60 results on '"Haozhe Piao"'
Search Results
2. Bacteria associated with glioma: a next wave in cancer treatment
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Yiming Meng, Jing Sun, Guirong Zhang, Tao Yu, and Haozhe Piao
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Microbiology (medical) ,Infectious Diseases ,Immunology ,Microbiology - Abstract
Malignant gliomas occur more often in adults and may affect any part of the central nervous system (CNS). Although their results could be better, surgical excision, postoperative radiation and chemotherapy, and electric field therapy are today’s mainstays of glioma care. However, bacteria can also exert anti-tumor effects via mechanisms such as immune regulation and bacterial toxins to promote apoptosis, inhibit angiogenesis, and rely on their natural characteristics to target the tumor microenvironment of hypoxia, low pH, high permeability, and immunosuppression. Tumor-targeted bacteria expressing anticancer medications will go to the cancer site, colonize the tumor, and then produce the therapeutic chemicals that kill the cancer cells. Targeting bacteria in cancer treatment has promising prospects. Rapid advances have been made in the study of bacterial treatment of tumors, including using bacterial outer membrane vesicles to load chemotherapy drugs or combine with nanomaterials to fight tumors, as well as the emergence of bacteria combined with chemotherapy, radiotherapy, and photothermal/photodynamic therapy. In this study, we look back at the previous years of research on bacteria-mediated glioma treatment and move forward to where we think it is headed.
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- 2023
3. Approaches for neutrophil imaging: an important step in personalized medicine
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Yiming, Meng, Jing, Sun, Guirong, Zhang, Tao, Yu, and Haozhe, Piao
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Neutrophils ,Neoplasms ,Tumor Microenvironment ,Leukocytes ,Humans ,Bioengineering ,General Medicine ,Precision Medicine ,Applied Microbiology and Biotechnology ,Biotechnology - Abstract
Neutrophils are the most abundant circulating leukocytes and the first line of defense against invading pathogens. They are key components of the innate immune system. Neutrophils also cause tissue damage in various autoimmune and inflammatory diseases and play an important role in cancer progression. Due to the complex relationship between various diseases and neutrophils, these cells have become potentially important targets for therapeutic interventions. Monitoring neutrophils in the tumor microenvironment is critical for tumor treatment and prognostic analysis but remains challenging. Molecular imaging technology has made great progress as a valuable tool for noninvasively visualizing biological events and establishing effective cancer diagnoses and treatment methods. Molecular probes designed based on the characteristics of neutrophils, such as their flexible morphology, the abundance of surface receptors, and the absence of immunogenicity, have shown great potential. This has created an opportunity for novel ideas and research methods for the diagnosis and targeted therapy of inflammatory diseases and tumors, with the goal of integrated diagnosis and treatment. This review discusses the diverse tumor detection and diagnostic imaging strategies based on neutrophils. It is anticipated that neutrophil-based imaging will soon be gradually integrated into clinical applications.Neutrophils play a role in promoting/inhibiting tumor growth in the tumor microenvironment.To be more conducive to discovering neutrophils in tumors and guiding treatment, medical imaging technology has developed stepwise.In the context of the intersection of imaging technology, great breakthroughs have been made in the individualized research of tumor diagnosis.This article contributes to the promotion of new multimodal molecular imaging technology and the application of rapid diagnosis individualization.
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- 2022
4. Carbonic anhydrase IX inhibitor S4 triggers immunogenic cell death in glioma cells via endoplasmic reticulum stress pathway
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Jing Cui, Huizhe Xu, Ji Shi, Kun Fang, Jia Liu, Feng Liu, Yi Chen, Haiyang Liang, Ye Zhang, and Haozhe Piao
- Abstract
Background Immunogenic cell death (ICD), which releases danger-associated molecular patterns (DAMP) that induce potent anticancer immune response, has emerged as a key component of therapy-induced anti-tumor immunity. The aim of this work was to analyze whether the carbonic anhydrase IX inhibitor S4 can elicit ICD in glioma cells. Methods The effects of S4 on glioma cell growth were evaluated using the CCK-8, clonogenic and sphere assays. Glioma cell apoptosis was determined by flow cytometry. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of S4-treated cells were concentrated for the determination of HMGB1and HSP70/90 expression by immunoblotting. RNA-seq was performed to compare gene expression profiles between S4-treated and control cells. Pharmacological inhibition of apoptosis, autophagy, necroptosis and endoplasmic reticulum (ER) stress was achieved by inhibitors. In vivo effects of S4 were evaluated in glioma xenografts. Immunohistochemistry (IHC) was performed to stain Ki67 and CRT. Results S4 significantly decreased the viability of glioma cells and induced apoptosis and autophagy. Moreover, S4 triggered CRT exposure and the release of HMGB1 and HSP70/90. Inhibition of either apoptosis or autophagy significantly reversed S4-induced release of DAMP molecules. RNA-seq analysis indicated that the ER stress pathway was deregulated upon exposure to S4. Both PERK-eIF2α and IRE1α- XBP1 axis were activated in S4-treated cells. Furthermore, pharmacological inhibition of PERK significantly suppressed S4-triggered ICD markers and autophagy. In glioma xerografts, S4 significantly reduced tumor growth. Conclusions Altogether, these findings suggest S4 as a novel ICD inducer in glioma and might have implications for S4-based immunotherapy.
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- 2023
5. Imaging glucose metabolism to reveal tumor progression
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Yiming Meng, Jing Sun, Guirong Zhang, Tao Yu, and Haozhe Piao
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Physiology ,Physiology (medical) - Abstract
Purpose: To analyze and review the progress of glucose metabolism-based molecular imaging in detecting tumors to guide clinicians for new management strategies.Summary: When metabolic abnormalities occur, termed the Warburg effect, it simultaneously enables excessive cell proliferation and inhibits cell apoptosis. Molecular imaging technology combines molecular biology and cell probe technology to visualize, characterize, and quantify processes at cellular and subcellular levels in vivo. Modern instruments, including molecular biochemistry, data processing, nanotechnology, and image processing, use molecular probes to perform real-time, non-invasive imaging of molecular and cellular events in living organisms.Conclusion: Molecular imaging is a non-invasive method for live detection, dynamic observation, and quantitative assessment of tumor glucose metabolism. It enables in-depth examination of the connection between the tumor microenvironment and tumor growth, providing a reliable assessment technique for scientific and clinical research. This new technique will facilitate the translation of fundamental research into clinical practice.
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- 2023
6. The prognostic significance of genes involved in glycolysis, immunity, and epithelial-to-mesenchymal transition in glioblastoma
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Yiming Meng, Jing Sun, Guirong Zhang, Tao Yu, and Haozhe Piao
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Glioblastoma (GBM) is the most prevalent form of primary brain cancer. In the therapeutic therapy of GBM, there are still several ambiguities. GBM patients urgently need further research to find significant prognostic markers and more effective treatment choices. However, current stage-based clinical approaches still need to be improved for predicting survival and making decisions. This research intended to develop a new GBM risk assessment model based on glycolysis, immunology, and epithelial-mesenchymal transition (EMT) gene signatures. In this analysis, the cohort was constructed using TCGA-GBM data. Leveraging bioinformatics and machine algorithms, we developed a risk model based on glycolysis, immunological, and EMT gene signatures, which was then employed to classify patients into high and low-risk categories. Subsequently, we evaluated whether the risk score was associated with the immunological microenvironment, immunotherapy response, and numerous anticancer drug sensitivity. The unique risk model based on glycolysis, immunological, and EMT gene signatures could assist in predicting clinical prognosis and directing therapy decisions for GBM patients.
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- 2023
7. Unexpected worsening of doxorubicin cardiotoxicity upon intermittent fasting
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Yiming Meng, Jing Sun, Guirong Zhang, Tao Yu, and Haozhe Piao
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General Medicine - Published
- 2023
8. Single-Cell Sequencing Analysis Identified ASTN2 as a Migration Biomarker in Adult Glioblastoma
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Tangjun, Guo, Aijun, Bao, Yandong, Xie, Jianting, Qiu, and Haozhe, Piao
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single-cell RNA sequencing ,glioblastoma ,ASTN2 ,prognosis ,General Neuroscience - Abstract
Glioblastoma is the most common and aggressive primary central nervous system malignant tumors. With the development of targeted sequencing and proteomic profiling technology, some new tumor types have been established and a series of novel molecular markers have also been identified. The 2021 updated World Health Organization classification of central nervous system tumors first mentioned the classification of adult glioma and pediatric glioma based on the molecular diagnosis. Thus, we used single-cell RNA sequencing analysis to explore the diversity and similarities in the occurrence and development of adult and pediatric types. ASTN2, which primarily encodes astrotactin, has been reported to be dysregulated in various neurodevelopmental disorders. Although some studies have demonstrated that ASTN2 plays an important role in glial-guided neuronal migration, there are no studies about its impact on glioblastoma cell migration. Subsequent single-cell RNA sequencing revealed ASTN2 to be a hub gene of a cell cluster which had a poor effect on clinical prognosis. Eventually, a western blot assay and a wound-healing assay first confirmed that ASTN2 expression in glioblastoma cell lines is higher than that in normal human astrocytes and affects the migration ability of glioblastoma cells, making it a potential therapeutic target.
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- 2022
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9. UM-164, a Dual Inhibitor of c-Src and p38 MAPK, Suppresses Proliferation of Glioma by Reducing YAP Activity
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Huizhe, Xu, Ye, Zhang, Jia, Liu, Jing, Cui, Yu, Gan, Zhisheng, Wu, Youwei, Chang, Rui, Sui, Yi, Chen, Ji, Shi, Haiyang, Liang, Qiang, Liu, Shulan, Sun, and Haozhe, Piao
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Cancer Research ,Oncology ,UM-164 ,glioma ,YAP ,proliferation ,c-Src ,p38 - Abstract
UM-164 is a dual inhibitor of c-Src and p38 MAPK, and has been a lead compound for targeting triple-negative breast cancer. UM-164 shows stronger binding to the active sites of Src compared with the conventional Src inhibitor Dasatinib. While Dasatinib has displayed some inhibitory effects on glioma growth in clinical trials, whether UM-164 can suppress glioma growth has not been reported. Here we show that UM-164 suppressed the proliferation, migration and spheroid formation of glioma cells, and induced cell cycle arrest in the G1 phase. Moreover, UM-164 triggered YAP translocation to the cytoplasm and reduced the activity of YAP, as evidenced by a luciferase assay. Accordingly, UM-164 markedly decreased the expression levels of YAP target genes CYR61 and AXL. Importantly, ectopic expression of wild-type YAP or YAP-5SA (YAP constitutively active mutant) could rescue the anti-proliferative effect induced by UM-164. Intriguingly, p38 MAPK appears to play a greater role than Src in UM-164-mediated inhibition of YAP activity. Furthermore, the in vitro anti-glioma effect mediated by UM-164 was confirmed in a xenograft glioma model. Together, these findings reveal a mechanism by which UM-164 suppresses the malignant phenotypes of glioma cells and might provide a rationale for UM-164-based anti-glioma clinical trials.
