteine. Tests for common thromophilic gene mutations including prothrombin 20210, factor V Leiden 1691, and methylene tetrahydrofolate reductase 677 were negative. To our knowledge, this is the first CAPS patient with molecular studies for genetic prothrombotic mutations. Our report showed that there was no association between the development of CAPS and inherited thromophilia.
- Published
- 2005
18. Impact of race on oropharyngeal squamous cell carcinoma presentation and outcomes among veterans
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Jose P, Zevallos, Vlad C, Sandulache, John, Hamblin, Heath D, Skinner, Jennifer, Kramer, Christine M, Hartman, Kelsey L, Horter, Syeling, Lai, Xiaodong, Zhou, and Elizabeth Y, Chiao
- Subjects
Adult ,Male ,Human papillomavirus 16 ,Alcohol Drinking ,Papillomavirus Infections ,Smoking ,Middle Aged ,Hospitals, Military ,Texas ,Disease-Free Survival ,White People ,Black or African American ,Oropharyngeal Neoplasms ,Risk Factors ,Carcinoma, Squamous Cell ,Humans ,Aged ,Retrospective Studies ,Veterans - Abstract
Racial disparities in oropharyngeal squamous cell carcinoma (SCC) have been demonstrated and attributed to differences in human papillomavirus (HPV) status. The purpose of this study was to examine racial disparities in oropharyngeal SCC among veterans.Retrospective review of patients with oropharyngeal SCC at a tertiary-care Veterans Affairs (VA) hospital. Adjusted Cox proportional hazards models were conducted to examine the effect of race on oropharyngeal SCC outcomes.Of 158 patients, 126 (79.7%) were white and 32 (20.3%) were African American. No difference in p16 tumor expression was noted between the groups. Five-year disease-free survival (DFS) was 42.6% and 55.1% for African Americans and whites, respectively (p = .372). Five-year overall survival (OS) for African Americans and whites was 54.6% and 51.8%, respectively (p = .768). On multivariate analysis, there was no significant difference in risk of recurrence or death by race.Racial disparities are largely ameliorated in patients with oropharyngeal SCC treated within the VA, there were no racial differences in p16 tumor expression, and outcomes remain poor.
- Published
- 2014
19. Primary splenic angiosarcoma associated with anemia, leukocytosis and thrombocytopenia
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Barina, Aqil, Linda K, Green, and Syeling, Lai
- Subjects
Male ,Radiography, Abdominal ,Fatal Outcome ,Leukocytosis ,Splenic Neoplasms ,Hemangiosarcoma ,Humans ,Anemia ,Middle Aged ,Tomography, X-Ray Computed ,Thrombocytopenia - Abstract
Primary angiosarcoma of the spleen is a rare neoplasm arising from endothelial cells. It is an aggressive neoplasm with a poor prognosis. We report a case of 61-year-old Caucasian man who presented with shortness of breath, anemia, leukocytosis, and thrombocytopenia. Ultrasound Sonogram (US) and Computed Tomography (CT) scans revealed a massively enlarged spleen with numerous enhancing hypodense lesions. The spleen was adherent to the omentum, retroperitoneum, and tail of the pancreas. Image-guided Fine Needle Aspiration (FNA) revealed an atypical spindle cell lesion. Resection of the spleen and attached tail of pancreas was performed. Histological examination and immunohistochemical studies revealed a diffuse vascular malignant neoplasm with features of angiosarcoma. The patient appeared disease free after resection. He died within 5 months of unknown etiology.
- Published
- 2014
20. Oropharyngeal squamous cell carcinoma in the veteran population: Association with traditional carcinogen exposure and poor clinical outcomes
- Author
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Vlad C, Sandulache, John, Hamblin, Syeling, Lai, Todd, Pezzi, Heath D, Skinner, Numan A, Khan, Shayan M, Dioun, Christine, Hartman, Jennifer, Kramer, Elizabeth, Chiao, Xiaodong, Zhou, and Jose P, Zevallos
- Subjects
Adult ,Male ,Hospitals, Veterans ,Kaplan-Meier Estimate ,Risk Assessment ,Disease-Free Survival ,Article ,Cohort Studies ,Humans ,Neoplasm Invasiveness ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Retrospective Studies ,Veterans ,Smoking ,Chemoradiotherapy ,Middle Aged ,Prognosis ,Survival Analysis ,Alcoholism ,Oropharyngeal Neoplasms ,Multivariate Analysis ,Carcinogens ,Carcinoma, Squamous Cell ,Neoplasm Recurrence, Local - Abstract
A significant fraction of oropharyngeal squamous cell carcinoma (SCC) cases is associated with traditional carcinogens; in these patients, treatment response and clinical outcomes remain poor.We evaluated patient, tumor, and treatment characteristics for 200 veterans with oropharyngeal SCC treated at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) between 2000 and 2012.Most patients (77%) were white and heavy smokers. Twenty-seven patients required tracheostomy and 63 required gastrostomy placement during treatment. Overall survival (OS) at 5 years was 40%. Survival was impacted by T classification, treatment intensity, completion of treatment, and p16 tumor status. Almost 30% of patients were unable to complete a treatment regimen consistent with National Comprehensive Cancer Network (NCCN) guidelines.Oropharyngeal SCC in veterans is associated with traditional carcinogens and poor clinical outcomes. Despite heavy smoking exposure, p16 tumor status significantly impacts survival. Careful consideration must be given to improving treatment paradigms for this cohort given their limited tolerance for treatment escalation.
