48 results on '"Xinming Su"'
Search Results
2. Harnessing extracellular vesicles using liquid biopsy for cancer diagnosis and monitoring: highlights from AACR Annual Meeting 2024
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Xinming Su, Zeping Shan, and Shiwei Duan
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Liquid biopsy ,Extracellular vesicles ,Cancer diagnosis ,Biomarkers ,Precision medicine ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Liquid biopsy, an advanced technology for analyzing body fluid samples, is gaining traction in cancer diagnostics and monitoring. Blood-based liquid biopsy, particularly focusing on cell-free DNAs (cf-DNAs), circulating tumor cells (CTCs), and extracellular vesicles (EVs), has garnered significant attention. EVs stand out for their potential in tumor diagnosis, prognosis prediction, and treatment response assessment, owing to their stable molecular cargo and clear extraction process. At the recent American Association for Cancer Research (AACR) Annual Meeting 2024, groundbreaking EVs-based liquid biopsy studies showcased promising strides in early detection and diagnosis of various cancers, including breast cancer (BC), high-grade serous ovarian cancer (HGSOC), pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), colon adenocarcinoma (COAD), head and neck cancer (HNC), neuroblastoma, and retinoblastoma (RB). Despite these advancements, challenges persist in translating EVs biomarkers into clinical practice. Overcoming these challenges promises to propel EVs-based liquid biopsy into a new era of personalized precision medicine, revolutionizing cancer detection, monitoring, and treatment.
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- 2024
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3. CircR-loop: a novel RNA:DNA interaction on genome instability
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Xinming Su, Yaojie Feng, Ruixiu Chen, and Shiwei Duan
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CircRNA ,R-Loops ,RNA–DNA interactions ,Gene regulation ,Regulatory mechanism ,Cytology ,QH573-671 - Abstract
Abstract CircR-loop, a recently unearthed regulatory mechanism situated at the crossroads of circular RNA and DNA interactions, constitute a subset of R-loop. This circR-loop have emerged as a crucial player in pivotal regulatory functions within both animal and plant systems. The journey into the realm of circR-loop commenced with their discovery within the human mitochondrial genome, where they serve as critical directors of mitochondrial DNA replication. In the plant kingdom, circR-loop wield influence over processes such as alternative splicing and centromere organization, impacting the intricacies of floral development and genome stability, respectively. Their significance extends to the animal domain, where circR-loop has captured attention for their roles in cancer-related phenomena, exerting control over transcription, chromatin architecture, and orchestrating responses to DNA damage. Moreover, their involvement in nuclear export anomalies further underscores their prominence in cellular regulation. This article summarizes the important regulatory mechanisms and physiological roles of circR-loop in plants and animals, and offers a comprehensive exploration of the methodologies employed for the identification, characterization, and functional analysis of circR-loop, underscoring the pressing need for innovative approaches that can effectively distinguish them from their linear RNA counterparts while elucidating their precise functions. Lastly, the article sheds light on the challenges and opportunities that lie ahead in the field of circR-loop research, emphasizing the vital importance of continued investigations to uncover their regulatory roles and potential applications in the realm of biology. In summary, circR-loop represents a captivating and novel regulatory mechanism with broad-reaching implications spanning the realms of genetics, epigenetics, and disease biology. Their exploration opens new avenues for comprehending gene regulation and holds significant promise for future therapeutic interventions.
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- 2024
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4. The stiffness of the extracellular matrix is a key factor in tumor progression
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Yue Zheng, Xinming Su, and Shiwei Duan
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Medicine - Published
- 2024
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5. Deciphering tumor microenvironment: CXCL9 and SPP1 as crucial determinants of tumor-associated macrophage polarity and prognostic indicators
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Xinming Su, Chenhao Liang, Ruixiu Chen, and Shiwei Duan
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Tumor microenvironment ,Tumor-associated macrophages ,Biomarkers ,CXCL9 ,SPP1 ,Prognosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract The tumor microenvironment (TME) is an intricate system comprised of tumor cells and the surrounding cellular and non-cellular components, exerting a pivotal influence on the initiation and progression of tumors. Exhibiting dynamic and diverse compositions as well as functional states across various tumors and patients, a profound comprehension of its specific internal interactions is indispensable for formulating efficacious anti-cancer treatment strategies. Extensive interactions among various immune cell types within the TME are well-documented, with their phenotypes and abundances closely linked to clinical prognoses. TME research is progressing towards greater complexity and precision, yet, to date, no representative TME biomarkers suitable for clinical applications have been definitively identified and validated. In a recent study, the collaborative actions of CXCL9 and SPP1 (CXCL9:SPP1) were found to collectively dictate the polarity of tumor-associated macrophages (TAMs) within the TME, exerting profound effects on tumor progression and treatment responses. The mutually exclusive expression of CXCL9:SPP1 in the TME not only governs TAM polarity but also exhibits strong correlations with immune cell profiles, antitumor factors, and patient outcomes, significantly influencing prognosis. This article consolidates the significance and prospects of CXCL9:SPP1 as a novel indicator for tumor development and prognosis, while also proposing future research directions and addressing potential challenges in this promising field.
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- 2024
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6. Targeted drug delivery systems for pancreatic ductal adenocarcinoma: overcoming tumor microenvironment challenges with CAF-specific nanoparticles
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Xinming Su, Zehua Wang, and Shiwei Duan
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Pancreatic ductal adenocarcinoma ,Tumor microenvironment ,Drug delivery systems ,Cancer-associated fibroblasts ,Nanoparticles ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Pancreatic ductal adenocarcinoma (PDAC) stands as a profoundly heterogeneous and aggressive malignancy, manifesting a discouragingly limited response to conventional therapeutic interventions. Within the intricate tapestry of the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) emerge as pivotal constituents, wielding the capacity to propel the malignant attributes of neoplastic cells while bolstering their deftness in thwarting treatments. The rapid evolution of nanomedicinal technologies ushers in fresh avenues for therapeutic paradigms meticulously honed to target CAFs. Notably, a recent proposition by Yuan et al. introduces a PDAC treatment strategy metaphorically akin to “shooting fish in a barrel.” By adeptly capitalizing on the spatial distribution of the CAF barricade encircling the tumor, this innovative approach orchestrates a metamorphosis of CAFs, transitioning them from impediments to drug delivery into reservoirs of therapeutic agents. The resultant outcome, an augmentation of chemotherapy and immunotherapy efficacy, attests to the transformative potential of this concept. The study not only bequeaths novel insights and methodologies to surmount barriers in drug delivery for tumor treatment but also holds promise in elevating the precision, efficacy, and safety of tailored therapeutic regimens. Within this discourse, we meticulously evaluate Yuan et al.'s research, scrutinizing its merits and limitations, and cast a forward-looking gaze upon the formulation, validation of efficacy, and clinical translation of nanomedicines targeting CAFs.
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- 2023
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7. Current insights into the oncogenic roles of lncRNA LINC00355
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Jinze Shen, Xinming Su, Ming Pan, Zehua Wang, Yufei Ke, Qurui Wang, Jingyin Dong, and Shiwei Duan
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ceRNA ,chemotherapy resistance ,lncRNA ,LINC00355 ,miRNA ,prognosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Long noncoding RNAs (lncRNAs) are a class of nonprotein‐coding transcripts that are longer than 200 nucleotides. LINC00355 is a lncRNA located on chromosome 13q21.31 and is consistently upregulated in various cancers. It regulates the expression of downstream genes at both transcriptional and posttranscriptional levels, including eight microRNAs (miR‐15a‐5p, miR‐34b‐5p, miR‐424‐5p, miR‐1225, miR‐217‐5p, miR‐6777‐3p, miR‐195, and miR‐466) and three protein‐coding genes (ITGA2, RAD18, and UBE3C). LINC00355 plays a role in regulating various biological processes such as cell cycle progression, proliferation, apoptosis, epithelial‐mesenchymal transition, invasion, and metastasis of cancer cells. It is involved in the regulation of the Wnt/β‐catenin signaling pathway and p53 signaling pathway. Upregulation of LINC00355 has been identified as a high‐risk factor in cancer patients and its increased expression is associated with poorer overall survival, recurrence‐free survival, and disease‐free survival. LINC00355 upregulation has been linked to several unfavorable clinical characteristics, including advanced tumor node metastasis and World Health Organization stages, reduced Karnofsky Performance Scale scores, increased tumor size, greater depth of invasion, and more extensive lymph node metastasis. LINC00355 induces chemotherapy resistance in cancer cells by regulating five downstream genes, namely HMGA2, ABCB1, ITGA2, WNT10B, and CCNE1 genes. In summary, LINC00355 is a potential oncogene with great potential as a diagnostic marker and therapeutic target for cancer.
