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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    

The impact of hypoxia in hepatocellular carcinoma metastasis

null

《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)    

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

null

《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    

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

null

《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    

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

null

《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    

Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis

null

《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    

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    

A case of primary neuroendocrine breast carcinoma that responded to neo-adjuvant chemotherapy

null

《医学前沿(英文)》 2015年 第9卷 第1期   页码 112-116 doi: 10.1007/s11684-014-0345-z

摘要:

Primary neuroendocrine breast carcinoma (NEBC) is a very rare type of breast cancer. Two characteristic biomarkers, namely, CgA and Syn, should be immunohistochemically detected to diagnose NEBC. In this study, a 43-year-old woman with a large mass of 8.3 cm × 2.9 cm in her right breast was reported. The patient was pathologically diagnosed with NEBC after specific markers, including CgA and Syn, as well as few differential markers, such as CK7, ER, PR, C-erbB-2, NSE, and E-cadherin, were immunohistochemically detected. The patient showed a remarkable response to four cycles of neo-adjuvant chemotherapy (partial response based on RECIST criteria) and sequentially underwent modified radical mastectomy. Moreover, the diagnosis and treatment of NEBC based on this case and available related literature were discussed.d literature were discussed.

关键词: neuroendocrine carcinoma     neo-adjuvant therapy     breast    

Expression and clinical implication of PRL-1 and PRL-3 in transitional cell carcinoma of bladder

Bin HAO, Changwei LIU, Huixiang LI

《医学前沿(英文)》 2009年 第3卷 第2期   页码 197-203 doi: 10.1007/s11684-009-0036-3

摘要: The mRNA and protein expression of phosphatase of regenerating liver 1 (PRL-1) and phosphatase of regenerating liver 3 (PRL-3) in transitional cell carcinoma of bladder (BTCC) and normal epithelia of bladder was investigated, and the relationship between the BTCC and pathological changes was clarified. The expression of PRL-1 and PRL-3 mRNA was detected by using reverse transcription polymerase chain reaction (RT-PCR) in 30 cases of BTCC and 10 cases of normal bladder, and the expression of PRL-1 and PRL-3 protein was checked by using immunohistochemistry in 30 cases of BTCC and 15 cases of normal bladder. The expression levels of PRL-1 and PRL-3 mRNA and protein were higher in BTCC than those in normal bladder epithelia ( <0.05). The increased expression of PRL-1 and PRL-3 mRNA and protein was detectable in deep invasion and metastasis of BTCC ( <0.05). There was no correlation between the expression of PRL-1 and PRL-3 and gender, age or recurrence of BTCC (all >0.05). A significantly positive correlation was found between PRL-1 and PRL-3 in BTCC ( <0.05). PRL-1 and PRL-3 are expressed consistently and may contribute to the growth, differentiation, invasion and metastasis of BTCC.

关键词: transitional cell carcinoma of bladder     phosphatase of regenerating liver 1     phosphatase of regenerating liver 3     reverse transcription polymerase chain reaction     immunohistochemistry    

Influence of Survivin-targeted siRNA on the biological features of colorectal carcinoma cells

XIONG Ying, GUO Wen, LI Ting, LI Ke

《医学前沿(英文)》 2007年 第1卷 第3期   页码 304-307 doi: 10.1007/s11684-007-0058-7

摘要: The transient transfection of survivin-targeted siRNA to Lovo cells and its influence on the biological features were studied. Two pairs of 19 base pairs (bp) siRNA-specific targeted survivin gene were designed and synthesized by transcription (Survivin-1, Survivin-2). After transient transfection of the two survivin-targeted siRNAs to Lovo cells by Lipofectamine™ 2000, the expression of survivin mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis was detected by flow cytometry and cell proliferation was evaluated by MTT assay. We found that the expression levels of survivin mRNA of the two RNAi groups (Survivin-1 group and Survivin-2 group) respectively decreased by 70% and 39.1% compared with the control Lovo’s. Seventy-two hours after transfection, apoptosis rates of the two RNAi groups were 21.51% and 26.28%, both of which were higher than control Lovo’s (9.03%). The results at 72 h after transfection were that the optical density (OD) at 490 nm of the two RNAi groups was 0.581±0.070 and 0.681±0.104, both of which were much lower than the control Lovo’s (2.060±0.272). Based on the results, we can draw a conclusion that the two survivin-targeted siRNAs successfully suppressed the expression of survivin mRNA, inhibited cell growth and induce cell apoptosis. It provides a powerful evidence for colorectal carcinoma gene therapy.