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- 2022
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10. Nuclear Aurora kinase A triggers programmed death‐ligand 1‐mediated immune suppression by activating MYC transcription in triple‐negative breast cancer
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Haozhe Piao, Fei Peng, Shulan Sun, Yunyong Liu, Wei Zhou, Xiaoyan Li, Yajing Zhan, Xiaoxi Li, Min Yan, Fan An, and Quentin Liu
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Cancer Research ,medicine.medical_treatment ,T cell ,Triple Negative Breast Neoplasms ,MYC ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,B7-H1 Antigen ,programmed death‐ligand 1 ,Aurora kinase A ,Mice ,Immune system ,Downregulation and upregulation ,Interferon ,medicine ,Animals ,Humans ,Kinase activity ,RC254-282 ,immune evasion ,Mice, Inbred BALB C ,Chemistry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunotherapy ,Original Articles ,medicine.anatomical_structure ,triple‐negative breast cancer ,Oncology ,Cancer research ,Leukocytes, Mononuclear ,Original Article ,Aurora Kinase A ,immunotherapy ,Carcinogenesis ,medicine.drug - Abstract
Background Increasing studies have reported that oncogenes regulate components of the immune system, suggesting that this is a mechanism for tumorigenesis. Aurora kinase A (AURKA), a serine/threonine kinase, is involved in cell mitosis and is essential for tumor cell proliferation, metastasis, and drug resistance. However, the mechanism by which AURKA is involved in immune response regulation is unclear. Therefore, this study aimed to investigate the role of AURKA in immune regulation in triple‐negative breast cancer (TNBC). Methods Peripheral blood mononuclear cells (PBMCs) were co‐cultured with TNBC cells. The xCELLigence Real‐Time Cell Analyzer‐MP system was used to detect the killing efficiency of immune cells on TNBC cells. The expression of immune effector molecules was tested by quantitative real‐time polymerase chain reaction (qRT‐PCR) to evaluate immune function. Furthermore, to validate AURKA‐regulated immune response in vivo, 4T1 murine breast cancer cell line with AURKA overexpression or downregulation was engrafted into BALB/c mice. The distribution and proportion of immune cells in tumors were further evaluated by immunohistochemistry and flow cytometry. Results Downregulation of AURKA in TNBC cells increased immune response by activating CD8+ T cell proliferation and activity. Nuclear rather than cytoplasmic AURKA‐derived programmed death‐ligand 1 (PD‐L1) expression was independent of its kinase activity. Mechanistic investigations showed that nuclear AURKA increased PD‐L1 expression via an MYC‐dependent pathway. PD‐L1 overexpression mostly reversed AURKA silencing‐induced expression of immune effector molecules, including interleukin‐ (IL‐2), interferon‐γ (IFN‐γ), and perforin. Moreover, AURKA expression was negatively correlated with the enrichment and activity of tumor‐infiltrating CD8+ T cells in 4T1 engrafted BALB/c mouse model. Conclusions Nuclear AURKA elevated PD‐L1 expression via an MYC‐dependent pathway and contributed to immune evasion in TNBC. Therapies targeting nuclear AURKA may restore immune responses against tumors., The present study showed that nuclear AURKA rather than its kinase activity induced PD‐L1 expression via a MYC‐dependent pathway. In addition, downregulation of AURKA led to increased CD8+ T cell infiltration and activation in vivo. Thus, our data provided evidences for the involvement of AURKA in immune evasion of triple‐negative breast cancer.
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- 2021
11. The three-dimension preclinical models for ferroptosis monitoring
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Yiming, Meng, Jing, Sun, Guirong, Zhang, Tao, Yu, and Haozhe, Piao
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Histology ,Biomedical Engineering ,Bioengineering ,Biotechnology - Abstract
As a new programmed cell death process, ferroptosis has shown great potential and uniqueness in experimental and treatment-resistant cancer models. Currently, the main tools for drug research targeting ferroptosis are tumor cells cultured in vitro and tumor models established in rodents. In contrast, increasing evidence indicates that reactivity may differ from modifications in mice or humans in the process of drug screening. With the blossoming of 3D culture technology, tumor organoid culture technology has gradually been utilized. Compared with traditional 2D culture and tumor tissue xenotransplantation, tumor organoids have a significantly higher success rate. They can be cultured quickly and at a lower cost, which is convenient for gene modification and large-scale drug screening. Thus, combining 3D cell culture technology, drug monitoring, and ferroptosis analysis is necessary to develop the impact of ferroptosis-related agents in tumor treatment.
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- 2022
12. Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma
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Xu, Guo, Rui, Sui, and Haozhe, Piao
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Extracellular Vesicles ,Brain Neoplasms ,Biomedical Engineering ,Humans ,Pharmaceutical Science ,Molecular Medicine ,Medicine (miscellaneous) ,Bioengineering ,Glioma ,Exosomes ,Prognosis ,Applied Microbiology and Biotechnology - Abstract
Small extracellular vesicles (SEVs) are extracellular vesicles containing DNA, RNA, and proteins and are involved in intercellular communication and function, playing an essential role in the growth and metastasis of tumors. SEVs are present in various body fluids and can be isolated and extracted from blood, urine, and cerebrospinal fluid. Under both physiological and pathological conditions, SEVs can be released by some cells, such as immune, stem, and tumor cells, in a cytosolic manner. SEVs secreted by tumor cells are called tumor-derived exosomes (TEXs) because of their origin in the corresponding parent cells. Glioma is the most common intracranial tumor, accounting for approximately half of the primary intracranial tumors, and is characterized by insidious onset, high morbidity, and high mortality rate. Complete removal of tumor tissues by surgery is difficult. Chemotherapy can improve the survival quality of patients to a certain extent; however, gliomas are prone to chemoresistance, which seriously affects the prognosis of patients. In recent years, TEXs have played a vital role in the occurrence, development, associated immune response, chemotherapy resistance, radiation therapy resistance, and metastasis of glioma. This article reviews the role of TEXs in glioma progression, drug resistance, and clinical diagnosis.
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- 2022
13. Osimertinib induces paraptosis and TRIP13 confers resistance in glioblastoma cells
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songshu meng, lulu hu, ji shi, Dachuan Shen, Xingyue Zhai, Dapeng Liang, Jing Wang, Chunrui Xie, Zhiyu Xia, Jing Cui, Feng Liu, Sha Du, and Haozhe Piao
- Abstract
Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor that has been evaluated in glioblastoma (GBM) in pre-clinical and clinical trials. However, the precise mechanism whereby Osimertinib induces GBM cell death as well as the underlying resistance mechanism to Osimertinibremain unclear. Here we show that Osimertinib induced paraptosis in GBM cells as evidenced by the formation of cytoplasmic vacuoles, accumulation of ubiquitinated proteins, and upregulation of endoplasmic reticulum (ER) stress markers like CHOP. In addition, apoptosis or autophagy was not responsible for Osimertinib-induced cell death. RNA-seq analysis revealed that ER stress was the mostly deregulated pathway upon Osimertinib exposure. Consistently, pharmacologically targeting the PERK-eIF2α axis impaired Osimertinib-induced paraptosis. Noteworthy, we show that the expression of thyroid receptor-interacting protein 13 (TRIP13), an AAA+ATPase, alleviated Osimertinib-triggered paraptosis, thus conferring resistance. Intriguingly, an AKT inhibitor MK-2206 downregulated TRIP13 abundance and synergized with Osimertinib to suppress TRIP13-high GBM cell growth in vitro and in vivo. Thus, this study reveals a novel mechanism of action associated with the anti-GBM effects of Osimertinib, which involves ER stress-regulated paraptosis. Furthermore, we identify a TRIP13-driven resistance mechanism against Osimeritinib in GBM and offer a MK-2206-based combination strategy to overcome such resistance.
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- 2022
14. Status and epidemiological characteristics of high-risk human papillomavirus infection in multiple centers in Shenyang
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Di Yang, Jing Zhang, Xiaoli Cui, Jian Ma, Chunyan Wang, and Haozhe Piao
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Microbiology (medical) ,Microbiology - Abstract
The different human papillomavirus (HPV) strains cause warts in various regions of the body. However, considering that the status and genotype distribution of HPV infection in women in Shenyang remain unknown, herein, we investigated the epidemiological characteristics of high-risk HPV (HR-HPV) infection in women in Shenyang, as well as the current state of HPV infection in Shenyang, to provide a theoretical basis for the prevention and treatment of cervical cancer. From December 2018 to December 2021, 6,432 urban and rural women from the Liaoning Cancer Hospital and the Sujiatun Women and Infants’ Hospital were assessed via the Thinprep cytology test (TCT) and HR-HPV detection. Of the 5,961 women enrolled, 739 were HPV positive (12.40%) and 562 were TCT positive (9.43%). Statistical analyses identified the following HPV risk factors: high school education or lower [OR = 1.426 (1.199–1.696), p < 0.001], age at first sexual encounter ≤ 19 years [OR = 1.496 (1.008–2.220), p = 0.046], and number of sexual partners > 1 [OR = 1.382 (1.081–1.768), p = 0.010], atypical squamous cells of undetermined significance (ASCUS) and above [OR = 10.788 (8.912–13.060), p < 0.001], non-condom-based contraception [OR = 1.437 (1.103–1.871), p = 0.007], nationalities other than Han [OR = 1.690 (1.187–2.406), p = 0.004], rural residence [OR = 1.210 (1.031–1.419), p = 0.020]. Compared to the HPV infection rate of women aged 56–65, that in women aged 35–45 [OR = 0.687 (0.549–0.860), p = 0.001] and 46–55 [OR = 0.740 (0.622–0.879), p = 0.001] decreased significantly. To conclude, risk factors of HPV infection among female patients include high school age and below, initial sexual encounter at age ≤ 19 years, number of sexual partners > 1, ASCUS and above, non-condom contraception, nationalities other than Han nationality and rural population. Collectively, this study provides insights for the improved prevention and treatment of cervical cancer.
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- 2022
15. Platelets: The Emerging Clinical Diagnostics and Therapy Selection of Cancer Liquid Biopsies
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Yang Zheng, Guirong Zhang, Yiming Meng, Jing Sun, Tao Yu, and Haozhe Piao
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0301 basic medicine ,diagnosis ,Review ,03 medical and health sciences ,0302 clinical medicine ,noninvasive ,Biopsy ,Medicine ,Pharmacology (medical) ,Platelet ,Liquid biopsy ,platelet ,liquid biopsy ,medicine.diagnostic_test ,business.industry ,Cancer ,medicine.disease ,Microvesicles ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,RNA ,Bone marrow ,Stem cell ,business - Abstract
Due to the inherent molecular heterogeneity of metastatic tumours and the dynamic evolution ability of tumour genomes, tumour tissues obtained through biopsy and other methods cannot capture all of the features of tumour genomes. A new diagnostic concept called “liquid biopsy” has received widespread attention in recent years. Liquid biopsy has changed the clinical practice of oncology and is widely used to guide targeted drug utilization, monitor disease progression and track drug resistance. The latest research subject in liquid biopsy is platelets. Platelets originate from multifunctional haematopoietic stem cells in the bone marrow haematopoietic system. They are small cells from the cytoplasm of bone marrow megakaryocytes. Their main physiological functions are to participate in the processes of physiological haemostasis and coagulation. Tumour cells transfer biomolecules (such as RNA) to platelets through direct contact and release of exosomes, which changes the platelet precursor RNA. Under the stimulation of tumour cells and the tumour microenvironment, platelet precursor mRNA is spliced into mature RNA and converted into functional protein to respond to external stimuli, forming tumour-educated platelets (TEPs). The detection of TEPs in the peripheral blood of patients is expected to be used in clinical tumour diagnosis. This emerging liquid biopsy method can replace and supplement the current tumour detection methods. Further research on the role of platelets in tumour diagnosis will help provide a novel theoretical basis for clinical tumour diagnosis.