- Published
- 2014
21. Association of the HLA-DRB1 with scleroderma in Chinese population
- Author
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Shicheng Guo, Li Jin, Wenyu Wu, Xiaodong Zhou, John D. Reveille, Syeling Lai, Maureen D. Mayes, Gang Guo, Li Yang, Rong Xiao, Lin Yi, Yuan Li, Hejian Zou, Dongyi He, Jiucun Wang, Shervin Assassi, Haiyan Chu, Xinjian Guo, and Wenzhen Tu
- Subjects
Male ,musculoskeletal diseases ,China ,Genotype ,Quantitative Trait Loci ,Immunology ,lcsh:Medicine ,Genome-wide association study ,Human leukocyte antigen ,Asian People ,Rheumatology ,Medicine and Health Sciences ,Humans ,Medicine ,Genetic Predisposition to Disease ,Allele ,skin and connective tissue diseases ,lcsh:Science ,HLA-DRB1 ,Genotyping ,Allele frequency ,Clinical Genetics ,Genetics ,Scleroderma, Systemic ,Multidisciplinary ,integumentary system ,business.industry ,Genetic heterogeneity ,lcsh:R ,Biology and Life Sciences ,Chinese people ,Female ,lcsh:Q ,business ,HLA-DRB1 Chains ,Research Article - Abstract
Multiple alleles of the Human leukocyte antigen (HLA) DRB1 have been strongly associated with systemic sclerosis (SSc) and its clinical or serological subsets. However, the associations vary in different ethnic populations. To define SSc-risk and/or -protective alleles of HLA-DRB1 in Chinese population, we studied a Han Chinese cohort containing 585 patients with SSc and 458 gender-matched, unrelated controls. The HLA-DRB1 genotyping was performed with sequence-based typing method. Exact p-values were obtained (Fisher’s test) from 2×2 tables of allele frequency and disease status. The major SSc-risk allele subtypes of HLA-DRB1 are the DRB1*15∶02 and *16∶02 in this Chinese cohort. Particularly, DRB1*15∶02 was most significantly associated with anti-centromere autoantibodies (ACA) positive, and DRB1*16∶02 with anti-topoisomerase I autoantibodies (ATA) positive patients. On the other hand, DRB1*01∶01 and *04∶06 were strong SSc-protective alleles in Chinese, especially in patients who were ACA positive and had diffuse cutaneous SSc (dcSSc), respectively. In addition, DRB1*11 and *07∶01 also showed significant association with SSc as a risk for and protection from SSc, respectively, and which is consistent with the studies of Spanish, US Caucasian and Hispanic populations. DRB1*15 was associated with ATA positive Chinese SSc that is consistent with Black South African and Korean SSc. These findings of HLA-DRB1 alleles in association with Chinese SSc provide the growing knowledge of genetics of SSc, and indicate that the genetic heterogeneity among ethnicities may significantly impact the complex trait of SSc.
- Published
- 2014
22. Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: Biological and clinical implications
- Author
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Gary L. Clayman, Jeffrey L. Myers, William F. Benedict, Syeling Lai, Adel K. El-Naggar, Jain Hua Zhou, Mario A. Luna, and Susan A. Tucker
- Subjects
Adult ,Male ,Tumor suppressor gene ,Cyclin D ,Blotting, Western ,Biology ,medicine.disease_cause ,Retinoblastoma Protein ,Pathology and Forensic Medicine ,Cyclin D1 ,medicine ,Humans ,Laryngeal Neoplasms ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Aged, 80 and over ,DNA Methylation ,Middle Aged ,Cell cycle ,Immunohistochemistry ,Squamous carcinoma ,Epidermoid carcinoma ,Mutation ,Carcinoma, Squamous Cell ,Cancer research ,biology.protein ,Female ,Mouth Neoplasms ,Carcinogenesis ,Immunostaining - Abstract
Cyclin D1, p16, and Rb genes play a critical role in the regulation of the G1-S transition of the cell cycle and are frequently altered in several neoplastic entities. Analysis of the protein products of these genes by molecular and immunohistochemical methods provides information on their functional status and allows for the phenotypic evaluation of tumor cells. We performed Western blotting and immunohistochemical analysis on tissues from 35 primary oral and laryngeal squamous carcinoma specimens with previous molecular analysis of the p16 gene and correlated the results with relevant clinicopathologic factors. Our study shows significant concordance between Western blotting and immunostaining results for cyclin D1 (P = .01), p16 proteins (P = .01), and Rb (P = .04). Heterogeneous staining of tumor cells and the positivity of non-neoplastic host elements for Rb by immunohistochemistry contributed to the discrepancy noted in some tumors by Western blotting. Significant reciprocal relationship between p16 and Rb proteins was observed (P < .001); in most tumors, absence of p16 (89%) and detectable Rb (94%) proteins were found. Two tumors had negative cyclin D1 expression, and one third overexpressed this protein. There was a lack of correlation between cyclin D1 overexpression and the clinicopathologic factors studied. Our results indicate that the absence of p16 in most of these tumors may constitute an early tumorigenic event and that the loss of the Rb function plays a minor role in HNSC.
