36 results on '"Zhen Shang"'
Search Results
2. Downregulation of circ_0012152 inhibits proliferation and induces apoptosis in acute myeloid leukemia cells through the miR‐625‐5p/SOX12 axis
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Jiaying Wu, Xi Ming, Zhen Shang, and Yi Xiao
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Cancer Research ,Down-Regulation ,Apoptosis ,Transfection ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Viability assay ,Progenitor cell ,Cell Proliferation ,Gene knockdown ,medicine.diagnostic_test ,Cell growth ,Chemistry ,Myeloid leukemia ,Hematology ,General Medicine ,Middle Aged ,Cell cycle ,Leukemia, Myeloid, Acute ,MicroRNAs ,Haematopoiesis ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Cancer research ,030215 immunology - Abstract
Acute myeloid leukemia (AML) is a highly heterogeneous disease featured by a clonal proliferation derived from primitive hematopoietic stem/progenitor cells. Circular RNAs (circRNAs) have been identified as crucial regulators in the progression of various cancers, including AML. However, the molecular mechanism of AML is still not definite. This study aimed to explore the influences of circ_0012152 on cell development in AML cells and the underlying regulatory mechanism. The expression of circ_0012152, microRNA-625-5p (miR-625-5p) and sex-determining region Y-related high mobility group box 12 (SOX12) was detected by quantitative real-time polymerase chain reaction. The proliferation of AML cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for cell viability, 5-ethynyl-2'-deoxyuridine incorporation assay for DNA biosynthesis and flow cytometry for cell cycle distribution, respectively. The death of AML cells was detected by flow cytometry. The protein expression was assessed by Western blot assay. Dual-luciferase reporter and RNA immunoprecipitation assays were carried out to examine the relationships among circ_0012152, miR-625-5p and SOX12. The expression of circ_0012152 was increased in AML tissues and cells and circ_0012152 knockdown suppressed proliferation and promoted death in AML cells. Further exploration revealed that circ_0012152 inhibited miR-625-5p expression and downregulation of miR-625-5p overturned the effects of circ_0012152 knockdown on proliferation and death in AML cells. Moreover, miR-625-5p targeted SOX12 and circ_0012152 facilitated the expression of SOX12 by relieving miR-625-5p-mediated inhibitory effect on SOX12 in AML cells. Circ_0012152 knockdown suppressed cell proliferation and promoted death by targeting SOX12 mediated by miR-625-5p in AML cells.
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- 2021
3. Restorative therapy using microglial depletion and repopulation for central nervous system injuries and diseases
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Weipeng Shi, Jing Zhang, Zhen Shang, Yingze Zhang, Yanzhi Xia, Haitao Fu, and Tengbo Yu
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Central Nervous System ,Mice ,Immunology ,Animals ,Brain ,Humans ,Trauma, Nervous System ,Immunology and Allergy ,Neurodegenerative Diseases ,Microglia - Abstract
Microglia are important resident immune cells in the central nervous system (CNS) and play an important role in its development, homeostasis, and disease treatments. Activated microglia perform diverse functions in mouse models of CNS neurodegenerative diseases or deficits. In humans, microglia have been linked to various neurodegenerative diseases. Following brain or spinal cord injury, microglia express pro- and anti-inflammatory phenotypes at different stages of recovery. With the development of pharmacological and genetic tools for microglial depletion, studies have demonstrated that microglial depletion exerts both positive and negative effects in the treatment of CNS diseases. Notably, microglial depletion provides an empty niche that stimulates production of new microglia. Microglial depletion and repopulation can not only treat diseases by eliminating dysfunctional microglia but can also provide an indication of the molecular mechanisms of diseases. Although this approach has shown impressive results, its use is still in its infancy. In this review, we summarize the current pharmacological and genetic tools for microglial depletion and highlight recent advances in microglial repopulation therapy for the treatment and functional recovery of neurological diseases and deficits. Finally, we briefly discuss the therapeutic challenges and prospective uses of microglial repopulation therapy.
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- 2022
4. The predictive value of regulatory T cells on glucocorticoid sensitivity in patients with immune thrombocytopenia: a multicentre, prospective clinical study
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Li Li, Wei Chang, Lifang Huang, Kaibo Gao, Donghua Zhang, Yanhong Zhao, Zhen Shang, Yi Li, Longlong Liu, X. L. Zhang, Jia Wei, Jingming Guo, Yan Hui, Long Wang, Xiwen Tong, Xia Mao, and Hang Xiang
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Adult ,Male ,Lymphocyte ,chemical and pharmacologic phenomena ,CD8-Positive T-Lymphocytes ,T-Lymphocytes, Regulatory ,Immune tolerance ,03 medical and health sciences ,0302 clinical medicine ,Glucocorticoid Sensitivity ,medicine ,Humans ,In patient ,Lymphocyte Count ,Prospective Studies ,Glucocorticoids ,Purpura, Thrombocytopenic, Idiopathic ,business.industry ,hemic and immune systems ,Hematology ,Middle Aged ,Predictive value ,Immune thrombocytopenia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,Prospective clinical study ,Female ,business ,CD8 ,Follow-Up Studies ,030215 immunology - Abstract
Glucocorticoids (GC) are used as the first-line treatment of immune thrombocytopenia (ITP), but 10-20% of patients are insensitive to them. Regulatory T cells (Tregs) can maintain immune tolerance in autoimmune diseases. The present research pooled 55 patients with newly diagnosed ITP and 44 healthy volunteers from seven hospitals. All patients received GC treatment and were divided into GC-sensitive and GC-insensitive groups according to the curative effect after 2 weeks of treatment. The levels of lymphocyte subgroups and Tregs were recorded. As the results indicated, the levels of CD8+ CD25str+ Tregs in the GC-sensitive group were significantly higher than that of the GC-insensitive group (P = 0·005). The optimal critical value of CD8+ CD25str+ Tregs to distinguish GC sensitivity was 0·09%. With GC therapy the level of CD45RO+ /CD8+ CD25str+ Tregs (activated type) decreased after treatment (P = 0·02) and the level of CD45RO- /CD8+ CD25str+ Tregs (initial type) increased slightly (P = 0·11). There were no obvious changes in the level of CD4+ Tregs. These findings support that the level of CD8+ CD25str+ Tregs and its subgroups have a predictive value in judging the sensitivity to GC among patients with ITP. Trial registration: www.chictr.org.cn; ChiCTR-OON-17014165.
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- 2021
5. Corrigendum to 'Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish'
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Jiaqi Tan, Lei Zhao, Gaoxiang Wang, Tongjuan Li, Dan Li, Qian Xu, Xing Chen, Zhen Shang, Jue Wang, and Jianfeng Zhou
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General Immunology and Microbiology ,Oncogene Proteins, Fusion ,General Medicine ,Histone-Lysine N-Methyltransferase ,General Biochemistry, Genetics and Molecular Biology ,Translocation, Genetic ,Hematopoiesis ,Disease Models, Animal ,Leukemia, Myeloid, Acute ,Medicine ,Animals ,Humans ,Corrigendum ,Myeloid-Lymphoid Leukemia Protein ,Zebrafish - Abstract
The 11q23 of the mixed lineage leukemia 1 (
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- 2022
6. Circ-SFMBT2 facilitates the malignant growth of acute myeloid leukemia cells by modulating miR-582-3p/ZBTB20 pathway
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Wei, Chang, Zhen, Shang, Xi, Ming, Jiaying, Wu, and Yi, Xiao
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Repressor Proteins ,Leukemia, Myeloid, Acute ,MicroRNAs ,Humans ,Apoptosis ,Nerve Tissue Proteins ,RNA, Circular ,Cell Proliferation ,Transcription Factors - Abstract
Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. Circular RNAs (circRNAs) play crucial roles in AML progression. This study aimed to explore the function and potential mechanism of circRNA Scm like with four mbt domains 2 (circ-SFMBT2; hsa_circ_0017639) in AML.The levels of circ-SFMBT2, microRNA-582-3p (miR-582-3p) and zinc finger and BTB domain containing 20 (ZBTB20) were measured by quantitative real-time PCR and Western blot. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry and transwell assays were used to evaluate cell proliferation, apoptosis, migration and invasion. Glycolysis was assessed by detecting glucose consumption, lactate production and ATP/ADP ratios. The related protein expression was examined by Western blot. The binding relationship between miR-582-3p and circ-SFMBT2/ZBTB20 was verified by dual-luciferase reporter assay.Circ-SFMBT2 and ZBTB20 levels were elevated, while miR-582-3p level was reduced in AML patients and cells. Depletion of circ-SFMBT2/ZBTB20 impeded proliferation, migration, invasion and glycolysis and induced apoptosis in AML cells. Moreover, circ-SFMBT2 facilitated AML progression by sponging miR-582-3p, and miR-582-3p targeted ZBTB20 to hinder AML development.Knockdown of circ-SFMBT2 suppressed AML progression by regulating the miR-582-3p/ZBTB20 axis, which might provide a potential therapeutic strategy for AML.
