最新刊期

    26 10 2016
    • 2016年第10期封面

      Vol. 26, Issue 10, (2016)
        
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    • 2016年第10期中文目录

      Vol. 26, Issue 10, (2016)
        
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    • 2016年第10期英文目录

      Vol. 26, Issue 10, (2016)
        
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    • 王奇峰, 徐清华, 陈金影
      Vol. 26, Issue 10, Pages: 801-812(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.001
      摘要:Background and purpose: Cancer of unknown primary (CUP) represents approximately 5%~10% of malignant neoplasms. For CUP patients, identification of tumor origin allows for more specific therapeutic regimens and improves outcomes. Methods: By retrieving the gene expression data from ArrayExpress and Gene Expression Omnibus data repositories, we established a comprehensive gene expression database of 5 800 tumor samples encompassing 22 main tumor types. The support vector machine-recursive feature elimination algorithm was used for feature selection and classification modelling. We further optimized the RNA isolation and real-time quantitative polymerase chain reaction (RTQ-PCR) methods for candidate gene expression profiling and applied the RTQ-PCR assays to a set of formalin-fixed, paraffin-embedded tumor samples. Results: Based on the pan-cancer transcriptome database, we identified a list of 96-tumor specific genes, including common tumor markers, such as cadherin 1 (CDH1), kallikrein-related peptidase 3 (KLK3), and epidermal growth factor receptor (EGFR). Furthermore, we successfully translated the microarray-based gene expression signature to the RTQ-PCR assays, which allowed an overall success rate of 88.4% (95%CI: 83.2%-92.4%) in classifying 22 different tumor types of 206 formalin-fixed, paraffin-embedded samples. Conclusion: The 96-gene RTQ-PCR assay represents a useful tool for accurately identifying tumor origins. The assay uses RTQ-PCR and routine formalin-fixed, paraffin-embedded samples, making it suitable for rapid clinical adoption.  
      关键词:Cancer of unknown primary;Tumor tissue origin;Gene expression profiling;Real-time quantitative polymerase chain reaction;Immunohistochemistry   
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    • miR-26a suppresses gastric cancer cell invasion by targeting MMP16