- Published
- 1999
23. Loss of retinoblastoma gene function and heterozygosity at the RB locus in renal cortical neoplasms
- Author
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Syeling Lai, William F. Benedict, Adel K. El-Naggar, and Susan A Silver
- Subjects
Adult ,Male ,Heterozygote ,Kidney Cortex ,Blotting, Western ,Locus (genetics) ,Biology ,medicine.disease_cause ,Retinoblastoma Protein ,Pathology and Forensic Medicine ,Loss of heterozygosity ,medicine ,Humans ,Genes, Retinoblastoma ,Aged ,Chromosome 13 ,Chromosomes, Human, Pair 13 ,Retinoblastoma ,Chromosome ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Kidney Neoplasms ,Blot ,Cancer research ,Female ,Chromosome Deletion ,Carcinogenesis - Abstract
Alteration of the retinoblastoma (RB) gene, located on chromosome 13q14, has been implicated in the pathogenesis and biological behavior of several human cancers. We investigated the RB gene status by Western blotting and immunohistochemical analysis, as well as loss of heterozygosity (LOH) at the RB locus in 21 primary human renal neoplasms (including 3 oncocytomas). In only 1 of 21 tumors was there a discrepancy between Western blot and immunochemical staining. Overall, LOH was noted in 6 of 12 informative cases. However, only one of the tumors with LOH at the RB locus had loss of RB protein expression by both Western blot and immunohistochemical analysis. Loss of RB function was found in 4 of 18 carcinomas and in none of 3 oncocytomas as determined by absent RB nuclear staining in tumor cells. LOH at chromosome 13q14 was more noted in high-grade, DNA aneuploid, high-stage tumors and in patients with poor outcome. These results imply that (1) there is likely another tumor-suppressor gene on chromosome 13 involved in renal carcinogenesis, (2) LOH at chromosome 13q loci may be associated with aggressive behavior, and (3) the loss of RB function may have a role in a subset of renal carcinomas.
- Published
- 1997
24. Sequential p53 mutation analysis of pre-invasive and invasive head and neck squamous carcinoma
- Author
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Syeling Lai, Randal S. Weber, Helmuth Goepfert, Adel K. El-Naggar, John G. Batsakis, M. Luna, and Xiao‐Dong ‐D Zhou
- Subjects
Adult ,Male ,Silent mutation ,Cancer Research ,Molecular Sequence Data ,Biology ,Exon ,Carcinoma ,medicine ,Humans ,Neoplastic transformation ,Gene ,Polymorphism, Single-Stranded Conformational ,Aged ,Base Sequence ,Single-strand conformation polymorphism ,Middle Aged ,Genes, p53 ,medicine.disease ,Stop codon ,Squamous carcinoma ,Oncology ,Head and Neck Neoplasms ,Mutation ,Carcinoma, Squamous Cell ,Cancer research ,Female - Abstract
Single-stranded conformation polymorphism (SSCP) and direct sequencing were performed on uninvolved mucosa, severe dysplasia and invasive carcinoma samples from 20 patients with head and neck squamous carcinoma. Seven (35%) of the non-invasive lesions and 15 (75%) of the invasive carcinomas manifested p53 mutations. Although the majority of mutations were mis-sense, resulting in single amino acid substitution, a silent mutation encoding for the same amino acid and 2 non-sense mutations encoding a stop codon were also observed. Mutations in invasive carcinoma were mostly in exon 8 and involved codons 296, 288 and 298; non-invasive lesions showed more mutations at exons 5 to 7. Five lesions showed simultaneous mutations in 2 different exons; in 3 both non-invasive and invasive carcinomas showed primary mutation at exons 5 to 7, and invasive carcinoma showed a secondary mutation at exon 8. Different codon mutations in the same exon between dysplastic and the corresponding carcinoma samples were found in 2 cases. p53 alterations were not observed in any of the normal mucosa samples. No apparent association between p53 mutations and conventional clinicopathologic parameters, including DNA content, was found in this cohort. Our study indicates that (i)p53 alteration is an early event in the genesis of a subset of head and neck squamous carcinomas, (ii) normal mucosa within the resected specimens lacked p53 mutation, (iii) sequential mutations of different exons of the p53 gene suggests accumulation of genetic alterations during the neoplastic transformation of these lesions and (iv) the difference in codon mutation of the same exon between dysplastic and corresponding carcinoma suggests an independent clonal development. © 1995 Wiley-Liss, Inc.