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- 2021
7. Comparison of different algorithms based on TKEO for EMG change point detection
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Shenglin, Wang, Shifan, Zhu, and Zhen, Shang
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Forearm ,Electromyography ,Physiology ,Physiology (medical) ,Biomedical Engineering ,Biophysics ,Humans ,Signal Processing, Computer-Assisted ,Muscle, Skeletal ,Algorithms - Abstract
Objective. A significant challenge in surface electromyography (EMG) is the accurate identification of onset and offset of muscle activation while maintaining high real-time performance. Teager–Kaiser energy operator (TKEO) is widely used in muscle activity monitoring systems because of its computational simplicity and strong real-time performance. However, in contrast to TKEO ontology, few studies have examined how well the energy operator variants from multiple fields perform in conditioning EMG signals. This paper aims to investigate the role of the energy operator and its variants in EMG change point detection by a threshold detector. Approach. To compare the stability and accuracy of TKEO and its variants for EMG change point detection, the EMG data of extensor carpi radialis longus and flexor carpi radialis were acquired from twenty participants operating a controller under normal and disturbed conditions, and EMG change point detection was performed by four energy operators and their rectified versions. Main results. Based on the ‘standard’ change points collected by the controller, the detection results were evaluated by three evaluation indexes: detection rate, F1 Score, and accuracy. The experimental results show that the multiresolution energy operator and the TKEO with rectified (abs-TKEO) are more suitable for EMG change point detection. Significance. This paper compared the effect of the energy operator and its variants on a threshold-based EMG change point detector. The experimental results in this paper can provide a reference for the selection of EMG signal conditioning methods to improve the detection performance of the EMG change point detector.
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- 2022
8. Totally laparoscopic anatomic S7 segmentectomy using in situ split along the right intersectoral and intersegmental planes
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Hongwei Zhang, Wan Yee Lau, Chang-zhen Shang, Yajin Chen, Jun Cao, Wenda Li, Rui Zhou, and Lei Zhang
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Adult ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Operative Time ,Hepatic Veins ,03 medical and health sciences ,0302 clinical medicine ,Blood loss ,Internal medicine ,medicine ,Hepatectomy ,Humans ,Laparoscopic resection ,Aged ,Retrospective Studies ,Right hepatic vein ,business.industry ,Liver Neoplasms ,Retrospective cohort study ,Hepatology ,Middle Aged ,Surgery ,030220 oncology & carcinogenesis ,Operative time ,030211 gastroenterology & hepatology ,Female ,Laparoscopy ,Right liver ,business ,Abdominal surgery - Abstract
The traditional open or laparoscopic segmentectomy of liver segment 7 (S7) requires exposing and controlling the root of the right hepatic vein(RHV)after full mobilization and lifting up of the right liver before liver transection. This approach violates the “no-touch” principle for malignant tumors, and makes laparoscopic resection technically challenging. So reports on isolated totally laparoscopic anatomic S7 segmentectomy have rarely been reported. This study describes our experience in laparoscopic anatomic S7 segmentectomy using in situ split along the right intersectoral and intersegmental planes of the liver. To our knowledge, this is the first description of this novel approach. From September 2017 to May 2019, patients who underwent laparoscopic anatomic S7 segmentectomy for hepatocellular carcinoma at the HPB Surgery Department, Sun Yat-Sen Memorial Hospital entered into this retrospective study. This in situ split approach was designed using main vessels as the plane markers of right intersectoral and intersegmental planes, along which liver transection was carried out. There was no need to mobilize the right liver and control the root of RHV. There were 9 women and 15 men. The average diameter of the tumors on preoperative CT/MR was 3.4 cm (range 2–6 cm). All the procedures were successfully carried out laparoscopically. There was no perioperative death. The average operative time was 216.5 min (range 180–310 min). The average blood loss was 320 ml (range 120–620 ml). Pathological study showed all the operations to be R0 resections. Laparoscopic anatomic S7 segmentectomy using the in situ split approach resulted in R0 liver resection in all our patients with primary liver cancer. The operation was technically feasible and it provided a better view and increased maneuverability in the cramped operative space compared with the traditional open/laparoscopic approach. The approach also better complies with the “no-touch” principle for malignant tumors. Its long-term oncological outcomes require further studies.
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- 2019
9. Integrated genomic analysis identifies deregulated JAK/STAT-MYC-biosynthesis axis in aggressive NK-cell leukemia
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Lingtong Hao, Wei-Li Zhao, Xinchang Zheng, Hongsheng Zhou, Xin Du, Jieping Chen, Lingshuang Sheng, Kuangguo Zhou, Di Wang, Hui Luo, Xuelian Hu, Jun Wu, Jianfeng Zhou, Na Wang, Lugui Qiu, Dan Liu, Lili Dong, Lijun Zhu, Gang Huang, Yuting Tang, Qilin Ao, Guoliang Qing, Yi Luo, Qianfei Wang, Xin Liu, Hudan Liu, Liang Huang, Li Fu, Xia Mao, Jin Yan, Min Xiao, Ding Ma, Jie Jin, Lihua Cao, Shaoping Ling, Jianlin He, Zhen Shang, Pinpin Sui, Shanlan Mo, Qifa Liu, Jianyong Li, and Hongyu Zhang
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STAT3 Transcription Factor ,0301 basic medicine ,medicine.medical_treatment ,Cell ,Gene Expression ,Statistics, Nonparametric ,Proto-Oncogene Proteins c-myc ,Transcriptome ,03 medical and health sciences ,Rare Diseases ,Aggressive NK-cell leukemia ,Cell Line, Tumor ,medicine ,Humans ,Molecular Targeted Therapy ,Phosphorylation ,STAT3 ,Molecular Biology ,Janus Kinases ,Whole Genome Sequencing ,biology ,Nucleotides ,Gene Expression Profiling ,JAK-STAT signaling pathway ,Cell Biology ,medicine.disease ,CD56 Antigen ,Interleukin-10 ,Killer Cells, Natural ,Leukemia, Large Granular Lymphocytic ,Gene expression profiling ,Leukemia ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,Mutation ,Cancer research ,biology.protein ,Original Article ,Glycolysis ,Signal Transduction - Abstract
Aggressive NK-cell leukemia (ANKL) is a rare form of NK cell neoplasm that is more prevalent among people from Asia and Central and South America. Patients usually die within days to months, even after receiving prompt therapeutic management. Here we performed the first comprehensive study of ANKL by integrating whole genome, transcriptome and targeted sequencing, cytokine array as well as functional assays. Mutations in the JAK-STAT pathway were identified in 48% (14/29) of ANKL patients, while the extracellular STAT3 stimulator IL10 was elevated by an average of 56-fold (P < 0.0001) in the plasma of all patients examined. Additional frequently mutated genes included TP53 (34%), TET2 (28%), CREBBP (21%) and MLL2 (21%). Patient NK leukemia cells showed prominent activation of STAT3 phosphorylation, MYC expression and transcriptional activities in multiple metabolic pathways. Functionally, STAT3 activation and MYC expression were critical for the proliferation and survival of ANKL cells. STAT signaling regulated the MYC transcription program, and both STAT signaling and MYC transcription were required to maintain the activation of nucleotide synthesis and glycolysis. Collectively, the JAK-STAT pathway represents a major target for genomic alterations and IL10 stimulation in ANKL. This newly discovered JAK/STAT-MYC-biosynthesis axis may provide opportunities for the development of novel therapeutic strategies in treating this subtype of leukemia.