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- 2023
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8. #22. Investigating the TGF-β/integrin β3 signaling axis as a mediator of chemoresistance in breast cancer bone metastasis
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Kristin A. Kwakwa, Gregory C. Fox, Michael H. Ross, Xinming Su, Yalin Xu, Netra Navadkar, Gregory M. Lanza, Christopher A. Maher, and Katherine N. Weilbaecher
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Diseases of the musculoskeletal system ,RC925-935 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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9. #46. cAMP-mediated acid signaling regulates tumor-myeloid-bone cell crosstalk in the bone-tumor microenvironment
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Kaylee O'Donnell, Xinming Su, Yalin Xu, Kristin A. Kwakwa, Deborah J. Veis, David G. DeNardo, Gregory M. Lanza, and Katherine N. Weilbaecher
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Diseases of the musculoskeletal system ,RC925-935 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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10. CDK4/6 inhibitor and doxorubicin synergistically inhibit breast cancer bone metastasis and enhance T-cell targeted therapy
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Xinming Su, Takayuki Kobayashi, Jingyu Xiang, Yalin Xu, Ayesha N. Shajahan-Haq, Mahta Mardani, Suleyman Noordeen, Kaylee O'Donnell, Kristin A. Kwakwa, Francesca Fontana, Deborah J. Veis, Gregory M. Lanza, and Katherine N. Weilbaecher
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Diseases of the musculoskeletal system ,RC925-935 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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11. Targeting stromal p38MAPKalpha triggers innate-adaptive anti-tumor immunity and sensitizes metastatic breast cancer to immunotherapy
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Douglas V. Faget, Xianmin Luo, Matthew J. Inkman, Qihao Ren, Xinming Su, Kai Ding, Michael R. Waters, Ganesh Kumar Raut, Gaurav Pandey, Paarth B. Dodhiawala, Renata Ramalho-Oliveira, Jiayu Ye, Thomas Cole, Bhavna Murali, Alexander Zheleznyak, Monica Shokeen, Kurt R. Weiss, Joseph B. Monahan, Carl J. DeSelm, Adrian V. Lee, Steffi Oesterreich, Katherine N. Weilbaecher, Jin Zhang, David G. DeNardo, and Sheila A. Stewart
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Diseases of the musculoskeletal system ,RC925-935 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
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12. Precise tumor treatment: pH‐responsive nanoparticles for modulating and real‐time monitoring tumor microenvironment
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Xinming Su, Zehua Wang, and Shiwei Duan
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Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Medical technology ,R855-855.5 - Published
- 2024
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13. Tumor‐derived extracellular vesicles and particles (EVPs): pivotal vectors in driving metabolic reprogramming
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Xinming Su, Peijie Zheng, and Shiwei Duan
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cancer ,chemotherapy toxicity ,extracellular vesicles and particles ,liver metabolism ,metabolic reprogramming ,nonalcoholic fatty liver disease ,Medicine - Published
- 2023
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14. Dysfunction and ceRNA network of the tumor suppressor miR-637 in cancer development and prognosis
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Jinze Shen, Chenhao Liang, Xinming Su, Qurui Wang, Yufei Ke, Jie Fang, Dayong Zhang, and Shiwei Duan
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miR-637 ,Cancer ,ceRNA ,Dysregulation ,Prognosis ,Drug resistance ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract MicroRNAs (miRNAs) are a class of small non-coding RNAs ranging from 17 to 25 nt in length. miR-637 is down-regulated in most cancers and up-regulated only in clear cell renal cell carcinoma (ccRCC). miR-637 can target 21 protein-coding genes, which are involved in the regulation of cell growth, cell cycle, cell proliferation, epithelial-mesenchymal transition (EMT), cancer cell invasion and metastasis, etc. In glioma, the transcription factor ZEB2 can bind to the miR-637 promoter region and inhibit miR-637 expression. Besides, miR-637 could be negatively regulated by competing endogenous RNA (ceRNAs) comprising 13 circular RNA (circRNAs) and 9 long non-coding RNA (lncRNAs). miR-637 is involved in regulating five signaling pathways, including the Jak/STAT3, Wnt/β-catenin, PI3K/AKT, and ERK signaling pathways. Low miR-637 expression was significantly associated with larger tumors and later tumor node metastasis (TNM) staging in cancer patients. Low miR-637 expression was also associated with poorer overall survival (OS) in cancer patients such as glioblastoma and low-grade gliomas (GBM/LGG), non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and ovarian cancer (OV). Low expression of miR-637 increases the resistance of colorectal cancer (CRC) and human cholangiocarcinoma (CHOL) cancer cells to three anticancer chemotherapeutics (gemcitabine (dFdC), cisplatin (DDP), and oxaliplatin (OXA)). Our work summarizes the abnormal expression of miR-637 in various cancers, expounds on the ceRNA regulatory network and signaling pathway involved in miR-637, and summarizes the effect of its abnormal expression on the biological behavior of tumor cells. At the same time, the relationship between the expression levels of miR-637 and its related molecules and the prognosis and pathological characteristics of patients was further summarized. Finally, our work points out the insufficiency of miR-637 in current studies and is expected to provide potential clues for future miR-637-related studies.
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- 2022
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15. Mapping knowledge structure and research of the biologic treatment of asthma: A bibliometric study
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Jiamin Sun, Shiyao Bai, Jieyu Zhao, Danling Li, Xueqing Ma, Lin Ma, and Xinming Su
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asthma ,biologics ,treatment ,visualization analysis ,bibliometric analysis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundBronchial asthma (asthma) is a chronic inflammatory disease of the airways, involving a variety of cells and cellular components, that manifests clinically as recurrent episodes of wheezing, shortness of breath, with or without chest tightness or cough, airway hyperresponsiveness, and variable airflow limitation. The number of people with asthma has reached 358 million worldwide and asthma causes huge economic loss. However, there is a subset of patients who are not sensitive to existing drugs and the existing drugs have many adverse effects. Therefore, it’s important to find new drugs for asthma patients.MethodsPublications related to biologics in asthma published from 2000 to 2022 were retrieved from Web of Science Core Collection. The search strategies were as follows: topic: TS=(biologic* OR “biologic* product*” OR “biologic* therap*” OR biotherapy* OR “biologic* agent*” OR Benralizumab OR “MEDI-563” OR Fasenra OR “BIW-8405” OR Dupilumab OR SAR231893 OR “SAR-231893” OR Dupixent OR REGN668 OR “REGN-668” OR Mepolizumab OR Bosatria OR “SB-240563” OR SB240563 OR Nucala OR Omalizumab OR Xolair OR Reslizumab OR “SCH-55700” OR SCH55700 OR “CEP-38072” OR CEP38072 OR Cinqair OR “DCP-835” OR DCP835 OR Tezspire OR “tezepelumab-ekko” OR “AMG-157” OR tezspire OR “MEDI-9929” OR “MEDI-19929” OR MEDI9929 OR Itepekimab OR “REGN-3500”OR REGN3500 OR “SAR-440340”OR SAR440340 OR Tralokinumab OR “CAT-354” OR Anrukinzumab OR “IMA-638” OR Lebrikizumab OR “RO-5490255”OR “RG-3637”OR “TNX-650”OR “MILR1444A”OR “MILR-1444A”OR”PRO301444”OR “PRO-301444”OR Pitrakinra OR altrakincept OR “AMG-317”OR”AMG317” OR Etokimab OR Pascolizumab OR “IMA-026”OR Enokizumab OR “MEDI-528”OR “7F3COM-2H2” OR 7F3COM2H2 OR Brodalumab OR “KHK-4827” OR “KHK4827”OR “AMG-827”OR Siliq OR Ligelizumab OR “QGE-031” OR QGE031 OR Quilizumab OR Talizumab OR “TNX-901” OR TNX901 OR Infliximab OR Etanercept OR “PRS-060”) AND TS=asthma*. The document type was set to articles and review articles and the language restriction was set to English. Three different analysis tools including one online platform, VOS viewer1.6.18, and CiteSpace V 6.1.R1 software were used to conduct this bibliometric study.ResultsThis bibliometric study included 1,267 English papers published in 244 journals from 2,012 institutions in 69 countries/regions. Omalizumab, benralizumab, mepolizumab, and tezepelumab in relation to asthma were the research hotspots in the field.ConclusionThis study systematically uncovers a holistic picture of existing literature related to the biologic treatment of asthma over the past 20 years. We consulted scholars in order to understand key information in this field from the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.
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- 2023
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16. Histone deacetylase 8 regulates NF-κB-related inflammation in asthmatic mice through H3K9 acetylation
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Yuan Ren, Menglu Li, Shiyao Bai, Xinming Su, and Peifang Wei
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Medicine - Published
- 2022
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17. Transferrin receptor in primary and metastatic breast cancer: Evaluation of expression and experimental modulation to improve molecular targeting.
