A Genetic Polymorphism in TOX3 Is Associated with Survival of Gastric Cancer in a Chinese Population

Zhang, Xiaojing; Zhu, Hao; Wu, Xiaomin; Wang, Meilin; Gu, Dongying; Gong, Weida; Xu, Zhi; Tan, Yongfei; Gong, Yongling; Zhou, Jianwei; Tang, Cuiju; Tong, Na; Chen, Jinfei; Zhang, Zhengdong

doi:10.1371/journal.pone.0072186

Cited by 16 publications

(14 citation statements)

References 22 publications

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“…Dittmer et al observed that overexpression of TOX3 protects neuronal cells from cell death by inducting anti-apoptotic transcripts and inhibiting pro-apoptotic transcripts; it depends on the phosphorylated CREB or CITED1 within the transcriptionally active complex interacting with the native CREB and inducing the CREB-responsive BCL-2 promoter ( 18 ). Furthermore, there are certain studies demonstrating that TOX3 is correlated with other carcinomas ( 19 – 21 ). A study by Birkenkamp-Demtroder et al revealed that TOX3 overexpression in bladder cancer cells reduces cell proliferation and affects the interferon signaling pathway ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

TOX3 protein expression is correlated with pathological characteristics in breast cancer

et al. 2016

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TOX3 is a newly identified gene that has been observed to correlate with breast cancer by genome-wide association studies (GWAS) in recent years. In addition, it has been noted that single-nucleotide polymorphisms (SNPs) in the TOX3 gene have a strong correlation with estrogen receptor (ER)-positive tumors. However, the role of TOX3 in breast carcinoma development is still unclear. There are limited studies on the subject of TOX3 mRNA expression in breast tumors and little information on the variation of TOX3 protein expression in relation to the clinical pathological features in breast cancer and healthy tissues. In this study, we characterize the protein expression of TOX3 in breast tumors with respect to various clinical and pathological characteristics and explore the correlation between TOX3 protein expression and ER-positive tumors. A breast cancer tissue microarray containing 267 human breast tumors and 25 healthy controls, breast cancer cell lines (ZR-75-1, MDA-MB-231, MCF-7 and Bcap-37) with positive or negative ER expression, tumor tissues and matched controls were used to analyze the protein expression levels of TOX3 by immunohistochemistry, western blot analysis and quantitative polymerase chain reaction. Among the 267 breast tumor specimens, ER expression was detected in 66 tumor tissues. The expression levels of TOX3 increased in breast carcinoma tissue compared with controls, and were higher in advanced carcinoma (T3 and T4), lymph node metastases tissues (N2) and stage III tissues. Furthermore, TOX3 protein expression was more intense in ER-positive tumors, but did not demonstrate a statistical significance. However, it was significantly increased in ER-positive breast cancer cell lines (ZR-75-1, MCF-7 and Bcap-37) compared with the MDA-MB-231 cell line, which had ER-negative expression. Our findings provide support to the hypothesis that TOX3 has a strong correlation with the development of breast cancer. The current study is likely to assist in investigating the mechanisms involved in breast cancer development.

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Section: Introductionmentioning

confidence: 99%

TOX3 protein expression is correlated with pathological characteristics in breast cancer

et al. 2016

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“…Taking together, these findings could help to understand the mechanism of action of TOX in CTCL and provide clues to novel therapeutics for CTCL. Several strategies have been employed to enhance the efficacy of current treatments and to find new therapeutic options to improve survival and quality of life for patients with SS and other forms of advanced CTCL [19,20,30]. TOX encodes a high-mobility group family (HMG) domain binding nuclear protein which regulates the differentiation of developing T cells.…”

Section: Discussionmentioning

confidence: 99%

Molecular profiling of TOX-deficient neoplastic cells in cutaneous T cell lymphoma