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- 2021
16. Multi-center clinical study using optical coherence tomography for evaluation of cervical lesions in-vivo
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Xiaoan Zhang, Chenchen Ren, Hao Hu, Haozhe Piao, Zhongna Shi, Huan Ma, Chunyan Wang, Baoping Zhang, Zhaoning Jiang, Xiuqin Wang, Baojin Wang, Huifen Wang, and Xianxu Zeng
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Adult ,genetic structures ,Science ,Statistics as Topic ,Uterine Cervical Neoplasms ,Diseases ,Cervix Uteri ,Article ,Clinical study ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Medical research ,Optical coherence tomography ,In vivo ,Biopsy ,Image Processing, Computer-Assisted ,Medicine ,Humans ,Prospective cohort study ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,eye diseases ,Diagnosis methods ,Cervical tissue ,Oncology ,Colposcopy ,030220 oncology & carcinogenesis ,Female ,Squamous Intraepithelial Lesions of the Cervix ,sense organs ,Neoplasm Grading ,business ,Nuclear medicine ,Tomography, Optical Coherence - Abstract
ObjectiveIn this prospective study of an in-vivo cervical examination using optical coherence tomography (OCT), we evaluated the diagnostic value of non-invasive and real-time OCT in cervical precancerous lesions and cancer diagnosis, and determined the characteristics of OCT images.Methods733 patients from 5 Chinese hospitals were inspected with OCT and colposcopy-directed biopsy. The OCT images were compared with the histological sections to find out the characteristics of various categories of lesions. The OCT images were also interpreted by 3 investigators to make a 2-class classification, and the results were compared against the pathological results.ResultsVarious structures of the cervical tissue were clearly observed in OCT images, which matched well with the corresponding histological sections. The OCT diagnosis results delivered a sensitivity of 87.0% (95% confidence interval, CI, 82.2%-90.7%), a specificity of 84.1% (95% CI, 80.3%-87.2%), and an overall accuracy of 85.1%.ConclusionBoth good consistency of OCT images and histological images and satisfactory diagnosis results were provided by OCT. Due to its features of non-invasion, real-time, and accuracy, OCT is valuable for the in-vivo evaluation of cervical lesions and has the potential to be one of the routine cervical diagnosis methods.
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- 2021
17. Carbonic anhydrase IX inhibitor S4 triggers immunogenic cell death in glioma cells via endoplasmic reticulum stress pathway
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Jing Cui, Huizhe Xu, Ji Shi, Kun Fang, Dapeng Liang, Feng Liu, Jing Wang, Chunrui Xie, Zhiyu Xia, Songshu Meng, Yumei Yan, and Haozhe Piao
- Abstract
Purpose: Immunogenic cell death (ICD), which releases danger-associated molecular patterns (DAMP) that induce potent anticancer immune response, has emerged as a key component of therapy-induced anti-tumor immunity. The aim of this work was to analyze whether the carbonic anhydrase IX inhibitor S4 can elicit ICD in glioma cells. Methods: The effects of S4 on glioma cell growth were evaluated using the CCK-8, clonogenic and sphere assays. Glioma cell apoptosis was determined by flow cytometry. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of S4-treated cells were concentrated for the determination of HMGB1and HSP70/90 expression by immunoblotting. RNA-seq was performed to compare gene expression profiles between S4-treated and control cells. Pharmacological inhibition of apoptosis, autophagy, necroptosis and endoplasmic reticulum (ER) stress was achieved by inhibitors. In vivo effects of S4 were evaluated in glioma xenografts. Immunohistochemistry (IHC) was performed to stain Ki67 and CRT.Results: S4 significantly decreased the viability of glioma cells and induced apoptosis and autophagy. Moreover, S4 triggered CRT exposure and the release of HMGB1 and HSP70/90. Inhibition of either apoptosis or autophagy significantly reversed S4-induced release of DAMP molecules. RNA-seq analysis indicated that the ER stress pathway was deregulated upon exposure to S4. Both PERK-eIF2α and IRE1α- XBP1 axis were activated in S4-treated cells. Furthermore, pharmacological inhibition of PERK significantly suppressed S4-triggered ICD markers and autophagy. In glioma xerografts, S4 significantly reduced tumor growth. Conclusions: Altogether, these findings suggest S4 as a novel ICD inducer in glioma and might have implications for S4-based immunotherapy.
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- 2022
18. Performance of human papillomavirus E6/E7 mRNA assay for primary cervical cancer screening and triage: Population-based screening in China
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Jing Zhang, Di Yang, Xiaoli Cui, Guangcong Liu, Zhumei Cui, Chunyan Wang, and Haozhe Piao
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Microbiology (medical) ,Adult ,China ,Immunology ,Papillomavirus Infections ,Uterine Cervical Neoplasms ,Alphapapillomavirus ,Middle Aged ,Microbiology ,Infectious Diseases ,Humans ,Female ,RNA, Messenger ,Triage ,Papillomaviridae ,Early Detection of Cancer ,Aged - Abstract
ObjectiveCervical cancer screening is very important in the prevention and treatment of cervical cancer. In China, the cervical screening strategy needs to be improved. To explore a suitable cervical screening strategy in China, we evaluated the performance of the human papillomavirus (HPV) E6/E7 mRNA (Aptima HPV (AHPV)) assay in primary screening and different triage strategies for women undergoing routine cervical screening.MethodsA total of 10,002 women aged 35 to 65 years of age were recruited in Liaoning Province and Qingdao City, China. Specimens were tested by liquid-based cytology (LBC) and the AHPV assay, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all high-risk HPV (HR-HPV)-positive samples. Test characteristics were calculated based on histological review.ResultsWe identified 109 women with high-grade squamous intraepithelial lesion or worse (HSIL+), including six with cervical cancer. The sensitivity of AHPV was clearly higher than that of LBC (92.7 [95% CI: 87.2, 97.2] vs. 67.9 [95% CI: 59.6, 76.1], p < 0.001). The specificity of AHPV was 93.0 (95% CI: 92.5, 93.5), which was lower than that of LBC (95.2 [95% CI: 94.8, 95.6], p < 0.001). There was no statistical difference between the positive predictive value of AHPV and LBC (13.5 [95% CI: 11.2, 16.2] vs. 14.3 [95% CI: 11.4, 17.6], p = 0.695). The difference of area under the curve (AUC) values between the AHPV test (0.928 [95% CI: 0.904, 0.953]) and LBC test (0.815 [95% CI: 0.771, 0.860]) in detecting HSIL+ was statistically significant (p < 0.001). Finally, among the three triage strategies, both the sensitivity (73.4 [95% CI: 65.1, 81.7]) and AUC (0.851 [95% CI: 0.809, 0.892]) of AHPV genotyping with reflex LBC triage were the greatest.ConclusionIn summary, the AHPV assay is both specific and sensitive for detecting HSIL+ and may be suitable for use in primary cervical cancer screening in China. AHPV genotyping with reflex LBC triage may be a feasible triage strategy.
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- 2022
19. A Meta-Analysis of Calcium Intake and Risk of Glioma
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Xu Guo and Haozhe Piao
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Cancer Research ,Nutrition and Dietetics ,Oncology ,Brain Neoplasms ,Odds Ratio ,Medicine (miscellaneous) ,Humans ,Calcium ,Glioma ,Publication Bias - Abstract
A meta-analysis was conducted to investigate the correlation between calcium intake and the risk of brain tumors (especially glioma).The PubMed, Web of Science, and Embase databases were searched for relevant papers on the association between calcium intake and glioma as of August 22, 2021. The odds ratio (OR) with a 95% confidence interval (CI) was calculated using a random-effects model. Egger's test was conducted to assess publication bias.The meta-analysis includes four studies. The meta-analysis showed that calcium intake and the risk of brain tumors have a significant negative relationship (OR = 0.28; 95% CI: 0.11 to 0.72;There is a significant negative association between calcium intake and brain tumors (especially gliomas), but more high-quality studies are needed to verify these results.
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- 2022
20. Thyroid receptor-interacting protein 13 and EGFR form a feedforward loop promoting glioblastoma growth
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Wei Cheng, Zhiyou Fang, Menglin Ren, Ji Shi, Lulu Hu, Qing Xu, Martin P. Barr, Songshu Meng, Jianmei Ma, Dapeng Liang, Chunyan Song, Xiaolin Bi, Dachuan Shen, Ke Jiang, Haozhe Piao, Sha Du, Shao Li, and Wenbin Li
- Subjects
0301 basic medicine ,Cancer Research ,Cell Cycle Proteins ,urologic and male genital diseases ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,Animals ,Humans ,Osimertinib ,Epidermal growth factor receptor ,Phosphorylation ,Tyrosine ,Feedback, Physiological ,Thyroid hormone receptor ,TRIP13 ,biology ,Brain Neoplasms ,Protein Stability ,urogenital system ,Cell growth ,Chemistry ,Prognosis ,nervous system diseases ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,HEK293 Cells ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,biology.protein ,ATPases Associated with Diverse Cellular Activities ,Glioblastoma ,Neoplasm Transplantation - Abstract
Epidermal growth factor receptor (EGFR) amplification and EGFRvIII mutation drive glioblastoma (GBM) pathogenesis, but their regulation remains elusive. Here we characterized the EGFR/EGFRvIII “interactome” in GBM and identified thyroid receptor-interacting protein 13 (TRIP13), an AAA + ATPase, as an EGFR/EGFRvIII-associated protein independent of its ATPase activity. Functionally, TRIP13 augmented EGFR pathway activation and contributed to EGFR/EGFRvIII-driven GBM growth in GBM spheroids and orthotopic GBM xenograft models. Mechanistically, TRIP13 enhanced EGFR protein abundance in part by preventing Cbl-mediated ubiquitination and proteasomal degradation. Reciprocally, TRIP13 was phosphorylated at tyrosine(Y) 56 by EGFRvIII and EGF-activated EGFR. Abrogating TRIP13 Y56 phosphorylation dramatically attenuated TRIP13 expression-enhanced EGFR signaling and GBM cell growth. Clinically, TRIP13 expression was upregulated in GBM specimens and associated with poor patient outcome. In GBM, TRIP13 localized to cell membrane and cytoplasma and exhibited oncogenic effects in vitro and in vivo, depending on EGFR signaling but not the TRIP13 ATPase activity. Collectively, our findings uncover that TRIP13 and EGFR form a feedforward loop to potentiate EGFR signaling in GBM growth and identify a previously unrecognized ATPase activity-independent mode of action of TRIP13 in GBM biology.