      陈治宇, 王辰辰, 胡 健
      Vol. 26, Issue 10, Pages: 813-819(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.002
      摘要:Background and purpose: Invasion and metastasis lead to poor prognosis in gastric cancer. In this study, we investigated the potential function of miR-26a in gastric cancer. Methods: Real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression of miR-26a in gastric cancer cells. In vitro CCK-8 assay, cloning formation assay and Matrigel-Transwell assay were used to evaluate the proliferation, migration and invasion of gastric cancer cells. A luciferase reporter assay was also conducted to confirm that matrix metalloproteinase-16 (MMP16) is a direct target of miR-26a. Results: miR-26a was down-regulated in gastric cancer tissues compared with that in non-cancerous tissues. Functional studies showed that miR-26a inhibited cell proliferation, colony formation, cell motility and invasion. However, miR-26a had no effect on cell proliferation. We also characterized MMP16 as a direct target of miR-26a. We showed that knocking down MMP16 in gastric cancer cells significantly decreased MMP16 expression and inhibited cell invasion, whereas ectopic MMP16 expression significantly abrogated the suppressed cell invasion induced by miR-26a. Conclusion: miR-26a suppresses gastric cancer cell invasion by targeting MMP16. miR-26a could represent a potential therapeutic target for gastric cancer.  
      关键词:miR-26a;Gastric cancer;Matrix metalloproteinase-16;Invasion   
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    • 李勇杰, 于庆龙, 潘际刚
      Vol. 26, Issue 10, Pages: 820-825(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.003
      摘要:Background and purpose: Ethanol has been reported to stimulate progression of breast cancer, yet the underlying mechanism is not fully understood. This study aimed to investigate effects of ethyl alcohol (EtOH) on the calcium-activated neutral protease (CANP)-cyclin E/focal adhesion kinase (FAK) signaling and cell migration in breast cancer cells, as well as the role of epidermal growth factor receptor (EGFR) in the EtOH-stimulated effects, in order to assess the signaling mechanism(s) underlying how EtOH enhances cancer progression. Methods: Human breast cancer cell line MCF-7 was employed as a model system, with MCF-10A mammary epithelial cells as control. In vitro wound healing assay was carried out to evaluate EtOH-induced cell migration. The effects of EtOH or epidermal growth factor on the proteolysis of cyclin E/FAK were detected by Western blot. EGFR inhibitor (EGFR-I) and a specific inhibitor for CANP, Calpeptin, were applied to pretreat cultured cells to explore their influences on the cell migration and cyclin E/FAK proteolysis triggered by EtOH. Results: Treatment of model cells with EtOH (0.3%) stimulated significant proteolysis of cyclin E/FAK in a dose-/time-dependent manner and increased migration (+47.30%, P<0.05) in MCF-7 breast cancer cells, but had no significant effect on migration in MCF-10A cells. Pretreatment with Calpeptin (10 μmol/L) significantly reduced EtOH (0.3%)- or EGFR (10 ng/mL)-induced cyclin E/FAK truncation. EGFR-I (3 μmol/L) profoundly reduced EtOH-indcued CANP dependent proteolysis of CANP1 and cyclin E/FAK as well as cell migration (-53.00%, P<0.01). Conclusion: EtOH significantly stimulates activation of CANP via EGFR pathway, resulting in proteolysis of cyclin E/FAK and migration in MCF-7 breast cancer cells, suggesting EGFR-CANP signaling to be a potential target for suppression of metastasis in breast cancer.  
      关键词:Ethanol;Epidermal growth factor receptor;Calcium-activated neutral protease;Migration;Breast cancer   
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    • 张文娟, 田 喆, 李有杰
      Vol. 26, Issue 10, Pages: 826-830(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.004
      摘要:Background and purpose: miR-196a2 functions as an oncogene during tumor initiation and progression. The up-regulation promotes tumor cell proliferation, invasion and metastasis. Therefore, it is promising to be an important tumor biomarker. The aim of this study was to investigate whether rs11614913, a gene polymorphic site of miR-196a2, is associated with the risk of leukemia. Methods: A case-control analysis was employed. Bone marrow or peripheral blood was collected from 210 leukemia patients diagnosed from Jan. 2009 to Jul. 2015 in Yantaishan Hospital (case group) as well as 250 healthy people who were physically examined during the same period (control group). Polymerase chain reaction-restriction fragment length polymorphism (PCR-PFLP) was used to detect the genotype of rs11614913. Application test was used to compare the difference in the frequency of each genotype between case group and control group. The odds ratio (OR) of SNP allelic genes was calculated using logistic regression analysis and 95%CI represented the risk of leukemia for each genotype. Results: The distribution differences in the frequency of T/T, C/C, C/T genotype of miR-196a2 rs11614913 between case group and control group were statistically significant (P<0.05). The risk of leukemia for individuals who carried mutant homozygous C/C was 2.661-fold higher than those carried wild-type homozygous T/T, and the difference was statistically significant (P<0.05). Conclusion: The miR-196a2 gene polymorphic site rs11614913 was associated with the risk of leukemia. Mutant homozygous C/C or C allelic gene carrying was probably a risk factor for leukemia.  
      关键词:miR-196a2;rs11614913;Single nucleotide polymorphism;Polymerase chain reaction-restriction fragment length polymorphism;Leukemia   
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    • 董一楠, 孔凡铭, 张新伟
      Vol. 26, Issue 10, Pages: 831-839(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.005
