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Search results for: ADAMTS8

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#33622125   2021/02/24 To Up

Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer.

Cetaceans are the longest-living species of mammals and the largest in the history of the planet. They have developed mechanisms against diseases such cancer, although the underlying molecular bases of these remain unknown. The goal of this study was to investigate the role of natural selection in the evolution of 1077 tumour suppressor genes (TSGs) in cetaceans. We used a comparative genomic approach to analyse two sources of molecular variation in the form of / rates and gene copy number variation. We found a signal of positive selection in the ancestor of cetaceans within the gene, an important regulator of DNA damage, tumour dissemination and immune system. Further, in the ancestor of baleen whales, we found six genes exhibiting positive selection relating to diseases such as breast carcinoma, lung neoplasm () and leukaemia (). The TSGs turnover rate (gene gain and loss) was almost 2.4-fold higher in cetaceans when compared with other mammals, and notably even faster in baleen whales. The molecular variants in TSGs found in baleen whales, combined with the faster gene turnover rate, could have favoured the evolution of their particular traits of anti-cancer resistance, gigantism and longevity. Additionally, we report 71 genes with duplications, of which 11 genes are linked to longevity (e.g. and ) and are important regulators of senescence, cell proliferation and metabolism. Overall, these results provide evolutionary evidence that natural selection in TSGs could act on species with large body sizes and extended lifespan, providing novel insights into the genetic basis of disease resistance.
Daniela Tejada-Martinez, João Pedro de Magalhães, Juan C Opazo

2774 related Products with: Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer.



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#33227396   2020/11/20 To Up

Low-intensity pulsed ultrasound promotes aggrecan expression via ZNT-9 in temporomandibular joint chondrocytes.

Temporomandibular joint osteoarthritis (TMJ-OA) is one of the most common joint diseases. It causes severe pain and poor quality of life. One key feature of TMJ-OA is degeneration of the chondrocyte extracellular matrix (ECM). Low-intensity pulsed ultrasound (LIPUS) can promote the synthesis of ECM in cartilage. However, the exact mechanism is still unclear. We aimed to explore the mechanism by which LIPUS promotes the expression of aggrecan in chondrocytes. In vivo, TMJ-OA rats established by unilateral occlusal trauma were treated with LIPUS. In our RNA sequencing data, we found that ADAMTS-8 was downregulated by LIPUS. In vitro, chondrocytes were treated with IL-1β and LIPUS. Among Zn exporters, ZNT-9 was specifically upregulated by LIPUS. Activation of ZNT-9 by LIPUS downregulated ECM-degrading enzymes (MMP-3, ADAMTS-5 and ADAMTS-8) and metal regulatory transcription factor-1 (MTF-1) and upregulated aggrecan in chondrocytes. Furthermore, ZNT-9 knockdown caused upregulation of MMP-3, ADAMTS-5, ADAMTS-8 and MTF-1, with concomitant downregulation of aggrecan. The opposite results were obtained after ZNT-9 overexpression. Our experiments demonstrate that LIPUS protects chondrocytes by increasing the expression of aggrecan through ZNT-9.
Dong He, Jing Wang, Yanhua Li, Gaoyi Wu, Guoxiong Zhu, Lei Chen

2284 related Products with: Low-intensity pulsed ultrasound promotes aggrecan expression via ZNT-9 in temporomandibular joint chondrocytes.

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#33054388   2020/10/15 To Up

Inhibits Progression of Esophageal Squamous Cell Carcinoma.

A disintegrin and metallopeptidase with thrombospondin motifs (ADAMTSs), which is frequently dysregulated in cancers and is involved in carcinogenesis and cancer progression. The present study identified that ADAMTS8 expression is downregulated in esophageal squamous cell carcinoma (ESCC) tissues when compared with nontumor tissue. The expression of ADAMTS8 is closely associated with clinical stage and lymph node metastasis in patients with ESCC. Furthermore, functional studies have shown that overexpression could reduce abilities of proliferation, migration, and invasion and promote apoptosis of ESCC cells. Meanwhile, monocyte chemotactic protein-1 and interleukin-6 are markedly deregulated by overexpression. Consistently, data showed that overexpression led to a reduction in tumor growth. These results indicate that altering expression could modify the outcomes of ESCC by inhibiting cell proliferation and invasion, while promoting the apoptosis of ECSS cells. Thus, represents a potential therapeutic target for ESCC therapy.
Zhonglin Wu, Yanjun Shi, Shuguang Ren, Yingchao Ju, Yueyang Hu, Jianhua Wu

1954 related Products with: Inhibits Progression of Esophageal Squamous Cell Carcinoma.