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- 2020
21. An immune-related nomogram model that predicts the overall survival of patients with lung adenocarcinoma
- Author
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Jing, Sun, Yan, Yan, Yiming, Meng, Yushu, Ma, Tianzhao, Du, Tao, Yu, and Haozhe, Piao
- Subjects
Cohort Studies ,Pulmonary and Respiratory Medicine ,Nomograms ,Lung Neoplasms ,Humans ,Adenocarcinoma of Lung ,Prognosis - Abstract
Background Lung adenocarcinoma accounts for approximately 40% of all primary lung cancers; however, the mortality rates remain high. Successfully predicting progression and overall (OS) time will provide clinicians with more options to manage this disease. Methods We analyzed RNA sequencing data from 510 cases of lung adenocarcinoma from The Cancer Genome Atlas database using CIBERSORT, ImmuCellAI, and ESTIMATE algorithms. Through these data we constructed 6 immune subtypes and then compared the difference of OS, immune infiltration level and gene expression between these immune subtypes. Also, all the subtypes and immune cells infiltration level were used to evaluate the relationship with prognosis and we introduced lasso-cox method to constructe an immune-related prognosis model. Finally we validated this model in another independent cohort. Results The C3 immune subtype of lung adenocarcinoma exhibited longer survival, whereas the C1 subtype was associated with a higher mutation rate of MUC17 and FLG genes compared with other subtypes. A multifactorial correlation analysis revealed that immune cell infiltration was closely associated with overall survival. Using data from 510 cases, we constructed a nomogram prediction model composed of clinicopathologic factors and immune signatures. This model produced a C-index of 0.73 and achieved a C-index of 0.844 using a validation set. Conclusions Through this study we constructed an immune related prognosis model to instruct lung adenocarcinoma’s OS and validated its value in another independent cohost. These results will be useful in guiding treatment for lung adenocarcinoma based on tumor immune profiles.
- Published
- 2022
22. A Pan-Cancer In Silico Analysis of the COVID-19 Internalization Protease: Transmembrane Proteaseserine-2
- Author
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Yiming Meng, Jing Sun, Guirong Zhang, Tao Yu, and Haozhe Piao
- Subjects
Genetics ,Molecular Medicine ,urologic and male genital diseases ,Genetics (clinical) - Abstract
The new coronavirus (2019-nCoV) is an emerging pathogen that can cause severe respiratory infections in humans. It is worth noting that many of the affected COVID-19 patients have malignant tumors. In addition, cancer has been identified as a personal risk factor for COVID-19. Transmembrane proteaseserine-2 (TMPRSS2) is a crucial host protease that mediates S protein activation and initially promotes virus entry into host cells. Moreover, it is abnormally expressed in a variety of tumors. However, the systematic analysis of TMPRSS2 aberrations in human cancer remains to be elucidated. Here, we analyzed the genetic changes, RNA expression, and DNA methylation of TMPRSS2 in more than 30 tumors. It has been reported that TMPRSS2 is overexpressed in tumors such as prostate adenocarcinoma (PRAD), and in contrast, the expression of TMPRSS2 is decreased in tumors such as head and neck cancer (HNSC). In addition, TMPRSS2 low DNA methylation was also found in most of these TMPRSS2 high-expressing tumors in this study. Clinical studies have found that there is a significant correlation between the expression of TMPRSS2 and the prognosis of some tumor patients. The expression of TMPRSS2 is also related to the infiltration of cancer-related fibroblasts, and the potential pathways and functional mechanisms were analyzed through KEGG/GO enrichment. In the end, our study planned the genetic and epigenetic variation of TMPRSS2 in human malignant tumors for the first time and provided a relatively comprehensive understanding of the carcinogenic effects of TMPRSS2.
- Published
- 2022
23. Clinical Prognostic Value of the PLOD Gene Family in Lung Adenocarcinoma
- Author
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Yiming Meng, Jing Sun, Guirong Zhang, Tao Yu, and Haozhe Piao
- Subjects
Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Molecular Biology ,Biochemistry - Abstract
Accumulating evidence has implicated members of the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene family, PLOD1, PLOD2, and PLOD3, in cancer progression and metastasis. However, their expression, prognostic value, and mechanisms underlying their roles in lung adenocarcinoma (LUAD) have not yet been reported. We downloaded PLOD data for LUAD and normal tissues from The Cancer Genome Atlas (TCGA). PLOD1-3 protein expression was evaluated using the Clinical Proteomics Tumor Analysis Consortium and Human Protein Atlas. Survival analysis was performed using the Kaplan–Meier method. A protein–protein interaction network was constructed using STRING software. The “ClusterProfiler” package was used for functional-enrichment analysis. The relationship between PLOD mRNA expression and immune infiltration was analyzed using the Tumor Immunity Assessment Resource and Tumor Immune System Interaction Database. The expression of PLODs in LUAD tissues was significantly upregulated compared with that in adjacent normal tissues. PLOD mRNA overexpression is associated with lymph node metastasis and high TNM staging. Receiver operating characteristic curve analysis showed that when the cut-off level was 6.073, the accuracy, sensitivity, and specificity of PLOD1 in distinguishing LUAD from adjacent controls were 84.4, 79.7, and 82.6%, respectively. The accuracy, sensitivity, and specificity of PLOD2 in distinguishing LUAD from adjacent controls were 81.0, 98.3, and 68.0%, respectively, at a cut-off value of 4.360. The accuracy, sensitivity, and specificity of PLOD3 in distinguishing LUAD from adjacent controls were 69.0, 86.4, and 52.0%, respectively, with a cut-off value of 5.499. Kaplan–Meier survival analysis demonstrated that LUAD patients with high PLODs had a worse prognosis than those with low PLODs. Correlation analysis showed that PLOD mRNA expression was related to immune infiltration and tumor purity. Upregulation of PLOD expression was significantly associated with poor survival and immune cell infiltration in LUAD. Our research shows that PLOD family members have potential as novel biomarkers for poor prognosis and as potential immunotherapy targets for LUAD.
- Published
- 2022
24. Sirtuin1 activator SRT2183 suppresses glioma cell growth involving activation of endoplasmic reticulum stress pathway
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Ji Shi and Haozhe Piao
- Published
- 2022
25. MOB2 suppresses GBM cell migration and invasion via regulation of FAK/Akt and cAMP/PKA signaling
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Ji Shi and Haozhe Piao
- Published
- 2022
26. MOB2 suppresses GBM cell migration and invasion via regulation of FAK/Akt and cAMP/PKA signaling
- Author
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Dachuan Shen, Gang Yao, Haozhe Piao, Yumei Yan, Dapeng Liang, Youwei Chang, Ye Zhang, Jia Liu, Songshu Meng, Guirong Zhang, Ke Jiang, Ji Shi, and Lulu Hu
- Subjects
0301 basic medicine ,Cancer Research ,Integrins ,Immunology ,Cell ,Integrin ,Mice, Nude ,Nerve Tissue Proteins ,Chick Embryo ,Transfection ,Article ,Focal adhesion ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Cell Movement ,medicine ,Cyclic AMP ,Animals ,Humans ,Neoplasm Invasiveness ,lcsh:QH573-671 ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Forskolin ,biology ,Brain Neoplasms ,lcsh:Cytology ,Cell migration ,Cell Biology ,Cyclic AMP-Dependent Protein Kinases ,Cell invasion ,CNS cancer ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Focal Adhesion Kinase 1 ,biology.protein ,Cancer research ,cAMP-dependent pathway ,Female ,Glioblastoma ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Mps one binder 2 (MOB2) regulates the NDR kinase family, however, whether and how it is implicated in cancer remain unknown. Here we show that MOB2 functions as a tumor suppressor in glioblastoma (GBM). Analysis of MOB2 expression in glioma patient specimens and bioinformatic analyses of public datasets revealed that MOB2 was downregulated at both mRNA and protein levels in GBM. Ectopic MOB2 expression suppressed, while depletion of MOB2 enhanced, the malignant phenotypes of GBM cells, such as clonogenic growth, anoikis resistance, and formation of focal adhesions, migration, and invasion. Moreover, depletion of MOB2 increased, while overexpression of MOB2 decreased, GBM cell metastasis in a chick chorioallantoic membrane model. Overexpression of MOB2-mediated antitumor effects were further confirmed in mouse xenograft models. Mechanistically, MOB2 negatively regulated the FAK/Akt pathway involving integrin. Notably, MOB2 interacted with and promoted PKA signaling in a cAMP-dependent manner. Furthermore, the cAMP activator Forskolin increased, while the PKA inhibitor H89 decreased, MOB2 expression in GBM cells. Functionally, MOB2 contributed to the cAMP/PKA signaling-regulated inactivation of FAK/Akt pathway and inhibition of GBM cell migration and invasion. Collectively, these findings suggest a role of MOB2 as a tumor suppressor in GBM via regulation of FAK/Akt signaling. Additionally, we uncover MOB2 as a novel regulator in cAMP/PKA signaling. Given that small compounds targeting FAK and cAMP pathway have been tested in clinical trials, we suggest that interference with MOB2 expression and function may support a theoretical and therapeutic basis for applications of these compounds.
- Published
- 2020
27. FKBP9 promotes the malignant behavior of glioblastoma cells and confers resistance to endoplasmic reticulum stress inducers
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Xiaohong Zhang, Songshu Meng, Yumei Yan, Haozhe Piao, Kun Fang, Tao Li, Ruoyu Wang, Songyan Wu, Jianmei Ma, Huizhe Xu, Xiukun Hou, Dapeng Liang, and Peng Liu
- Subjects
0301 basic medicine ,Cancer Research ,Cell Survival ,Cell ,Unfolded protein response (UPR) ,Chick Embryo ,lcsh:RC254-282 ,Chorioallantoic Membrane ,Tacrolimus Binding Proteins ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,Glioma ,Cell Line, Tumor ,medicine ,Animals ,Humans ,ASK1 ,Clonogenic assay ,Gene knockdown ,FK506-binding protein 9 ,Chemistry ,Brain Neoplasms ,Endoplasmic reticulum ,Research ,Ubiquitination ,medicine.disease ,Endoplasmic Reticulum Stress ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Endoplasmic reticulum (ER) stress ,030104 developmental biology ,medicine.anatomical_structure ,HEK293 Cells ,Oncology ,Cell culture ,Drug Resistance, Neoplasm ,IRE1α-XBP1 ,030220 oncology & carcinogenesis ,Proteolysis ,Cancer research ,Glioblastoma ,Neoplasm Transplantation ,Signal Transduction - Abstract
Background FK506-binding protein 9 (FKBP9) is amplified in high-grade gliomas (HGGs). However, the roles and mechanism(s) of FKBP9 in glioma are unknown. Methods The expression of FKBP9 in clinical glioma tissues was detected by immunohistochemistry (IHC). The correlation between FKBP9 expression levels and the clinical prognosis of glioma patients was examined by bioinformatic analysis. Glioblastoma (GBM) cell lines stably depleted of FKBP9 were established using lentiviruses expressing shRNAs against FKBP9. The effects of FKBP9 on GBM cells were determined by cell-based analyses, including anchorage-independent growth, spheroid formation, transwell invasion assay, confocal microscopy, immunoblot (IB) and coimmunoprecipitation assays. In vivo tumor growth was determined in both chick chorioallantoic membrane (CAM) and mouse xenograft models. Results High FKBP9 expression correlated with poor prognosis in glioma patients. Knockdown of FKBP9 markedly suppressed the malignant phenotype of GBM cells in vitro and inhibited tumor growth in vivo. Mechanistically, FKBP9 expression induced the activation of p38MAPK signaling via ASK1. Furthermore, ASK1-p38 signaling contributed to the FKBP9-mediated effects on GBM cell clonogenic growth. In addition, depletion of FKBP9 activated the IRE1α-XBP1 pathway, which played a role in the FKBP9-mediated oncogenic effects. Importantly, FKBP9 expression conferred GBM cell resistance to endoplasmic reticulum (ER) stress inducers that caused FKBP9 ubiquitination and degradation. Conclusions Our findings suggest an oncogenic role for FKBP9 in GBM and reveal FKBP9 as a novel mediator in the IRE1α-XBP1 pathway.