      摘要:Background and purpose: Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is one of the ASPP family. It binds to p53 to inhibit the transcriptional activity of p53-target genes and cell apoptosis, which is associated with tumor formation. Previously, we found a new subtype of iASPP, iASPP splice variant (iASPP-SV), which is a nuclear protein containing 407 amino acid residues and can bind to p53, inhibiting p53 transcriptional activity. However, the relationship of iASPP-SV and breast cancer is still obscure. Therefore, the purpose of this research was to study the role of iASPP-SV on breast cancer tumorigenesis and progression. Methods: 5’-rapid amplification of cDNA ends (RACE) was used to identify the 5’-end of iASPP-SV mRNA in MCF-7 cells. HEK 293 cells were transfected with pFLAG-iASPP-SV and pFLAG-iASPP (828). Then Western blot was used to identify whether endogenous iASPPSV was expressed in HEK 293 cells and 8 types of human tumor cell lines. This study established the stable clones of NIH 3T3 expressing FLAG-iASPP-SV and FLAG-iASPP (828). Cell proliferation assay, colony formation and soft agar colony formation assay were used to identify whether iASPP-SV and iASPP (828) can promote cell proliferation and iASPP-SV is an oncogene. Real-time fluorescent quantitative polymerase chain reactive (RTFQ-PCR) was used to detect the levels of iASPP-SV and iASPP (828) mRNA in primary breast cancers. Luciferase assays were used to identify the relationships between iASPP-SV, iASPP (828), p53 and NF-κB p65. Results: The study identified that iASPP-SV was encoded by previously reported NF-κB p65 subunit (RelA)-associated inhibitor (RAI), and endogenously expressed in many human cancer cell lines. Analysis of cell proliferation, colony formation assay and soft agar assay for colony formation identified that similarly to iASPP (828), iASPP-SV promoted tumor cell proliferation and acted as an oncogene. RTFQ-PCR result showed that the median values of iASPP-SV and iASPP (828) in breast cancers with wild-type p53 were more significantly over-expressed than those of mutant p53. Luciferase assays showed that iASPP-SV and iASPP (828) could suppress NF-κB p65 transcriptional activity. Thus iASPP family may participate in the regulation of p53 and NF-κB activity, which imply that iASPP perhaps shows pro- or anti-survival activities when it interacts with different proteins. Conclusion: These findings indicate that iASPP-SV may be a potential target for breast cancer therapy.  
      关键词:p53凋亡刺激蛋白抑制剂;p53凋亡刺激蛋白抑制剂剪切变异体;p53;NF-κB;乳腺癌   
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    • 孙轶群, 童 彤, 毛 健
      Vol. 26, Issue 10, Pages: 840-847(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.006
      摘要:Background and purpose: The lymph node metastatic model of rectal tumor is a useful tool for the research on tumor occurrence, development, metastasis and antineoplastic therapy. There are few reports about establishment of larger animal model. This study aimed to establish feasible and reproducible lymph node metastatic models of VX2 tumor in rabbits. Methods: The VX2 tumor tissue was put into the puncture needle. The VX2 tumor tissue in the needle was orthotopically transplanted into the rectal wall of the New Zealand white rabbits successfully. Twenty New Zealand white rabbits were transplanted. Two experimental rabbits were scanned by MR weekly. Tumor growth curve and lymph node numbers were observed on MR. Experimental rabbit tumor volumes were measured by MR post-processing software. The rectal tumor and surrounding lymph nodes were resected, and the specimens were fixed. The sections were stained with HE. We explored the relationship between tumor volume and growth time, the number of metastatic lymph nodes and tumor volume, respectively. Results: Thirteen models were successfully established with a rate of 65%. Tumors limited in the rectal wall were observed on the fourth week. Tumor size increased over time. There was significant difference in the tumor volume between different periods (growth cycle number) (F=52.865, P<0.05). There was a significantly positive correlation between tumor volume and the growth cycle number (r=0.910, P<0.05). The metastatic lymph nodes could be observed when VT>9 cm3. The number of metastatic lymph node increased obviously from the ninth week. The more tumor volume, the greater the number of metastatic lymph nodes was observed (F=92.531, P<0.05). There was a significantly positive correlation between the number of metastatic lymph nodes and the tumor volume (r=0.945, P<0.05). Conclusion: Metastatic lymph node models of VX2 tumor in New Zealand white rabbits were established successfully. This model has some value in the research on local growth, invasion mechanism, lymph node metastasis and biological characteristics of rectal cancer.  
      关键词:Model;Rectal cancer;Metastatic lymph node   
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    • 段佳君, 邹天宁, 张 季
      Vol. 26, Issue 10, Pages: 848-853(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.007
      摘要:Background and purpose: Estrogen receptor (ER)-positive breast cancer always presents a dilemma for resistance to endocrine therapy in a long time. The recent studies showed that the expression of estrogenresponsive finger protein (Efp) and polo-like kinase 3 (Plk3) had a close relationship with breast cancer development. This study was to explore the expression correlation between Efp and Plk3 in ER-positive breast cancer in order to understand the influence of Efp and Plk3 on the drug resistance. Methods: The expression of Efp and Plk3 in 74 cases of ER-positive breast cancer was detected by SP immunohistochemistry. The clinical significance was then analyzed. Real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) and Western blot were used to detect the expression of Efp and Plk3 in ER-positive MCF-7 cells. Results: No significant relationship was found between Efp and Plk3 expression and the clinicopathological features of 74 cases of ER-positive breast cancer (P>0.05). The number of cases whose Efp showed positive expression was 51 (68.9%), while the number of cases whose Plk3 showed positive expression was 23 (31.1%). Chi-square test analysis showed the expression of Efp and Plk3 was negatively correlated in 74 cases of ER-positive breast cancer (χ2=8.837, P<0.05). The result of RTFQ-PCR showed that the expression of Efp mRNA in MCF-7 cells was up-regulated by estrogen stimulation, whereas Plk3 mRNA was not changed. The result of Western blot showed that the expression of Efp protein in MCF-7 cells was increased by estrogen and MG132 stimulation, whereas Plk3 protein was decreased. Conclusion: The expression of the Efp protein is negatively correlated with Plk3 protein in ER-positive breast cancer. High expression of Efp may be involved in the resistance to endocrine therapy.  
      关键词:Breast cancer;Estrogen receptor;Estrogen-responsive finger protein;Polo-like kinase 3;Drug resistance   