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- 2017
10. MYC/BCL2/BCL6 triple hit and TP53 deletion in a case of high-grade B cell lymphoma receiving CAR T cell immunotherapy
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Jue Wang, Jinhuan Xu, Weigang Li, Yi Xiao, Jin Wang, Cheng He, Jianfeng Zhou, Min Xiao, Liang Huang, Meilan Zhang, Kefeng Shen, Jiachen Wang, Qinlu Li, Yuqi Guan, Liting Chen, Zhen Shang, Wei Zhang, Na Wang, and Li Yang
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Adult ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,Immunology ,Immunotherapy, Adoptive ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Immunology and Allergy ,Antigenic Drift and Shift ,RC254-282 ,B cell ,Pharmacology ,Receptors, Chimeric Antigen ,business.industry ,High grade B-cell lymphoma ,Genetic Variation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunotherapy ,medicine.disease ,BCL6 ,Chimeric antigen receptor ,030104 developmental biology ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Proto-Oncogene Proteins c-bcl-6 ,Cancer research ,Molecular Medicine ,Lymphoma, Large B-Cell, Diffuse ,Tumor Suppressor Protein p53 ,Car t cells ,business ,Diffuse large B-cell lymphoma ,Gene Deletion - Abstract
Immunotherapy has become one of the most effective treatments for refractory/relapsed (r/r) B cell lymphoma.[1][1] In particular, chimeric antigen receptor (CAR) T cell immunotherapy has recently been found to be a highly effective treatment for r/r diffuse large B cell lymphoma (DLBCL).[2][2] High
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- 2021
11. Combined inhibition of Notch and FLT3 produces synergistic cytotoxic effects in FLT3/ITD
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Dan, Li, Tongjuan, Li, Zhen, Shang, Lei, Zhao, Qian, Xu, Jiaqi, Tan, Yun, Qin, Yuanyuan, Zhang, Yang, Cao, Na, Wang, Liang, Huang, Xiaojian, Zhu, Kuangguo, Zhou, Liting, Chen, Chunrui, Li, Ting, Xie, Yi, Yang, Jue, Wang, and Jianfeng, Zhou
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Niacinamide ,Receptors, CXCR3 ,Antineoplastic Agents ,Apoptosis ,Sorafenib ,Xenograft Model Antitumor Assays ,Leukemia, Myeloid, Acute ,fms-Like Tyrosine Kinase 3 ,Genes, Duplicate ,Tandem Repeat Sequences ,Cell Line, Tumor ,Mutation ,Humans ,Amyloid Precursor Protein Secretases ,Protein Kinase Inhibitors ,Cell Proliferation ,Signal Transduction - Abstract
Internal tandem duplication (ITD) mutations of FMS-like tyrosine kinase-3 (FLT3) are the most frequent genetic alterations in acute myeloid leukemia (AML) and predict a poor prognosis. FLT3 tyrosine kinase inhibitors (TKIs) provide short-term clinical responses, but the long-term prognosis of FLT3/ITD
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- 2019
12. Aggressive NK-cell leukemia: clinical subtypes, molecular features, and treatment outcomes
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Qian Wang, Jieping Chen, Liang Huang, Xia Mao, Wei-Li Zhao, Qifa Liu, Na Wang, Peng Zhang, Qilin Ao, Jianyong Li, Gao Ll, Min Xiao, Fu L, Dan Liu, Zhou Hs, Dao Wen Wang, Wei Zhang, Yuting Tang, Zhen Shang, Lugui Qiu, Hui Luo, Zhou M, Lingshuang Sheng, Lijun Zhu, Jian Huang, Yi Luo, Xuelian Hu, Zhang Hy, Jie Jin, Xin Du, Gang Huang, Shaoping Ling, Kuangguo Zhou, and Jiaxi Zhou
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Adult ,Male ,0301 basic medicine ,Oncology ,China ,medicine.medical_specialty ,Treatment outcome ,MEDLINE ,lcsh:RC254-282 ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Aggressive NK-cell leukemia ,Internal medicine ,Correspondence ,medicine ,Humans ,Acute lymphocytic leukaemia ,Young adult ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Hematology ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Leukemia, Large Granular Lymphocytic ,Leukemia ,Treatment Outcome ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,business - Published
- 2017
13. Blocking TRPA1 and TNF-α Signal Improves Bortezomib-Induced Neuropathic Pain
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Chunrui Li, Taoran Deng, Di Wang, Zhen Shang, and Yi Xiao
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0301 basic medicine ,Male ,Chemotherapeutics ,Physiology ,Antineoplastic Agents ,Pharmacology ,TRPA1 ,lcsh:Physiology ,lcsh:Biochemistry ,Bortezomib ,03 medical and health sciences ,Transient receptor potential channel ,0302 clinical medicine ,Dorsal root ganglion ,medicine ,Animals ,Humans ,lcsh:QD415-436 ,Rats, Wistar ,Receptor ,TRPA1 Cation Channel ,lcsh:QP1-981 ,business.industry ,Tumor Necrosis Factor-alpha ,medicine.disease ,Cryopyrin-Associated Periodic Syndromes ,Neuropathy ,030104 developmental biology ,Peripheral neuropathy ,medicine.anatomical_structure ,Hyperalgesia ,TNF-α ,Neuropathic pain ,Cold sensitivity ,Neuralgia ,Tumor necrosis factor alpha ,Female ,medicine.symptom ,business ,Multiple Myeloma ,030217 neurology & neurosurgery ,medicine.drug ,Signal Transduction - Abstract
Background/Aims: Bortezomib (BTZ) is largely used as a chemotherapeutic agent for the treatment of multiple myeloma. However, one of the significant limiting complications of BTZ is painful peripheral neuropathy during BTZ therapy. The purpose of this study was to examine the underlying mechanisms leading to neuropathic pain induced by BTZ. Methods: ELISA and western blot analysis were used to examine the levels of tumor necrosis factor alpha (TNF-α) and its receptor, transient receptor potential ankyrin 1 (TRPA1) and intracellular p38-MAPK and JNK signal in the lumbar dorsal root ganglion. Behavioral test was performed to determine mechanical pain and cold sensitivity in a rat model. Results: Systemic injection of BTZ significantly increased mechanical pain and cold sensitivity as compared with control animals (P< 0.05 vs. control rats). Our data also showed that protein expression of TRPA1 was upregulated in the dorsal root ganglion of BTZ rats and blocking TRPA1 attenuated mechanical pain and cold sensitivity in control rats and BTZ rats (P< 0.05 vs. vehicle control). Notably, the inhibitory effect of blocking TRPA1 on mechanical pain and cold sensitivity was smaller in BTZ rats than that in control rats. In addition, a blockade of TNF-α attenuated intracellular p38-MAPK and JNK signal in the dorsal root ganglion. This also decreased TRPA1 expression and alleviated mechanical hyperalgesia and cold hypersensitivity in BTZ rats. Conclusion: We revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ. The data also suggest that blocking TRPA1 and tumor necrosis factor alpha is beneficial to alleviate neuropathic pain during BTZ intervention.
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- 2017
14. PAX5 haploinsufficiency induce cancer cell dormancy in Raji cells
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Tong-Juan Li, Jia Gu, Xing Fu, Jue Wang, Wei Huang, Zhen Shang, Lei Zhao, Xue Liang, Wei Zhang, and Jianfeng Zhou
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0301 basic medicine ,Male ,viruses ,medicine.medical_treatment ,chemical and pharmacologic phenomena ,Haploinsufficiency ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Recurrence ,hemic and lymphatic diseases ,Cell Line, Tumor ,medicine ,Humans ,Cell Proliferation ,Gene Editing ,Chemotherapy ,Mutation ,Cell Cycle ,PAX5 Transcription Factor ,hemic and immune systems ,Cell Biology ,Burkitt Lymphoma ,Raji cell ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,Dormancy ,PAX5 - Abstract
PAX5 mutations have important role in leukemogenesis and leukemia relapse, cancer cell dormancy participates in cancer relapse, but there was no report about PAX5 mutation inducing cancer cell dormancy. we constructed the PAX5 deletion Raji cell lines using gene editing technology, evaluated dormancy biological characteristics of cell lines. Our results showed PAX5 haploinsufficiency restrained the proliferation of Raji cells, induced G0/G1 arrest of Raji cells, reduced chemotherapy sensitivity. The tumor formation rate reduced in PAX5 mutation Raji cells. Our results showed PAX5 insufficiency induced cancer cell dormancy in Raji cell.
