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Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2

《医学前沿（英文）》 2023年 第17卷 第3期   页码 503-517 doi: 10.1007/s11684-022-0947-9

摘要： Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.

关键词： ALDOB     kidney cancer     cell proliferation    

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Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma

《医学前沿（英文）》 doi: 10.1007/s11684-023-1029-3

摘要： Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma: a multi-center integrated analysis of microbiome, metabolome, and transcriptome data

关键词： tumor prognosis molecular     Microbiome subsets determine     center analysis microbiome     transcriptome data    

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Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient samples

《医学前沿（英文）》 2022年 第16卷 第4期   页码 596-609 doi: 10.1007/s11684-021-0868-z

摘要： Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.

关键词： innate immune checkpoint     Siglec10     kidney renal clear cell carcinoma    

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Effect of renal function and hemodialysis on the serum tumor markers in patients with chronic kidney

YU Xiaofang, XU Xialian, YE Zhibin

《医学前沿（英文）》 2007年 第1卷 第3期   页码 308-311 doi: 10.1007/s11684-007-0059-6

摘要： In patients with chronic renal failure, whether they have had hemodialysis or not, the specificity of some of the serum tumor markers for the diagnosis of the corresponding tumors is decreased while others remain as valuable as they are in patients with normal kidney function. The detection of tumor markers is extensively used for the diagnosis of corresponding tumors. It has been recently shown that some tumor markers are higher in patients with chronic kidney disease (CKD) than in the normal population. The effects of renal function and hemodialysis were examined on serum levels of some of the tumor markers including CEA, CA, CA, AFP, CA, CA, CYFRA, NSE, SCC-Ag, PSA, and fPSA. The 232 non-dialysis patients with CKD and 37 chronic uremic patients treated with maintenance hemodialysis were enrolled in this study. The 232 non-dialysis patients were divided into three groups according to their Ccr. In group 1, Ccr was ≤25 mL/min. In group 2, Ccr was between 25 and 50 mL/min. In group 3, Ccr was ≥50 mL/min. The male patients were also divided into three groups to compare the serum levels of PSA and fPSA among the three groups. Nine tumor markers in 37 uremic patients were tested. For comparison, 37 non-dialysis patients with similar Ccr of the same age and gender served as controls. There existed significant differences in serum levels of CEA, CA, CYFRA, NSE, and SCC-Ag among different Ccr groups and the markers bore a negative correlation with Ccr. There were no significant differences among the three groups in the serum concentrations of CA, AFP, CA, CA, PSA and fPSA. The serum levels of CA and NSE were significantly higher (199, CYFRA, NSE, CA and SCC-Ag for the diagnosis of the corresponding tumors was decreased while serum AFP, CA, CA, PSA and fPSA were as valuable as they were in patients with normal kidney function. Hemodialysis further increased the serum level of CA and NSE.

关键词： CKD     non-dialysis     valuable     detection     chronic    

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Normoalbuminuric diabetic kidney disease

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 310-318 doi: 10.1007/s11684-017-0542-7

摘要：

Diabetic kidney disease (DKD) is one of the primary causes of end-stage renal disease (ESRD). Early diagnosis is very important in preventing the development of DKD. Urinary albumin excretion rate (UAER) and glomerular filtration rate (GFR) are widely accepted as criteria for the diagnosis and clinical grading of DKD, and microalbuminuria has been recommended as the first clinical sign of DKD. The natural history of DKD has been divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. However, this clinical paradigm has been questioned recently, as studies have shown that a portion of diabetes mellitus (DM) patients with normoalbuminuria have progressive renal insufficiency, referred to as normoalbuminuric diabetic kidney disease (NADKD) or nonalbuminuric diabetic nephropathy. Epidemiologic research has demonstrated that normoalbuminuric diabetic kidney disease is common, and the large number of NADKD patients suggests that the traditional paradigm needs to be shifted. Currently, the pathogenesis of NADKD remains unclear, but many clinical studies have identified some clinical and pathological features of NADKD. In addition, the long-term outcomes of NADKD patients remain controversial. In this article, we reviewed the latest studies addressing the pathogenesis, pathology, treatment and prevention of NADKD.

关键词： diabetes     diabetic kidney disease     normoalbuminuria     renal impairment    

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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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evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2

null

《医学前沿（英文）》 2014年 第8卷 第4期   页码 471-476 doi: 10.1007/s11684-014-0365-8

摘要：

This work aims to estimate the value of diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) in detecting early-stage kidney injury in type 2 diabetic patients with normoalbuminuria (NAU) versus microalbuminuria (MAU) prospectively. A total of 30 T2DM patients with normal kidney function were recruited and assigned to the NAU group (n = 14) or MAU group (n= 16) according to 8 h overnight urinary albuminuria excretion rate (AER) results. A contemporary cohort of health check-up recipients were included as controls (n = 12). DWI and DTI scans were performed on bilateral kidney using SE single-shot EPI, and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the renal parenchyma was determined from ADC and FA maps of the three groups. ADC and FA values were compared among the three groups. According to DWI with a b value of 400 s/mm2, the MAU and NAU groups showed significantly lowered mean ADC values compared with the healthy controls (P<0.01). The mean ADC in the MAU group [(2.22±0.07)×10–3 mm2/s] was slightly lower than that of the NAU group [(2.31±0.22)×10–3 mm2/s], but this difference was not statistically significant (P>0.05). The FA value in the MAU group was higher than that in the control group (0.45±0.07 vs. 0.39±0.03, P = 0.004) but did not differ from that in the NAU group (0.42±0.03) (P>0.05). ADC and FA values may be more sensitive than urine AER in reflecting early-stage kidney injury and, hence, may facilitate earlier detection and quantitative evaluation of kidney injury in T2DM patients. Combined evaluation of ADC and FA values may provide a better quantitative approach for identifying diabetic nephropathy at early disease stages.