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- 2020
28. Comparison of intraoperative magnetic resonance imaging, ultrasound, 5-aminolevulinic acid, and neuronavigation for guidance in glioma resection: A network meta-analysis
- Author
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Ji Shi, Dongman Ye, Haozhe Piao, and Tao Yu
- Subjects
medicine.medical_specialty ,Neuronavigation ,Interventional magnetic resonance imaging ,Cochrane Library ,lcsh:RC254-282 ,law.invention ,Randomized controlled trial ,law ,glioma ,medicine ,magnetic resonance imaging ,resection ,Prospective cohort study ,network analysis ,medicine.diagnostic_test ,neuronavigation ,business.industry ,ultrasound ,Magnetic resonance imaging ,Retrospective cohort study ,Odds ratio ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,5-aminolevulinic acid ,conventional surgery ,intraoperative ,Radiology ,business - Abstract
Background and Aim: Gliomas are the most common type of brain tumor in the world. Surgical resection is one of the most effective therapeutic methods in terms of patient prognosis. However, it is difficult for neurosurgeons and health-care providers to select which imaging technology to best support the procedure. These technologies included intraoperative magnetic resonance imaging (iMRI), intraoperative ultrasound (iUS), fluorescence guidance with 5-aminolevulinic acid (5-ALA), and intraoperative neuronavigation. Hence, in this study, we compared the gross total resection (GTR), postoperative complications within or outside of the central nervous system, and postoperative clinical improvement by multiple meta-analyses, which allows the integration of data through direct and indirect comparisons.Materials and Methods: The PubMed, Cochrane Library, Web of Science, Embase, China Knowledge Resource Integrated Database, and WanFang databases were searched for publications before April 2018. Randomized controlled trials, two-arm and three-arm prospective studies, and retrospective studies in patients who underwent surgical treatment for glioma were included. The most important outcome measures were the rates of GTR, postoperative complications, and clinical improvement. Results: In terms of GTR, iMRI (odds ratio [OR] = 5.70, 95% confidence interval [CI]: 3.40–9.60), iUS (OR = 2.70, 95% CI: 1.10–6.90), 5-ALA (OR = 2.40, 95% CI: 0.64–8.90), and neuronavigation (OR = 1.90, 95% CI: 1.20–3.10) were found to be more effective than conventional surgery. In addition, iUS (OR = 0.15, 95% CI: 0.04–0.52), iMRI (OR = 0.24, 95% CI: 0.14–0.43), and neuronavigation (OR = 0.34, 95% CI: 0.18–0.56) were more found to result in fewer complications than conventional surgery. Furthermore, patients' clinical improvement was better with iMRI (OR = 8.10, 95% CI: 3.00–25.00), iUS (OR = 4.90, 95% CI: 0.76–33.00), and neuronavigation (OR = 2.60, 95% CI: 1.00–7.20) than with conventional surgery. Conclusions: The developed ranking probability table indicated that iMRI was superior in terms of the GTR and clinical improvement, while iUS was the least likely to result in postoperative complications. Hence, it was concluded that iMRI or iUS is the most advantageous imaging modality.
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- 2020
29. East meets West for the treatment of glioma: A discussion of real-world cases
- Author
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Linan Liu, Haozhe Piao, Ye Zhang, Chengcheng Guo, Felix Sahm, Ulrich Herrlinger, Zhongping Chen, and Li Zhu
- Subjects
Oncology ,medicine.medical_specialty ,Bevacizumab ,diagnosis ,temozolomide ,bevacizumab ,chemotherapy ,lcsh:RC254-282 ,Internal medicine ,Glioma ,medicine ,individualized treatment ,Medical history ,radiotherapy ,Temozolomide ,business.industry ,Standard treatment ,glioblastoma ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,tumor recurrence ,anaplastic oligodendroglioma ,Regimen ,Oligodendroglioma ,business ,Chemoradiotherapy ,high-grade glioma ,medicine.drug - Abstract
Background and Aim: The standard of care for patients with gliomas should follow established guidelines. In real-world management, however, the management sometimes deviates from these guidelines. We organized a discussion of real-world clinical cases and summarized different considerations from Chinese and European specialists.Case Presentation: A multidisciplinary team comprising experts from Europe and China discussed two patients with glioma treated at Sun Yat-sen University Cancer Center and Liaoning Cancer Hospital and Institute, China. Patient 1 was a 43-year-old man with a recurrent oligodendroglioma in the left frontal lobe diagnosed based on histology alone. He had undergone a biopsy and was diagnosed with an oligodendroglioma 3 years previously. He underwent chemoradiotherapy followed by 12 cycles of chemotherapy with temozolomide (TMZ), and complete remission was achieved. However, the tumor recurred within a short period of time and was resected by a second surgery. The pathologic diagnosis of the recurrent tumor was a glioblastoma because 1p/19q was intact when detected by sequencing. Pathologic consultation from another hospital still considered an anaplastic oligodendroglioma based on the positive result of 1p19q loss of heterozygosity (LOH) determined by fluorescence in situ hybridization. Patient 2 was a 50-year-old man with a left temporal glioblastoma. He underwent tumor resection but no radiotherapy. After seven cycles of TMZ (5/28-day regimen), his symptoms deteriorated, and his treatment was changed to a TMZ dose-dense regimen (7 days on/7 days off) and bevacizumab (7.5 mg/kg every 2 weeks), plus tumor-treating field therapy. Consultation Results: The pathological diagnosis based on biopsy for Patient 1 was an oligodendroglioma (World Health Organization Grade II), whereas the result of the second surgical sample was glioblastoma or anaplastic oligodendroglioma (questionable). Although the accuracy of fluorescence in situ hybridization for the detection of 1p/19q LOH requires improvement, 1p/19q LOH is typically not reconstituted in oligodendroglioma. More likely, it was due to sampling; a positive observation field may be missed with consequent negative results, and both oligodendroglioma (with 1p/19q co-deletion and isocitrate dehydrogenase mutation) and astrocytoma (without 1p/19q co-deletion) may exist. With respect to further treatment for cases such as Patient 1, both Chinese and European experts agree that procarbazine + lomustine chemotherapy is appropriate, while re-irradiation is suggested only if the tumor recurs outside the original radiotherapy field or within the radiotherapy field in the future. Considering the medical history, the rapid tumor regrowth without postoperative radiotherapy in Patient 2 was not surprising. After application of a rescue treatment regimen, the general condition of the patient improved, which may have resulted from the bevacizumab. A consensus was reached between the Chinese and European experts regarding subsequent treatment of Patient 2. Continuation of TMZ and bevacizumab was suggested until further deterioration. Whether tumor-treating field therapy should play a role in this patient could not be evaluated. However, some other molecular targeted agents (e.g. vascular endothelial growth factor receptor tyrosine kinase inhibitors such as regorafenib or apatinib) after bevacizumab failure, the effectiveness of these drugs remains unclear. Conclusion: In clinical practice, although we should follow established guidelines, the final treatment regimen requires informed consent from the patient. Thus, some real-world cases may deviate from the established guidelines. When patients reach end-stage disease with a marked decrease in their performance status and no standard treatment options, active antitumor treatment might be more likely to be attempted in China, while symptomatic treatment is more frequently performed in Europe. Although treatment philosophies for patients with glioma are slightly different between Eastern and Western medical experts, any treatment strategies should satisfy these patients.
- Published
- 2020
30. Application of Radiomics for Personalized Treatment of Cancer Patients
- Author
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Haozhe Piao, Tao Yu, Na Qu, Jing Sun, Yiming Meng, and Guirong Zhang
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Combined use ,Personalized treatment ,Cancer ,Computed tomography ,Magnetic resonance imaging ,Histopathological examination ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Radiomics ,Positron emission tomography ,030220 oncology & carcinogenesis ,medicine ,Medical physics ,business - Abstract
Radiomics is a novel concept that relies on obtaining image data from examinations such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET). With the appropriate algorithm, the extracted results have broad applicability and potential for a massive positive impact in radiology. For example, clinicians can verify treatment efficiency, predict the location of tumor metastasis, correlate results with a histopathological examination, or more accurately define the type of cancer. Combining radiomics with other testing techniques allows every patient to have a personalized treatment plan that is essential for advanced examination and treatment. This article explains the process of radiomics, including data collection mechanisms, combined use with genomics, and artificial intelligence and immunology techniques, which may solve many of the challenges faced by doctors in diagnosing and treating their patients.
- Published
- 2019
31. Research Progress of circRNAs in Glioblastoma
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Xu Guo and Haozhe Piao
- Subjects
QH301-705.5 ,urogenital system ,Cell growth ,glioblastoma ,Review ,Cell Biology ,Biology ,urologic and male genital diseases ,medicine.disease ,female genital diseases and pregnancy complications ,nervous system diseases ,Cell and Developmental Biology ,Biological property ,miRNAs sponge ,medicine ,Cancer research ,non-coding RNAs ,biomarker ,Biomarker (medicine) ,circRNAs ,Biology (General) ,Developmental Biology ,Glioblastoma - Abstract
Circular RNAs (circRNAs) are a class of single-stranded covalently closed non-coding RNAs without a 5′ cap structure or 3′ terminal poly (A) tail, which are expressed in a variety of tissues and cells with conserved, stable and specific characteristics. Glioblastoma (GBM) is the most aggressive and lethal tumor in the central nervous system, characterized by high recurrence and mortality rates. The specific expression of circRNAs in GBM has demonstrated their potential to become new biomarkers for the development of GBM. The specific expression of circRNAs in GBM has shown their potential as new biomarkers for GBM cell proliferation, apoptosis, migration and invasion, which provides new ideas for GBM treatment. In this paper, we will review the biological properties and functions of circRNAs and their biological roles and clinical applications in GBM.
- Published
- 2021
32. A Pan-Cancer
- Author
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Yiming, Meng, Jing, Sun, Guirong, Zhang, Tao, Yu, and Haozhe, Piao
- Abstract
The new coronavirus (2019-nCoV) is an emerging pathogen that can cause severe respiratory infections in humans. It is worth noting that many of the affected COVID-19 patients have malignant tumors. In addition, cancer has been identified as a personal risk factor for COVID-19. Transmembrane proteaseserine-2 (TMPRSS2) is a crucial host protease that mediates S protein activation and initially promotes virus entry into host cells. Moreover, it is abnormally expressed in a variety of tumors. However, the systematic analysis of TMPRSS2 aberrations in human cancer remains to be elucidated. Here, we analyzed the genetic changes, RNA expression, and DNA methylation of TMPRSS2 in more than 30 tumors. It has been reported that TMPRSS2 is overexpressed in tumors such as prostate adenocarcinoma (PRAD), and in contrast, the expression of TMPRSS2 is decreased in tumors such as head and neck cancer (HNSC). In addition, TMPRSS2 low DNA methylation was also found in most of these TMPRSS2 high-expressing tumors in this study. Clinical studies have found that there is a significant correlation between the expression of TMPRSS2 and the prognosis of some tumor patients. The expression of TMPRSS2 is also related to the infiltration of cancer-related fibroblasts, and the potential pathways and functional mechanisms were analyzed through KEGG/GO enrichment. In the end, our study planned the genetic and epigenetic variation of TMPRSS2 in human malignant tumors for the first time and provided a relatively comprehensive understanding of the carcinogenic effects of TMPRSS2.