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Francesca Fontana, Alison K Esser, Christopher Egbulefu, Partha Karmakar, Xinming Su, John S Allen, Yalin Xu, Jennifer L Davis, Ariel Gabay, Jingyu Xiang, Kristin A Kwakwa, Brad Manion, Suzanne Bakewell, Shunqiang Li, Haeseong Park, Gregory M Lanza, Samuel Achilefu, and Katherine N Weilbaecher
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Medicine ,Science - Abstract
BackgroundConjugation of transferrin (Tf) to imaging or nanotherapeutic agents is a promising strategy to target breast cancer. Since the efficacy of these biomaterials often depends on the overexpression of the targeted receptor, we set out to survey expression of transferrin receptor (TfR) in primary and metastatic breast cancer samples, including metastases and relapse, and investigate its modulation in experimental models.MethodsGene expression was investigated by datamining in twelve publicly-available datasets. Dedicated Tissue microarrays (TMAs) were generated to evaluate matched primary and bone metastases as well as and pre and post chemotherapy tumors from the same patient. TMA were stained with the FDA-approved MRQ-48 antibody against TfR and graded by staining intensity (H-score). Patient-derived xenografts (PDX) and isogenic metastatic mouse models were used to study in vivo TfR expression and uptake of transferrin.ResultsTFRC gene and protein expression were high in breast cancer of all subtypes and stages, and in 60-85% of bone metastases. TfR was detectable after neoadjuvant chemotherapy, albeit with some variability. Fluorophore-conjugated transferrin iron chelator deferoxamine (DFO) enhanced TfR uptake in human breast cancer cells in vitro and proved transferrin localization at metastatic sites and correlation of tumor burden relative to untreated tumor mice.ConclusionsTfR is expressed in breast cancer, primary, metastatic, and after neoadjuvant chemotherapy. Variability in expression of TfR suggests that evaluation of the expression of TfR in individual patients could identify the best candidates for targeting. Further, systemic iron chelation with DFO may upregulate receptor expression and improve uptake of therapeutics or tracers that use transferrin as a homing ligand.
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- 2023
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18. N-cadherin in osteolineage cells modulates stromal support of tumor growth
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Francesca Fontana, Jingyu Xiang, Xinming Su, Eric Tycksen, Rachel Nassau, Gregory Fox, Giulia Leanza, Katherine Weilbaecher, and Roberto Civitelli
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N-cadherin ,Bone-tumor cell interactions ,Tumor microenvironment ,Transcriptomics ,Diseases of the musculoskeletal system ,RC925-935 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Tumor growth and metastases are dependent on interactions between cancer cells and the local environment. Expression of the cell–cell adhesion molecule N-cadherin (Ncad) is associated with highly aggressive cancers, and its expression by osteogenic cells has been proposed to provide a molecular “dock” for disseminated tumor cells to establish in pre-metastatic niches within the bone. To test this biologic model, we conditionally deleted the Ncad gene (Cdh2) in osteolineage cells using Osx-cre (cKO). Contrary to expectations, the metastatic breast cancer cell line PyMT-BO1 was able to form tumors in bone and to induce osteolysis in cKO as well as in control mice. Despite absence of Ncad, bone marrow stromal cells isolated from cKO mice were able to engage in direct cell–cell interactions with tumor cells expressing either N- or E-cadherin. However, subcutaneous PyMT-BO1 and B16F10 tumors grew larger in cKO relative to control littermates. Cell tracking experiments using the Ai9 reporter revealed the presence of Osx+ and Ncad+ cells in the stroma of extra-skeletal tumors and in a small population of lung cells. Gene expression analysis by RNAseq of Osx+ cells isolated from extra-skeletal tumors revealed alterations of pro-tumorigenic signaling pathways in cKO cells relative to control Osx+ cells. Thus, Ncad in Osx+ cells is not necessary for the establishment of bone metastases, but in extra-skeletal tumors it regulates pro-tumorigenic support by the microenvironment.
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- 2021
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19. Hepatic lipids promote liver metastasis
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Yongjia Li, Xinming Su, Nidhi Rohatgi, Yan Zhang, Jonathan R. Brestoff, Kooresh I. Shoghi, Yalin Xu, Clay F. Semenkovich, Charles A. Harris, Lindsay L. Peterson, Katherine N. Weilbaecher, Steven L. Teitelbaum, and Wei Zou
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Hepatology ,Oncology ,Medicine - Abstract
Obesity predisposes to cancer and a virtual universality of nonalcoholic fatty liver disease (NAFLD). However, the impact of hepatic steatosis on liver metastasis is enigmatic. We find that while control mice were relatively resistant to hepatic metastasis, those which were lipodystrophic or obese, with NAFLD, had a dramatic increase in breast cancer and melanoma liver metastases. NAFLD promotes liver metastasis by reciprocal activation initiated by tumor-induced triglyceride lipolysis in juxtaposed hepatocytes. The lipolytic products are transferred to cancer cells via fatty acid transporter protein 1, where they are metabolized by mitochondrial oxidation to promote tumor growth. The histology of human liver metastasis indicated the same occurs in humans. Furthermore, comparison of isolates of normal and fatty liver established that steatotic lipids had enhanced tumor-stimulating capacity. Normalization of glucose metabolism by metformin did not reduce steatosis-induced metastasis, establishing the process is not mediated by the metabolic syndrome. Alternatively, eradication of NAFLD in lipodystrophic mice by adipose tissue transplantation reduced breast cancer metastasis to that of control mice, indicating the steatosis-induced predisposition is reversible.
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- 2020
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20. High Q Dielectric Titanium Tellurite Thick Films on Alumina Substrates for High Frequency Telecommunications
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Xinming Su, Alexander Tkach, Jerzy Krupka, and Paula M. Vilarinho
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TiTe3O8 thick films ,electrophoretic deposition ,alumina substrates ,high-Q dielectrics ,microwave properties ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
The vital role of high-quality-factor (Q) high-frequency (f) dielectric resonators in the growing microwave telecommunication, satellite broadcasting and intelligent transport systems has long motivated the search for new, small size, and lightweight integrated components and packages, prepared by low cost and sustainable processes. One approach is replacing the currently used bulk ceramic dielectrics by thick films of low-sintering-temperature dielectrics fabricated by affordable processes. Here we demonstrate the fabrication of high-Q TiTe3O8 thick films directly on low loss Al2O3 substrates by electrophoretic deposition using sacrificial carbon layer. Nineteen-micrometre-thick TiTe3O8 films on Al2O3 sintered at 700 °C are found to have a relative permittivity εr of 32 and Q × f > 21,000 GHz. Being thus able to measure and provide for the first time the microwave dielectric properties of these films, our results suggest that TiTe3O8 films on Al2O3 substrates are suitable for microlayer microstrip array applications.
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- 2022
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21. Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance
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Melissa A. Meyer, John M. Baer, Brett L. Knolhoff, Timothy M. Nywening, Roheena Z. Panni, Xinming Su, Katherine N. Weilbaecher, William G. Hawkins, Cynthia Ma, Ryan C. Fields, David C. Linehan, Grant A. Challen, Roberta Faccio, Rebecca L. Aft, and David G. DeNardo
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Science - Abstract
Tumors escape the immune system through many mechanisms. Here the authors show that certain tumors inhibit anti-tumor immunity by stopping the production of conventional dendritic cells (cDCs) in the bone marrow, therefore depleting the pool of cDCs available to present antigen to CD8+ T cells.
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- 2018
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22. Stromal-Initiated Changes in the Bone Promote Metastatic Niche Development
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Xianmin Luo, Yujie Fu, Andrew J. Loza, Bhavna Murali, Kathleen M. Leahy, Megan K. Ruhland, Margery Gang, Xinming Su, Ali Zamani, Yu Shi, Kory J. Lavine, David M. Ornitz, Katherine N. Weilbaecher, Fanxin Long, Deborah V. Novack, Roberta Faccio, Gregory D. Longmore, and Sheila A. Stewart
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Biology (General) ,QH301-705.5 - Abstract
More than 85% of advanced breast cancer patients suffer from metastatic bone lesions, yet the mechanisms that facilitate these metastases remain poorly understood. Recent studies suggest that tumor-derived factors initiate changes within the tumor microenvironment to facilitate metastasis. However, whether stromal-initiated changes are sufficient to drive increased metastasis in the bone remains an open question. Thus, we developed a model to induce reactive senescent osteoblasts and found that they increased breast cancer colonization of the bone. Analysis of senescent osteoblasts revealed that they failed to mineralize bone matrix and increased local osteoclastogenesis, the latter process being driven by the senescence-associated secretory phenotype factor, IL-6. Neutralization of IL-6 was sufficient to limit senescence-induced osteoclastogenesis and tumor cell localization to bone, thereby reducing tumor burden. Together, these data suggest that a reactive stromal compartment can condition the niche, in the absence of tumor-derived signals, to facilitate metastatic tumor growth in the bone.