- Published
- 1995
25. Abstract A48: Overexpression of Semaphorin-3E enhances pancreatic cancer cell proliferation ad is associated with patient poor survival
- Author
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Syeling Lai, Dali Li, Lin-Kin Yong, William E. Fisher, Changyi Chen, Qianxin Mo, Qizhi Yao, Ethan Poteet, and Zhengdong Liang
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,endocrine system diseases ,Cell growth ,Cancer ,Biology ,medicine.disease ,Metastasis ,Downregulation and upregulation ,Cell culture ,Internal medicine ,Pancreatic cancer ,medicine ,Immunohistochemistry ,Survival rate - Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death in the US with a 5-year survival rate of less than 6%. There is an urgent need for a better understanding of PDAC in order to find better therapeutic targets. Two recent large-scale genomic analyses of human PDAC have uncovered increased copy numbers of an axon-guidance gene SEMA3E that codes for Semaphorin-3E (Sema3E). Several recent reports have implicated Sema3E in metastasis of breast and colon cancers, particularly in promoting tumor cell migration and invasion, as well as inducing epithelial-to-mesenchymal transition (EMT). Here, we evaluated Sema3E expression levels in human pancreatic cancer tissue samples and correlation with patient survival; we further studied roles of Sema3E in pancreatic cancer cell proliferation. Materials and Methods: To determine expression levels of Sema3E in PDAC, qPCR analysis was performed on resected human PDAC samples and matched tissue controls, and immunohistochemical (IHC) analysis was performed on resected human PDAC tissues and tissues from a mouse model of PDAC. To generate Sema3E-overexpressing stable cells, human PDAC cell lines were transduced with Sema3E-expressing lentivirus or vector control. To generate Sema3E knock-down cell lines, CRISPR/Cas9 system was used to target Sema3E in the genome. MTT assay was performed on Sema3E-overexpressed cells to determine the effects of Sema3E on cell proliferation. Results: Using qPCR, Sema3E was found to be significantly upregulated in 46% of human PDAC samples (n=24), with an average fold-change of 9.54. IHC analyses of human and mouse PDAC revealed higher expression of Sema3E in tumor cells compared to normal cells (n=54). Interestingly, in human PDAC, Sema3E expression was concentrated in the nuclei of tumor cells while it has been reported to be a secreted protein. We found a positive correlation between high N/C ratio of Sema3E expression (i.e. expression in the nucleus relative to the cytoplasm) and poor survival. In addition, we also found overexpression of Sema3E is correlated with patient poor survival by analyzing a TCGA dataset (n=78). Overexpression of Sema3E in human PDAC cell lines enhanced cell proliferation and migration in vitro, while knocking-down Sema3E resulted in reduced cell proliferation. Conclusions: Our findings indicate that Sema3E is overexpressed in PDAC and is correlated with patient poor survival. Sema3E may play a pathogenic role in PDAC progression by enhancing tumor cell proliferation. These findings suggest that Sema3E could be an attractive novel therapeutic target for PDAC. Citation Format: Lin-Kin Yong, Syeling Lai, Zhengdong Liang, Dali Li, Ethan Poteet, William Fisher, Qianxin Mo, Changyi Chen, Qizhi Yao. Overexpression of Semaphorin-3E enhances pancreatic cancer cell proliferation ad is associated with patient poor survival. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A48.
- Published
- 2016
26. Correlation of Comorbidities and Immune Cellular Response in Biopsies and Surgical Resections of Gout
- Author
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Syeling Lai and Xiaodong Zhou
- Subjects
Pathology ,medicine.medical_specialty ,Cell type ,business.industry ,H&E stain ,General Medicine ,medicine.disease ,Gout ,chemistry.chemical_compound ,Immune system ,chemistry ,Giant cell ,Diabetes mellitus ,Hyperlipidemia ,medicine ,Uric acid ,business - Abstract
Background: There are many published studies of comorbidities and in vitro analysis of inflammatory mechanism in gout, but only few in vivo tissue examinations for immune response cells were reported. The association of comorbidities and immune cell response has not been well documented. Our objective is to examine the immune cell types and quantity in gout tissue, identify clinical parameters of gout associated risk factors in corresponding patients, and analyze the association of individual cell type with comorbidities. Methods: Biopsied or resected tissues from 33 patients diagnosed as gout were used for this study. Cell count was performed on Hematoxylin and Eosin stained sections for macrophages, plasma cells, neutrophils and on immunostained slides for T- and B-lymphocyte. Results: The mean patient age was 62 year-old with 57.6% patients over 60 year-old. Mean serum uric acid level was 8.5 mg/dl. The average body mass index was 30.6 kg/m2. Majority of the patients had history of hypertension (93.9%). There were 34.4% and 28.1% of patients admitted history of smoking and alcohol intake, respectively. Hyperlipidemia and diabetes mellitus were seen in 78.8% and 45.5% of patients, respectively. H and E stained sections demonstrated the crystalline deposits rimmed by palisading multinucleated giant cells, macrophages, and chronic inflammatory cells. Average cell counts of T-cells, B-cells, multinucleated giant cells, mononucleated macrophages, plasma cells and neutrophils are: 33.0, 11.8, 7.3, 26.8, 0.38, and 7.4 cells/ High Power Field respectively. Of significant values are associations of plasma cells and B-cell with hypertension, T-cell with hyperlipidemia, uric acid with smoking as well as multinucleated giant cells with uric acid. Conclusion: Most of the gout patients showed an elevated uric acid level. The participating inflammatory cells in local tissues were predominantly T-lymphocytes, macrophages and multinucleated giant cells. Comorbidity factors including hypertension, hyperlipidemia, diabetes, smoking and drinking may precipitate gout by stimulating immune cell proliferation.
