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The Global ETD Search service is a free service for researchers
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Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 1 to 4 of 4 (0.017 seconds)| 1 |
E2F1 Up-regulates STMN1 in Hepatocelluar CarcinomasHorng, Kuo-chan 28 August 2007 (has links)
In a preliminary cDNA microarray data-mining, stathmin (STMN1) was identified to be up-regulated in the Hepatocellular carcinomas (HCC). A further screening on HCC cell lines and some tissue specimens at both the mRNA and protein levels, STMN1 was confirmed to be a HCC tumor marker. However, the underlying mechanism that regulates STMN1 up-regulation in HCC is still unknown. The objective of this study was to identify the potential factors that up-regulate STMN1 mRNA and protein levels in HCC. Three HCC cell lines (SK-Hep1, Hep-3B and Hep-G2) and fifty-eight specimens (liver tumor and adjacent nontumor tissues in the same patient) were obtained. Quantitative real-time polymerase chain reaction and western blotting identified up-regulations of STMN1 at both mRNAs and proteins levels in three HCC cell lines and 58 specimens. Immunofluorescence assays further detected its cytoplasmical subcellular localization. Among tumor specimens, the STMN1 protein was significantly correlated with its mRNA expression level (In HCC; N=35; r=0.843; p<0.05; In Metastasis; N=11; r=0.947; p<0.05). In 46 tissue specimens (HCC=35; Metastasis=11), the expression level of E2F1 transcription factor was found to be up-regulated significantly in tumor specimens (p<0.05) and parallel to the STMN1 protein (In HCC; N=35; r=0.556; p<0.05; In Metastasis; N=11; r=0.524; p<0.05). In synchronized SK-Hep1 and Hep-3B cells, it hypothesizes that STMN1 expression is, in part, under the control of E2F1 transcription factors. Moreover, comparative mapping and chromatin immunoprecipitation assay confirmed two E2F1 and three MYC binding sites (the E box) in the STMN1 proximal promoter region. STMN1 proteins were down regulated after the electroporation of shE2F1 in SK-Hep1 cells in 31~36%. In conclusion, the high level of STMN1 protein was resulted from STMN1 mRNA up-regulation and E2F1 might play an important role to transactivate STMN1 gene in HCC and liver metastasis.
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Prognostic and Predictive Factors in Bladder Cancer / Prognostic and Predictive Factors in Bladder CancerHemdan, Tammer January 2016 (has links)
Bladder cancer is a potentially curable malignancy; however in regards to the state of current therapy regimens, a plateau has been reached in both the non-muscle and muscle invasive types. To obtain effective treatment, and consequently a decreased mortality, it has become imperative to test and understand aspects affecting therapy response. The aim of this thesis is to illustrate a better understanding of clinical factors affecting therapy response using new drug combinations and new tumor markers alongside established risk criteria. In Paper I we reported the 5 year follow up from a multicenter, prospectively randomized study and we evaluated the 5-year outcomes of BCG alone compared to a combination of epirubicin and interferon-a2b in the treatment of patients with T1 bladder cancer. Treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant Cis was not predictive of failure of BCG therapy. Independent factor for treatment failure was remaining T1 stage at second resection. In Paper II &III we investigated the validity of emmprin, survivin and CCTα proteins as biomarkers for response and survival before neoadjuvant cisplatin chemotherapy. Bladder tumor specimens were obtained before therapy from a total of 250 patients with T1-T4 bladder cancer enrolled in 2 randomized trials comparing neoadjuvant chemotherapy before cystectomy with a surgery only arm. Protein expression was determined by immunohistochemistry (IHC). Patients in the chemotherapy cohort with negative emmprin and CCTα expression had significantly better overall survival (OS) than those with positive expression. In Paper IV primary end point was examining STMN1 as prognostic factor in bladder cancer. Analysis was performed on three bladder cancer patient cohorts using IHC, western blot and a bladder cancer cell line. High levels of STMN1, expression correlated to shorter disease-specific survival and the growth and migration of the cells were significantly reduced when transfecting the cells with STMN1 siRNA. Conclusion Risk assessment and predictors of outcomes could help in individualized treatment and follow up. Biomarkers will become more important for treatment choices in bladder cancer management.
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Role of Differential Stathmin Phosphorylation in Regulating Epithelial Mesenchyme TransitionPecquet, Alison 24 May 2022 (has links)
No description available.
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Proteomic Analysis of Urinary Bladder Cancer : Aiming for Novel BiomarkersLindén, Mårten January 2013 (has links)
Urinary bladder cancer is a heterogeneous disease appearing in different forms, e.g. non-muscle invasive and muscle invasive. For all variants, the expression of proteins is interesting to analyze for diagnostic, predictive, prognostic and drug targeting purposes, since it reflects the altered gene expression causing the cancer. Since urothelial cells of the bladder are in direct contact with urine it is likely that this body fluid contains cancer-related proteins. In Paper I, unbiased analysis of proteins in urine from urinary bladder cancer patients and controls, using label-free quantification by mass spectrometry, was applied and four interesting proteins APOE, FGB, LRG and SERPINA1 were selected and further analyzed with western and dot blot. In Paper II, two more proteins, POLR1E and TOP2A, were validated as relevant proteins in bladder cancer urine. In Paper III and IV, the proteins GAL1 and STMN1 were investigated for their prognostic and therapeutic target potential in bladder cancer. In Paper II, III and IV, the expression of seven of the proteins were analyzed on tissue microarrays representing tumour tissue from 360 patients with different tumour stages. For the proteins identified by the urine screening approach, their protein expressions were confirmed in bladder cancer tissue. The expression level in tissue of five of the proteins, APOE, FGB, POLR1E (Paper II), GAL1 (Paper III) and STMN1 (Paper IV), increased with tumour stage, showing diagnostic relevance and three of the proteins, SERPINA1 (Paper II), STMN1 (Paper IV) and GAL1 (Paper III) had prognostic potential in urinary bladder cancer. In addition, GAL1 and STMN1 were demonstrated to be highly expressed in metastatic disease and inhibition of STMN1 reduced cell growth (Paper III and IV), indicating that these proteins are promising drug targets in urinary bladder cancer. In conclusion, the approach of this thesis has generated several candidate protein biomarkers in urine and tissue, validated with independent methods, which have the potential to improve the care for bladder cancer patients.
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