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- 2016
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23. Association of Dietary Vitamin A and β-Carotene Intake with the Risk of Lung Cancer: A Meta-Analysis of 19 Publications
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Na Yu, Xinming Su, Zanfeng Wang, Bing Dai, and Jian Kang
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vitamin A ,β-carotene ,lung cancer ,meta-analysis ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Whether dietary β-carotene and vitamin A intake protect against lung cancer risk is not clear. Therefore, we performed this meta-analysis to investigate the association between them. The related articles were searched using the databases PubMed and the Web of Knowledge up to May 2015. We used the random-effect model to estimate the relative risk (RR) and their 95% CI. Small-study effect was assessed using Egger’s test. In total, 19 studies comprising 10,261 lung cancer cases met the inclusion criteria. The pooled RR and their 95% CI was 0.855 (0.739–0.989) for higher category of dietary vitamin A intake and lung cancer risk, especially among Asian populations and in the cohort studies. Evidence from 18 studies suggested that higher category of dietary β-carotene intake could reduce lung cancer risk (0.768 (0.675–0.874)).The associations were also significant in American and Asian populations. In conclusions, higher category of dietary β-carotene and vitamin A intakes could reduce the risk of lung cancer. However, the dose-response analysis was not performed due to the limited data in each individual study. Due to this limitation, further studies with detailed dose, cases and person-years for β-carotene and vitamin A of each category are wanted to assess this dose-response association.
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- 2015
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24. Computer-aided Design for the Route of the Test Waveguides
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Runze Wang, Yabin Jian, Xiaofang Yin, YaQin Hou, and XinMing Su
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Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
With the rapid development of China's space industry, digitization and intelligent is the tendency of the future. The applications of the waveguide are gradually widespread. During the thermal test phase, the routes of the test waveguides are similar for each spacecraft. Although the waveguides are highly standardized, so far it needs engineers to design the particular route of the test waveguidess, then map the engineering drawing for every test. In order to efficiently design the route of waveguide, it needs to design an application to help the engineers. With the help of the MFC(Microsoft Foundation Classes) and the pro/toolkit, it is easily to do the modeling and simulation. After automatic design the particular the route of the waveguide, the API of AutoCAD type library is used to help to modify the engineer drawing. Engineers can supervise every step of this application, and easily to modify the key parameters.
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- 2018
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25. Whole Genome Sequence of Multiple Myeloma-Prone C57BL/KaLwRij Mouse Strain Suggests the Origin of Disease Involves Multiple Cell Types.
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Sarah R Amend, William C Wilson, Liang Chu, Lan Lu, Pengyuan Liu, Daniel Serie, Xinming Su, Yalin Xu, Dingyan Wang, Anthony Gramolini, Xiao-Yan Wen, Julie O'Neal, Michelle Hurchla, Celine M Vachon, Graham Colditz, Ravi Vij, Katherine N Weilbaecher, and Michael H Tomasson
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Medicine ,Science - Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is the requisite precursor to multiple myeloma (MM), a malignancy of antibody-producing plasma B-cells. The genetic basis of MGUS and its progression to MM remains poorly understood. C57BL/KaLwRij (KaLwRij) is a spontaneously-derived inbred mouse strain with a high frequency of benign idiopathic paraproteinemia (BIP), a phenotype with similarities to MGUS including progression to MM. Using mouse haplotype analysis, human MM SNP array data, and whole exome and whole genome sequencing of KaLwRij mice, we identified novel KaLwRij gene variants, including deletion of Samsn1 and deleterious point mutations in Tnfrsf22 and Tnfrsf23. These variants significantly affected multiple cell types implicated in MM pathogenesis including B-cells, macrophages, and bone marrow stromal cells. These data demonstrate that multiple cell types contribute to MM development prior to the acquisition of somatic driver mutations in KaLwRij mice, and suggest that MM may an inherently non-cell autonomous malignancy.
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- 2015
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26. Preliminary studies on the molecular mechanism of intramuscular fat deposition in the longest dorsal muscle of sheep
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Xuwen Shao, Xintan Lu, Xinming Sun, Huaizhi Jiang, and Yang Chen
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Small-tailed frigid sheep ,Longest dorsal muscle ,Intramuscular fat ,Growth and development ,Transcriptomics ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Intramuscular fat content is an important index reflecting the quality of mutton, which directly affects the flavor and tenderness of mutton. Livestock and poultry intramuscular fat content is influenced by genetics, nutritional level, and environmental factors. Key regulatory factors play a crucial role in intramuscular fat deposition. However, there is a limited amount of research on the identification and function of key genes involved in intramuscular fat content deposition specifically in sheep. Results Histological differences in the longest dorsal muscle of the small-tailed frigid sheep increased in diameter and decreased in several muscle fibers with increasing monthly age; The intramuscular fat content of the longest dorsal muscle of the small-tailed cold sheep varied with age, with a minimum of 1 month of age, a maximum of 6 months of age, and a minimum of 12 months of age. Transcriptomic sequencing and bioinformatics analysis revealed a large number of differential genes in the longest dorsal muscles of little-tailed billy goats of different months of age, which were enriched in multiple GO entries and KEGG pathways. Among them, the pathway associated with intramuscular fat was the AMPK signaling pathway, and the related genes were PPARGC1A and ADIPOQ; Immunohistochemical studies showed that PPARGC1A and ADIPOQ proteins were expressed in connective tissues, cell membranes, and, to a lesser extent, the cytoplasm of the longest dorsal muscle of the little-tailed frigid sheep; Real-time PCR and Western Blot validation showed that PPARGC1A and ADIPOQ were both expressed in the longest dorsal muscle of the little-tailed frigid sheep at different ages, and there were age differences in the amount of expression. The ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle, and the PPARGC1A gene was positively correlated with the intramuscular fat content of the longest dorsal muscle; As inferred from the above results, the ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle (r = -0.793, P
- Published
- 2024
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27. Breast cancer–derived GM-CSF regulates arginase 1 in myeloid cells to promote an immunosuppressive microenvironment
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Jingyu Xiang, Wen-Chih Lee, Junyi Su, Leonel Hernandez-Aya, Jad I. Belle, Gregory M. Lanza, Christopher Egbulefu, Gregory C. Fox, Deborah J. Veis, Katherine N. Weilbaecher, Samuel Achilefu, Yalin Xu, Kristin A. Kwakwa, Xinming Su, Jennifer L. Davis, Wing Hing Wong, Helen M Tomasson, Partha Karmakar, David G. DeNardo, Melisa A Meyer, Sheila A. Stewart, Takayuki Kobayashi, Francesca Fontana, and Suzanne J. Bakewell
- Subjects
Myeloid ,medicine.medical_treatment ,T cell ,Breast Neoplasms ,complex mixtures ,Mice ,Breast cancer ,Cancer immunotherapy ,Cell Line, Tumor ,Cyclic AMP ,Immune Tolerance ,Tumor Microenvironment ,Medicine ,Animals ,Humans ,Myeloid Cells ,Tumor microenvironment ,Arginase ,business.industry ,Granulocyte-Macrophage Colony-Stimulating Factor ,General Medicine ,Immunotherapy ,medicine.disease ,Immune checkpoint ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Tumor progression ,Cancer research ,Female ,business ,Research Article - Abstract
Tumor-infiltrating myeloid cells contribute to the development of the immunosuppressive tumor microenvironment. Myeloid cell expression of arginase 1 (ARG1) promotes a protumor phenotype by inhibiting T cell function and depleting extracellular l-arginine, but the mechanism underlying this expression, especially in breast cancer, is poorly understood. In breast cancer clinical samples and in our mouse models, we identified tumor-derived GM-CSF as the primary regulator of myeloid cell ARG1 expression and local immune suppression through a gene-KO screen of breast tumor cell-produced factors. The induction of myeloid cell ARG1 required GM-CSF and a low pH environment. GM-CSF signaling through STAT3 and p38 MAPK and acid signaling through cAMP were required to activate myeloid cell ARG1 expression in a STAT6-independent manner. Importantly, breast tumor cell-derived GM-CSF promoted tumor progression by inhibiting host antitumor immunity, driving a significant accumulation of ARG1-expressing myeloid cells compared with lung and melanoma tumors with minimal GM-CSF expression. Blockade of tumoral GM-CSF enhanced the efficacy of tumor-specific adoptive T cell therapy and immune checkpoint blockade. Taken together, we show that breast tumor cell-derived GM-CSF contributes to the development of the immunosuppressive breast cancer microenvironment by regulating myeloid cell ARG1 expression and can be targeted to enhance breast cancer immunotherapy.