- Published
- 2012
27. Cyclooxygenase-2 protein reduces tamoxifen and N-(4-hydroxyphenyl)retinamide inhibitory effects in breast cancer cells
- Author
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Syeling Lai, Yu Jiang Li, Yolanda Gutiérrez-Puente, William Fraser Symmans, Ana M. Tari, and Ann Marie Simeone
- Subjects
Selective Estrogen Receptor Modulators ,medicine.medical_specialty ,Fenretinide ,Antineoplastic Agents ,Breast Neoplasms ,Pathology and Forensic Medicine ,Inhibitory Concentration 50 ,Breast cancer ,Internal medicine ,Cell Line, Tumor ,medicine ,Humans ,Raloxifene ,skin and connective tissue diseases ,Molecular Biology ,business.industry ,Kinase ,Membrane Proteins ,Cell Biology ,medicine.disease ,Antiestrogen ,Clone Cells ,Tamoxifen ,Endocrinology ,Selective estrogen receptor modulator ,Cyclooxygenase 2 ,Drug Resistance, Neoplasm ,Cancer cell ,Cancer research ,Female ,business ,Estrogen receptor alpha ,medicine.drug - Abstract
Approximately 30-40% of estrogen receptor alpha (ERalpha)-positive breast tumors express high levels of the cyclooxygenase-2 (COX-2) protein, and these high levels have been associated with a poorer prognosis in breast cancer patients. We speculate that high levels of COX-2 induce drug resistance in ERalpha-positive breast tumors, thus reducing the survival rate of patients with such tumors. Human breast cancer cell lines that express high levels of COX-2 are generally ERalpha negative. To determine whether COX-2 induces drug resistance, plasmids encoding the COX-2 gene were stably transfected into ERalpha-positive MCF-7 human breast cancer cells (MCF-7/COX-2). MCF-7/COX-2 cells were resistant to the selective estrogen receptor modulator tamoxifen but not to its analog, raloxifene. MCF-7/COX-2 cells were also resistant to the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) but not to its analog, all-trans retinoic acid. In contrast, the sensitivities of MCF-7/COX-2 cells to doxorubicin and paclitaxel were similar to those of the parental MCF-7 cells. We then determined which COX-2 product, prostaglandin E2 (PGE2) or prostaglandin F2alpha is involved in the COX-2-mediated drug resistance. PGE2, but not PGF2alpha, blocked the antiproliferative effects of tamoxifen and 4-HPR. Agonists that activate PGE2 receptors and their downstream kinase effectors, protein kinases A and C, also blocked the growth inhibitory effects of these drugs. Increased levels of Bcl-2 and Bcl-XL proteins have been reported in mammary tumors of COX-2 transgenic mice and in human colon cancer cell lines that have high levels of COX-2. However, we did not observe any changes in Bcl-2, Bcl-XL, or Bax expression induced by COX-2 or PGE2. Here we report the novel findings that COX-2 uses PGE2 to stimulate the activities of protein kinases A and C to induce selectively tamoxifen and 4-HPR resistance in ERalpha-positive breast cancer cells.
- Published
- 2005
28. Differential expression profiling of head and neck squamous carcinoma: significance in their phenotypic and biological classification
- Author
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Madelene M. Coombes, Bao Le, Feng Zhan, Gary L. Clayman, J. Jack Lee, Adel K. El-Naggar, Waun Ki Hong, Syeling Lai, Hyung Woo Kim, and Mario A. Luna
- Subjects
Adult ,Male ,Cancer Research ,DNA, Complementary ,Biology ,Bioinformatics ,Genome ,Gene expression ,Genetics ,Humans ,Molecular Biology ,Gene ,Aged ,Microarray analysis techniques ,Gene Expression Profiling ,Cell Differentiation ,Middle Aged ,Phenotype ,Squamous carcinoma ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,Epidermoid carcinoma ,Head and Neck Neoplasms ,Subtraction Technique ,Cancer research ,Carcinoma, Squamous Cell ,Female ,Cell Division - Abstract
The genetic events associated with the development and progression of head and neck squamous carcinoma (HNSC) are largely unknown. We analysed 12 matched pairs of histologically normal squamous mucosa and tumor specimens from six conventional and six phenotypic variants HNSC to define the differentially expressed genes in these tumors. Parallel expression analysis of 8055 unique genes was performed, and the level of the hybridization signal for each gene was measured after normalization. Hierarchical cluster analysis of the expressed genes showed distinct inter- and intra-tumoral patterns in and between conventional squamous carcinoma and squamous carcinoma variants. We also identified 26 (0.32%) differentially expressed genes that were consistently different between matched pairs of normal and tumor specimens; a selected set of the overexpressed genes was validated using real-time quantitative RT-PCR. The majority of the genes were associated with differentiation and proliferation. Our study defines a set of genes that could form the basis for the construction of limited HNSC targeted expression array and in-depth studies and further highlights gene profile differences that may be useful in pathobiologic classification of HNSC.