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- 2017
15. Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells
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Hao ming Lin, Jin xing Wei, Peiqing Liu, Yun le Wan, Qing fang Han, Yang Cao, Jun Min, Guo lin Li, Rui Zhou, Li Lv, Hai He, Jun Cao, Chang zhen Shang, and Gang Zhou
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Vacuolar Proton-Translocating ATPases ,Tumor microenvironment ,Carcinoma, Hepatocellular ,Endosomal Sorting Complexes Required for Transport ,Hepatology ,Endosome ,Tumor Suppressor Proteins ,Liver Neoplasms ,Biology ,Exosomes ,digestive system diseases ,Article ,ESCRT ,Microvesicles ,Cell biology ,MicroRNAs ,Paracrine signalling ,Cancer cell ,Tumor Cells, Cultured ,Cancer research ,ATPases Associated with Diverse Cellular Activities ,Humans ,Genes, Tumor Suppressor ,Autocrine signalling ,PI3K/AKT/mTOR pathway - Abstract
The incidence of hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related death worldwide, accounting for 90% of all primary liver neoplasias, is increasing.1 Recent studies have demonstrated that microRNAs (miRNAs) can act as oncogenes or tumor suppressors, and miRNA dysregulation may play an important role in cancer onset and progression.2, 3 Transcriptional and epigenetic regulations may play a major role in miRNA expression.4 However, the molecular mechanisms involved in disorders associated with miRNAs remain unclear. In recent years, miRNAs within exosomes have gained significant attention due to their potential role in delineating the molecular pathogenesis of cancer.5, 6 Exosomes are small (40-100 nm) cell-derived extracellular vesicles that initially form with the maturation of multivesicular bodies as intraluminal vesicles (ILVs).7 These ILVs are released in the extracellular medium by fusion of the limiting membrane with the plasma membrane and are thereafter known as “exosomes.”7 Cancer cells secrete exosomes that function in an autocrine or paracrine manner to modulate the tumor microenvironment.8-10 Accumulating evidence indicates that exosomes are involved in cell–cell communication by delivering proteins and nucleic acids to recipient cells, thereby impacting the biological processes in recipient cells.7, 11 However, little is known about whether exosomes can function as mediators by self-regulation of miRNA expression profiles. Cargo sorting of ILVs (exosomes) depends on the endosomal sorting complex required for transport (ESCRT) machinery.12 Loss-of-function mutations in ESCRT components lead to disorders of cargoes within ILVs, which could lead to alterations in several signaling pathways.13, 14 Membrane neck cleavage mediated by ESCRT-III is crucial for the formation of ILVs, which is regulated by Vps4.15 In humans, there are two paralogs of the yeast Vps4, Vps4A and Vps4B, both of which exhibit functions that are similar to that of the protein in yeast. Recent studies have shown that Vps4 is responsible for hepatitis B virus budding and the release of infectious hepatitis C virus particles.16, 17 Rodahl et al. reported that disruption of Vps4 and c-Jun N-terminal kinase function could cause tumor growth in Drosophila. 18 Until now, the role of Vps4 in human cancer development has been poorly understood. In this study, we demonstrated that Vps4A is frequently down-regulated in HCC tissues. Ectopic expression of Vps4A led to significant repression of HCC growth and metastasis. Our study provides mechanistic evidence that Vps4A interferes with the biological activity of exosomes and the cell response to exosomes through affecting exosomal miRNA secretion and uptake. Overexpression of Vps4A can lead to inactivation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. These results implicate Vps4A as a novel tumor suppressor for HCC.
- Published
- 2015
16. Identification of Significant Pathways Induced by PAX5 Haploinsufficiency Based on Protein-Protein Interaction Networks and Cluster Analysis in Raji Cell Line
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Jue Wang, Jia Gu, Tongjuan Li, Jianfeng Zhou, xue liang, Lei Zhao, Xing Fu, Wei Huang, and Zhen Shang
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0301 basic medicine ,Article Subject ,Carcinogenesis ,Amino Acid Motifs ,Genetic Vectors ,lcsh:Medicine ,Haploinsufficiency ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Genomic Instability ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Cell Line, Tumor ,Protein Interaction Mapping ,medicine ,Immune Tolerance ,Cluster Analysis ,Humans ,Transcription factor ,Alleles ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Inflammation ,Mutation ,General Immunology and Microbiology ,Gene Expression Profiling ,lcsh:R ,HEK 293 cells ,PAX5 Transcription Factor ,Computational Biology ,General Medicine ,Raji cell ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,HEK293 Cells ,030220 oncology & carcinogenesis ,Cancer research ,CRISPR-Cas Systems ,Signal Transduction ,Research Article - Abstract
PAX5 encodes a transcription factor essential for B-cell differentiation, and PAX5 haploinsufficiency is involved in tumorigenesis. There were few studies on how PAX5 haploinsufficiency regulated genes expression to promote tumorigenesis. In this study, we constructed the cell model of PAX5 haploinsufficiency using gene editing technology in Raji cells, detected differentially expressed genes in PAX5 haploinsufficiency Raji cells, and used protein-protein interaction networks and cluster analysis to comprehensively investigate the cellular pathways involved in PAX5 haploinsufficiency. The clusters of gene transcription, inflammatory and immune response, and cancer pathways were identified as three important pathways associated with PAX5 haploinsufficiency in Raji cells. These changes hinted that the mechanism of PAX5 haploinsufficiency promoting tumorigenesis may be related to genomic instability, immune tolerance, and tumor pathways.
- Published
- 2016
17. PAX5 alteration-associated gene-expression signatures in B-cell acute lymphoblastic leukemia
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Yuechao Zhao, Kuangguo Zhou, Wei Huang, Zhen Shang, and Yanling Xu
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Male ,medicine.medical_specialty ,Ubiquitin-Protein Ligases ,Biology ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,hemic and lymphatic diseases ,Internal medicine ,Gene expression ,Ring finger ,medicine ,Cluster Analysis ,Humans ,Child ,Gene ,Genetics ,Regulation of gene expression ,Hematology ,Gene Expression Regulation, Leukemic ,Accession number (library science) ,Gene Expression Profiling ,PAX5 Transcription Factor ,Infant ,Gene expression profiling ,medicine.anatomical_structure ,Child, Preschool ,Cancer research ,Female ,PAX5 ,Carrier Proteins ,Transcriptome - Abstract
The paired box domain gene 5 (PAX5) is frequently altered in both childhood and adult B-cell acute lymphoblastic leukemia, and takes part in leukemogenesis. We analyzed data from the database of Gene Expression Omnibus (accession number: GSE11877) using bioinformatical and statistical methods. The results showed that cases of PAX5 alteration can cluster using unsupervised clustering algorithms, and one gene, zinc and ring finger 1 (ZNRF1), was characterized and validated by quantitative RT-PCR. ZNRF1 may be associated with leukemogenesis of ALL with PAX5 alteration.
- Published
- 2013
18. FLT3-ITD-associated gene-expression signatures in NPM1-mutated cytogenetically normal acute myeloid leukemia
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Jianfeng Zhou, Di Wang, Kuangguo Zhou, Liang Huang, Jue Wang, Zhen Shang, Yunfan Yang, Na Wang, and Danmei Xu
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Adult ,Male ,NPM1 ,Myeloid ,Adolescent ,Microarray ,Biology ,Cohort Studies ,Young Adult ,LAPTM4B ,Gene Duplication ,hemic and lymphatic diseases ,Gene duplication ,medicine ,Cluster Analysis ,Humans ,Regulation of gene expression ,Genetics ,Gene Expression Regulation, Leukemic ,Gene Expression Profiling ,Nuclear Proteins ,Reproducibility of Results ,Hematology ,Middle Aged ,medicine.disease ,Gene expression profiling ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,fms-Like Tyrosine Kinase 3 ,Tandem Repeat Sequences ,Mutation ,Cancer research ,Female ,Nucleophosmin - Abstract
Concomitance of the FLT3-ITD mutation is associated with poor prognosis in NPM1-mutated cytogenetically normal acute myeloid leukemia (CN-AML) patients, and precise studies on its role in leukemogenesis are needed; these may be elucidated at the molecular level by gene express profiling. In the present study, we built a gene-expression-based classifier using prediction analysis of microarray to characterize the FLT3-ITD signature in NPM1-mutated CN-AML patients, which comprised 10 annotated genes, and demonstrated an overall accuracy of 83.8 % in cross-validation. To characterize the signature in another way, differential expression was revealed for 34 genes by class comparison, and the up-regulation of LAPTM4B and MIR155HG was validated by quantitative RT-PCR in our small cohort of NPM1-mutated CN-AML samples, which appeared to be associated with this specific subtype. The 10-gene classifier and differentially expressed genes identified in this study indicate a potential utility for risk-assessed treatment stratification, and suggest new therapeutic targets for these high-risk AML patients.
- Published
- 2012
19. TALENs-mediated gene disruption of FLT3 in leukemia cells: Using genome-editing approach for exploring the molecular basis of gene abnormality
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Jue Wang, Jianfeng Zhou, Shiqiu Zhou, Min Xiao, Ding Ma, Zheng Hu, Pengfei Zhou, Lei Zhao, Liang Huang, Mi Zhou, Zhen Shang, Xiaoxi Zhou, Tongjuan Li, Na Wang, and Yang Cao
- Subjects
Genetics ,Multidisciplinary ,Leukemia ,Mutant ,Clone (cell biology) ,Gene Abnormality ,Haploinsufficiency ,Mice, SCID ,Gene mutation ,Biology ,Jurkat cells ,Article ,Jurkat Cells ,Mice ,fms-Like Tyrosine Kinase 3 ,Codon, Nonsense ,Mice, Inbred NOD ,hemic and lymphatic diseases ,Gene expression ,Animals ,Humans ,K562 Cells ,Gene ,K562 cells ,Signal Transduction - Abstract
Novel analytic tools are needed to elucidate the molecular basis of leukemia-relevant gene mutations in the post-genome era. We generated isogenic leukemia cell clones in which the FLT3 gene was disrupted in a single allele using TALENs. Isogenic clones with mono-allelic disrupted FLT3 were compared to an isogenic wild-type control clone and parental leukemia cells for transcriptional expression, downstream FLT3 signaling and proliferation capacity. The global gene expression profiles of mutant K562 clones and corresponding wild-type controls were compared using RNA-seq. The transcriptional levels and the ligand-dependent autophosphorylation of FLT3 were decreased in the mutant clones. TALENs-mediated FLT3 haplo-insufficiency impaired cell proliferation and colony formation in vitro. These inhibitory effects were maintained in vivo, improving the survival of NOD/SCID mice transplanted with mutant K562 clones. Cluster analysis revealed that the gene expression pattern of isogenic clones was determined by the FLT3 mutant status rather than the deviation among individual isogenic clones. Differentially expressed genes between the mutant and wild-type clones revealed an activation of nonsense-mediated decay pathway in mutant K562 clones as well as an inhibited FLT3 signaling. Our data support that this genome-editing approach is a robust and generally applicable platform to explore the molecular bases of gene mutations.
