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The expression of E-cadherin and β-catenin in squamous cell carcinoma of the esophagusNkosi, Cornelius Muzi January 2010 (has links)
Thesis (M Med (Anatomical Pathology))--University of Limpopo, 2010. / Background
Esophageal squamous cell carcinoma (SCC) remains a disease of poor prognosis. Early diagnosis is compromised by the delayed onset of symptoms. By the time of surgical intervention metastases and organ infiltration have already occurred this reduces the prognosis significantly and the 5-year survival rate of operative advanced esophageal SCC remains poor. In order to select an appropriate therapeutic regime and guard against both over- and under treatment, reproducible prognostic markers are needed at the time of diagnosis. The study evaluates the phenotypic expression of E-cadherin and β- catenin in SCC of the esophagus.
Methods: The expression patterns of both β-catenin and E-cadherin was determined using immunohistochemistry technique in patients with esophageal SCC with the application of the Broders and Brynes grading systems in assessing clinical outcome. Forty four cases were randomly selected, one case was esophagectomy, and 43 were endoscopic biopsies with one case of Broders Grade I, 37 Grade II and 6 Grade III and 9 cases had pattern 2 and 35 had pattern 3 with Brynes Grade.
Results: The reduced expression of E-cadherin and β-catenin was 45.5% and 47.7% respectively. No significant level was observed with E-cadherin (P= 0.20) and for β-catenin (P= 0.18) but the low protein level of both biomarkers was associated with tumor cell differentiation with Broders classification. The reduced expression of E-cadherin on invasive tumor front was 27% and 57% for reduced expression of β-catenin. The level of significance was found to be (P=1.00) for E-cadherin expression and (P=0.02) for β-catenin. E-cadherin and β-catenin showed reduced expression on invading tumor front and β-catenin was associated with tumor cell invasiveness.
Conclusion: The expression of E-cadherin and β-catenin with regard to Broders classification showed no significance on tumor cell differentiation and these expressions do not play a role in guiding nor predict the behavior or progression of the tumor. However, the assessment β-catenin on the tumor invasive front (Brynes) shows a high correlated with tumor behavior as it is involved in regulation E-cadherin function.
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Bilateral breast cancer incidence and survivalMcCaul, Kieran January 2006 (has links)
Introduction - This study re - examined the epidemiology of bilateral breast cancer with regard to the age at diagnosis and histology of the first breast cancer, and examined the effect of bilateral breast cancer on breast cancer survival. Methods - A cohort of US women with breast cancer was identified using cancer registry data for the period 1973 to 2000 obtained from the Surveillance, Epidemiology, and End Results ( SEER ) Program. In this cohort, incidence cases of bilateral breast cancer were identified and rates calculated per 1,000 person - years and the effect on survival of a diagnosis of a bilateral breast cancer was determined using time - dependent proportional hazard regression. Results - The overall incidence of bilateral breast cancer was 5.5 per 1,000 person - years and, apart from an elevation in incidence in the first year, was constant over time. In age - cohorts of young women, age - specific rates of bilateral breast cancer were found to decline as these women aged, approaching the incidence observed in older age cohorts. In older age - cohorts, age - specific rates were comparatively constant until age 75 - 79 years, after which age - specific rates began to decline regardless of age at first diagnosis.Differences in the crude incidence of bilateral breast cancer in sub - cohorts of women with lobular carcinoma ( 6.56 per 1,000 person - years ) and infiltrating ductal carcinoma ( 5.31 per 1,000 person - years ) were largely explained by differential incidence in the first year following diagnosis of the first breast cancer. Diagnosis of bilateral breast cancer increased the risk of breast cancer mortality, independent of the interval between the first and second breast cancer. Stage of both the first and second breast cancers was found to be the most important determinant of risk. Conclusions - This study found that the pattern of age - specific incidence of bilateral breast cancer was consistent with effects already well established in the literature describing the incidence of first primary breast cancer - pre - menopausal effects in young women and underascertainment in older women. Estimates of the incidence of bilateral breast cancer were subject to bias caused by an elevation in the incidence in the first year following diagnosis of the first breast cancer. This was most likely an effect of increased surveillance. This explained to a large extent, associations between the histology of the first breast cancer and the incidence of bilateral breast cancer observed in earlier studies. This study challenged the currently accepted view that bilateral breast cancer was a sign of increased susceptibility to breast cancer. Instead it is argued that the constant annual incidence of bilateral breast cancer suggests a final, discrete stage in a multistage carcinogenesis process. It is further argued that the observed incidence of bilateral breast cancer allows us to estimate the incidence of breast cancer in the population among women reaching this final stage within their lifetime. It is conservatively estimated that by age 75 to 79 years only half the women in the population have reached this final stage. This implies that in half the population of women, breast cancer either never initiates or progresses so slowly that the final stage of carcinogenesis is not reached within their lifetime. / Thesis (Ph.D.)--School of Population Health and Clinical Practice, 2006.