- Published
- 2001
29. p73 gene alterations and expression in primary oral and laryngeal squamous carcinomas
- Author
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Syeling Lai, Madelene M. Coombes, Guillermina Lozano, Scott M. Lippman, Betsy Mims, Gary L. Clayman, Mario A. Luna, and Adel K. El-Naggar
- Subjects
Silent mutation ,Adult ,Male ,Cancer Research ,Tumor suppressor gene ,Locus (genetics) ,Biology ,medicine.disease_cause ,Gene product ,Loss of heterozygosity ,Cohort Studies ,medicine ,Humans ,Genes, Tumor Suppressor ,Gene ,Laryngeal Neoplasms ,DNA Primers ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Tumor Suppressor Proteins ,Nuclear Proteins ,Tumor Protein p73 ,General Medicine ,Middle Aged ,Molecular biology ,Squamous carcinoma ,DNA-Binding Proteins ,Chromosomes, Human, Pair 1 ,Mutation ,Cancer research ,Carcinoma, Squamous Cell ,Mutagenesis, Site-Directed ,Female ,Mouth Neoplasms ,Carcinogenesis - Abstract
p73, a recently identified gene, maps to chromosome region 1p36.3, which is frequently deleted in a variety of solid tumors. Although the gene shares sequence and functional homologies with p53, its suppressor function has not been proven. We investigated for the first time the genetic and expression status of the p73 gene and analyzed its flanking microsatellite loci on chromosome 1p36.3 in 67 primary oral and laryngeal squamous cell carcinomas to determine their association with these tumors. Our results reveal two missense mutations at codons 469 and 477 and a silent mutation at codon 349 in the C-terminal domain. Site-directed mutagenesis of p73 cDNA with these mutations and a p21 transactivation assay failed to show any significant functional consequences of these mutations. Microsatellite analysis of the flanking loci of p73 in region 1p36 showed overall alterations (loss of heterozygosity and instability) frequency of 39%, 16% at the proximal marker and 46% at the distal markers. Of the 21 cases for which we did protein expression analyses, 11 tumors had a >2-fold variation compared with matching histologically normal mucosa. Our study shows that: (i) intragenic alterations in this gene are rare and lack functional significance; (ii) its variable expression argues against a tumor suppressor function; (iii) this gene plays a minor role in head and neck squamous carcinoma; (iv) a distal site to this gene on 1p36 may harbor another suppressor gene.
- Published
- 2001
30. Frequent loss of imprinting at the IGF2 and H19 genes in head and neck squamous carcinoma
- Author
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Helmuth Goepfert, Waun Ki Hong, Susan A. Tucker, Gary L. Clayman, Vicki Huff, Adel K. El-Naggar, and Syeling Lai
- Subjects
Adult ,Male ,Cancer Research ,Heterozygote ,RNA, Untranslated ,Somatic cell ,Muscle Proteins ,medicine.disease_cause ,Genomic Imprinting ,Insulin-Like Growth Factor II ,Genetics ,medicine ,Humans ,Epigenetics ,Imprinting (psychology) ,Molecular Biology ,Aged ,DNA Primers ,Aged, 80 and over ,biology ,Base Sequence ,Chromosomes, Human, Pair 11 ,Homozygote ,Middle Aged ,female genital diseases and pregnancy complications ,Squamous carcinoma ,Epidermoid carcinoma ,Head and Neck Neoplasms ,Insulin-like growth factor 2 ,embryonic structures ,biology.protein ,Cancer research ,Carcinoma, Squamous Cell ,Female ,RNA, Long Noncoding ,Carcinogenesis ,Genomic imprinting - Abstract
Genomic imprinting is an inherited epigenetic phenomenon that results in parental – origin – specific gene expression in somatic cells. Relaxation or loss of this feature in certain genes has been demonstrated in several pediatric and adult neoplasms, suggesting an association with tumorigenesis. We analysed 64 primary untreated head and neck squamous carcinoma for the loss of imprinting in the IGF2 and H19 genes to determine the implications of this alteration in the development and progression of these tumors. Forty-nine (77%) of the 64 tumors were informative for imprinting analyses of these genes. IGF2 and H19 were imprinted in all normal squamous epithelium examined. Twelve (37.5%) of 32 tumors informative for H19 and 11 (40.7%) of 27 tumors informative for IGF2 manifested loss of imprinting. Ten tumors were informative for both genes, of which four maintained the constitutional imprinting and six showed loss of imprinting at either H19 or IGF2. These data suggest that loss of imprinting at the IGF2 and H19 loci play a role in the oncogenesis of head and neck carcinoma.