关键词: control     therapy     influence     Survivin-1     colorectal carcinoma    

Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric

Jianpeng Liu, Xinhua Chen, Shusen Zheng

《医学前沿(英文)》 2021年 第15卷 第2期   页码 170-177 doi: 10.1007/s11684-020-0747-z

摘要: Nanosecond pulsed electric field (nsPEF) is a novel, nonthermal, and minimally invasive modality that can ablate solid tumors by inducing apoptosis. Recent animal experiments show that nsPEF can induce the immunogenic cell death of hepatocellular carcinoma (HCC) and stimulate the host’s immune response to kill residual tumor cells and decrease distant metastatic tumors. nsPEF-induced immunity is of great clinical importance because the nonthermal ablation may enhance the immune memory, which can prevent HCC recurrence and metastasis. This review summarized the most advanced research on the effect of nsPEF. The possible mechanisms of how locoregional nsPEF ablation enhances the systemic anticancer immune responses were illustrated. nsPEF stimulates the host immune system to boost stimulation and prevail suppression. Also, nsPEF increases the dendritic cell loading and inhibits the regulatory responses, thereby improving immune stimulation and limiting immunosuppression in HCC-bearing hosts. Therefore, nsPEF has excellent potential for HCC treatment.

关键词: nanosecond pulsed electric fields (nsPEF)     hepatocellular carcinoma (HCC)     immune response     recurrence     metastasis    

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

null

《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    

Small cell carcinoma of the urinary bladder without gross hematuria: a case report

null

《医学前沿(英文)》 2015年 第9卷 第3期   页码 384-387 doi: 10.1007/s11684-015-0405-z

摘要:

Small cell carcinoma of the urinary bladder (SCCB) is a rare and aggressive form of bladder cancer with poor prognosis. Hematuria is the main symptom of this malignancy, and most patients have a history of smoking. The disease incidence of malignant bladder tumors in China is approximately 0.74%. Early and accurate diagnosis of SCCB can ensure timely and appropriate treatment of this malignant disease. Oncologic surgery is the standard treatment; however, it may not be a curative approach. Chemotherapy and/or radiotherapy should be performed following surgical removal. This case report describes a patient with a single neoplasm diagnosed as SCCB that arose because of recurrence of bladder cancer after bladder tumor resection. In contrast to previously reported cases, this patient had no gross hematuria and no history of smoking.

关键词: carcinoma     small cell     urinary bladder neoplasms     diagnosis    

Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma

《医学前沿(英文)》 2023年 第17卷 第4期   页码 729-746 doi: 10.1007/s11684-022-0978-2

摘要: The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

关键词: hepatocellular carcinoma     YAP1     Akkermansia muciniphila     anti-PD-1     dihydroartemisinin     bile acid    

p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell

Junfang JI, Kun WU, Min WU, Qimin ZHAN,

《医学前沿(英文)》 2010年 第4卷 第4期   页码 412-418 doi: 10.1007/s11684-010-0260-x

摘要: mutations have been found in many esophageal squamous cell carcinoma (ESCC) clinical specimens and cell lines. We reasoned that functional inactivation of wild-type or the functional activation of mutant-type might exist in these specimens and cell lines. In this study, we identified the correlation between p53 functional activation and its genotype in five different ESCC cell lines. To examine the potential p53 activation in a certain ESCC cell line, DNA damage methods including X-ray exposure and cisplatin treatment were employed to treat cells. Further, the expression of p53 protein and four transcripts of well-known p53 target genes were investigated using Western blot and reverse transcription-polymerase chain reaction (RT-PCR) after cell exposure to DNA damage. The results showed that in KYSE 30 cell line with mutant and KYSE 150 with wild-type , p53 could be activated by DNA damages. However, p53 could not be activated following the DNA damages in YES 2 with wild-type , KYSE 70 with mutant , and EC9706 with unknown genotype. All our data indicated that p53 function in certain cells is not closely correlated with its genotype. To judge p53 function in a particular cell line, it is important to examine the p53 functional activation, but not to simply rely on the genotype.

关键词: p53     esophageal squamous cell carcinoma     DNA damage    

标题 作者 时间 类型 操作

Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma and

期刊论文

The impact of hypoxia in hepatocellular carcinoma metastasis

null

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

A case of primary neuroendocrine breast carcinoma that responded to neo-adjuvant chemotherapy

null

期刊论文

Expression and clinical implication of PRL-1 and PRL-3 in transitional cell carcinoma of bladder

Bin HAO, Changwei LIU, Huixiang LI

期刊论文

Influence of Survivin-targeted siRNA on the biological features of colorectal carcinoma cells

XIONG Ying, GUO Wen, LI Ting, LI Ke

期刊论文

Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric

Jianpeng Liu, Xinhua Chen, Shusen Zheng

期刊论文

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

null

期刊论文

Small cell carcinoma of the urinary bladder without gross hematuria: a case report

null

期刊论文

Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma

期刊论文

p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell

Junfang JI, Kun WU, Min WU, Qimin ZHAN,

期刊论文