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    • 郑鑫林, 夏学阳, 张金周
      Vol. 26, Issue 10, Pages: 854-860(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.008
      摘要:Background and purpose: For stage Ⅰ non-small cell lung cancer (NSCLC), video-assisted thoracic segmentectomy is given much attention to by thoracic surgeon because of the less tissue damages. However, video-assisted thoracic lobectomy is still considered as the standard treatment in the world. Therefore, this study was to evaluate the clinical effect after video-assisted thoracic segmentectomy and lobectomy in patients with stage Ⅰ NSCLC in order to provide reference for clinical application. Methods: The comparative studies on video-assisted thoracic segmentectomy and lobectomy treating stage I NSCLC were retrieved from PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, CBM, VIP, and Wanfang Data. All data were acquired until July 2015. Literature screening according to data extraction and quality assessment was completed by two reviewers independently. Meta-analysis was conducted by RevMan 5.3 software which was offered by Cochrane network. Results: A total of 11 articles involving 1 677 patients were finally included. The results of meta-analysis indicated that: for stage Ⅰ NSCLC, compared with video-assisted thoracic lobectomy, the effect of video-assisted thoracic segmentectomy was alike in total mortality (OR=0.77, 95%CI: 0.48 to 1.21, P=0.25), 5-year mortality (OR=0.77, 95%CI: 0.52 to 1.14, P=0.19) and systemic complications (OR=0.76, 95%CI: 0.53 to 1.09, P=0.13), but could reduce blood loss [difference in means (MD)=-41.16, 95%CI: -59.46 to -22.86, P<0.000 1], chest tube duration (MD=-0.29, 95%CI: -0.49 to -0.09, P=0.005) and the length of hospital stay (MD=-0.74, 95%CI: -1.44 to -0.05, P=0.04). Conclusion: Compared with video-assisted thoracic lobectomy, video-assisted thoracic segmentectomy can significantly reduce blood loss, chest tube duration and length of hospital stay. However, the two kinds of operation methods achieved the same effects on the total mortality, 5-year mortality and systemic complications. Thoracoscopic segmentectomy may be an alternative to thoracic lobectomy.  
      关键词:Segmentectomy;Lobectomy;Non-small cell lung cancer;Meta-analysis   
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    • 许彭鹏, 钱 樱, 陈秋生
      Vol. 26, Issue 10, Pages: 861-865(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.009
      摘要:Background and purpose: The prognostic capability of traditional prognostic index like follicular lymphoma international prognostic index (FLIPI) is limited in the rituximab era. This study was to investigate the prognostic significance of peripheral blood absolute lymphocyte count/absolute monocyte count (ALC/AMC) in Chinese patients with follicular lymphoma (FL). Methods: This study retrospectively analyzed 136 newly diagnosed FL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)-like chemotherapy in Department of Hematology, Ruijin Hospital from Jan. 2003 to Dec. 2013, and further classified these patients according to FLIPI scoring system. Results: According to FLIPI, 61 patients (44.9%) were stratified into the low-risk (0-1 points) group, 42 cases (30.9%) into the intermediate-risk (2 points) group, and 33 cases (24.2%) into the high-risk (3-5 points) group. The overall response rate and 2-year progression-free survival (PFS) of the 3 risk groups were 88.5%, 95.2%, and 78.8% (P=0.090), and 91.4%, 74.6%, and 47.8% (log-rank=23.3,P<0.001), respectively. The overall response rate and 2-year PFS for patients with ALC/AMC≥4.7 and <4.7 were 91.9%, 68.6% (P=0.005) and 96.0%, 69.7% (log-rank=13.0, P<0.001), respectively. In the multivariate study, ALC/AMC≥4.7 was independent of FLIPI and was able to distinguish the FLIPI low-risk and intermediate-risk patients (log-rank=7.535, P=0.006). Conclusion: For FL patients treated with R-CHOPlike regimens, ALC/AMC is a simple and effective biomarker reflecting tumor microenvironment and human immunity, and could be considered for prognosis evaluation.  
      关键词:Follicular lymphoma;Absolute lymphocyte count/absolute monocyte count;Follicular lymphoma international prognostic index;Rituximab   
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    • 张 悦, 张遵城, 焦 妍
      Vol. 26, Issue 10, Pages: 866-869(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.010
      摘要:Background and purpose: Although FDG tumor imaging has been applied in clinic widely, dual-phase imaging can provide much more information about the FDG uptaking of pulmonary lesions. The purpose of the study was to evaluate the usefulness of dual-phase 18F-FDG coincidence detection SPECT/CT imaging in the differential diagnosis of the pulmonary lesions. Methods: There were 28 patients with pulmonary lesions which were detected by CT. All the patients undertook the SPECT/CT imaging at 2 time-phases respectively: early imaging at 40-60 min and delayed imaging at 2-3 h after the intravenous injection of FDG. Data processing: calculating the radio of T and N in early and delayed imaging respectively; T: The radioactive count of the lesions; N: The radioactive count of the normal tissue; and the change rate: ΔT/N. ROC was used to find out the threshold of T1/N1, T2/N2及ΔT/N in the differential diagnosis between benign and malignant lesions. AUC was used to evaluate the diagnosis value of the dual-phase and single-phase imaging. Results: The threshold of T1/N1 in early imaging was 2.65, whereas AUC was 0.767. The sensitivity, specificity and accuracy were 83.3%, 30% and 64.3%, respectively. The threshold of T2/N2 in delayed imaging was 3.14, whereas AUC was 0.847. The sensitivity, specificity and accuracy were 94.4%, 60.0% and 82.1%, respectively. The threshold of ΔT/N in delayed imaging was 16.9%, whereas AUC is 0.950. The sensitivity, specificity and accuracy were 88.5%, 71.4% and 86.2%, respectively. Conclusion: Dual-phase 18F-FDG coincidence detection SPECT/CT imaging has much higher accuracy and specificity. However it still has false positivity, and should be analyzed with CT and clinical history.  
      关键词:Dual phase;18F-FDG;Coincidence Detection;SPECT/CT;Lung cancer;Differential diagnosis   
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    • The association between metabolic syndrome and renal cell carcinoma