- Published
- 1999
31. Accuracy of a Malignant or Suspicious Diagnosis on Pancreatic FNA with Immediate Cytopathologist Assessment: A Review of 200 Malignant Cases Over 22 Years
- Author
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Syeling Lai and Linda K. Green
- Subjects
medicine.medical_specialty ,business.industry ,medicine ,Radiology ,business ,Pathology and Forensic Medicine - Published
- 2013
32. Non-radioactive DNA probe and polymerase chain reaction procedures for the specific detection of Acanthamoeba
- Author
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Morteza Asgari, Syeling Lai, and Henry R. Henney
- Subjects
Molecular Sequence Data ,Acanthamoeba ,Polymerase Chain Reaction ,Sensitivity and Specificity ,law.invention ,Restriction fragment ,Microbiology ,Plasmid ,law ,parasitic diseases ,Animals ,Humans ,Molecular Biology ,Polymerase chain reaction ,biology ,Base Sequence ,Inverse polymerase chain reaction ,Hybridization probe ,Nucleic Acid Hybridization ,Cell Biology ,Amebiasis ,DNA, Protozoan ,biology.organism_classification ,DNA extraction ,Molecular biology ,eye diseases ,biology.protein ,Acanthamoeba castellanii ,DNA Probes - Abstract
Acanthamoebae are potential pathogens which can cause serious infections of humans. A non-radioactive rDNA probe and polymerase chain reaction (PCR) amplification procedures which are specific, rapid, sensitive and safe for the detection of Acanthamoeba have been developed. A restriction fragment (126 bp; ArDNA-a) from a variable region of the cloned 26S rDNA unit of Acanthamoeba castellanii (from plasmid pAR2) was labelled by biotinylation. Cells and DNAs were incubated with the labelled rDNA probe to define conditions providing the highest hybridization specificity for Acanthamoeba by both colorimetric and chemiluminescent assays. Four recent isolates of Acanthamoeba, Acanthamoeba polyphaga, various bacteria, Herpes simplex virus, other eukaryotic amoebae and human cell lines, were sources of DNA for testing. The rDNA probe was found to be highly specific for Acanthamoeba and is capable of directly detecting about 250 cells without prior DNA purification. PCR primers for this unique ArDNA-a fragment have also been designed. Amplification of the targeted sequence by PCR using those primers yielded a single product which was specifically generated for Acanthamoeba template DNA and not DNA from the other control cells. This PCR procedure provided increased sensitivity with the direct detection of as few as 10 Acanthamoeba cells.
- Published
- 1994
33. Decreased catalytic function with altered sumoylation of DNA topoisomerase I in the nuclei of scleroderma fibroblasts
- Author
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Roozbeh Sharif, Xiaodong Zhou, Filemon K. Tan, Syeling Lai, Shervin Assassi, Wei Lin, Tom Xia, Xinjian Guo, Frank C. Arnett, and Mavin J Fritzler
- Subjects
Male ,Cell type ,Immunoprecipitation ,Blotting, Western ,Immunology ,SUMO protein ,Biology ,Real-Time Polymerase Chain Reaction ,Transfection ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,medicine ,Humans ,Immunology and Allergy ,RNA, Small Interfering ,skin and connective tissue diseases ,030304 developmental biology ,Cell Nucleus ,0303 health sciences ,Scleroderma, Systemic ,integumentary system ,Reverse Transcriptase Polymerase Chain Reaction ,Sumoylation ,RNA ,Fibroblasts ,Immunohistochemistry ,Molecular biology ,Cell biology ,Blot ,Cell nucleus ,medicine.anatomical_structure ,Real-time polymerase chain reaction ,DNA Topoisomerases, Type I ,030220 oncology & carcinogenesis ,Biocatalysis ,Female ,sense organs ,Research Article - Abstract
Introduction Sumoylation is involved in nucleolus-nucleoplasm transport of DNA topoisomerase I (topo I), which may associate with changes of cellular and topo I functions. Skin fibroblasts of patients with systemic sclerosis (SSc) exhibit profibrotic cellular changes. The aims of this study were to examine the catalytic function and sumoylation of topo I in the nuclei of SSc fibroblasts, a major cell type involved in the fibrotic process. Methods Eleven pairs of fibroblast strains obtained from nonlesional skin biopsies of SSc patients and age/sex/ethnicity-matched normal controls were examined for catalytic function of nuclear topo I. Immunoprecipitation (IP)-Western blots were used to examine sumoylation of fibroblast topo I. Real-time quantitative RT-PCR was used to measure transcript levels of SUMO1 and COL1A2 in the fibroblasts. Results Topo I in nuclear extracts of SSc fibroblasts generally showed a significantly lower efficiency than that of normal fibroblasts in relaxing equivalent amounts of supercoiled DNA. Increased sumoylation of topo I was clearly observed in 7 of 11 SSc fibroblast strains. Inhibition of SUMO1 with SUMO1 siRNA improved the catalytic efficiency of topo I in the SSc fibroblasts. In contrast, sumoylation of recombinant topo I proteins reduced their catalytic function. Conclusions The catalytic function of topo I was decreased in SSc fibroblasts, to which increased sumoylation of topo I may contribute.