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- 2015
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20. JARID2 inhibits leukemia cell proliferation by regulating CCND1 expression
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Chang-Liang Su, Zhen Shang, Tao-Ran Deng, and Yi Xiao
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Adult ,Male ,Down-Regulation ,Leukemia inhibitory factor receptor ,Histones ,Promyelocytic leukemia protein ,Mice ,Young Adult ,hemic and lymphatic diseases ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Cyclin D1 ,Acute monocytic leukemia ,Aged ,Cell Proliferation ,Aged, 80 and over ,Chromosome Aberrations ,ABL ,Leukemia ,biology ,Cell growth ,Gene Expression Regulation, Leukemic ,Cell Cycle ,Polycomb Repressive Complex 2 ,Hematology ,Cell cycle ,Middle Aged ,medicine.disease ,Molecular biology ,Tumor Burden ,Disease Models, Animal ,biology.protein ,Heterografts ,Ectopic expression ,Female - Abstract
It has recently been shown that JARID2 contributes to the malignant character of solid tumors, such as epithelial-mesenchymal transition in lung and colon cancer cell lines, but its role in leukemia progression is unexplored. In this study, we explored the effect and underlying molecular mechanism of JARID2 on leukemia cell proliferation. Real-time PCR and Western assay were carried out to detect JARID2 and CCND1 expression. Cell number and cell cycle change were detected using hemocytometer and flow cytometry, and a ChIP assay was utilized to investigate JARID2 and H3K27me3 enrichment on the CCND1 promoter. JARID2 is down-regulated in B-chronic lymphocytic leukemia (B-CLL) and acute monocytic leukemia (AMOL), and knockdown of JARID2 promotes leukemia cell proliferation via acceleration of the G1/S transition. Conversely, ectopic expression of JARID2 inhibits these malignant phenotypes. Mechanistic studies show that JARID2 negatively regulates CCND1 expression by increasing H3K27 trimethylation on the CCND1 promoter. Our findings indicate that JARID2 is a negative regulator of leukemia cell proliferation, and functions as potential tumor suppressor in leukemia.
- Published
- 2015
21. The correlation between neurosteroids and neurotransmitters with liver yang rising and liver qi stagnation types of premenstrual syndrome
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Tian Xia, Yue Xiang Ma, Hui Yun Zhang, Ya Zhen Shang, Hui Gao, and Mingqi Qiao
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Adult ,medicine.medical_specialty ,Serotonin ,Neuroactive steroid ,Qi ,Endocrinology, Diabetes and Metabolism ,Dopamine ,Pregnanolone ,Luteal phase ,Premenstrual Syndrome ,chemistry.chemical_compound ,Young Adult ,Endocrinology ,Internal medicine ,Follicular phase ,medicine ,Humans ,Yin-Yang ,Testosterone ,Medicine, Chinese Traditional ,Progesterone ,gamma-Aminobutyric Acid ,Neurotransmitter Agents ,business.industry ,Allopregnanolone ,Obstetrics and Gynecology ,Radioimmunoassay ,Dehydroepiandrosterone ,Middle Aged ,chemistry ,Liver ,Pregnenolone ,Female ,business ,medicine.drug ,Hormone - Abstract
To investigate neural-reproductive hormonal basis of liver yang rising (LYR), liver qi stagnation (LQS) premenstrual syndrome (PMS), and to develop standardized diagnostic criteria for PMS.HPLC, HPLC-MC, ELISA and radioimmunoassay were used to compare levels of serum hormones, plasma neurotransmitters and neurosteroids between LYR PMS patients, LQS PMS patients and healthy controls (30 subjects in each group).Of the measures, all three groups exhibited no significant differences during the follicular phase. In contrast, during the luteal phase, LYR PMS testosterone levels tended to be higher than controls, while dopamine and 5-HT of the LYR PMS group were significantly higher. Conversely, γ-aminobutyric acid in the LYR PMS group was significantly lower than controls (p 0.05). On the other hand, epinephrine and norepinephrine levels in both PMS groups were significantly higher than controls (p 0.05), while pregnenolone and allopregnanolone of LYR and LQS groups were significantly lower than controls, with dehydroepiandrosterone (DHEA) being significantly higher than controls (p 0.05). The ratios of DHEA/allopregnanolone and DHEA/pregnenolone of both PMS groups were significantly higher than the control group, with the LYR PMS group ratios being significantly higher than in the LQS PMS group (p 0.05).The decrease in pregnenolone and allopregnenolone, increase in DHEA, DHEA/allopregnanolone and DHEA/pregnenolone during the luteal phase may be one of the biological bases for anger in LYR PMS patients and depression in LQS PMS patients.
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- 2014
22. Methylenetetrahydrofolate reductase polymorphisms and susceptibility to acute lymphoblastic leukemia in a Chinese population: a meta-analysis
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Yi Xiao, Zhen Shang, Chang-Liang Su, and Tao-Ran Deng
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Oncology ,Genetic Markers ,Male ,Cancer Research ,medicine.medical_specialty ,China ,Adolescent ,Lymphoblastic Leukemia ,Population ,Polymorphism, Single Nucleotide ,Young Adult ,Age Distribution ,Risk Factors ,Internal medicine ,Biomarkers, Tumor ,Prevalence ,Medicine ,Mthfr c677t ,Humans ,Genetic Predisposition to Disease ,Sex Distribution ,education ,Child ,Methylenetetrahydrofolate Reductase (NADPH2) ,Genetics ,Chinese population ,education.field_of_study ,biology ,business.industry ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,digestive system diseases ,Sample size determination ,Meta-analysis ,Methylenetetrahydrofolate reductase ,Potential biomarkers ,Child, Preschool ,biology.protein ,Female ,business - Abstract
SummaryBackground: Although many epidemiologic studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their association with acute lymphoblastic leukemia (ALL), definitive conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of ALL, a meta-analysis was performed in a Chinese population. Materials and Methods: A computerized literature search was carried out in PubMed, the Chinese Biomedicine (CBM) database, China National Knowledge Infrastructure (CNKI) platform, and the Wanfang database (Chinese) to collect relevant articles. Results: A total of 11 articles including 1,738 ALL cases and 2,438 controls were included in this meta-analysis. Overall, a significantly decreased association was found between the MTHFR C677T polymorphism and ALL risk when all studies in Chinese populations were pooled into the meta-analysis. In subgroup analyses stratified by age, ethnicity, and source of controls, the same results were observed in children, in population-based studies, and in people with no stated ethnicity. However, a significantly increased association was also found for MTHFR C677T in hospital-based studies, and for MTHFR A1298C in people with no stated ethnicity. Conclusion: Our results suggest that the MTHFR C677T and A1298C polymorphisms may be potential biomarkers for ALL risk in Chinese populations, and studies with a larger sample size and wider population spectrum are required before definitive conclusions can be drawn.