      李 慧, 王弘恺, 顾伟杰
      Vol. 26, Issue 10, Pages: 870-874(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.011
      摘要:Background and purpose: The association between metabolic syndrome (MS) and renal cell carcinoma (RCC) is still unknown. The aim of this study was to elucidate how MS correlates with the prevalence and malignancy of RCC. Methods: This study enrolled 398 RCC patients (350 clear cell RCC patients, 5 XP11.2 translocation RCC patients, 16 papillary RCC patients and 27 chromophobe RCC patients), 160 normal persons, and 32 benign renal tumor patients. The metabolic status of the patients was assessed, and the link between MS and the prevalence or malignancy of RCC was calculated. Results: Clear cell RCC patients had significantly higher rates of hypertension, higher body mass index (BMI) and longer waist circumference. Forty-eight percent clear cell RCC patients had MS, while the number was 33% for papillary RCC, 26% for chromophobe RCC, 0% for XP11.2, 17% for AML, and 25% for normal people. MS patients had significant higher rates of having clear cell RCC than no-MS patients, however this kind of difference was not seen in other types of RCC. Clear cell RCC patients with higher Furhman grade had lower rates of MS. Conclusion: Patients with MS are more likely to develop clear cell RCC. Patients with high Furhman grade tumors have low MS rates, indicating that high grade tumor may have other originating mechanisms other than metabolic disorders.  
      关键词:Metabolic syndrome;Renal cell carcinoma;Cancer prevalence;Furhman grade   
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    • 杨舒雯, 马 奔, 周 力
      Vol. 26, Issue 10, Pages: 875-880(2016) DOI: 10.19401/j.cnki.1007-3639.2016.10.012
      摘要:Stanniocalcin (STC) was first found as a calcium- and phosphate-regulating hormone produced in bony fish by the corpuscles of Stannius. In mammals, the homolog STC-1 displays a relative high amino acid sequence identity (nearly 50%) with fish STC, and STC-2 has a lower identity (nearly 35%) with STC-1 and fish STC. Both STC-1 and STC-2 are expressed in a variety of tissues. The functions of STC have not been understood. But some findings have been reported on their cellular localization, gene structure, and expression in different physiological and pathological conditions, which will be clues in elucidating the functions of STC in mammals. Moreover, STC-1 and STC-2 are expressed in many tumor cell lines, suggesting other biological functions of STC in mammals other than mineral metabolism.  
      关键词:Stanniocalcin;Tumor;Cell proliferation;Tumor microenvironmemt   
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