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Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han population of Northern

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《医学前沿（英文）》 2014年 第8卷 第1期   页码 113-117 doi: 10.1007/s11684-014-0310-x

摘要：

Papillary thyroid carcinoma (PTC) is one of the most common tumors of the thyroid gland. The common risk factors of PTC include ionizing radiation, positive family history, and thyroid nodular disease. PTC was identified in Europeans by conducting a genome-wide association study, and a strong association signal with PTC was observed in rs944289 and NKX2-1 (located at the 14q13.3 locus), which was probably the genetic risk factor of PTC. This study aimed to examine the association of this gene with PTC in Chinese. A total of 354 patients with PTC and 360 healthy control subjects from the Han population of Northern China were recruited in the study. These individuals were genotyped to determine rs12589672, rs12894724, rs2076751, and rs944289. The association of rs944289 with PTC was obtained (C vs. T, P=0.027, OR=1.264, 95% CI=1.026-1.557; and C/C-C/T vs. T/T, P=0.034, OR=1.474, 95% CI=1.028-2.112). Conducting a subgroup analysis, we found a marginal difference in the allele frequency distribution of rs944289 (adjusted P=0.062) between the patients with PTC and multi-nodular goiter and the control subjects. We also observed an interaction (P=0.029; OR=2.578, 95% CI=1.104-6.023) between rs944289 and diabetes in patients with PTC. In conclusion, rs944289 was associated with an increased risk of PTC in the Han population of Northern China, but no clear association was observed in either of the tag single nucleotide polymorphisms of NKX2-1.

关键词： NKX2-1     papillary thyroid carcinoma     the Han population of Northern China     association    

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mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroidcarcinoma

《医学前沿（英文）》 doi: 10.1007/s11684-023-0999-5

摘要： Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson’s correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial–to–mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.

关键词： thyroid carcinoma     mesenchymal stem cell     extracellular vesicle     GTF2I     FAT1     CDK4    

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The effect of orbital radiation therapy on thyroid-associated orbitopathy complicated with dysthyroid

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《医学前沿（英文）》 2017年 第11卷 第3期   页码 359-364 doi: 10.1007/s11684-017-0528-5

摘要：

Thyroid-associated orbitopathy (TAO) is an inflammatory autoimmune disorder. The most serious complication of TAO is dysthyroid optic neuropathy (DON), which can lead to permanent vision loss because of volume expansion in the orbital apex. Orbital radiation therapy (ORT) is an anti-inflammatory treatment used in the treatment of active TAO. Clinical studies support radiotherapy as having a modest effect on DON, and early radiotherapy may protect against disease progression to DON. Current studies suggest that radiotherapy is generally safe. However, risks still exist in some cases. The possible effects of radiotherapy on TAO, especially complicated with DON, are reviewed. The effects of radiotherapy on DON are not completely known, and evidence from standardized, prospective, and multicenter clinical trials is still lacking.

关键词： thyroid-associated orbitopathy     dysthyroid optic neuropathy     orbital radiation therapy    

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Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma and

《医学前沿（英文）》 2023年 第17卷 第1期   页码 132-142 doi: 10.1007/s11684-022-0938-x

摘要： Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.

关键词： nasopharyngeal carcinoma     WGCNA     RFC4     proliferation    

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Analyses of levels of thyroid hormones and its receptor expression in puerperants and newborns from an

JU Ying, CHEN Lan, JIANG Qi, YANG Kedi, CHEN Xuemin, XU Guojian, LI Liping

《医学前沿（英文）》 2008年 第2卷 第3期   页码 276-282 doi: 10.1007/s11684-008-0052-8

摘要： In this study, the serum levels, including thyroid hormones free triiodothyronine (FT), free thyroxine(FT),thyroid stimulating hormone(TSH)among the subjects from the exposed group ( = 48) and the control group ( = 45) were detected by immuno radiometric assay (IRMA). The expression levels of TR?1, TR?1, TSHR mRNA in placentas and umbilical cords were detected by fluorescent quantitative real-time PCR (FQ-PCR). The correlations between the thyroid hormone levels in maternal serum and umbilical serum, and between the expression levels of its receptors mRNA in placentas and umbilical cords were determined. We found that the FT levels of both maternal serum and umbilical cord serum in the exposed group were lower than those in the control ( < 0.05). However, the increased TSH levels in the exposed group had statistically significance compared to those in the control group ( < 0.05). The TR?1 and TR?1 mRNA levels both in placentas and umbilical cords in the exposed group were lower than those in the control group ( < 0.05 and 0.01). However, the TSHR mRNA levels in the exposed group were significantly different compared to those in the control group ( < 0.01). The serum FT4 and TSH levels of parturient women were positively correlated with those of the newborns in both groups ( < 0.05 and 0.01). The mRNA levels of TR?1, TR?1 and TSHR in the placentas were positively correlated with those in umbilical cords in both groups ( < 0.01). The findings suggest that some environmental pollutants existing in the electronic waste (e-waste) dismantling region may affect the health of local parturient women and newborns, representing changes both in serum levels of thyroid hormones and in mRNA expression of its receptors.