- Published
- 2021
28. Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance
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Brett L. Knolhoff, Rebecca Aft, Cynthia X. Ma, Roberta Faccio, William G. Hawkins, Xinming Su, David G. DeNardo, David C. Linehan, Ryan C. Fields, Grant A. Challen, Timothy M. Nywening, Melissa A. Meyer, John M. Baer, Roheena Z. Panni, and Katherine N. Weilbaecher
- Subjects
0301 basic medicine ,T-Lymphocytes ,Thrombomodulin ,medicine.medical_treatment ,Cellular differentiation ,General Physics and Astronomy ,CD8-Positive T-Lymphocytes ,Mice ,0302 clinical medicine ,lcsh:Science ,Immunologic Surveillance ,Oligonucleotide Array Sequence Analysis ,Mice, Inbred BALB C ,Multidisciplinary ,Stem Cells ,Cell Differentiation ,3. Good health ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Antigens, Surface ,Interferon Regulatory Factors ,Cytokines ,Female ,Immunotherapy ,Myelopoiesis ,Integrin alpha Chains ,Science ,Antineoplastic Agents ,Bone Marrow Cells ,Breast Neoplasms ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Antigens, CD ,Immunity ,medicine ,Animals ,Humans ,business.industry ,Dendritic Cells ,General Chemistry ,Dendritic cell ,Mice, Inbred C57BL ,Pancreatic Neoplasms ,Disease Models, Animal ,030104 developmental biology ,Tumor progression ,Cancer research ,lcsh:Q ,Bone marrow ,IRF8 ,business - Abstract
Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, whereby the expansion of immunosuppressive myeloid cells can impair tumor immunity. As myeloid cells and conventional dendritic cells (cDCs) are derived from the same progenitors, we postulated that myelopoiesis might impact cDC development. The cDC subset, cDC1, which includes human CD141+ DCs and mouse CD103+ DCs, supports anti-tumor immunity by stimulating CD8+ T-cell responses. Here, to understand how cDC1 development changes during tumor progression, we investigated cDC bone marrow progenitors. We found localized breast and pancreatic cancers induce systemic decreases in cDC1s and their progenitors. Mechanistically, tumor-produced granulocyte-stimulating factor downregulates interferon regulatory factor-8 in cDC progenitors, and thus results in reduced cDC1 development. Tumor-induced reductions in cDC1 development impair anti-tumor CD8+ T-cell responses and correlate with poor patient outcomes. These data suggest immune surveillance can be impaired by tumor-induced alterations in cDC development., Tumors escape the immune system through many mechanisms. Here the authors show that certain tumors inhibit anti-tumor immunity by stopping the production of conventional dendritic cells (cDCs) in the bone marrow, therefore depleting the pool of cDCs available to present antigen to CD8+ T cells.
- Published
- 2018
29. HTLV-1 viral oncogene HBZ drives bone destruction in adult T cell leukemia
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Xiaogang Cheng, Xinming Su, Gregory C. Fox, Deborah J. Veis, Francesca Fontana, Junyi Su, John C. S. Harding, Hemalatha Sundaramoorthi, Alison K. Esser, Takayuki Kobayashi, Stefan Niewiesk, Yizhen Jia, Patrick L. Green, Yalin Xu, Jingyu Xiang, Amanda R. Panfil, Thomas J. Rosol, Wing Hing Wong, Devra Huey, Katherine N. Weilbaecher, Lee Ratner, and Daniel Rauch
- Subjects
0301 basic medicine ,Male ,Bone disease ,viruses ,T-cell leukemia ,Viral Oncogene ,Retroviridae Proteins ,Osteoclasts ,Kaplan-Meier Estimate ,medicine.disease_cause ,Mice ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Medicine ,Leukemia-Lymphoma, Adult T-Cell ,610 Medicine & health ,Mice, Knockout ,Human T-lymphotropic virus 1 ,biology ,General Medicine ,Gene Expression Regulation, Neoplastic ,Denosumab ,medicine.anatomical_structure ,Basic-Leucine Zipper Transcription Factors ,RANKL ,030220 oncology & carcinogenesis ,Disease Progression ,Heterografts ,Female ,medicine.drug ,Research Article ,Adult ,T cell ,Bone and Bones ,03 medical and health sciences ,Animals ,Humans ,Bone Resorption ,business.industry ,RANK Ligand ,medicine.disease ,Lymphoma ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Cancer research ,biology.protein ,business ,Carcinogenesis ,Transcriptome - Abstract
Osteolytic bone lesions and hypercalcemia are common, serious complications in adult T cell leukemia/lymphoma (ATL), an aggressive T cell malignancy associated with human T cell leukemia virus type 1 (HTLV-1) infection. The HTLV-1 viral oncogene HBZ has been implicated in ATL tumorigenesis and bone loss. In this study, we evaluated the role of HBZ on ATL-associated bone destruction using HTLV-1 infection and disease progression mouse models. Humanized mice infected with HTLV-1 developed lymphoproliferative disease and continuous, progressive osteolytic bone lesions. HTLV-1 lacking HBZ displayed only modest delays to lymphoproliferative disease but significantly decreased disease-associated bone loss compared with HTLV-1-infected mice. Gene expression array of acute ATL patient samples demonstrated increased expression of RANKL, a critical regulator of osteoclasts. We found that HBZ regulated RANKL in a c-Fos-dependent manner. Treatment of HTLV-1-infected humanized mice with denosumab, a monoclonal antibody against human RANKL, alleviated bone loss. Using patient-derived xenografts from primary human ATL cells to induce lymphoproliferative disease, we also observed profound tumor-induced bone destruction and increased c-Fos and RANKL gene expression. Together, these data show the critical role of HBZ in driving ATL-associated bone loss through RANKL and identify denosumab as a potential treatment to prevent bone complications in ATL patients.
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- 2019
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30. Breast cancer-derived GM-CSF regulates arginase 1 in myeloid cells to promote an immunosuppressive microenvironment.
- Author
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Xinming Su, Yalin Xu, Fox, Gregory C., Jingyu Xiang, Kwakwa, Kristin A., Davis, Jennifer L., Belle, Jad I., Wen-Chih Lee, Wong, Wing H., Fontana, Francesca, Hernandez-Aya, Leonel F., Takayuki Kobayashi, Tomasson, Helen M., Junyi Su, Bakewell, Suzanne J., Stewart, Sheila A., Egbulefu, Christopher, Karmakar, Partha, Meyer, Melisa A., and Veis, Deborah J.
- Subjects
- *
MYELOID cells , *GRANULOCYTE-macrophage colony-stimulating factor , *ARGINASE , *IMMUNE checkpoint proteins , *IMMUNOSUPPRESSION , *ARGININE - Abstract
Tumor-infiltrating myeloid cells contribute to the development of the immunosuppressive tumor microenvironment. Myeloid cell expression of arginase 1 (ARG1) promotes a protumor phenotype by inhibiting T cell function and depleting extracellular l-arginine, but the mechanism underlying this expression, especially in breast cancer, is poorly understood. In breast cancer clinical samples and in our mouse models, we identified tumor-derived GM-CSF as the primary regulator of myeloid cell ARG1 expression and local immune suppression through a gene-KO screen of breast tumor cell-produced factors. The induction of myeloid cell ARG1 required GM-CSF and a low pH environment. GM-CSF signaling through STAT3 and p38 MAPK and acid signaling through cAMP were required to activate myeloid cell ARG1 expression in a STAT6-independent manner. Importantly, breast tumor cell-derived GM-CSF promoted tumor progression by inhibiting host antitumor immunity, driving a significant accumulation of ARG1-expressing myeloid cells compared with lung and melanoma tumors with minimal GM-CSF expression. Blockade of tumoral GM-CSF enhanced the efficacy of tumor-specific adoptive T cell therapy and immune checkpoint blockade. Taken together, we show that breast tumor cell-derived GM-CSF contributes to the development of the immunosuppressive breast cancer microenvironment by regulating myeloid cell ARG1 expression and can be targeted to enhance breast cancer immunotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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31. Therapeutic effects of histone deacetylase inhibitors in a murine asthma model
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Xuan Zhao, Jian Kang, Yuan Ren, Menglu Li, Xinming Su, Na Yu, and Lingfei Kong
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0301 basic medicine ,medicine.medical_specialty ,Allergy ,Neurology ,Indoles ,Airway hyperresponsiveness ,Immunology ,Hydroxamic Acids ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Histone deacetylase ,Anti-Asthmatic Agents ,Bronchial asthma ,Lung ,Pharmacology ,Mice, Inbred BALB C ,business.industry ,Therapeutic effect ,Airway inflammation ,respiratory system ,medicine.disease ,Rheumatology ,Actins ,Asthma ,respiratory tract diseases ,Original Research Paper ,Histone Deacetylase Inhibitors ,Disease Models, Animal ,030104 developmental biology ,030220 oncology & carcinogenesis ,Airway Remodeling ,Cytokines ,Female ,Collagen ,Bronchial Hyperreactivity ,Airway ,business ,Bronchoalveolar Lavage Fluid - Abstract
Objective and design To investigate the therapeutic effects of various HDAC inhibitors on the development of chronic allergic airway disease in mice with airway inflammation, airway remodeling, and airway hyperresponsiveness. Subjects Wild-type BALB/C mice (N = 72). Treatment Tubastatin A HCl [TSA, a selective histone deacetylase 6 (HDAC6) inhibitor], PCI-34051 (a selective HDAC8 inhibitor), and givinostat (a broad-spectrum HDAC inhibitor that inhibits class I and class II HDACs and several pro-inflammatory cytokines). Methods Mice were divided into six groups: control, asthma, dexamethasone (positive control), TSA, PCI-34051, and givinostat (n = 12 per group). Twenty-four hours after OVA nebulization, airway hyperresponsiveness, inflammation, and remodeling were assessed. Results The chronic asthma mouse model produced typical airway inflammation, airway remodeling, and airway hyperresponsiveness. Administration of PCI-34051 and dexamethasone reduced the eosinophilic inflammation and airway hyperresponsiveness in asthma to reduce the airway remodeling. Treatment with Tubastatin A HCl reduced airway inflammation and was associated with decreased IL-4, IL-5 and total inflammatory cell count, as well as goblet cell metaplasia and subepithelial fibrosis; however, this outcome was not as effective as that with dexamethasone. TGF-β1 expression in the cytoplasm of airway epithelium of mice in the Tubastatin A HCl group was reduced and expression of α-SMA in the airway smooth muscle was also decreased. Conclusions The results suggested that treatment with HDAC inhibitors can reduce airway inflammation, airway remodeling, and airway hyperresponsiveness in chronic allergic airway disease in mice.