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- 2014
23. Laparoscopic surgery minimizes the release of circulating tumor cells compared to open surgery for hepatocellular carcinoma
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Xue Zhou, Chang-zhen Shang, Zejian Huang, Hongwei Zhang, Yajin Chen, Wenda Li, and Lei Zhang
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Laparoscopic surgery ,Adult ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,medicine.medical_treatment ,Circulating tumor cell ,Internal medicine ,medicine ,Hepatectomy ,Humans ,Neoplasm Metastasis ,Laparoscopy ,Aged ,Laparotomy ,medicine.diagnostic_test ,business.industry ,Liver Neoplasms ,Hepatology ,Middle Aged ,medicine.disease ,Neoplastic Cells, Circulating ,Primary tumor ,Surgery ,Hepatocellular carcinoma ,Cancer cell ,Female ,business ,Abdominal surgery - Abstract
The aim of this study was to determine whether tumor manipulation enhances cancer cell release from the primary tumor in HCC patients and which surgical approach, open surgery or laparoscopic resection, is superior with respect to preventing tumor cells from scattering in the blood.A total of 26 HCC patients were prospectively randomized to receive either open surgery (n = 14) or laparoscopic surgery (n = 12). Blood samples were obtained at three time points: preoperative, postoperative, and 24 h after surgery. The CD45(-)/CD44(+)/CD90(+) cells were obtained and counted using quantitative flow cytometry. The serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF-α) were also compared between the two groups.There was no significant difference between the laparoscopic and open groups in terms of patient characteristics. The levels of CCSCs increased immediately after surgical manipulation, and the laparoscopy group released fewer tumor cells into the blood stream. The amount of CCSCs in both groups decreased to reach a similar level 24 h after surgery. Both IL-6 and IL-8 increased after surgery, and the mean postoperative increases in IL-6 and IL-8 serum levels were significantly less in the laparoscopic group than in the open group. The TNF-α levels showed no differences at any time point.Our results showed that patients with laparoscopic surgery have lower IL-6, IL-8 secretion and less CTCs, which may suggest an advantage by restricting CTCs release and a preserved immune response. Further studies are needed to investigate the relationship between the number of CCSCs after surgery and long-term survival rates.
- Published
- 2014
24. Incidence and risk of cardiotoxicity associated with bortezomib in the treatment of cancer: a systematic review and meta-analysis
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Jia Wei, Zhen Shang, Yi Xiao, and Jin Yin
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Risk ,Oncology ,Drugs and Devices ,medicine.medical_specialty ,Systematic Reviews ,Heart Diseases ,Clinical Research Design ,Cancer Treatment ,lcsh:Medicine ,Antineoplastic Agents ,Cardiovascular ,Toxicology ,Cardiovascular Pharmacology ,law.invention ,Bortezomib ,Randomized controlled trial ,law ,Neoplasms ,Internal medicine ,Epidemiology of cancer ,Odds Ratio ,medicine ,Humans ,Drug Interactions ,lcsh:Science ,Cardiotoxicity ,Multidisciplinary ,business.industry ,Incidence ,lcsh:R ,Publication bias ,Odds ratio ,Chemotherapy and Drug Treatment ,Boronic Acids ,Surgery ,Clinical trial ,Pyrazines ,Meta-analysis ,Medicine ,Oncology Agents ,lcsh:Q ,Meta-Analyses ,business ,Research Article ,medicine.drug - Abstract
Background We conducted a systematic review and meta-analysis to clarify the incidence and risk of cardiotoxicity associated with bortezomib in cancer patients. Methods Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to July 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating bortezomib in cancer patients with adequate data on cardiotoxicity. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies. Results A total of 5718 patients with a variety of malignancies from 25 clinical trials were included in our analysis. The incidence of all-grade and high-grade cardiotoxicity associated with bortezomib was 3.8% (95%CI: 2.6–5.6%) and 2.3% (1.6–3.5%), with a mortality of 3.0% (1.4–6.5%). Patients treated with bortezomib did not significantly increase the risk of all-grade (OR 1.15, 95%CI: 0.82–1.62, p = 0.41) and high-grade (OR 1.13, 95%CI: 0.58–2.24, p = 0.72) cardiotoxicity compared with patients treated with control medication. Sub-group analysis showed that the incidence of cardiotoxicity varied with tumor types, treatment regimens and phases of trials. No evidence of publication bias was observed. Conclusions The use of bortezomib does not significantly increase the risk of cardiotoxicity compared to control patients. Further studies are recommended to investigate this association and risk differences among different tumor types, treatment regimens and phases of trials.
- Published
- 2014
25. Predictive factors of thyroid cancer in patients with Graves' disease
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Xiaoyi Wang, Meng Ren, Ming Tong Xu, Li Yan, Chang Zhen Shang, Jing Lu Zhang, Hua Cheng, and Mu Chao Wu
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Thyroid nodules ,Adult ,Male ,endocrine system ,medicine.medical_specialty ,Pathology ,endocrine system diseases ,Graves' disease ,medicine.medical_treatment ,Gastroenterology ,Papillary thyroid cancer ,Metastasis ,Thyroid carcinoma ,Risk Factors ,Internal medicine ,medicine ,Prevalence ,Humans ,Thyroid Neoplasms ,Thyroid Nodule ,Thyroid cancer ,Retrospective Studies ,Ultrasonography ,business.industry ,Thyroid ,Thyroidectomy ,Middle Aged ,medicine.disease ,Prognosis ,Graves Disease ,medicine.anatomical_structure ,Surgery ,Female ,business - Abstract
The best preoperative examination in Graves’ disease with thyroid cancer still remains uncertain. The objectives of the present study were to investigate the prevalence of thyroid cancer in Graves’ disease patients, and to identify the predictive factors and ultrasonographic features of thyroid cancer that may aid the preoperative diagnosis in Graves’ disease. This retrospective study included 423 patients with Graves’ disease who underwent surgical treatment from 2002 to 2012 at our institution. The clinical features and ultrasonographic findings of thyroid nodules were recorded. The diagnosis of thyroid cancer was determined according to the pathological results. Thyroid cancer was discovered in 58 of the 423 (13.7 %) surgically treated Graves’ disease patients; 46 of those 58 patients had thyroid nodules, and the other 12 patients were diagnosed with incidentally discovered thyroid carcinomas without thyroid nodules. Among the 58 patients with thyroid cancer, papillary microcarcinomas were discovered in 50 patients, and multifocality and lymph node involvement were detected in the other 8 patients. Multivariate regression analysis showed younger age was the only significant factor predictive of metastatic thyroid cancer. Ultrasonographic findings of calcification and intranodular blood flow in thyroid nodules indicate that they are more likely to harbor thyroid cancers. Because the influencing factor of metastatic thyroid cancers in Graves’ disease is young age, every suspicious nodule in Graves’ disease patients should be evaluated and treated carefully, especially in younger patients because of the potential for metastasis.
- Published
- 2013
26. [Mutation of isocitrate dehydrogenase 2 (IDH2) gene in Chinese AML patients and its clinical significance]
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Zhen, Shang, Di, Wang, Ming, Xiao, Jue, Wang, Tong-Juan, Li, Yue-Chao, Zhao, Chun-Rui, Li, and Jian-Feng, Zhou
- Subjects
Adult ,Male ,Adolescent ,Genotype ,Remission Induction ,Nuclear Proteins ,Middle Aged ,Prognosis ,Isocitrate Dehydrogenase ,DNA Methyltransferase 3A ,Leukemia, Myeloid, Acute ,Young Adult ,Asian People ,fms-Like Tyrosine Kinase 3 ,Karyotyping ,Mutation ,Humans ,Female ,DNA (Cytosine-5-)-Methyltransferases ,WT1 Proteins ,Nucleophosmin ,Aged - Abstract
This study was purpose to analyze the frequency and of isocitrate dehydrogenase 2 (IDH2) gene mutation in acute myeloid leukemia (AML) and its clinic significance. The multiplex polymerase chain reaction (PCR) and sequencing were performed to screen 192 AML patients for exon 4 of the IDH2 gene. FLT3, NPM1, CEBPA, c-kit and WT1 mutations were also included in analysis. The results showed that IDH2 mutation was found in 14 (7.29%) of 192 patients. There were 9 AML patients with R140Q mutation, 1 patient with R140W mutation, and 1 patient with R172K mutation. IDH2 aberrations significantly more were detected in French-American-British (FAB) M5 (P0.005) than other types. There was no statistical difference in age, sex, WBC, platelet count, bone marrow blasts count, hemoglobin as compared with IDH2 wild-type. For immunotype analysis, IDH2 mutation patients were more likely to express CD34 and CD13, less CD36. IDH2 mutation combined with FLT3/ITD mutation was found in 7 cases, with CEBPA mutation in 4 cases, with NPM1 mutation in 4 cases, with Dnmt3a mutation in 5 cases, neither with c-kit, IDH1 or WT1 mutation for no one, which revealed a significant interaction between IDH2 mutation and the FLT3/ITD positive genotype, Dnmt3a mutated, and IDH1 wild-type. IDH2 mutation was detected in 5 (8.47%) of 59 CN-AML. There was no significant difference of IDH2 mutation incidence between the normal and abnormal karyotype. The CR rate was higher in IDH2 R140 mutated patients than wild-type ones, but there was no significant in the two group. It is concluded that the rate of IDH2 mutation is 7.29% in Chinese AML patients and 7.81% in CN-AML. IDH2 mutation is significantly associated with AML-M5, FLT3/ITD, Dnmt3a, IDH1 wild-type and fusion gene wild-type, but not with age, leucocyte and platelet counts in peripheral blood, karyotype, NPM1, CEBPA, c-kit or WT1 mutation. And IDH2 R140 mutation has no impact on CR rate.