- Published
- 2021
33. Precise gliomas therapy: Hypoxia-activated prodrugs sensitized by nano-photosensitizers
- Author
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Han Zhang, Chao Shi, Fuping Han, Mengqi Li, He Ma, Rui Sui, Saran Long, Wen Sun, Jianjun Du, Jiangli Fan, Haozhe Piao, and Xiaojun Peng
- Subjects
Indoles ,Photosensitizing Agents ,Biophysics ,Antineoplastic Agents ,Bioengineering ,Glioma ,Isoindoles ,Biomaterials ,Zinc Compounds ,Mechanics of Materials ,Cell Line, Tumor ,Neoplasms ,Organometallic Compounds ,Tumor Microenvironment ,Ceramics and Composites ,Humans ,Prodrugs ,Hypoxia ,Reactive Oxygen Species ,Tirapazamine - Abstract
Hypoxia is one of the prominent features of solid tumors. Hypoxia activated prodrugs (HAPs), selectively killing hypoxic cells, possess the potential to transform hypoxia from a nuisance to an advantage in precision therapy. Exhibiting a more significant hypoxic microenvironment, gliomas, as the most frequent and incurable neurological tumors, provide HAPs a more attractive therapeutic prospect. However, the insufficient hypoxia and the obstruction of the blood-brain barrier (BBB) severely limit the activation and bio-availability of HAPs. Herein, a novel nanoparticle iRGD@ZnPc + TPZ was designed and synthesized to achieve gliomas inhibition by encapsulating tirapazamine (TPZ) as a HAP and zinc phthalocyanine (ZnPc) as a photosensitizer to enhance hypoxia. iRGD@ZnPc + TPZ can realize breakthrough BBB, deep penetration, and significant retention in gliomas, which is attributed to the iRGD-mediated receptor targeting and active transport. After being internalized by tumor cells and radiated, ZnPc efficiently consumes intratumoral Osub2/subto produce reactive oxygen species, which not only implements tumor suppression, but also intensify hypoxia to activate TPZ for amplifying chemotherapy. The photosensitizer-enhanced activation of HAPs inhibits gliomas growth. This study provides a new strategy with sensitizing and activating HAPs for gliomas treatment in clinical.
- Published
- 2022
34. Clinical Prognostic Value of the
- Author
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Yiming, Meng, Jing, Sun, Guirong, Zhang, Tao, Yu, and Haozhe, Piao
- Abstract
Accumulating evidence has implicated members of the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene family, PLOD1, PLOD2, and PLOD3, in cancer progression and metastasis. However, their expression, prognostic value, and mechanisms underlying their roles in lung adenocarcinoma (LUAD) have not yet been reported. We downloaded PLOD data for LUAD and normal tissues from The Cancer Genome Atlas (TCGA). PLOD1-3 protein expression was evaluated using the Clinical Proteomics Tumor Analysis Consortium and Human Protein Atlas. Survival analysis was performed using the Kaplan-Meier method. A protein-protein interaction network was constructed using STRING software. The "ClusterProfiler" package was used for functional-enrichment analysis. The relationship between PLOD mRNA expression and immune infiltration was analyzed using the Tumor Immunity Assessment Resource and Tumor Immune System Interaction Database. The expression of PLODs in LUAD tissues was significantly upregulated compared with that in adjacent normal tissues. PLOD mRNA overexpression is associated with lymph node metastasis and high TNM staging. Receiver operating characteristic curve analysis showed that when the cut-off level was 6.073, the accuracy, sensitivity, and specificity of PLOD1 in distinguishing LUAD from adjacent controls were 84.4, 79.7, and 82.6%, respectively. The accuracy, sensitivity, and specificity of PLOD2 in distinguishing LUAD from adjacent controls were 81.0, 98.3, and 68.0%, respectively, at a cut-off value of 4.360. The accuracy, sensitivity, and specificity of PLOD3 in distinguishing LUAD from adjacent controls were 69.0, 86.4, and 52.0%, respectively, with a cut-off value of 5.499. Kaplan-Meier survival analysis demonstrated that LUAD patients with high PLODs had a worse prognosis than those with low PLODs. Correlation analysis showed that PLOD mRNA expression was related to immune infiltration and tumor purity. Upregulation of PLOD expression was significantly associated with poor survival and immune cell infiltration in LUAD. Our research shows that PLOD family members have potential as novel biomarkers for poor prognosis and as potential immunotherapy targets for LUAD.
- Published
- 2021
35. A Comparison of Epidemiological Characteristics of Central Nervous System Tumours in China and Globally from 1990 to 2019
- Author
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Bo Zhu, Bing Yao, Xiaomei Wu, Shuang Xu, and Haozhe Piao
- Subjects
medicine.medical_specialty ,China ,Joinpoint regression ,Epidemiology ,business.industry ,Mortality rate ,Incidence (epidemiology) ,Incidence ,Central Nervous System Neoplasms ,Cohort effect ,Cost of Illness ,Child, Preschool ,Medicine ,Humans ,Neurology (clinical) ,Quality-Adjusted Life Years ,business ,Medical costs ,Disease burden ,Demography ,Aged - Abstract
Background: Despite their great disease burden, there have been few studies on the epidemiology of central nervous system tumours (CNSTs) in China. We used the latest data updated by GBD to analyse the trends of incidence, mortality, and disability-adjusted life years (DALYs) for CNSTs in China versus globally. Methods: Epidemiological data on CNSTs were extracted from GBD 2019. We used Joinpoint regression analysis to calculate the magnitude and direction of the trends and the age-period-cohort method to analyse the age, period, and cohort effects of the trend. Results: From 1990 to 2019, the 106.52% increase in Chinese incident cases was higher than the global increase (94.35%). The 67.32% increase in cancer deaths and 16.03% increase in DALYs were lower than the global increases (cancer death: 76.36%; DALYs: 40.06%). The age-standardized incidence rates (ASIRs) in China were higher than the global ASIRs, and the increase in China was higher than that globally. Although the age-standardized mortality rates and age-standardized DALY rates in China were higher, their increases in China were less than those globally. Both in China and globally, the number and incidence, mortality, and DALYs by age group showed a bimodal distribution (younger than 5 years and older), and the peak in the older age group showed a backwards trend. The proportion of incident cases, cancer deaths, and DALYs also increased in the older age group. In the age-period-cohort model, the local drifts in the older age group were above zero. Conclusions: The burden of CNSTs is very serious in China, and we should pay attention to the key populations, early diagnosis technology, improvements in medical technology, and ways to reduce medical costs. We believe our results could help policymakers allocate resources efficiently to reduce the burden of CNSTs.
- Published
- 2021
36. Long noncoding RNA SNHG3 promotes glioma tumorigenesis by sponging miR-485-5p to upregulate LMX1B expression
- Author
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Jian Zheng, Haozhe Piao, Ming-Jun Yu, Xu Guo, and Hong-Yu Zhao
- Subjects
Medicine (General) ,LIM-Homeodomain Proteins ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,Downregulation and upregulation ,SNHG3 ,Glioma ,Cell Line, Tumor ,medicine ,Gene silencing ,Humans ,Small nucleolar RNA ,Transcription factor ,miR‐485‐5p ,business.industry ,Brain Neoplasms ,RNA ,General Medicine ,medicine.disease ,Long non-coding RNA ,Up-Regulation ,MicroRNAs ,xenografts ,030220 oncology & carcinogenesis ,Cancer research ,030211 gastroenterology & hepatology ,RNA, Long Noncoding ,business ,Carcinogenesis ,LMX1B ,Transcription Factors - Abstract
LIM homeobox transcription factor 1‐beta (LMX1B) has recently been found to be highly expressed in advanced gliomas and is associated with poor survival. However, the regulatory molecular mechanism of LMX1B expression in gliomas remains unclear. In this study, bioinformatics analysis showed that miR‐485‐5p may be the potential upstream regulator of LMX1B, and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) may function as a competitive endogenous RNA to sponge miR‐485‐5p. In addition, the expression of SNHG3 and LMX1B in advanced glioma tissues was significantly upregulated, while the expression of miR‐485‐5p was significantly downregulated. SNHG3 overexpression reduced the expression of miR‐485‐5p; increased the expression of LMX1B; and promoted the proliferation, migration, and invasion of glioma cells. In contrast, miR‐485‐5p overexpression reduced the expression of LMX1B and inhibited cell proliferation, migration, and invasion. The luciferase reporter assay and RNA immunoprecipitation assay further confirmed the interaction between SNHG3 and miR‐485‐5p and between miR‐485‐5p and LMX1B. In addition, subcutaneous and orthotropic xenograft models confirmed that lncRNA SNHG3 silencing or miR‐485‐5p overexpression significantly reduced the growth of glioma xenografts and prolonged survival time. These results indicate that lncRNA SNHG3 can regulate the expression of LMX1B by sponging miR‐485‐5p, thereby promoting the proliferation, migration, and invasion of glioma cells. This study provides the first evidence that the SNHG3/miR‐485‐5p/LMX1B axis is involved in glioma tumorigenesis and highlights the potential of SNHG3 and miR‐485‐5p as therapeutic targets for glioma.
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- 2021
37. Application of Multiparametric Intraoperative Ultrasound in Glioma Surgery
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Ye Zhang, Xi Zhao, Bing Yao, Ji Shi, Peixin Sun, Haozhe Piao, and Yuanyuan Hao
- Subjects
medicine.medical_specialty ,Contrast Media ,Review Article ,General Biochemistry, Genetics and Molecular Biology ,030218 nuclear medicine & medical imaging ,Intraoperative ultrasound ,03 medical and health sciences ,0302 clinical medicine ,Glioma ,Monitoring, Intraoperative ,medicine ,Humans ,Neuronavigation ,Ultrasonography ,General Immunology and Microbiology ,Tumor size ,business.industry ,Brain Neoplasms ,Ultrasound ,Glioma surgery ,General Medicine ,Gold standard (test) ,medicine.disease ,Gross Total Resection ,Medicine ,Radiology ,Neurosurgery ,business ,030217 neurology & neurosurgery - Abstract
Gliomas are the most invasive and fatal primary malignancy of the central nervous system that have poor prognosis, with maximal safe resection representing the gold standard for surgical treatment. To achieve gross total resection (GTR), neurosurgery relies heavily on generating continuous, real-time, intraoperative glioma descriptions based on image guidance. Given the limitations of currently available equipment, developing a real-time image-guided resection technique that provides reliable functional and anatomical information during intraoperative settings is imperative. Nowadays, the application of intraoperative ultrasound (IOUS) has been shown to improve resection rates and maximize brain function preservation. IOUS, which presents an attractive option due to its low cost, minimal operational flow interruptions, and lack of radiation exposure, is able to provide real-time localization and accurate tumor size and shape descriptions while helping distinguish residual tumors and addressing brain shift. Moreover, the application of new advancements in ultrasound technology, such as contrast-enhanced ultrasound, three-dimensional ultrasound, navigable ultrasound, ultrasound elastography, and functional ultrasound, could help to achieve GTR during glioma surgery. The current review describes current advancements in ultrasound technology and evaluates the role and limitation of IOUS in glioma surgery.