- Published
- 2016
32. Novel ERα positive breast cancer model with estrogen independent growth in the bone microenvironment
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Xinming Su, Aude Hélène Capietto, Roberta Faccio, Julie A. Allen, Deborah V. Novack, Robert D. Schreiber, Biancamaria Ricci, and Szeman Ruby Chan
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0301 basic medicine ,Male ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,medicine.drug_class ,skeletal metastasis ,Estrogen receptor ,Bone Neoplasms ,Breast Neoplasms ,bone ,endocrine resistance ,03 medical and health sciences ,Mice ,Breast cancer ,breast cancer ,Internal medicine ,Cell Line, Tumor ,medicine ,Tumor Microenvironment ,Animals ,Aromatase ,Neoplasm Metastasis ,Mice, Knockout ,biology ,business.industry ,Ovary ,Estrogen Receptor alpha ,Estrogens ,medicine.disease ,3. Good health ,030104 developmental biology ,Endocrinology ,Phenotype ,Oncology ,Cell culture ,Estrogen ,Drug Resistance, Neoplasm ,Cancer cell ,biology.protein ,Ovariectomized rat ,Cancer research ,Female ,Neoplasm Recurrence, Local ,business ,hormone resistance ,Receptors, Progesterone ,Neoplasm Transplantation ,Hormone ,Research Paper - Abstract
// Aude-Helene Capietto 1, 4, * , Szeman Ruby Chan 2, 5, * , Biancamaria Ricci 1 , Julie A. Allen 2 , Xinming Su 3 , Deborah V Novack 2, 3 , Robert D. Schreiber 2 , Roberta Faccio 1 1 Department of Orthopedics, Washington University School of Medicine, St. Louis, MO, USA 2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA 3 Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA 4 Present address: Genentech, South San Francisco, CA, USA 5 Present address: Janssen Research and Development, Johnson and Johnson, Spring House, PA, USA * These authors contributed equally to this work Correspondence to: Roberta Faccio, email: faccior@wustl.edu Keywords: skeletal metastasis, breast cancer, endocrine resistance, bone, hormone resistance Received: July 17, 2015 Accepted: May 09, 2016 Published: July 06, 2016 ABSTRACT Despite successful therapeutic options for estrogen receptor-α (ERα)+ breast cancer, resistance to endocrine therapy frequently occurs leading to tumor recurrence. In addition to intrinsic changes in the cancer cells, herein we demonstrate that tumor cell-microenvironment interactions can drive recurrence at specific sites. By using two ERα+ cell lines derived from spontaneous mammary carcinomas in STAT1−/− mice (SSM2, SSM3), we establish that the bone microenvironment offers growth advantage over primary site or lung in the absence of ovarian hormones. While SSM3 did not engraft at primary and skeletal locations in the absence of estrogen, SSM2 selectively grew in bone of ovariectomized mice and following administration of aromatase inhibitors. However, SSM2 growth remained hormone-dependent at extraskeletal sites. Unexpectedly, bone-residing SSM2 cells retained ERα expression and JAK2/STAT3 activation regardless of the hormonal status. These data position the bone microenvironment as a unique site for acquisition of tumor/estrogen independency and identify the first ERα+ hormone-independent tumor model in immunocompetent mice.
- Published
- 2016
33. Stromal-Initiated Changes in the Bone Promote Metastatic Niche Development
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David M. Ornitz, Yu Shi, Bhavna Murali, Xinming Su, Kathleen M. Leahy, Roberta Faccio, Margery Gang, Fanxin Long, Yujie Fu, Kory J. Lavine, Sheila A. Stewart, Xianmin Luo, Ali Zamani, Deborah V. Novack, Gregory D. Longmore, Katherine N. Weilbaecher, Andrew J. Loza, and Megan K. Ruhland
- Subjects
0301 basic medicine ,Stromal cell ,Bone Neoplasms ,Mice, Transgenic ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Mice ,03 medical and health sciences ,Breast cancer ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Neoplasm Metastasis ,Interleukin 6 ,lcsh:QH301-705.5 ,Cellular Senescence ,Tumor microenvironment ,Osteoblasts ,Interleukin-6 ,Mammary Neoplasms, Experimental ,Cancer ,food and beverages ,medicine.disease ,Neoplasm Proteins ,030104 developmental biology ,lcsh:Biology (General) ,Immunology ,Cancer research ,biology.protein ,Experimental pathology ,Female ,Cell aging - Abstract
SummaryMore than 85% of advanced breast cancer patients suffer from metastatic bone lesions, yet the mechanisms that facilitate these metastases remain poorly understood. Recent studies suggest that tumor-derived factors initiate changes within the tumor microenvironment to facilitate metastasis. However, whether stromal-initiated changes are sufficient to drive increased metastasis in the bone remains an open question. Thus, we developed a model to induce reactive senescent osteoblasts and found that they increased breast cancer colonization of the bone. Analysis of senescent osteoblasts revealed that they failed to mineralize bone matrix and increased local osteoclastogenesis, the latter process being driven by the senescence-associated secretory phenotype factor, IL-6. Neutralization of IL-6 was sufficient to limit senescence-induced osteoclastogenesis and tumor cell localization to bone, thereby reducing tumor burden. Together, these data suggest that a reactive stromal compartment can condition the niche, in the absence of tumor-derived signals, to facilitate metastatic tumor growth in the bone.
- Published
- 2016
34. Identification of histone acetylation in a murine model of allergic asthma by proteomic analysis.
- Author
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Yuan Ren, Menglu Li, Shiyao Bai, Lingfei Kong, and Xinming Su
- Published
- 2021
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35. Bone-induced expression of integrin β3 enables targeted nanotherapy of breast cancer metastases
- Author
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Yalin Xu, Dipanjan Pan, Grace Hu, Gregory C. Fox, Khalid S. Mohammad, Xiaoxia Yang, Joshua S. Novack, Deborah V. Novack, Alison K. Esser, Thomas J. Walsh, James A. J. Fitzpatrick, Anne H. Schmieder, Graham A. Colditz, Gabriel H. Lukaszewicz, David L. Waning, Katherine N. Weilbaecher, Gregory M. Lanza, Elizabeth Cordell, Xinming Su, Theresa A. Guise, and Michael H. Ross
- Subjects
0301 basic medicine ,CA15-3 ,Oncology ,Cancer Research ,medicine.medical_specialty ,Mice, Nude ,Bone Neoplasms ,Breast Neoplasms ,Docetaxel ,Article ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Transforming Growth Factor beta ,Internal medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Mice, Inbred BALB C ,biology ,business.industry ,Integrin beta3 ,Cancer ,Transforming growth factor beta ,medicine.disease ,Integrin alphaVbeta3 ,Metastatic breast cancer ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Nanoparticles ,Female ,Taxoids ,business ,medicine.drug ,Signal Transduction - Abstract
Bone metastases occur in approximately 70% of metastatic breast cancer patients, often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. In this study, we provide preclinical evidence for an antimetastatic therapy based on targeting integrin β3 (β3), which is selectively induced on breast cancer cells in bone by the local bone microenvironment. In a preclinical model of breast cancer, β3 was strongly expressed on bone metastatic cancer cells, but not primary mammary tumors or visceral metastases. In tumor tissue from breast cancer patients, β3 was significantly elevated on bone metastases relative to primary tumors from the same patient (n = 42). Mechanistic investigations revealed that TGFβ signaling through SMAD2/SMAD3 was necessary for breast cancer induction of β3 within the bone. Using a micelle-based nanoparticle therapy that recognizes integrin αvβ3 (αvβ3-MPs of ∼12.5 nm), we demonstrated specific localization to breast cancer bone metastases in mice. Using this system for targeted delivery of the chemotherapeutic docetaxel, we showed that bone tumor burden could be reduced significantly with less bone destruction and less hepatotoxicity compared with equimolar doses of free docetaxel. Furthermore, mice treated with αvβ3-MP-docetaxel exhibited a significant decrease in bone-residing tumor cell proliferation compared with free docetaxel. Taken together, our results offer preclinical proof of concept for a method to enhance delivery of chemotherapeutics to breast cancer cells within the bone by exploiting their selective expression of integrin αvβ3 at that metastatic site. Cancer Res; 77(22); 6299–312. ©2017 AACR.