关键词： type 2 diabetes mellitus     microalbuminuria     diffusion weighted imaging     diffusion tensor imaging     early-stage kidney injury    

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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    

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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    

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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    

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Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

《医学前沿（英文）》 2023年 第17卷 第2期   页码 290-303 doi: 10.1007/s11684-022-0956-8

摘要： Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

关键词： benzydamine     cyclin-dependent kinase 2     patient-derived xenograft     esophageal squamous cell carcinoma    

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Relative expression of PTTG and bFGF in oral squamous cell carcinoma and Tca8113

Yumei DING BM , Lili CHEN MD , Bo CHENG PhD , Handong ZHANG MM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 357-362 doi: 10.1007/s11684-009-0046-1

摘要： The purpose of this study was to investigate the expression of pituitary tumor transforming gene (PTTG) and basic fibroblast growth factor (bFGF) in oral squamous cell carcinoma (OSCC) and tongue cancer cell line Tca8113, as well as their effects on each other. We detected PTTG protein and bFGF in OSCC tissues from 56 cases using the streptavidin-biotin peroxidase (S-P) method; additionally, after being treated with different concentrations of anti bFGF or PTTG antibody, PTTG or bFGF expression in Tca8113 was examined by immunocytochemistry. The results were as follows: (1) Positive rates of PTTG protein and bFGF were 78.2% and 67.3% in OSCC, respectively, which were significantly higher than those in normal mucosal tissues (<0.05). PTTG protein was significantly up-regulated in poorly and moderately differentiated tumors compared to well differentiated tumors (<0.05), and there was also a significant difference between tumors with lymph node metastasis and tumors without lymph node metastasis (<0.05). PTTG protein expression was positively correlated with bFGF ( = 0.382, <0.05); (2) PTTG protein emitted strong fluorescence in Tca8113, and it decreased after being treated with anti-bFGF antibody. Anti-PTTG antibody also had an inhibitive effect on bFGF expression. In summary, the overexpression of PTTG protein is closely related with OSCC differentiation and lymph node metastasis. PTTG protein expression conforms to bFGF in OSCC tissues and Tca8113 cells. Detection of both PTTG and bFGF may help to judge the degree of malignancy and prognosis of patients with OSCC.

关键词： carcinoma     squamous cell     pituitary tumor transforming gene (PTTG) protein     basic fibroblast growth factor    

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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    

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negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cellcarcinoma

《医学前沿（英文）》 2023年 第17卷 第1期   页码 119-131 doi: 10.1007/s11684-022-0949-7

摘要： Treating patients with esophageal squamous cell carcinoma (ESCC) is challenging due to the high chemoresistance. Growth differentiation factor 15 (GDF15) is crucial in the development of various types of tumors and negatively related to the prognosis of ESCC patients according to our previous research. In this study, the link between GDF15 and chemotherapy resistance in ESCC was further explored. The relationship between GDF15 and the chemotherapy response was investigated through in vitro and in vivo studies. ESCC patients with high levels of GDF15 expression showed an inferior chemotherapeutic response. GDF15 improved the tolerance of ESCC cell lines to low-dose cisplatin by regulating AKT phosphorylation via TGFBR2. Through an in vivo study, we further validated that the anti-GDF15 antibody improved the tumor inhibition effect of cisplatin. Metabolomics showed that GDF15 could alter cellular metabolism and enhance the expression of UGT1A. AKT and TGFBR2 inhibition resulted in the reversal of the GDF15-induced expression of UGT1A, indicating that TGFBR2-AKT pathway-dependent metabolic pathways were involved in the resistance of ESCC cells to cisplatin. The present investigation suggests that a high level of GDF15 expression leads to ESCC chemoresistance and that GDF15 can be targeted during chemotherapy, resulting in beneficial therapeutic outcomes.

关键词： GDF15     esophageal squamous cell carcinoma     chemoresistance     cellular metabolism     TGFBR2     AKT    

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Molecular alterations and clinical relevance in esophageal squamous cell carcinoma

null

《医学前沿（英文）》 2013年 第7卷 第4期   页码 401-410 doi: 10.1007/s11684-013-0286-y

摘要：

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of gastrointestinal cancers, and the fourth leading cause of cancer-related deaths in China. Early detection and intervention in time may dramatically increase the survival of the patients by initiating treatment regimens during earlier stages of ESCC or even during precancerous stages. Molecular classification will be useful for subtyping esophageal tumors or precancerous lesions to improve current therapeutics or early intervention of the disease. In this review, we summarize the findings in investigating the molecular alterations and clinical relevance of ESCC.

关键词： esophageal squamous cell carcinoma (ESCC)     early detection     molecular classification     molecular markers    

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标题 作者 时间 类型 操作

Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2

期刊论文

Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma

期刊论文

Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient samples

期刊论文

Effect of renal function and hemodialysis on the serum tumor markers in patients with chronic kidney

YU Xiaofang, XU Xialian, YE Zhibin

期刊论文

Normoalbuminuric diabetic kidney disease

null

期刊论文

Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma and

期刊论文

evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2

null

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

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

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

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

期刊论文

Relative expression of PTTG and bFGF in oral squamous cell carcinoma and Tca8113

Yumei DING BM , Lili CHEN MD , Bo CHENG PhD , Handong ZHANG MM ,

期刊论文

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

null

期刊论文

negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cellcarcinoma

期刊论文

Molecular alterations and clinical relevance in esophageal squamous cell carcinoma

null

期刊论文