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Regulatory mechanisms for abnormal expression of the human breast cancer specific gene 1 in breast cancer cells

Science China(Life Sciences) 2006年第4期49卷 403-408页

作者： LU Aiping1, LI Qing1, LIU Jingwen2 1. Department of Pathology, Peking University School of Oncology, Beijing cancer Hospital, Beijing 100036, China 2. VA Palo alto Health Care System, Palo Alto, California, CA 94304, USA Department of Pathology Peking University School of Oncology Beijing Cancer Hospital Beijing 100036 China VA Palo alto Health Care System Palo Alto California CA 94304 USA

Breast cancer-specific gene 1 (BCSG1), also referred as synuclein γ, was originally iso-lated from a human breast cancer cDNA library and the protein is mainly localized to presynaptic terminals in the nervous system. BCSG1 is not expressed in normal or benign breast lesions, but expressed at an extremely high level in the vast majority of the advanced staged breast carcinomas and ovarian carcinomas. Overexpression of BCSG1 in cancer cells led to significant increase in cell proliferation, motility and invasiveness, and metastasis. To elucidate the molecular mechanism and regulation for abnormal transcription of BCSG1, a variety of BCSG1 promoter luciferase reporters were constructed including 3′ end deleted sequences, Sp1 deleted, and activator protein-1 (AP1) domains mutated. Transient transfection assay was used to detect the transcriptional activation of BCSG1 promoters. Results showed that the Sp1 sequence in 5′-flanking region was involved in the basal transcriptional activities of BCSG1 without cell-type specificity. In comparison to pGL3-1249, the reporter activities of pGL3-1553 in BCSG1-negative MCF-7 cells and pGL3-1759 in HepG2 cells were notably decreased. Mutations at AP1 sites in BCSG1 intron 1 significantly reduced the promoter ac-tivity in all cell lines. Transcription factors, c-jun, c-fos and cyclin AMP-responsive element binding (CREB) protein, could markedly enhance the promoter activities. Thus, our results suggest that the abnormal expression of BCSG1 in breast cancer cells is likely regulated by multiple mechanisms. The 5′ flanking region of BCSG1 provides the basal transcriptional activity without cell type specificity. A critical promoter element involved in abnormal expression of BCSG1 presents in the first exon. The cell type specificity of BCSG1 transcription is probably affected through intronic cis-regulatory se-quences. AP1 domains in the first intron play an important role in control of BCSG1 transcription.

关键词： breast cancer-specific gene 1, promoter, transcriptional activity.

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Enzymatically controlled DNA tetrahedron nanoprobes for specific imaging of ATP in tumor

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Chinese Chemical Letters 2024年第8期35卷 221-224页

作者： Xiaohong Wen Mei Yang Lie Li Mingmin Huang Wei Cui Suping Li Haiyan Chen Chen Li Qiuping Guo College of Biology State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringKey Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan ProvinceHunan UniversityChangsha 410082China

Intracellular ATP is an emerging biomarker for cancer early diagnosis because it is a key messenger for regulating the proliferation and migration of cancer ***,the conventional ATP biosensing strat-egy is often limited by the undesired on-target off-tumor ***,we reported a novel strategy to design enzymatically controlled DNA tetrahedron nanoprobes(En-DT)for biosensing and imaging ATP in tumor *** En-DT was designed via rational engineering of structure-switching aptamers with the incorporation of an enzyme-activatable site and further conjugation on the DNA *** En-DT could be catalytically activated by apurinic/apyrimidinic endonuclease 1(APE1)in cancer cells,but they did not respond to ATP in normal cells,thereby enabling cancer-specific ATP biosensing and imaging in vitro and in vivo with improved tumor *** strategy would facilitate the precise detection of a broad range of biomarker in tumors and may promote the development of smart probes for cancer diagnosis.