- Published
- 2017
36. Association of glutathione S-transferase M1 and T1 genotypes with asthma: A meta-analysis.
- Author
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Xinming Su, Yuan Ren, Menglu Li, Lingfei Kong, Jian Kang, Su, Xinming, Ren, Yuan, Li, Menglu, Kong, Lingfei, and Kang, Jian
- Published
- 2020
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37. Research on High Temperature Protection Technology of Infrared Temperature Measuring Equipment in Space Environment.
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Zeyuan, Liu, Yonghong, Shang, Xinming, Su, Jing, Wen, and Boying, Lin
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- 2020
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38. New Cu3TeO6 Ceramics: Phase Formation and Dielectric Properties
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Xiao Li Zhu, Xinming Su, Zhonghua Wang, and Paula M. Vilarinho
- Subjects
Arrhenius equation ,Materials science ,Analytical chemistry ,Mineralogy ,Relative permittivity ,Dielectric ,Tellurate ,BI2O3-TIO2-TEO2 SYSTEM ,symbols.namesake ,chemistry.chemical_compound ,CUTEO3 ,chemistry ,CUTE2O5 ,visual_art ,visual_art.visual_art_medium ,symbols ,General Materials Science ,Dielectric loss ,CRYSTAL-STRUCTURE ,Ceramic ,Ceramic capacitor ,Temperature coefficient - Abstract
Targeting low temperature cofired ceramics (LTCC) applications and base-metal electrode multilayer ceramic capacitors (BME-MLCCs), ceramics of a new composition, tricopper tellurate (Cu3TeO6), are reported here. The crystal structure of Cu3TeO6 was determined to be cubic, Ia3, with the unit cell parameter a = 9.538 angstrom. The sequence of phase formation is proposed with the oxidation of tetravalent tellurium (Te4+) into hexavalent tellurium (Te6+) as a key step for the formation of Cu3TeO6. Ceramics sintered at 865 degrees C with densities of 94% exhibit two dielectric anomalies in the temperature dependence of the dielectric response, around -150 degrees C and +50 degrees C, respectively, accompanied by obvious frequency dispersion of the relative permittivity (epsilon(r)) and dielectric losses (tan delta), with an Arrhenius like behavior. A temperature stable dielectric region (near room temperature) formed between the two anomalies with epsilon(r) similar to 12 and tan delta similar to 0.01, and a very low positive temperature coefficient of the relative permittivity (TC epsilon(r)), 2.07 X 10(-4) degrees C-1, was obtained in the same region. The low temperature dielectric anomaly is associated with the possible mixed Cu+/Cu2+ valence in Cu3TeO6 ceramics, while the high temperature anomaly is attributed to point defect ordering, including V-O, Cu-Cu2+(+)',which might be formed during sintering. Therefore, Cu3TeO6 ceramics are of interest in view of not only the possible applications in BME-MLCCs, LTCC, and related technologies, but also for their possible compatibility with low cost abundant Cu electrodes.
- Published
- 2014
39. Characteristics and prediction of permian tight glutenite reservoirs in dinan 15 well block, junggar basin
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Xin Wei, Xinming Sun, Xuejiao Yuan, and Yiming Yang
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reservoir characteristics ,reservoir prediction ,upper wuerhe formation ,permian ,dongdaohaizi sag ,junggar basin ,Science - Abstract
Glutenite reservoirs are characterized by rapid lateral change, strong heterogeneity, and complex main controlling factors. This research aims to identify macro and micro characteristics of glutenite reservoirs and establish criteria for identifying favorable reservoirs studies. To this end, the tight sandy conglomerate of the Upper Wuerhe Formation in the Permian Upper Wuerhe Formation in the Dinan 15 well area of the eastern slope of the Dongdaohaizi sag in the Junggar Basin is studied. The core observation, physical property analysis, sensitivity analysis, casting thin section, scanning electron microscope and logging data are adopted to comprehensively analyze the characteristics of glutenite reservoirs. By integrating various reservoir characteristic parameters, this work constructed a new set of reservoir evaluation criteria to predict favorable areas for the Upper Wuerhe Formation in Dongdaohaizi Sag. The results show that the lithology of the Upper Wuerhe Formation in the Dinan 15 well area is dominated by gray glutenite; the reservoir is an ultra-low porosity and ultra-low permeability reservoir with moderately weak water sensitivity and weak velocity sensitivity. The reservoir space types of the layers are mainly intergranular pores; the shape of the mercury intrusion curve and the pore throat radius distribution of the samples show that the reservoir is skewed, poorly sorted, and has the characteristics of small pores and thin throats. This work constructed evaluation criteria for reservoirs from I to III by utilizing lithology, physical properties, sensitivity, reservoir space type, and microstructural characteristics as key parameters. The favorable reservoir distribution area is mainly located in the west of the block, which is the focus of the next exploration of the Upper Wuerhe Formation area. The research results improved understanding of glutenite reservoir characteristics and will serve as significant guidance for the oil and gas exploration in the Dinan 15 well area.
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- 2022
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40. Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance.
- Author
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Meyer, Melissa A., Baer, John M., Knolhoff, Brett L., Nywening, Timothy M., Panni, Roheena Z., Xinming Su, Weilbaecher, Katherine N., Hawkins, William G., Ma, Cynthia, Fields, Ryan C., Linehan, David C., Challen, Grant A., Faccio, Roberta, Aft, Rebecca L., and DeNardo, David G.
- Subjects
PANCREATIC cancer ,BREAST cancer ,INTERFERON regulatory factors ,BONE marrow ,CANCER invasiveness - Abstract
Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, whereby the expansion of immunosuppressive myeloid cells can impair tumor immunity. As myeloid cells and conventional dendritic cells (cDCs) are derived from the same progenitors, we postulated that myelopoiesis might impact cDC development. The cDC subset, cDC1, which includes human CD141
+ DCs and mouse CD103+ DCs, supports anti-tumor immunity by stimulating CD8+ T-cell responses. Here, to understand how cDC1 development changes during tumor progression, we investigated cDC bone marrow progenitors. We found localized breast and pancreatic cancers induce systemic decreases in cDC1s and their progenitors. Mechanistically, tumor-produced granulocytestimulating factor downregulates interferon regulatory factor-8 in cDC progenitors, and thus results in reduced cDC1 development. Tumor-induced reductions in cDC1 development impair anti-tumor CD8+ T-cell responses and correlate with poor patient outcomes. These data suggest immune surveillance can be impaired by tumor-induced alterations in cDC development. [ABSTRACT FROM AUTHOR]- Published
- 2018
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41. Vibration and Noise Analysis and Experimental Study of Rail Conveyor
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Nini Hao, Xinming Sun, Mengchao Zhang, Yuan Zhang, Xingyu Wang, and Xiaoting Yi
- Subjects
rail conveyor ,vibration noise ,spectrum analysis ,field experiments ,Chemical technology ,TP1-1185 - Abstract
The rail conveyor is a new type of energy-saving system for the long-distance transportation of bulk materials. Operating noise is an urgent problem that the current model faces. It will cause noise pollution and affect the health of workers. In this paper, the factors causing vibration and noise are analyzed by modeling the wheel-rail system and the supporting truss structure. Based on the built test platform, the system vibration of the vertical steering wheel, the track support truss, and the track connection were measured, and the vibration characteristics at different positions were analyzed. Based on the established noise and vibration model, the distribution and occurrence rules of system noise under different operating speeds and fastener stiffness conditions were obtained. The experimental results show that the vibration amplitude of the frame near the head of the conveyor is the largest. The amplitude under the condition of 2 m/s running speed at the same position is 4 times that under the condition of 1 m/s. At different welds of the track, the width and depth of the rail gap have a great influence on the vibration impact, which is mainly due to the impact of the uneven impedance at the track gap, and the greater the running speed, the more obvious the vibration impact. The simulation results show the trend of noise generation, the speed of the trolley, and the stiffness of the track fasteners have a positive effect on the generation of noise in the low-frequency region. The research results of this paper will play an important role in the noise and vibration analysis of rail conveyors and help to optimize the structure design of the track transmission system.
- Published
- 2023
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42. Prevalence of Comorbidities in Asthma and Nonasthma Patients.
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Xinming Su, Yuan Ren, Menglu Li, Xuan Zhao, Lingfei Kong, and Jian Kang
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- 2016
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43. The ADP receptor P2RY12 regulates osteoclast function and pathologic bone remodeling.
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Xinming Su, Floyd, Desiree H., Hughes, Alun, Jingyu Xiang, Schneider, Jochen G., Uluckan, Ozge, Heller, Emanuela, Hongju Deng, Wei Zou, Craft, Clarissa S., Kaiming Wu, Hirbe, Angela C., Grabowska, Dorota, Eagleton, Mark C., Townsley, Sarah, Collins, Lynne, Piwnica-Worms, David, Steinberg, Thomas H., Novack, Deborah V., and Conley, Pamela B.