关键词： control     immuno radiometric     FT     TSH     exposed    

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The impact of hypoxia in hepatocellular carcinoma metastasis

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《医学前沿（英文）》 2014年 第8卷 第1期   页码 33-41 doi: 10.1007/s11684-013-0301-3

摘要：

Hypoxia is a common phenomenon in hepatocellular carcinoma (HCC). Hypoxia stabilizes transcription factor, hypoxia-inducible factor (HIF), to activate gene transcription. Expression of HIF is closely associated with metastasis and poor prognosis in HCC. HIF mediates expression of genes that are involved in every step of HCC metastasis including epithelial-mesenchymal transition, invasion of the extracellular matrix, intravasation, extravasation, and secondar y growth of the metastases. Because HIF is the central regulator of HCC metastasis, HIF inhibitors are attractive tools when used alone or as combined treatment to curb HCC metastasis. This review will summarize the current findings on the impact of hypoxia/HIF in HCC, with a particular focus on cancer metastasis.

关键词： hypoxia     hepatocellular carcinoma (HCC)     metastasis     hypoxia-inducible factor (HIF)    

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Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during

Wei Wang, Shuqin Jiang, Zhirui Cui, Xiangyang Luo, Lingli Shi, Heli Zheng

《医学前沿（英文）》 2018年 第12卷 第5期   页码 580-585 doi: 10.1007/s11684-017-0585-9

摘要：

This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5–3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.

关键词： therapeutic     idiopathic short-stature children     free T4     the first year     recombinant human growth hormone    

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Atypical pituitary hormone–target tissue axis

《医学前沿（英文）》 2023年 第17卷 第1期   页码 1-17 doi: 10.1007/s11684-022-0973-7

摘要： A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an “atypical pituitary hormone–target tissue axis.” This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the “atypical pituitary hormone–target tissue axis” could enable the identification of novel therapeutic targets for metabolic diseases.

关键词： thyroid-stimulating hormone     follicle-stimulating hormone     luteinizing hormone     adrenocorticotrophic hormone     prolactin    

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Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

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《医学前沿（英文）》 2014年 第8卷 第1期   页码 24-32 doi: 10.1007/s11684-014-0312-8

摘要：

In this review, we summarize the novel findings from our series of studies on the leading metastasis-related gene, osteopontin (OPN). In our previous gene expression profiling study, OPN was identified as one of the leading genes associated with the metastasis of hepatocellular carcinoma (HCC). We focused on OPN to evaluate its prognostic values and important roles in HCC metastasis. A retrospective study of large cohorts of HCC patients demonstrated that plasma OPN level was one of the leading independent prognostic factors for HCC patients, even in the early stage of HCC, and could serve as a surrogate serologic biomarker for monitoring the treatment response and tumor recurrence after HCC resection. Using both in vitro and in vivoinvestigations, we found that OPN has an important role in metastasis and tumor growth of HCC and is an attractive potential therapeutic target for combating HCC metastasis. We also found that OPN+ HCC cells have much more amplifications at chromosomal regions, and promoter polymorphisms are important in the regulation of OPN expression and tumor growth and lung metastasis of HCC.

关键词： osteopontin (OPN)     hepatocellular carcinoma     metastasis     prognosis     therapeutic target     biomarker     genetic polymorphism    

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Natural killer cells in hepatocellular carcinoma: current status and perspectives for future immunotherapeutic

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 509-521 doi: 10.1007/s11684-017-0546-3

摘要：

Hepatocellular carcinoma (HCC) is currently the fifth most common malignancy and the third leading cause of cancer-related mortalities worldwide. In the last few years, treatments for HCC have significantly improved from a mere surgical resection to a series of minimally invasive therapies and targeted drugs. However, recurrence frequently occurs even upon curative therapeutics, and drug therapies generally produce disappointing results, with the overall prognosis dismal. This challenging clinical scenario warrants new effective and life-prolonging strategies for patients with HCC. Compelling evidence suggests that NK cells play a critical role in the immune function of the liver and in the immune defenses against HCC, indicating that HCC might be an ideal target for NK cell-based immunotherapies. To obtain comprehensive insights into the putative influence of NK cells on HCC, this paper summarizes current knowledge on NK cells in HCC and discusses the usefulness and prospects of NK cell-based immunotherapies. Critical issues that require consideration for the successful clinical translation of NK cell-based therapies are also addressed. If appropriately used and further optimized, NK cell-based therapies could dominate important roles in the future immunotherapeutic market of HCC.