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#32904790   2020/08/21 To Up

ADAMTS8 Inhibits Cell Proliferation and Invasion, and Induces Apoptosis in Breast Cancer.

A disintegrin and metallopeptidase with thrombospondin motifs (ADAMTSs), whose expression is dysregulated in various cancers, is implicated in cancer development. Herein, we aimed to investigate the functional role of ADAMTS8 in breast cancer (BC) and explore the underlying mechanisms.
Kun Zhang, Ruoxi Tian, Guanglin Wang, Jianfeng Zhang, Hongqin Ma, Xuhua Hu, Jinchuan Xi, Guiying Wang

1461 related Products with: ADAMTS8 Inhibits Cell Proliferation and Invasion, and Induces Apoptosis in Breast Cancer.

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#32855969   2020/08/14 To Up

Transcriptomics Study to Determine the Molecular Mechanism by which sIL-13R2-Fc Inhibits Caudal Intervertebral Disc Degeneration in Rats.

Intervertebral disc degeneration is related to tissue fibrosis. ADAMTS can degrade the important components of the ECM during the process of intervertebral disc degeneration, ultimately resulting in the loss of intervertebral disc function. sIL-13R2-Fc can inhibit fibrosis and slow down the degeneration process, but the mechanism involved remains unclear.
Xin Wang, Jianshi Tan, Junhao Sun, Pengzhong Fang, Jinlei Chen, Wen Yuan, Huajiang Chen, Yang Liu

1345 related Products with: Transcriptomics Study to Determine the Molecular Mechanism by which sIL-13R2-Fc Inhibits Caudal Intervertebral Disc Degeneration in Rats.

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#32774167   2020/08/05 To Up

Significance of tumor mutation burden combined with immune infiltrates in the progression and prognosis of ovarian cancer.

Ovarian cancer (OC) is the most malignant tumor in the female reproductive system. About 75% of OC in complete remission of clinical symptoms still develop a recurrence. Therefore, searching for new treatment methods plays an important role in improving the prognosis of OC.
Fangfang Bi, Ying Chen, Qing Yang

1304 related Products with: Significance of tumor mutation burden combined with immune infiltrates in the progression and prognosis of ovarian cancer.



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#32296631   2020/03/31 To Up

Bioinformatics Identified 17 Immune Genes as Prognostic Biomarkers for Breast Cancer: Application Study Based on Artificial Intelligence Algorithms.

An increasing body of evidence supports the association of immune genes with tumorigenesis and prognosis of breast cancer (BC). This research aims at exploring potential regulatory mechanisms and identifying immunogenic prognostic markers for BC, which were used to construct a prognostic signature for disease-free survival (DFS) of BC based on artificial intelligence algorithms. Differentially expressed immune genes were identified between normal tissues and tumor tissues. Univariate Cox regression identified potential prognostic immune genes. Thirty-four transcription factors and 34 immune genes were used to develop an immune regulatory network. The artificial intelligence survival prediction system was developed based on three artificial intelligence algorithms. Multivariate Cox analyses determined 17 immune genes (ADAMTS8, IFNG, XG, APOA5, SIAH2, C2CD2, STAR, CAMP, CDH19, NTSR1, PCDHA1, AMELX, FREM1, CLEC10A, CD1B, CD6, and LTA) as prognostic biomarkers for BC. A prognostic nomogram was constructed on these prognostic genes. Concordance indexes were 0.782, 0.734, and 0.735 for 1-, 3-, and 5- year DFS. The DFS in high-risk group was significantly worse than that in low-risk group. Artificial intelligence survival prediction system provided three individual mortality risk predictive curves based on three artificial intelligence algorithms. In conclusion, comprehensive bioinformatics identified 17 immune genes as potential prognostic biomarkers, which might be potential candidates of immunotherapy targets in BC patients. The current study depicted regulatory network between transcription factors and immune genes, which was helpful to deepen the understanding of immune regulatory mechanisms for BC cancer. Two artificial intelligence survival predictive systems are available at https://zhangzhiqiao7.shinyapps.io/Smart_Cancer_Survival_Predictive_System_16_BC_C1005/ and https://zhangzhiqiao8.shinyapps.io/Gene_Survival_Subgroup_Analysis_16_BC_C1005/. These novel artificial intelligence survival predictive systems will be helpful to improve individualized treatment decision-making.
Zhiqiao Zhang, Jing Li, Tingshan He, Jianqiang Ding

1870 related Products with: Bioinformatics Identified 17 Immune Genes as Prognostic Biomarkers for Breast Cancer: Application Study Based on Artificial Intelligence Algorithms.