关键词： Enzyme-controlled APE1 DNA tetrahedron cancer-specific ATP biosensing

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Surgical complexity and prognostic outcome of small volume renal cell carcinoma with high-level venous tumor thrombus and large volume renal cell carcinoma with low-level thrombus

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Chinese Medical Journal 2019年第15期132卷 1780-1787页

作者： Zhuo Liu Xun Zhao Hong-Xian Zhang Li-Wei Li Shi-Ying Tang Guo-Liang Wang Shu-Dong Zhang Shu-Min Wang Lu-Lin Ma Xiao-Jun Tian Department of Urology Peking University Third Hospital Beijing 100191 China Department of Ultrasound Peking University Third Hospital Beijing 100191 China

Background:Radical nephrectomy with thrombectomy is one of the most difficult and complicated urological *** the roles of renal tumor volume and thrombus level in surgical complexity and prognostic outcome are not *** study aimed to evaluate the surgical complexity and prognostic outcome between the volume of renal cell carcinoma (RCC) and the level of venous tumor ***:The clinical data of 67 RCC cases with renal vein or inferior vena cava (IVC) tumor thrombus from January 2015 to May 2018 were retrospectively *** these 67 cases,21 (31.3%) were small tumors with high-level thrombus (tumor ≤7 cm in diameter and thrombus Neves Level Ⅱ-Ⅳ),while 46 (68.7%) were large tumors with low-level thrombus group (tumor >7 cm in diameter and thrombus Level 0-Ⅰ).Clinical features,operation details,and pathology data were *** and multivariable logistic regression analyses were applied to evaluate the risk factors for small tumor with high-level ***:Patients with small tumors and high-level thrombus were more likely to have longer operative time (421.9 ± 135.1 min vs.282.2 ± 101.9 min,t=4.685,P < 0.001),more surgical bleeding volume (1200 [325,2900] mL vs.500 [180,1000] mL,U =270.000,P =0.004),more surgical blood transfusion volume (800 [0,1400] mL vs.0 [0,800] mL,U =287.500,P =0.004),more plasma transfusion volume (0 [0,800] mL vs.0 [0,0] mL,U =319.000,P =0.004),higher percentage of open operative approach (76.2% vs.32.6%,x2 =11.015,P =0.001),higher percentage of IVC resection (33.3% vs.0%,x2 =17.122,P < 0.001),and higher percentage of post-operative complications (52.4% vs.19.6%,x2 =7.415,P =0.010) than patients with large tumors and low-level *** multivariate analysis,decreased hemoglobin (Hb)(odds ratio [OR]:0.956,95 % confidence interval [CI]:0.926-0.986,P =0.005) and non-sarcomatoid differentiation (OR:0.050,95% CI:0.004-0.664,P =0.023) were more likely to form small tumors with high-level tumor t

关键词： Inferior vena cava Tumor thrombus Renal cell carcinoma cancer-specific survival Prognosis Neves classification

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The Impact of Radical Prostatectomy on the Survival of Patients with Carcinosarcoma of the Prostate

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Journal of cancer Therapy 2011年第4期2卷 475-480页

作者： Jue Wang Fenwei Wang 不详

Background: The objective of this study was to evaluate the impact of radical prostatectomy on carcinosarcoma of the prostate. Methods: Patients diagnosed with carcinosarcoma of the prostate from 1977 through 2007 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Outcomes were examined with Kaplan-Meier survival analysis and Cox models. The association between clinical and demographic characteristics and survival of carcinosarcoma of the prostate was examined. Results: A total of fifty-four cases of histology confirmed carcinosarcoma of the prostate were identified. Median age of the patients was 74 years (range 28 - 94). Of the patients with a known tumor stage, all but one patient had a locally advanced or distant stage;all of the patients with known histology grade had poorly or undifferentiated histology. Twenty (37%) patients underwent transurethral resection only and Fourteen (25.9%) patients underwent radical prostatectomy. Eight (14%) patients received radiation therapy in combination with surgery. The median cancer specific survival was 16 months (95% CI 0 - 32 months). 1-, 3-, and 5- year cancer specific survival rate were 55.1%, 32.3% and 21.1%. In a multivariate analysis, radical prostatectomy was found to be a significant prognostic factor for cancer-specific survival. Conclusions: Carcinosarcoma of the prostate commonly occurs in older patients and associated with aggressive disease and poor prognosis. Radical prostatectomy is the only treatment modality that significantly improves survival. Emphasis on early diagnosis and detection and multimodality therapy of this disease is needed to improve the outcome for patients with this malignancy.

关键词： Carcinosarcoma of the Prostate Surveillance Epidemiology End Results (SEER) Prostatectomy cancer-specific Survival (CSS)

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