关键词： natural killer cell     hepatocellular carcinoma     immunotherapy    

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Effect of traditional Chinese medicine combined with Western therapy on primary hepatic carcinoma: a

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《医学前沿（英文）》 2017年 第11卷 第2期   页码 191-202 doi: 10.1007/s11684-017-0512-0

摘要：

Primary hepatic carcinoma (PHC) is a common malignant tumor in China. Cancer is comprehensively treated with various therapeutic regimes, including traditional Chinese medicine (TCM). TCM has been widely used to improve the quality of life, delay the time of cancer progression, and prolong the median survival time. This systematic review with meta-analysis aimed to assess the effect of TCM combined with Western therapy on primary hepatic carcinoma. A comprehensive literature search was conducted in six databases, including CNKI, VIP, Wan-Fang Database, CBM, PubMed, and Cochrane library. A total of 44 randomized controlled trials (RCTs) involving 3429 participants suffering from PHC were selected. Meta-analysis results indicated that the overall effect of TCM and Western integrative treatment on PHC was higher than that of Western intervention alone, which can postpone tumor recurrence and metastasis and prolong the overall survival time of patients with PHC. Although the obtained evidence remained weak because of the poor methodological quality of the included studies, this review provided relevant data supporting the efficacy and safety of TCM combined with Western therapies. In future research, individual RCT studies should incorporate accepted standards for trial design and reporting, proper outcome indicators according to international standards, blinding in allocation concealment, and valid follow-up periods.

关键词： traditional Chinese medicine     primary hepatic carcinoma     meta-analysis    

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Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis

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《医学前沿（英文）》 2016年 第10卷 第2期   页码 183-190 doi: 10.1007/s11684-016-0440-4

摘要：

We performed weighted gene coexpression network analysis (WGCNA) to gain insights into the molecular aspects of hepatocellular carcinoma (HCC). Raw microarray datasets (including 488 samples) were downloaded from the Gene Expression Omnibus (GEO) website. Data were normalized using the RMA algorithm. We utilized the WGCNA to identify the coexpressed genes (modules) after non-specific filtering. Correlation and survival analyses were conducted using the modules, and gene ontology (GO) enrichment was applied to explore the possible mechanisms. Eight distinct modules were identified by the WGCNA. Pink and red modules were associated with liver function, whereas turquoise and black modules were inversely correlated with tumor staging. Poor outcomes were found in the low expression group in the turquoise module and in the high expression group in the red module. In addition, GO enrichment analysis suggested that inflammation, immune, virus-related, and interferon-mediated pathways were enriched in the turquoise module. Several potential biomarkers, such as cyclin-dependent kinase 1 (CDK1), topoisomerase 2α (TOP2A), and serpin peptidase inhibitor clade C (antithrombin) member 1 (SERPINC1), were also identified. In conclusion, gene signatures identified from the genome-based assays could contribute to HCC stratification. WGCNA was able to identify significant groups of genes associated with cancer prognosis.

关键词： hepatocellular carcinoma     coexpression     module     microarray     prognosis    

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Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

Amy Lee, Fa-Chyi Lee

《医学前沿（英文）》 2020年 第14卷 第3期   页码 273-283 doi: 10.1007/s11684-019-0728-2

摘要： In terms of global cancer-related deaths, hepatocellular carcinoma (HCC) has the fourth highest mortality rate. Up until 2017, treatment of advanced HCC was largely limited to sorafenib, an oral tyrosine kinase inhibitor, with little to no success in the development of alternative treatment options. However, in the past two years, there has been an unprecedented increase in both the number and type of treatment options available for HCC. As of 2019, the US FDA has approved four oral tyrosine kinase inhibitors, two immune checkpoint inhibitors, and one anti-angiogenesis antibody for the treatment of HCC. Even with this new variety, systemic treatment of advanced HCC remains largely unsatisfactory, and the median survival rate stands at approximately one year. The expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in 2019. The use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or anti-angiogenesis medications is the current clinical research trend, the results of which are eagerly anticipated. Despite limited progress in survival, HCC research is currently experiencing a period of growth and innovation, and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.