- Published
- 2013
27. [Detection of isocitrate dehydrogenase 1 gene mutation in 205 AML patients and its clinical significance]
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Zhen, Shang, Di, Wang, Ming, Xiao, Zhe, Geng, Hai-Xia, Wang, Jue, Wang, Yan-Ling, Xu, Tong-Juan, Li, Jian-Feng, Zhou, and Chun-Rui, Li
- Subjects
Adult ,Male ,Adolescent ,DNA Mutational Analysis ,Middle Aged ,Isocitrate Dehydrogenase ,Leukemia, Myeloid, Acute ,Young Adult ,Karyotyping ,Mutation ,Humans ,Female ,Nucleophosmin ,Aged - Abstract
This study was purposed to detect the mutation of isocitrate dehydrogenase 1 (IDH-1) gene in patients with acute myeloid leukemia (AML) and to explore its clinical significance. The genomic DNA was extracted from mononuclear cells (MNC) of bone marrow or peripheral blood in 205 adult AML patients, the exon 4 of IDH1 gene was amplified by PCR, then the sequencing and comparison were performed. The results showed that IDH1 mutation was detected in 9 (4.39%) of 205 AML patients. There were 6 cases of R132H mutation, 1 of R132L mutation, 1 of R132G mutation and 1 of R132S mutation. Significantly more IDH1 aberrations were detected in AML-M2 (P = 0.002) than other types. And the 9 patients with IDH1 mutation were characterized by low platelet count which was lower than patients with wild type IDH1 (P = 0.003). IDH1 mutation combined with FLT3/ITD mutation was found in 5 cases, c-kit mutation in 1, NPM1 mutation in 2, and IDH1 mutation with CEBPA or WT1 mutation was not found, which revealed a significant interaction between IDH1 mutation and the FLT3/ITD positive genotype or the CEBPA wild-type. IDH1 mutation were detected in 4 of 71 (5.63%) CN-AML. There was no significant difference of IDH1 mutation incidence between the normal and abnormal karyotypes. It is concluded that the rate of IDH1 mutation was 4.39% in Chinese AML patients. IDH1 mutation is significantly associated with AML-M2, lower platelet counts in peripheral blood, FLT3/ITD mutation and CEBPA wild-type, but not with age, white blood cell count in peripheral blood, karyotype, NPM1, c-kit or WT1 mutation.
- Published
- 2012
28. Establishment of xenotransplantation model of human CN-AML with FLT3-ITD (mut) /NPM1 (-) in NOD/SCID mice
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Di Wang, Zhen Shang, Tongjuan Li, Na Wang, Liang Huang, Jue Wang, Min Xiao, and Jianfeng Zhou
- Subjects
Adult ,Male ,NPM1 ,Adolescent ,Xenotransplantation ,medicine.medical_treatment ,Transplantation, Heterologous ,Biomedical Engineering ,Spleen ,Nod ,Mice, SCID ,Biochemistry ,Biomaterials ,Young Adult ,Mice, Inbred NOD ,hemic and lymphatic diseases ,Cell Line, Tumor ,Genetics ,medicine ,Animals ,Humans ,Earth-Surface Processes ,Aged ,Mice, Knockout ,business.industry ,Nuclear Proteins ,Middle Aged ,medicine.disease ,Leukemia ,Disease Models, Animal ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,fms-Like Tyrosine Kinase 3 ,Fms-Like Tyrosine Kinase 3 ,Immunology ,Cytarabine ,Female ,Bone marrow ,business ,Nucleophosmin ,Neoplasm Transplantation ,medicine.drug - Abstract
Patients with FLT3-ITD (mut) /NPM1 (-) cytogenetically normal acute myeloid leukemia (CN-AML), as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD (mut) /NPM1 (-) CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells. The FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary generation models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully established xenotransplantation model of human FLT3-ITD (mut) /NPM1 (-) CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.
- Published
- 2012
29. Potential application of IDH1 and IDH2 mutations as prognostic indicators in non-promyelocytic acute myeloid leukemia: a meta-analysis
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Jue Wang, Kuangguo Zhou, Zhen Shang, Jianfeng Zhou, Lijun Jiang, and Liang Huang
- Subjects
Male ,Cancer Research ,NPM1 ,Myeloid ,IDH1 ,Trisomy 8 ,medicine.disease_cause ,IDH2 ,Disease-Free Survival ,Biomarkers, Tumor ,Medicine ,Humans ,Mutation ,business.industry ,Myeloid leukemia ,Nuclear Proteins ,Hematology ,medicine.disease ,Prognosis ,Isocitrate Dehydrogenase ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Oncology ,Immunology ,Cancer research ,Regression Analysis ,Female ,business ,Nucleophosmin - Abstract
Recurrent mutations of isocitrate dehydrogenase isoforms 1 and 2 (IDH1 and IDH2) have recently been studied in adult patients with acute myeloid leukemia (AML). A meta-analysis was performed to demonstrate their controversial prognostic impacts. The associations of IDH1 or IDH2 mutations with other molecular abnormalities were also investigated. In patients with AML, IDH1/2 mutations were significantly associated with normal karyotype and isolated trisomy 8 (p < .05). After adjusting for well-studied prognostic factors, IDH1 mutation seems to be associated with subtle but significantly inferior event-free survival (EFS) (p = 0.02) and possible adverse overall survival (OS) (p = 0.13) in patients with AML, especially in the favorable genotype subset with mutated NPM1 but without FLT3-ITD mutation (p < 0.05). Longer OS (p = 0.01) and better EFS tendency (p = 0.18) are implicated in patients with IDH2 mutations, which suggests that IDH2 mutations appear to confer a favorable prognosis. Moreover, IDH1 and IDH2 mutations may play a more important role in abnormal cytogenetics subgroups such as isolated trisomy 8. Screening of IDH1/2 mutations could help to identify patients at high risk within some subsets of AML.
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- 2012
30. [Analysis of IKAROS6 expression in 73 patients with chronic myelogenous leukemia]
- Author
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Min, Xiao, Ying, Wu, Yang, Yang, Zhen, Shang, Zhen-Ya, Hong, Di, Wang, Jian-Feng, Zhou, and Chun-Rui, Li
- Subjects
Adult ,Male ,Adolescent ,Gene Expression ,Middle Aged ,Prognosis ,Ikaros Transcription Factor ,Young Adult ,Karyotyping ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Humans ,Female ,Child ,Aged - Abstract
This study was aimed to evaluate IKAROS6 expression in patients with chronic myelogenous leukemia (CML) and its clinical significance. cDNAs from 73 CML patients were amplified by PCR and sequenced for IKAROS expression to elucidate clinical characteristics in IKAROS6 positive patients. The results showed that there was no IKAROS6 gene expression in 8 healthy controls and 15 CML patients in chronic phase and accelerated phase, and 15 cases (35.71%) were IKAROS6 positive in lymphoblast crisis samples among 42 newly diagnosed CML; however, none was found in myeloblast crisis of 16 newly diagnosed CML. Among 42 lymphoblast crisis of CML, the complete remission (CR) rate of IKAROS6 expression positive patients reached 40% (6/15), which was obviously lower than that in IKAROS6 negative patients (85.19%, 23/27) (p0.01), IKAROS6 positive patients relapsed after CR for 15 (2 - 18) months with relapse rate 66.7% (4/6), which was higher than that in expressed wild type IKAROS gene patients (21.74%, 5/23) (p0.05). It is concluded that abnormal expression of IKAROS gene dominated by IKAROS6 isoforms can be detected in lymphoblast crisis samples of CML patients. Abnormal expression of IKAROS gene may be an important factor in lymphoblast crisis of CML. Therefore, detection of IKAROS gene expression may be important for target therapy and evaluation of clinical prognosis of CML patients.