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#32033751   2020/02/06 To Up

ADAMTS8 is frequently down-regulated in colorectal cancer and functions as a tumor suppressor.

Colorectal cancer (CRC) is known for being a great threat to human health due to its high incidence and mortality. ADAMTS8 that belongs to the zinc metalloproteinases family acts as a tumor suppressor and is silenced by CpG methylation in several carcinomas through previous studies, but its functions in CRC remain unknown. In this report, we analyzed its expression in CRC cell lines and primary CRC tumor tissues. The results showed that ADAMTS8 was significantly down-regulated in CRC cell lines and primary tumor tissues and its expression was restored in Lovo cell lines with treatment DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine and TSA. Over-expression of ADAMTS8 in HCT116 and HT-29 resulted in inhibited cell proliferation and induced apoptosis. We also observed that ADAMTS8 suppressed cell invasion and migration. In addition, ADAMTS8 induced cell cycle arrest in G2/M phase. Furthermore, we found that ADAMTS8 led to the decrease of BCL-XL, phospho-GSK3β, β-catenin and c-myc as well as increase of cleaved caspase-9, Bax and PARP. Our findings suggest that ADAMTS8 may be considered as a functional tumor suppressor gene in CRC and has the potential to be developed as a valuable biomarker.
Lin Li, Shiyun Yuan, Xunping Zhao, Tao Luo

1701 related Products with: ADAMTS8 is frequently down-regulated in colorectal cancer and functions as a tumor suppressor.

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#31782329   2019/11/29 To Up

The investigation of serum levels of ADAMTS 5 and 8 (the A disintegrin and metalloproteinase with thrombospondin motifs) in the etiology of endometrial cancer.

The aim of this study was to investigate the serum levels of the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5 and 8 in patients diagnosed with endometrial cancer. Our study included 41 patients diagnosed with endometrial cancer. The control group consisted of 41 patients diagnosed with benign endometrial pathology. The serum samples were centrifuged and stored at -80 °C. The serum levels of ADAMTS were significantly higher (<.001), whereas the levels of ADAMTS 8 were significantly lower in patients diagnosed with cancer (<.001). In addition to the presence of known factors in the aetiology of endometrial cancer, the effect of inflammatory factors and some new proteins has centred on the causes of tumourigenesis in recent years. In this sense, these proteins, called the ADAMTS, are the source of new studies.Impact Statement When the recent studies about endometrial cancer are evaluated, it is seen that the effects of chronic inflammation and cytokines have gained importance in its aetiology. The A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) gene family consist of 19 proteases that play essential role in the formation of the extracellular matrix (ECM) and interact with inflammatory cytokines. These proteases and their substrates provide a wide range of functions in different tissues, including ECM remodelling, angiogenesis, fibrosis and coagulation. ADAMTS 5, which causes the degradation of the ECM with Aggrecanase activity, was found to be significantly higher in patients diagnosed with cancer and ADAMTS 8 with anti-angiogenesis activity was significantly lower in patients diagnosed with endometrial cancer. In this study, it is understood that the effect of inflammatory mediators is remarkably important in the aetiology of endometrial cancer, as in many types of organ specific cancer.
Ercan Yilmaz, Rauf Melekoglu, Cagatay Taskapan, Fatma Olmez Budak, Serhat Toprak

1476 related Products with: The investigation of serum levels of ADAMTS 5 and 8 (the A disintegrin and metalloproteinase with thrombospondin motifs) in the etiology of endometrial cancer.

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#31556812   2019/09/26 To Up

ADAMTS8 Promotes the Development of Pulmonary Arterial Hypertension and Right Ventricular Failure: A Possible Novel Therapeutic Target.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling with aberrant pulmonary artery smooth muscle cells (PASMCs) proliferation, endothelial dysfunction, and extracellular matrix remodeling.
Junichi Omura, Kimio Satoh, Nobuhiro Kikuchi, Taijyu Satoh, Ryo Kurosawa, Masamichi Nogi, Tomohiro Ohtsuki, Md Elias Al-Mamun, Mohammad Abdul Hai Siddique, Nobuhiro Yaoita, Shinichiro Sunamura, Satoshi Miyata, Yasushi Hoshikawa, Yoshinori Okada, Hiroaki Shimokawa

1908 related Products with: ADAMTS8 Promotes the Development of Pulmonary Arterial Hypertension and Right Ventricular Failure: A Possible Novel Therapeutic Target.

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