- Published
- 2021
38. Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancer
- Author
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Jin Gu, Haozhe Piao, Fang Liu, Fei Ma, Xiaoyu Yang, Chenghai Xue, Shuang Zhao, Liren Liu, and Zhong‐guo Zhang
- Subjects
0301 basic medicine ,Cancer Research ,Somatic cell ,Colorectal cancer ,Clinical Decision-Making ,survival ,lcsh:RC254-282 ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Exome Sequencing ,Humans ,Medicine ,Gene Regulatory Networks ,Radiology, Nuclear Medicine and imaging ,In patient ,Gene ,Neoplasm Staging ,Original Research ,Cancer Biology ,algorithm ,business.industry ,Mechanism (biology) ,Liver Neoplasms ,liver metastases lesions ,Microsatellite instability ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Survival Analysis ,somatic alterations ,Phenotype ,030104 developmental biology ,cancer pathways ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Microsatellite Instability ,Colorectal Neoplasms ,business ,Algorithms - Abstract
Background The quantity of metastases lesions is an important reference when it comes to making a more informed treatment decision for patients with colorectal cancer liver metastases. However, the molecular alterations in patients with different numbers of lesions have not been systematically studied. Methods We investigated somatic alterations and microsatellite instability (MSI) of liver metastases from patients with single, multiple or diffuse metastasis lesions. A new algorithm “Pathway Damage Score” was developed to comprehensively assess the functional impact of somatic alterations at the pathway level. Pathogenic pathways of different metastasis were identified and their prognosis effects were evaluated. Furthermore, the subnetworks and affected phenotypes of the altered genes in each pathogenic pathway were analyzed. Results Somatic alterations and altered genes occurred sporadically as well as in MSI state in different metastasis types, although MSS patients had more metastatic lesions than that of the MSI patients. Every metastasis group has their own pathogenic pathways and damaged “Cargo recognition for clathrin‐mediated endocytosis” is significantly associated with poor prognosis (P
- Published
- 2019
39. Retracted : Long noncoding RNA MT1JP inhibits proliferation, invasion, and migration while promoting apoptosis of glioma cells through the activation of PTEN/Akt signaling pathway
- Author
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Hanyang Liang, Rui Sui, Haozhe Piao, Ye Zhang, Ji Shi, and Yi Chen
- Subjects
0301 basic medicine ,Physiology ,Clinical Biochemistry ,Apoptosis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,In vivo ,Cell Line, Tumor ,Glioma ,medicine ,Animals ,Humans ,PTEN ,Neoplasm Invasiveness ,neoplasms ,Cell Proliferation ,Expression vector ,biology ,Akt/PKB signaling pathway ,Chemistry ,PTEN Phosphohydrolase ,Cell Biology ,Transfection ,medicine.disease ,Long non-coding RNA ,nervous system diseases ,Gene Expression Regulation, Neoplastic ,Oncogene Protein v-akt ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Heterografts ,RNA, Long Noncoding ,Signal Transduction - Abstract
This study is carried out to elucidate the role of long noncoding RNAs (lncRNAs) MT1JP in proliferation, invasion, migration, and apoptosis of glioma cells through the regulation of PTEN/Akt signaling pathway. The expression of MT1JP in 80 normal brain tissues and 138 glioma tissues, as well as glioma cell lines, was detected by quantitative reverse-transcription polymerase chain reaction. Besides, glioma cells with overexpression and low expression of MT1JP were constructed to confirm the role of MT1JP in proliferation, invasion, migration, and apoptosis of glioma cells and the growth of glioma cells in vivo through the regulation of PTEN/Akt signaling pathway. MT1JP expression was downregulated in glioma tissues and cells. The low expression of MT1JP was considered as an independent risk factor for predicting overall survival in gliomas. After transfection of MT1JP overexpression plasmid, glioma cells showed decreased proliferation, migration and invasion ability, increased apoptosis rate, and decreased the tumorigenic ability of nude mice. The trends were opposite in glioma cells transfected with MT1JP poor expression plasmid. Collectively, our study suggests that lncRNA MT1JP is responsible for inhibiting proliferation, invasion, and migration while promoting apoptosis of glioma cells through the activation of PTEN/Akt signaling pathway.
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- 2019
40. Bufalin Induces Apoptosis and Improves the Sensitivity of Human Glioma Stem-Like Cells to Temozolamide
- Author
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Bing Yao, Guirong Zhang, Rui Sui, Tao Tang, Yi Chen, Xu Guo, Peixin Sun, Jia Liu, Ying Zhang, Shulan Sun, Ji Shi, Haiyang Liang, Ke Jiang, Haozhe Piao, and Ye Zhang
- Subjects
0301 basic medicine ,endocrine system ,Cancer Research ,Telomerase ,Poly ADP ribose polymerase ,Apoptosis ,Antineoplastic Agents ,Caspase 3 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Glioma ,Temozolomide ,medicine ,Humans ,Telomerase reverse transcriptase ,Cell Proliferation ,Chemistry ,Bufalin ,General Medicine ,Cancer stem-like cells ,medicine.disease ,Temozolomide (TMZ) ,Bufanolides ,030104 developmental biology ,Oncology ,Drug Resistance, Neoplasm ,Cell culture ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Cancer research - Abstract
Glioma is the most common malignant tumor of the central nervous system, and it is characterized by high relapse and fatality rates and poor prognosis. Bufalin is one of the main ingredients of Chan-su, a traditional Chinese medicine (TCM) extracted from toad venom. Previous studies revealed that bufalin exerted inhibitory effects on a variety of tumor cells. To demonstrate the inhibitory effect of bufalin on glioma cells and glioma stem-like cells (GSCs) and discuss the underlying mechanism, the proliferation of glioma cells was detected by MTT and colony formation assays following treatment with bufalin. In addition, we investigated whether bufalin inhibits or kills GSCs using flow cytometry, Western blotting, and reverse transcription polymerase chain reaction analysis (RT-PCR). Finally, we investigated whether bufalin could improve the therapeutic effect of temozolomide (TMZ) and discussed the underlying mechanism. Taken together, our data demonstrated that bufalin inhibits glioma cell growth and proliferation, inhibits GSC proliferation, and kills GSCs. Bufalin was found to induce the apoptosis of GSCs by upregulating the expression of the apoptotic proteins cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) and by downregulating the expression of human telomerase reverse transcriptase, which is a marker of telomerase activity. Bufalin also improved the inhibitory effect of TMZ on GSCs by activating the mitochondrial apoptotic pathway. These results suggest that bufalin damages GSCs, induces apoptosis, and enhances the sensitivity of GSCs to TMZ.
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- 2019
41. The biological macromolecule Nocardia rubra cell‐wall skeleton as an avenue for cell‐based immunotherapy
- Author
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Cuicui Kong, Jing Sun, Yushu Ma, Tao Yu, Haozhe Piao, Mingsheng Shi, Guirong Zhang, Ning Nan, Heng Dou, Xiaonan Wang, and Yiming Meng
- Subjects
0301 basic medicine ,Physiology ,medicine.medical_treatment ,Clinical Biochemistry ,Cell ,Cell Biology ,Immunotherapy ,Cell Wall Skeleton ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,chemistry ,Downregulation and upregulation ,Apoptosis ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Propidium iodide ,Cytotoxicity - Abstract
Promoting the antitumor effects of cell-based immunotherapy for clinical application remains a difficult challenge. Nocardia rubra cell-wall skeleton (N-CWS) is an immunotherapeutic agent for cancers that have been proven to possess the ability to activate immune response without showing toxicity. However, its effects on immune cells that are derived from tumor patients and cultured in vitro remain unclear. As expected, N-CWS can enhance the proliferation and viability of cytokine-induced killer (CIK) cells, dendritic cells (DCs), and natural killer (NK) cells. The maturation of DCs and specific cytotoxicity against NK cells and CIK cells were consistently promoted. The TUNEL-staining and the Annexin V/propidium iodide assay revealed that after treatment with N-CWS, the stimulated CIK/NK cells could induce DNA breaks in tumor cells. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed upregulation of proapoptotic biomarkers (caspase-3 and caspase-9) and a downregulation of the antiapoptotic biomarker Bcl-2 in the tumor cells of the N-CWS-treated group, indicating that N-CWS could induce hepatocellular carcinoma cell apoptosis via CIK/NK cells. Finally, CIK/NK cells could notably suppress the invasion and migration of tumor cells in the presence of N-CWS. Our study provides evidence that N-CWS could significantly increase the growth of CIK cells, DCs, and NK cells, particularly due to its robust antitumor activities by inducing apoptosis, and attenuate the invasion and migration of tumor cells.
- Published
- 2019
42. The antitumor effects of Newcastle disease virus on glioma
- Author
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Ye Zhang, Ji Shi, HaoZhe Piao, Bing Yao, and Peixin Sun
- Subjects
biology ,business.industry ,Glioma ,medicine ,Cancer research ,General Medicine ,biology.organism_classification ,medicine.disease ,business ,Newcastle disease ,Virus - Published
- 2019
43. Identification the Clinical Value of PLOD Family Members in Lung Adenocarcinoma: A Comprehensive Analysis
- Author
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Yiming Meng, Jing Sun, Guirong Zhang, Tao Yu, and Haozhe Piao
- Subjects
History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2021
44. Role of Exosomes in the Progression, Diagnosis, and Treatment of Gliomas
- Author
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Yuanyuan Hao, Ji Shi, Xi Zhao, Bing Yao, Peixin Sun, Ye Zhang, and Haozhe Piao
- Subjects
medicine.medical_treatment ,030204 cardiovascular system & hematology ,Exosomes ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Glioma ,Humans ,Medicine ,Review Articles ,Chemotherapy ,Tumor microenvironment ,Brain Neoplasms ,business.industry ,General Medicine ,Prognosis ,medicine.disease ,Microvesicles ,Radiation therapy ,Tumor progression ,030220 oncology & carcinogenesis ,Drug delivery ,Disease Progression ,Cancer research ,Biological Markers ,Immunotherapy ,business - Abstract
Gliomas are the most common primary malignant brain tumors associated with a low survival rate. Even after surgery, radiotherapy, and chemotherapy, gliomas still have a poor prognosis. Extracellular vesicles are a heterogeneous group of cell-derived membranous structures. Exosomes are a type of extracellular vesicles, their size ranges from 30 nm to 100 nm. Recent studies have proved that glioma cells could release numerous exosomes; therefore, exosomes have gained increasing attention in glioma-related research. Recent studies have confirmed the importance of extracellular vesicles, particularly exosomes, in the development of brain tumors, including gliomas. Exosomes mediate intercellular communication in the tumor microenvironment by transporting biomolecules (proteins, lipids, deoxyribonucleic acid, and ribonucleic acid); thereby playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can traverse the blood-brain barrier and promote tumor progression by modifying the tumor microenvironment. Based on their structural and functional characteristics, exosomes are demonstrating their value not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting glioma cells. Therefore, exosomes are a promising therapeutic target for the diagnosis, prognosis, and treatment of malignant gliomas. More research will be needed before exosomes can be used in clinical applications. Here, we describe the exosomes, their morphology, and their roles in the diagnosis and progression of gliomas. In addition, we discuss the potential of exosomes as a therapeutic target/drug delivery system for patients with gliomas.