关键词： hepatocellular carcinoma     tyrosine kinase inhibitor     check point inhibitor     anti-angiogenesis    

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甲状腺乳头状癌菌群失调及与肿瘤信号通路异常的相关性研究 Article

喻爽, 丁彦强, 王雪洁, Siu Kin Ng, 曹思婷, 刘伟鑫, 郭朱明, 谢宇彬, 洪澍彬, 许丽霞, 李晓星, 李杰, 吕伟明, 彭穗, 李延兵, 沈祖尧, 于君, 肖海鹏

《工程（英文）》 2023年 第28卷 第9期   页码 179-192 doi: 10.1016/j.eng.2023.01.007

摘要：

研究表明微生态失调在多种肿瘤的发生发展中起至关重要的作用。然而，对于甲状腺肿瘤中细菌是否参与肿瘤的发生仍不清楚。本研究中，我们旨在探索甲状腺组织中的菌群特征及其对甲状腺乳头状癌（PTC）的作用。我们同时对 340 例PTC和甲状腺良性结节 （BTN） 患者的肿瘤组织及其邻近正常组织进行菌群分析和转录组测序。在PTC、BTN及其邻近无肿瘤组织中鉴定出明显不同的菌群特征。我们通过免疫组化染色、细菌原位杂交和电镜观察验证了甲状腺组织内细菌的存在。与BTN相比，我们发现在PTC中有17个菌属存在显著丰度差异，其中PTC中富集菌Rhodococcus、Neisseria、Streptococcus、Halomonas和Devosia存在促癌作用；以及丰度降低的Amycolatopsis则可能有抑癌作用。这些丰度存在明显差异的细菌可以鉴别PTC组织（PTC-T）与BTN组织（BTN-T），曲线下面积（AUC）为81.66%。微生物网络分析表明，PTC组织内细菌间的相互关联性高于BTN组织。同时，在合并桥本甲状腺炎组织的PTC中发现与免疫相关的菌属（Erwinia、Bacillus 和 Acinetobacter）明显富集。此外，我们联合转录组测序分析提示PTC富集菌与肿瘤相关信号通路的关键基因如BRAF、KRAS、IRAK4、CTNNB1、PIK3CA、MAP3K7 和 EGFR存在正相关性。总的来说，我们的研究结果表明，甲状腺肿瘤组织内存在菌群失调，并可能通过肿瘤相关信号通路参与PTC的发生。

关键词： 甲状腺乳头状癌     甲状腺良性结节     细菌     转录组     桥本甲状腺炎    

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Progress and challenges in RET-targeted cancer therapy

《医学前沿（英文）》 2023年 第17卷 第2期   页码 207-219 doi: 10.1007/s11684-023-0985-y

摘要： The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

关键词： pralsetinib     selpercatinib     RET-alteration     lung cancer     thyroid cancer     tumor-agnostic therapy     drug resistance    

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标题 作者 时间 类型 操作

Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han population of Northern

null

期刊论文

mesenchymal stem cells promotes the expression of tumor-suppressive FAT1 and inhibits stemness maintenance in thyroidcarcinoma

期刊论文

The effect of orbital radiation therapy on thyroid-associated orbitopathy complicated with dysthyroid

null

期刊论文

Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma and

期刊论文

Analyses of levels of thyroid hormones and its receptor expression in puerperants and newborns from an

JU Ying, CHEN Lan, JIANG Qi, YANG Kedi, CHEN Xuemin, XU Guojian, LI Liping

期刊论文

The impact of hypoxia in hepatocellular carcinoma metastasis

null

期刊论文

Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during

Wei Wang, Shuqin Jiang, Zhirui Cui, Xiangyang Luo, Lingli Shi, Heli Zheng

期刊论文

Atypical pituitary hormone–target tissue axis

期刊论文

Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies

null

期刊论文

Natural killer cells in hepatocellular carcinoma: current status and perspectives for future immunotherapeutic

null

期刊论文

Effect of traditional Chinese medicine combined with Western therapy on primary hepatic carcinoma: a

null

期刊论文

Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis

null

期刊论文

Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

Amy Lee, Fa-Chyi Lee

期刊论文

甲状腺乳头状癌菌群失调及与肿瘤信号通路异常的相关性研究

喻爽, 丁彦强, 王雪洁, Siu Kin Ng, 曹思婷, 刘伟鑫, 郭朱明, 谢宇彬, 洪澍彬, 许丽霞, 李晓星, 李杰, 吕伟明, 彭穗, 李延兵, 沈祖尧, 于君, 肖海鹏

期刊论文

Progress and challenges in RET-targeted cancer therapy

期刊论文