- Published
- 2011
31. [Application of FICTION technique to the detection of genetic aberrations in multiple myeloma]
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Di, Wang, Liang, Huang, Heng, Zhang, Zhe, Geng, Zhen, Shang, Jian-feng, Zhou, and Chun-rui, Li
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Adult ,Aged, 80 and over ,Male ,Cytogenetics ,Fluorescent Antibody Technique ,Humans ,Female ,Middle Aged ,Multiple Myeloma ,In Situ Hybridization, Fluorescence ,Aged ,Immunophenotyping - Abstract
To investigate the diagnostic value of FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms) technique, combining immunofluorescence and fluorescence in situ hybridization (FISH), to detect genetic aberrations in multiple myeloma (MM).Bone marrow samples were collected from 18 MM and 2 plasma cell leukemia (PCL) patients. Probes targeting IgH and MMSET were prepared using a Nick Translation Kit from Bacterial artificial chromosome (BAC) clones. The immunophenotyping was achieved via the CD138 tyramide signal amplification (TSA)-mediated immunofluorescence, followed by FISH with the prepared probes \[t(4;14), t(11;14), t(14;16)\] and the commercial deletion probes (13q and p53) to detect common genetic aberrations in MM.All the 20 samples were assayed with the probes mentioned above, and revealed 4 cases with t(4;14), 6 with t(11;14), 1 with t(14;16), 3 with p53 deletion; and 8 with 13q deletion. The remaining 4 cases had none of the 5 aberrations.FICTION technique facilitates the detection of genetic abnormalities of MM in situ; enhances both efficiency and sensitivity of positive detection, thus, could be used as the screening test of molecular diagnosis of MM to guide coming-up risk-adapted therapy and evaluate prognosis.
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- 2011
32. [Splenic autotransplantation combined with lower esophagus transaction in the treatment of hepatic cirrhosis induced portal hypertension]
- Author
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Chang-zhen, Shang, Ya-jin, Chen, Hong-wei, Zhang, Lei, Zhang, Jun, Cao, Xiao-xiong, Peng, and Ji-sheng, Chen
- Subjects
Adult ,Aged, 80 and over ,Liver Cirrhosis ,Male ,Anastomosis, Surgical ,Middle Aged ,Transplantation, Autologous ,Young Adult ,Esophagus ,Treatment Outcome ,Hypertension, Portal ,Humans ,Female ,Spleen ,Aged - Abstract
To study the therapeutic effect of splenic autotransplantation combined with lower esophagus transaction anastomosis in the treatment of liver cirrhosis induced portal hypertension.Thirty-six patients admitted from January 2003 to December 2006 were randomly divided into splenic autotransplantation group undergoing splenic autotransplantation after splenectomy combined with lower esophagus transaction anastomosis, and splenectomy group only undergoing splenectomy combined with lower esophagus transaction anastomosis. The general conduction, splenic scanning, liver function, and the level of serum Tuftsin and IgM of each patient were observed before and after operation.The levels of Tuftsin and IgM in splenic autotransplantation group were significant higher than that of splenectomy group 2 months after the operation, and the liver function showed no significant difference between these two groups. Splenic tissue was detected in the retroperitoneal space by 99mTc-DRBC 2 months after operation.Splenic autotransplantation combined with lower esophagus transaction anastomosis is a safe and effective treatment strategy for patients with liver cirrhosis induced portal hypertension, and the spleen tissue transplanted into the retroperitoneal space can partially preserve the immune function.
- Published
- 2009
33. Effect of Scutellaria flavonoids on KCN-induced damages in rat pheochromocytoma PC12 cells
- Author
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Ya Zhen, Shang, Bo Wen, Qin, Jian Jun, Cheng, and Hong, Miao
- Subjects
Flavonoids ,Neurons ,Oxidative Stress ,Cell Survival ,Animals ,Humans ,Neurodegenerative Diseases ,Hypoxia, Brain ,Potassium Cyanide ,PC12 Cells ,Antioxidants ,Rats ,Scutellaria baicalensis - Abstract
Cerebral hypoxia is known to be involved in many neurodegenerative diseases such as Alzheimer's and cerebrovascular dementia. The present study was designed to investigate the effects of flavonoids from aerial part of Scutellaria baicalensis Georgi (SSF) on potassium cyanide (KCN) -induced hypoxic cytotoxicity in rat pheochromocytoma cell line PC12, and to understand the probable mechanism.The rat pheochromocytoma cell line PC12 was subjected to hypoxia by 200 microM KCN for 30 min. The cytotoxicity of KCN was assessed by cell viability assay, morphological observation, lactate dehydrogenase (LDH) release, malondialdehyde (MDA) production, and the activities of superoxide dismutase (SOD) and Na+-K+-ATPase measurements. The effects of SSF on the changes induced by KCN in PC12 cells were detected.Treatment of PC12 cells with 200 micriM KCN for 30 min increased cell death when compared with control, as assayed by MTT reduction, morphological observation and lactate dehydrogenase release measurement. These cell lesions were accompanied by disorders in SOD and Na+-K+-ATPase activities as well as MDA production. In contrast, the PC12 cells pre-treated with SSF for 24 h prior to 200 microM KCN exposure have shown protection against hypoxic toxicity. The KCN - induced decreased cell viability and activities of SOD and Na+-K+-ATPase, as well as increased MDA production were reversed by SSF pre-treatment.SSF exerted neuroprotections against KCN - induced hypoxic cytotoxicity in PC12 cells and the probable mechanisms involved free radicals and energy metabolism. Our findings may have implications in future in the treatment of neurodegenerative diseases.
- Published
- 2008
34. [Diagnosis and treatment of primary tumor of small intestine: a report of 58 cases]
- Author
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Lei, Zhang, Ya-jin, Chen, Chang-zhen, Shang, Feng, Zhong, Hong-wei, Zhang, and Ji-sheng, Chen
- Subjects
Adult ,Male ,Intestinal Neoplasms ,Intestine, Small ,Humans ,Female ,Middle Aged ,Aged ,Retrospective Studies - Abstract
To summarize the pathological classification, clinical symptom and experience in the diagnosis and treatment of primary tumor of small intestine.Data of 58 patients with primary tumor of small intestine pathologically confirmed from Oct. 1996 to Oct. 2006 were analyzed retrospectively.Thirteen patient (22.4%) had primary benign tumors of small intestine and 45 patient (77.6%) had primary malignant tumors of small intestine. The major clinical signs of primary tumor of small intestine included hemorrhage(85%), abdomen pain(19%), abdomen mass and intestine obstruction(16%). Forty- eight patients (82.8%) were diagnosed by laparotomy of abdominal cavity and misdiagnosed preoperatively as other diseases.Primary tumors of small intestine are difficult to be diagnosed preoperatively. CT scan, digital subtraction angiography and radionuclide imaging are helpful for the diagnosis. Laparotomy of abdominal cavity is the main choice for those patients with suspicious tumor of small intestine.
- Published
- 2007
35. [Investigation on psychological health of workers in a steel factory]
- Author
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You-gong, Su, Hui-zhen, Shang, Jian-ya, Sun, and Hui-shen, Wang
- Subjects
Adult ,Male ,Mental Health ,Adolescent ,Steel ,Occupational Exposure ,Surveys and Questionnaires ,Humans ,Dust ,Female ,Middle Aged - Published
- 2006
36. Total laparoscopic liver resection in 78 patients
- Author
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Chang-zhen Shang, Ze-Jian Huang, Ya-jin Chen, Lei Zhang, and Hongwei Zhang
- Subjects
Adult ,Male ,Laparoscopic surgery ,medicine.medical_specialty ,Blood transfusion ,Brief Article ,Colorectal cancer ,medicine.medical_treatment ,Single Center ,Young Adult ,medicine ,Hepatectomy ,Humans ,Laparoscopy ,Aged ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Liver Neoplasms ,Gastroenterology ,General Medicine ,Perioperative ,Middle Aged ,medicine.disease ,Surgery ,Treatment Outcome ,Hepatocellular carcinoma ,Female ,Liver function ,business - Abstract
AIM: To summarize the clinical experience of laparoscopic hepatectomy at a single center. METHODS: Between November 2003 and March 2009, 78 patients with hepatocellular carcinoma (n = 39), metastatic liver carcinoma (n = 10), and benign liver neoplasms (n = 29) underwent laparoscopic hepatectomy in our unit. A retrospective analysis was done on the clinical outcomes of the 78 patients. RESULTS: The lesions were located in segments I (n = 3), II (n = 16), III (n = 24), IV (n = 11), V (n = 11), VI (n = 9), and VIII (n = 4). The lesion sizes ranged from 0.8 to 15 cm. The number of lesions was three (n = 4), two (n = 8) and one (n = 66) in the study cohort. The surgical procedures included left hemi-hepatectomy (n = 7), left lateral lobectomy (n = 14), segmentectomy (n = 11), local resection (n = 39), and resection of metastatic liver lesions during laparoscopic surgery for rectal cancer (n = 7). Laparoscopic liver resection was successful in all patients, with no conversion to open procedures. Only four patients received blood transfusion (400-800 mL). There were no perioperative complications, such as bleeding and biliary leakage. The liver function of all patients recovered within 1 wk, and no liver failure occurred. CONCLUSION: Laparoscopic hepatectomy is a safe and feasible operation with minimal surgical trauma. It should be performed by a surgeon with sufficient experience in open hepatic resection and who is proficient in laparoscopy.
- Published
- 2009
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