- Published
- 2011
34. Nucleotide sequence of a portion of the 26S rDNA of Acanthamoeba
- Author
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Syeling Lai and Henry R. Henney
- Subjects
Genetics ,biology ,Molecular Sequence Data ,Nucleic acid sequence ,Acanthamoeba ,DNA, Protozoan ,biology.organism_classification ,DNA, Ribosomal ,law.invention ,Restriction map ,law ,RNA, Ribosomal ,Recombinant DNA ,Acanthamoeba castellanii ,Protozoa ,Animals ,Base sequence ,Ribosomal DNA - Published
- 1993
35. Primary Splenic Angiosarcoma Associated with Anemia, Leukocytosis and Thrombocytopenia.
- Author
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Aqil, Barina, Green, Linda K., and Syeling Lai
- Published
- 2014
36. Decreased catalytic function with altered sumoylation of DNA topoisomerase I in the nuclei of scleroderma fibroblasts.
- Author
-
Xiaodong Zhou, Wei Lin, Tan, Filemon K., Assassi, Shervin, Fritzler, Mavin J., Xinjian Guo, Sharif, Roozbeh, Tom Xia, Syeling Lai, and Arnett, Frank C.
- Published
- 2011
- Full Text
- View/download PDF
37. Cyclooxygenase-2 protein reduces tamoxifen and N-(4-hydroxyphenyl)retinamide inhibitory effects in breast cancer cells.
- Author
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Tari, Ana M., Simeone, Ann-Marie, Yu-Jiang Li, Gutierrez-Puente, Yolanda, Syeling Lai, and Symmans, William F.
- Published
- 2005
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38. Attenuation of fibrosis in vitro and in vivo with SPARC siRNA
- Author
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Syeling Lai, Xinjian Guo, Xuefeng Zhang, Jiucun Wang, Xiaodong Zhou, Benoit de Crombrugghe, Sonali Sonnylal, and Frank C. Arnett
- Subjects
Pulmonary Fibrosis ,Immunology ,Receptor, Transforming Growth Factor-beta Type I ,Gene Expression ,Mice, Transgenic ,Protein Serine-Threonine Kinases ,Transfection ,Bleomycin ,Collagen Type I ,Extracellular matrix ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Rheumatology ,In vivo ,Fibrosis ,Research article ,Pulmonary fibrosis ,medicine ,Animals ,Immunology and Allergy ,Osteonectin ,Gene Knock-In Techniques ,Gene Silencing ,RNA, Small Interfering ,Lung ,Cells, Cultured ,Skin ,030304 developmental biology ,0303 health sciences ,biology ,integumentary system ,Matricellular protein ,Connective Tissue Growth Factor ,Fibroblasts ,medicine.disease ,Molecular biology ,Mice, Inbred C57BL ,CTGF ,Disease Models, Animal ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Receptors, Transforming Growth Factor beta - Abstract
Introduction SPARC is a matricellular protein, which, along with other extracellular matrix components including collagens, is commonly over-expressed in fibrotic diseases. The purpose of this study was to examine whether inhibition of SPARC can regulate collagen expression in vitro and in vivo, and subsequently attenuate fibrotic stimulation by bleomycin in mouse skin and lungs. Methods In in vitro studies, skin fibroblasts obtained from a Tgfbr1 knock-in mouse (TBR1CA; Cre-ER) were transfected with SPARC siRNA. Gene and protein expressions of the Col1a2 and the Ctgf were examined by real-time RT-PCR and Western blotting, respectively. In in vivo studies, C57BL/6 mice were induced for skin and lung fibrosis by bleomycin and followed by SPARC siRNA treatment through subcutaneous injection and intratracheal instillation, respectively. The pathological changes of skin and lungs were assessed by hematoxylin and eosin and Masson's trichrome stains. The expression changes of collagen in the tissues were assessed by real-time RT-PCR and non-crosslinked fibrillar collagen content assays. Results SPARC siRNA significantly reduced gene and protein expression of collagen type 1 in fibroblasts obtained from the TBR1CA; Cre-ER mouse that was induced for constitutively active TGF-β receptor I. Skin and lung fibrosis induced by bleomycin was markedly reduced by treatment with SPARC siRNA. The anti-fibrotic effect of SPARC siRNA in vivo was accompanied by an inhibition of Ctgf expression in these same tissues. Conclusions Specific inhibition of SPARC effectively reduced fibrotic changes in vitro and in vivo. SPARC inhibition may represent a potential therapeutic approach to fibrotic diseases.
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