Huang

Wang

et al. 2019

Arch Dermatol Res

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Cutaneous T cell lymphoma (CTCL) is a rare but potentially devastating primary cutaneous lymphoma. CTCL is characterized by localization of neoplastic T lymphocytes to the skin, with mycosis fungoides (MF) and its leukemic form, Sézary syndrome (SS) being the most common variants. Thymocyte selection-associated high-mobility group box (TOX) gene has been found to be highly expressed in MF and SS. It is reported that higher expression levels of TOX in patients will increase risks of disease progression and poor prognosis. However, the molecular events leading to these abnormalities have not been well understood. To better understand the molecular mechanism underlying TOX-mediated differentially expressed genes (DEGs) in CTCL, and to identify DEGs pathways triggered after knockdown of TOX gene in the CTCL cell line Hut78, we employed two shRNA-mediated lentiviruses to knock down TOX gene in the skin lymphoma cell line HuT78. RNA sequencing (RNAseq) analysis was applied to analyze DEGs, DEGs GO and their corresponding pathways. Knockdown of TOX can induce upregulation of 547 genes and downregulation of 649 genes, respectively. HOXC9 was the most significant downregulated gene. Most DEGs are enriched in malignancies and relate to the Wnt and mTOR signaling pathways, and therefore they can regulate cellular processes and induce different biological regulation. Transcriptome analysis of DEGs after knockdown of TOX in our study provides insights into the mechanism of TOX in CTCL and suggests candidate targets for therapy of CTCL.

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“…Besides, the efficacy of 5-Fu is positively associated with its action duration (Hu et al, 2013;Yoney et al, 2013). In general, the release time of 5-Fu wrapped with adjuvant is not more than 1 day, whereas that of sustained-release 5-Fu implantation is more than 10 days, which overcomes the disadvantage of conventional chemotherapeutic drugs with short action duration Zhang et al, 2013) . Such preparations can also be easily placed at any site of residual tumours during surgery and stably maintain a higher drug concentrations at the administered area for a long time, being conductive to killing the residual tumours not removed during surgery, micrometastases and intraperitoneal free cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Experimental Study on Sustained-release 5-Fluorouracil Implantation in Canine Peritoneum and Para-aortic Abdominalis

Guo

Nie²,

Shen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Objective: To observe local and systemic toxicity after sustained-release 5-fluorouracil (5-Fu) implantation in canine peritoneum and para-aortic abdominalis and the changes of drug concentration in the local implanted tissue with time. Methods: 300 mg sustained-release 5-Fu was implanted into canine peritoneum and para-aorta abdominalis. Samples were taken 3, 5, 7 and 10 days after implantation for assessment of changes and systemic reactions. High performance liquid chromatography was applied to detect the drug concentrations of peritoneal tissue at different distances from the implanted site, lymphatic tissue of para-aortic abdominalis, peripheral blood and portal venous blood. Results: 10 days after implantation, the drug concentrations in the peritoneum, lymphatic tissue and portal vein remained relatively high within 5 cm of the implanted site. There appeared inflammatory reaction in the local implanted tissue, but no visible pathological changes such as cell degeneration and necrosis, and systemic reaction like anorexia, nausea, vomiting and fever. Conclusions: Sustained-release 5-Fu implantation in canine peritoneum and para-aortic abdominalis can maintain a relatively high tumourinhibiting concentration for a longer time in the local implanted area and portal vein, and has mild local and systemic reactions. Besides, it is safe and effective to prevent or treat recurrence of gastrointestinal tumours and liver metastasis.

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A Genetic Polymorphism in TOX3 Is Associated with Survival of Gastric Cancer in a Chinese Population

Cited by 16 publications

References 22 publications

TOX3 protein expression is correlated with pathological characteristics in breast cancer

TOX3 protein expression is correlated with pathological characteristics in breast cancer

Molecular profiling of TOX-deficient neoplastic cells in cutaneous T cell lymphoma

Experimental Study on Sustained-release 5-Fluorouracil Implantation in Canine Peritoneum and Para-aortic Abdominalis

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