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ADENOSINE diphosphate , *OSTEOCLASTS , *BONE remodeling , *OSTEOPOROSIS , *PURINERGIC receptors , *G protein coupled receptors , *BLOOD platelet aggregation - Abstract
The adenosine diphosphate (ADP) receptor P2RY12 (purinergic receptor P2Y, G protein coupled, 12) plays a critical role in platelet aggregation, and P2RY12 inhibitors are used clinically to prevent cardiac and cerebral thrombotic events. Extracellular ADP has also been shown to increase osteoclast (OC) activity, but the role of P2RY12 in OC biology is unknown. Here, we examined the role of mouse P2RY12 in OC function. Mice lacking P2ry12 had decreased OC activity and were partially protected from age-associated bone loss. P2ry12-/- OCs exhibited intact differentiation markers, but diminished resorptive function. Extracellular ADP enhanced OC adhesion and resorptive activity of WT, but not P2ry12-/-, OCs. In platelets, ADP stimulation of P2RY12 resulted in GTPase Ras-related protein (RAP1) activation and subsequent αIIbβ3 integrin activation. Likewise, we found that ADP stimulation induced RAP1 activation in WT and integrin β3 gene knockout (Itgb3-/-) OCs, but its effects were substantially blunted in P2ry12-/- OCs. In vivo, P2ry12-/- mice were partially protected from pathologic bone loss associated with serum transfer arthritis, tumor growth in bone, and ovariectomy-induced osteoporosis: all conditions associated with increased extracellular ADP. Finally, mice treated with the clinical inhibitor of P2RY12, clopidogrel, were protected from pathologic osteolysis. These results demonstrate that P2RY12 is the primary ADP receptor in OCs and suggest that P2RY12 inhibition is a potential therapeutic target for pathologic bone loss. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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44. Altered Cofactor Preference of Thermostable StDAPDH by a Single Mutation at K159
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Xiuzhen Gao, Qinyuan Ma, Huihui Song, Xinming Sun, Zhiyun Li, and Mingfei Liu
- Subjects
meso-diaminopimelate dehydrogenase ,d-amino acid ,thermostable enzyme ,cofactor engineering ,molecular dynamics simulations ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
D-amino acid production from 2-keto acid by reductive amination is an attractive pathway because of its high yield and environmental safety. StDAPDH, a meso-diaminopimelate dehydrogenase (meso-DAPDH) from Symbiobacterium thermophilum, was the first meso-DAPDH to show amination of 2-keto acids. Furthermore, StDAPDH shows excellent thermostability compared to other meso-DAPDHs. However, the cofactor of StDAPDH is NADP(H), which is less common than NAD(H) in industrial applications. Therefore, cofactor engineering for StDAPDH is needed. In this study, the highly conserved cofactor binding sites around the adenosine moiety of NADPH were targeted to determine cofactor specificity. Lysine residues within a loop were found to be critical for the cofactor specificity of StDAPDH. Replacement of lysine with arginine resulted in the activity of pyruvic acid with NADH as the cofactor. The affinity of K159R to pyruvic acid was equal with NADH or NADPH as the cofactor, regardless of the mutation. Molecular dynamics simulations revealed that the large steric hindrance of arginine and the interaction of the salt bridge between NADH and arginine may have restricted the free movement of NADH, which prompted the formation of a stable active conformation of mutant K159R. These results provide further understanding of the catalytic mechanism of StDAPDH and guidance for the cofactor engineering of StDAPDH.
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- 2020
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45. Temperature Prediction of Solar Array Vacuum Heat Test Based on Deep Belief Network.
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Hao Dong, Junwu Deng, Ziming Wang, Shuo Liang, and Xinming Su
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- 2019
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46. Experimental Verification of the Thermal Flutter Criterion for a Slender Cantilever Boom.
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Dengge Jin, Chao Fan, Jing Wang, Yanqiang Bi, Xinming Su, Guoqing Liu, and Zhihai Xiang
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- 2022
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47. Heparanase Blockade as a Novel Dual-Targeting Therapy for COVID-19.
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Jingyu Xiang, Mijia Lu, Min Shi, Xiaogang Cheng, Kwakwa, Kristin A., Davis, Jennifer L., Xinming Su, Bakewell, Suzanne J., Yuexiu Zhang, Fontana, Francesca, Yalin Xu, Veis, Deborah J., DiPersio, John F., Ratner, Lee, Sanderson, Ralph D., Noseda, Alessandro, Mollah, Shamim, Jianrong Li, and Weilbaecher, Katherine N.
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COVID-19 , *SARS-CoV-2 , *COVID-19 treatment , *HEPARANASE , *VIRUS diseases , *HEPARAN sulfate proteoglycans - Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused over 5 million deaths worldwide. Pneumonia and systemic inflammation contribute to its high mortality. Many viruses use heparan sulfate proteoglycans as coreceptors for viral entry, and heparanase (HPSE) is a known regulator of both viral entry and inflammatory cytokines. We evaluated the heparanase inhibitor Roneparstat, a modified heparin with minimum anticoagulant activity, in pathophysiology and therapy for COVID-19. We found that Roneparstat significantly decreased the infectivity of SARS-CoV-2, SARS-CoV-1, and retroviruses (human Tlymphotropic virus 1 [HTLV-1] and HIV-1) in vitro. Single-cell RNA sequencing (scRNA-seq) analysis of cells from the bronchoalveolar lavage fluid of COVID-19 patients revealed a marked increase in HPSE gene expression in CD681 macrophages compared to healthy controls. Elevated levels of HPSE expression in macrophages correlated with the severity of COVID-19 and the expression of inflammatory cytokine genes, including IL6, TNF, IL1B, and CCL2. In line with this finding, we found a marked induction of HPSE and numerous inflammatory cytokines in human macrophages challenged with SARS-CoV-2 S1 protein. Treatment with Roneparstat significantly attenuated SARS-CoV-2 S1 protein-mediated inflammatory cytokine release from human macrophages, through disruption of NF-k B signaling. HPSE knockdown in a macrophage cell line also showed diminished inflammatory cytokine production during S1 protein challenge. Taken together, this study provides a proof of concept that heparanase is a target for SARS-CoV-2-mediated pathogenesis and that Roneparstat may serve as a dual-targeted therapy to reduce viral infection and inflammation in COVID-19. IMPORTANCE The complex pathogenesis of COVID-19 consists of two major pathological phases: an initial infection phase elicited by SARS-CoV-2 entry and replication and an inflammation phase that could lead to tissue damage, which can evolve into acute respiratory failure or even death. While the development and deployment of vaccines are ongoing, effective therapy for COVID-19 is still urgently needed. In this study, we explored HPSE blockade with Roneparstat, a phase I clinically tested HPSE inhibitor, in the context of COVID-19 pathogenesis. Treatment with Roneparstat showed wide-spectrum anti-infection activities against SARS-CoV-2, HTLV-1, and HIV- 1 in vitro. In addition, HPSE blockade with Roneparstat significantly attenuated SARSCoV- 2 S1 protein-induced inflammatory cytokine release from human macrophages through disruption of NF-k B signaling. Together, this study provides a proof of principle for the use of Roneparstat as a dual-targeting therapy for COVID-19 to decrease viral infection and dampen the proinflammatory immune response mediated by macrophages. [ABSTRACT FROM AUTHOR]
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- 2022
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48. Hedgehog Signaling Inhibition Blocks Growth of Resistant Tumors through Effects on Tumor Microenvironment.
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Heller, Emanuela, Hurchla, Michelle A., Jingyu Xiang, Xinming Su, Chen, Sara, Schneider, Jochen, Kyu-Sang Joeng, Vidal, Marcos, Goldberg, Leah, Hongju Deng, Hornick, Mary C., Prior, Julie L., Piwnica-Worms, David, Fanxin Long, Cagan, Ross, and Weilbaecher, Katherine N.
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HEDGEHOG signaling proteins , *TUMORS , *CELL transformation , *CANCER , *STROMAL cells - Abstract
Hedgehog (Hh) signaling is implicated in bone development and cellular transformation. Here we show that inhibition of Hh pathway activity inhibits tumor growth through effects on the microenvironment. Pharmacologic inhibition of the Hh effector Smoothened (Smo) increased trabecular bone in vivo and inhibited osteoclastogenesis in vitro. In addition, enhanced Hh signaling due to heterozygosity of the Hh inhibitory receptor Patched (Ptchl+/-) increased bone resorption, suggesting direct regulation of osteoclast (OC) activity by the Hh pathway. Ptch+/- mice had increased bone metastatic and subcutaneous tumor growth, suggesting that increased Hh activation in host cells promoted tumor growth. Subcutaneous growth of Hh-resistant tumor cells was inhibited by LDE225, a novel orally bioavailable SMO antagonist, consistent with effects on tumor microenvironment. Knockdown of the Hh ligand Sonic Hh (SHH) in these cells decreased subcutaneous tumor growth and decreased stromal cell production of interleukin-6, indicating that tumor-derived Hh ligands stimulated tumor growth in a paracrine fashion. Together our findings show that inhibition of the Hh pathway can reduce tumor burden, regardless of tumor Hh responsiveness, through effects on tumor cells, OCs, and stromal cells within the tumor microenvironment. Hh may be a promising therapeutic target for solid cancers and bone metastases. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
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