- Published
- 2020
45. LMX1B-associated gankyrin expression predicts poor prognosis in glioma patients
- Author
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Yixue Xue, Yunhui Liu, Haozhe Piao, Xu Guo, and Hong-Yu Zhao
- Subjects
0301 basic medicine ,Medicine (General) ,2019-20 coronavirus outbreak ,Poor prognosis ,Coronavirus disease 2019 (COVID-19) ,Gankyrin ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,LIM-Homeodomain Proteins ,gankyrin ,Biochemistry ,Pre-Clinical Research Report ,03 medical and health sciences ,glioblastoma multiforme ,R5-920 ,0302 clinical medicine ,Glioma ,Medicine ,Humans ,Promoter Regions, Genetic ,Transcription factor ,transcription factor ,biology ,business.industry ,Brain Neoplasms ,Biochemistry (medical) ,NF-kappa B ,Cell Biology ,General Medicine ,medicine.disease ,Prognosis ,030104 developmental biology ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,business ,LMX1B ,Transcription Factors - Abstract
Objective To explore the potential of the transcription factor LMX1B and downstream gankyrin as prognostic biomarkers of glioma. Methods The expression levels of gankyrin and LMX1B were detected in 52 normal brain specimens and 339 glioma specimens. Correlations of gankyrin and LMX1B expression levels with pathological stages and clinical characteristics were statistically analyzed. Furthermore, the binding of LMX1B to the gankyrin promoter was evaluated using ALGGEN PROMO. Results Levels of LMX1B and gankyrin were significantly increased in tumor tissue, and were significantly associated with advanced glioma grade and poor survival. Compared with gankyrin- and LMX1B-negative glioma, the mean survival of patients with higher gankyrin and LMX1B expression was significantly reduced, from 83.46 to 18.87 months and from 63.79 to 18.29 months, respectively. Furthermore, LMX1B had a moderate positive correlation with gankyrin expression (Pearson’s r = 0.650), and it was also found to act as a transcription factor with NF-κB and E47 on the gankyrin promoter. Conclusions Increased expression of LMX1B and gankyrin has independent prognostic value in glioma patients. The transcription factor LMX1B may have an upstream role in the mechanism of action.
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- 2020
46. Letter to the Editor. Residual meningiomas
- Author
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Rui Sui and Haozhe Piao
- Subjects
medicine.medical_specialty ,Letter to the editor ,business.industry ,General surgery ,Medicine ,General Medicine ,business ,Residual - Published
- 2020
47. Overexpression of microRNA-129-5p in glioblastoma inhibits cell proliferation, migration, and colony-forming ability by targeting ZFP36L1
- Author
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Bing Yao, Xu Guo, Peixin Sun, Ye Zhang, and Haozhe Piao
- Subjects
0301 basic medicine ,Cell Survival ,medicine.medical_treatment ,proliferation ,Down-Regulation ,medicine.disease_cause ,Glioblastoma multiforme ,migration ,GBM ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Genes, Tumor Suppressor ,Neoplasm Invasiveness ,U87 ,Cell Proliferation ,Oligonucleotide Array Sequence Analysis ,lcsh:R5-920 ,Microarray analysis techniques ,Cell growth ,business.industry ,Brain Neoplasms ,General Medicine ,colony-forming ability ,tumor-suppressor ,nervous system diseases ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,miR-129-5p ,Cell culture ,030220 oncology & carcinogenesis ,Astrocytes ,ZFP36L1 ,Cancer research ,Neoplasm Recurrence, Local ,Carcinogenesis ,business ,Butyrate Response Factor 1 ,Glioblastoma ,lcsh:Medicine (General) ,Research Article - Abstract
Glioblastoma multiforme (GBM) is a highly invasive cancer with a high recurrence rate. The prognosis of GBM patients remains poor, even after standard surgical resection combined with chemoradiotherapy. Thus, there is an urgent need for new therapeutic targets in GBM. In recent years, microRNAs have received considerable attention due to their important role in tumor development and progression. In this study, we investigated the role of miR-129-5p and miR-129-5p/ZFP36L1 axis in GBM tumorigenesis. Analysis of GSE103228 microarray data from the GEO database showed that miR-129-5p was significantly downregulated in GBM vs. normal brain tissues. Quantitative reverse transcription PCR analysis of miR-129-5p expression in seven GBM cell lines (LN229, A172, U87, T98G, U251, H4, and LN118) vs. normal human astrocytes (NHA) showed miR-129-5p was significantly downregulated in GBM cells. Overexpression of miR-129-5p in LN229 and A172 cells significantly suppressed cell proliferation, migration, invasion, and colony-forming ability. Target Scan analysis identified ZFP36L1 as the target of miR-129-5p. UALCAN dataset analysis found that ZFP36L1 was significantly upregulated in GBM vs. normal brain tissues, and high ZFP36L1 expression was positively associated with the poor survival of GBM patients. Western blot analysis demonstrated that ZFP36L1 was significantly upregulated in seven GBM cell lines vs. NHA. Overexpression of miR-129-5p in LN229 and A172 cells significantly inhibited ZFP36L1 mRNA and protein expression, while overexpression of ZFP36L1 in LN229 and A172 cells reversed miR-129-5p-mediated inhibition on GBM tumorigenesis. Our results revealed an important role of miR-129-5p in the negative regulation of ZFP36L1 expression in GBM, suggesting new candidates for targeted therapy in GBM patients.
- Published
- 2019
48. Application of molecular imaging technology in tumor immunotherapy
- Author
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Jing Sun, Guirong Zhang, Tao Yu, Na Qv, Yiming Meng, and Haozhe Piao
- Subjects
0301 basic medicine ,Tumor microenvironment ,medicine.diagnostic_test ,Combination therapy ,medicine.medical_treatment ,Immunology ,Selection strategy ,Immunotherapy ,Biology ,Bioinformatics ,Molecular Imaging ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Cancer immunotherapy ,Positron emission tomography ,Neoplasms ,medicine ,Animals ,Humans ,Molecular imaging ,Emission computed tomography ,030215 immunology - Abstract
Cancer immunotherapy, due to its high anti-tumor efficacy, has attracted considerable attention globally from experts in various fields. However, immunotherapy could be severely toxic; not all patients may respond, thus requiring combination therapy. Therefore, a reasonable selection strategy for early treatment is urgently needed. It is vital to capture the dynamic, heterogeneous, and complex tumor behavior considering the absence of ideal companion biomarkers. Since tumor immune response involves tumor cells, several other cell types, and molecules in the tumor microenvironment, detection is very complex and variable. However, molecular imaging technology, namely the non-invasive whole-body molecular imaging by positron emission tomography and single-photon emission computed tomography, has shown considerable promise in tumor detection and cancer immunotherapy response. Identification of potential novel imaging biomarkers will allow a personalized treatment plan for every patient. Future imaging strategies for these molecules used alone or in combination or continuously, might help stratify patients before or during the early stages of immunotherapy, and might address the immunotherapy challenges encountered by the oncologists.
- Published
- 2019
49. LncRNA SRA1 is down-regulated in HPV-negative cervical squamous cell carcinoma and regulates cancer cell behaviors
- Author
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Yunyong Liu, Haozhe Piao, Mengdan Li, and Huihui Yu
- Subjects
HPV ,Cervical Squamous Cell Carcinoma ,business.industry ,miR-9 ,Biophysics ,Cell Biology ,Biochemistry ,lncRNA SRA1 ,HPV Negative ,Cancer cell ,cervical squamous cell carcinoma ,Cancer research ,Medicine ,Human papillomavirus ,business ,Molecular Biology ,Research Articles ,Research Article - Abstract
LncRNA SRA1 plays important roles in several types of human diseases. The present study aimed to explore the role of SRA1 in cervical squamous cell carcinoma (CSCC). In the present study, we showed that plasma SRA1 was down-regulated in human papillomavirus (HPV)-negative CSCC patients but not in HPV-positive CSCC patients compared with healthy females. Down-regulated SRA1 distinguished HPV-negative CSCC patients from HPV-positive CSCC patients and healthy females. In HPV-negative CSCC patients, miR-9 was up-regulated and inversely correlated with SRA1. In HPV-negative CSCC cells, SRA1 overexpression caused the down-regulated miR-9, while miR-9 overexpression failed to affect SRA1. Moreover, SRA1 overexpression caused decreased, while miR-9 overexpression caused increased proliferation, migration and invasion rates of cancer cells. In addition, miR-9 overexpression attenuated the effects of SRA1 overexpression. Therefore, SRA1 is down-regulated in HPV-negative CSCC and regulates cancer cell behaviors possibly by down-regulating miR-9.
- Published
- 2019
50. Sirtuin1 activator SRT2183 suppresses glioma cell growth involving activation of endoplasmic reticulum stress pathway
- Author
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Lulu Hu, Haozhe Piao, Huizhe Xu, Songshu Meng, Ke Jiang, Ye Zhang, Tian Ye, Ji Shi, Liwen Wei, and Lingkai Kong
- Subjects
STAT3 Transcription Factor ,0301 basic medicine ,Cancer Research ,Apoptosis ,Heterocyclic Compounds, 4 or More Rings ,lcsh:RC254-282 ,NF-κB ,STAT3 ,03 medical and health sciences ,0302 clinical medicine ,Sirtuin 1 ,Downregulation and upregulation ,Cell Line, Tumor ,Neurosphere ,Glioma ,Autophagy ,Human Umbilical Vein Endothelial Cells ,Genetics ,medicine ,Humans ,Phosphorylation ,Cell Proliferation ,Sirt1 ,biology ,Brain Neoplasms ,Cell growth ,Chemistry ,NF-kappa B ,Acetylation ,Cell Cycle Checkpoints ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Endoplasmic reticulum stress ,Cancer research ,Unfolded protein response ,biology.protein ,Glioblastoma ,Microtubule-Associated Proteins ,Research Article ,Signal Transduction - Abstract
Background Glioblastoma (GBM) is an extremely deadly form of brain cancer with limited treatment options and thus novel therapeutic modalities are necessary. Histone deacetylase inhibitors (HDACi) have demonstrated clinical and preclinical activities against GBM. (Silent mating type information regulation 2 homolog, Sirt1) abbreviated as Sirtuin 1, has been implicated in GBM. We explored the activity of the Sirt1 activator SRT2183 in glioma cell lines in terms of biological response. Methods The effects of SRT2183 on glioma cell growth and neurosphere survival were evaluated in vitro using the CCK-8, clonogenic and neurosphere assays, respectively. Glioma cell cycle arrest and apoptosis were determined by flow cytometry. SRT2183-induced autophagy was investigated by detection of GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) puncta, conversion of the nonlipidated form of LC3 (LC3-I) to the phosphatidylethanolamine-conjugated form (LC3-II). Acetylation of STAT3 and NF-κB in SRT2183-treated glioma cells was examined using immunoprecipitation. The expression levels of anti-apoptotic proteins were assayed by immunoblotting. Results SRT2183 suppressed glioma cell growth and destroyed neurospheres in vitro. Furthermore, SRT2183 induced glioma cell cycle arrest and apoptosis, accompanying by upregulation of the pro-apoptotic Bim and downregulation of Bcl-2 and Bcl-xL. Notably, ER stress was triggered in glioma cells upon exposure to SRT2183 while the pre-exposure to 4-PBA, an ER stress inhibitor, significantly antagonized SRT2183-mediated growth inhibition in glioma cells. In addition, SRT2183 induced autophagy in glioma cells and pharmacological modulation of autophagy appeared not to affect SRT2183-inhibited cell growth. Of interest, the acetylation and phosphorylation of p65 NF-κB and STAT3 in glioma cells were differentially affected by SRT2183. Conclusions Our data suggest the ER stress pathway is involved in SRT2183-mediated growth inhibition in glioma. Further investigation in vivo is needed to consolidate the data.
- Published
- 2019
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