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The Prognostic Role and Expression of the Ubiquitin Ligase Subunits Skp2 and Cks1 in Hepatocellular CarcinomaHuang, Chinh-wen 15 August 2007 (has links)
The incidence of hepatocellular carcinoma (HCC) is high in Taiwan, because Taiwan is one of HBV-endemic areas. Moreover, HCCs are the 2nd most common cause of death caused by malignancies in Taiwan. Early detection of HCC can improve the survival rate because the stage is one of important prognostic factors. Alpha-fetoprotein (AFP) is the most important tumor marker for diagnosis of HCC and surveillance of treatment. However, the sensitivity, the specificity and positive predictive value of AFP are not very satisfactory. The cell cycle inhibitor p27kip1 is known as a potential prognostic marker for HCC. Decreased expression of cell cycle inhibitor p27kip1 is associated with poor prognosis in HCC. The decreased expression of p27kip1 results from increased ubiquitin-proteosome degradation. S-phase kinase associated protein (Skp2) and cyclin-dependent kinase subunit 1 (Cks1) are the subunits of the ubiquitin ligases responsible for the ubiquitin-proteosome degradation of p27kip1. The increased expression of Skp2 and Cks1 were found in many kinds of human cancers. However, there is no report about the relationship between Cks1, Skp2 and p27kip1 expression in hepatocellular carcinoma. In the present study, we investigated the expression of Cks1, Skp2 and p27kip1 and their prognostic roles in hepatocellular carcinoma.
We used highly specific antibodies in immunohistochemistry to examine the expressions of Cks1, Skp2, and p27kip1 on paraffin-embedded tissue section from 75 patients with hepatocellular carcinoma. Meanwhile, we also analyzed the clinical significance of these three proteins with the various clinicopathological factors and follow-up data.
Well-differentiated HCCs tended to express higher level of p27kip1 (55.6%), and lower levels of Skp2 (66.7%) and Cks1 (77.8%). Poorly differentiated HCCs tended to express lower level of p27kip1 (64.3%). The expression of Cks1 was significantly associated with the expression of Skp2 (P=0.000). In contrast, there were no inverse relationships between the expression of p27kip1 and the expressions of Skp2 and Cks1 in the present study. The expressions of p27kip1, Skp2, and Cks1 were significantly associated with disease stage (AJCC TNM stage system and CLIP scoring system). Moreover, there were significant associations between overall survival rates and the expressions of Skp2 and Cks1 (P = 0.036 and 0.015, respectively). Patients with higher expression of Skp2 and Cks1 had worse survival rates.
This is the first report of the expression and prognostic role of Cks1 in HCC. Higher expression of Skp2 and Cks1 were significantly associated with advanced stage and poor prognosis. Thus, both Skp2 and Cks1 may be considered as potential novel prognostic markers providing more accurate prediction of prognosis combined with AFP and therapeutic targets in HCCs.
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Study of Stroma in Scirrhous Gastric CarcinomaKONDO, TATSUHEI, KOJIMA, TAKASHI, TERABE, KEISUKE, WATANABE, TADASHI, KAMEI, HIDEO 01 1900 (has links)
No description available.
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The Biological Significance of Alpha-methylacyl-CoA racemase (AMACR) Overexpression in Gallbladder CarcinomaYang, Shu-jing 08 February 2010 (has links)
Alpha-methyacyl-CoA racemase (AMACR) is a critical peroxisomal and mitochondrial enzyme, encodes a key enzyme in the catabolism of long-chain fatty acid thus is indispensable in the £]-oxidation of fatty acid to generate biological energy. AMACR stands in many organs with only very low expression level and its overexpression is exclusively in neoplastic conditions. Recently, AMACR overexpresison has been discerned to relevant to tumor progression of prostate, gastric, and colon cancers, and its overexpression has now been introduced in pathological differential diagnosis of prostate carcinoma from non-malignant mimickers. By using 89 gallbladder carcinoma (GBCA) samples for AMACR immunostaining we found AMACR overexpression is frequently discerned in GBCA. It not only significantly correlates with numerous adverse clinicopathologic factors but also manifests a significant independent predictor of worse outcome in GBCA patients. In multivariate comparison, higher tumor stage represented the strongest prognosticator (p = 0.0101), followed by old patient age (p = 0.0378). Moreover, AMACR overexpression also identified patients at around 2-fold higher risk of disease-specific death (p = 0.0452). By Western blot analyses, we found AMACR expression in the metastatic cells, RCB1129, was apparently more abundant than that in its primary lesion RCB1130. By XTT analyses, the viability of both RCB1129 and RCB1130 cells were significantly decreased by AMACR inhibitor. The RCB1129 cell line, with more abundant AMACR protein expression, was more resistant to AMACR inhibitor treatment than RCB1130 cell line at various drug concentrations. Our data suggest AMACR is a prognostic marker that can serve as a promising therapeutic target in gallbladder cancer.
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The Expression of TSG101 in Squamous Cell CarcinomaChen, Ching-mei 02 September 2004 (has links)
Inactivation of mouse tumor susceptibility gene tsg101 leads to neoplastic transformation which could reversed by restoration of tsg101 protein activity. In the varieties of human malignancies, no genomic defect could be identified questioning the role of TSG101as a classical tumor suppressor. Subsequent studies revealed presence of abnormal TSG101 transcripts in both tumor tissues and its normal counter parts, as well as in embryonic tissues. Hence, the relationship between TSG101 and human cancer development remains unclear. The previous studies have demonstrated that TSG101 has multiple biological functions, including regulations of protein degradation through ubiquitination, transcriptional, protein trafficking, cell survival and proliferation and epithelial cell differentiation. To further investigate the role of TSG101 in tumorigenesis, we employed immunohistochemistry and in situ hybridization analysis to study the expressions of TSG101 protein and mRNA in squamous cell carcinomas of different differentiation status. In addition, we scrutinized the relationship between TSG101 expression and the changs of cell cycle-related tumor suppressors and markers of epithelial differentiation, cell growth, tumor metastasis and apoptosis. The results reveal that TSG101 protein and mRNA are consistently expressed in the epidermal cells residing in the suprabasal, granular and cornified layers, but only weakly expressed in the cells of basal layer. The expressions of TSG101 are down regulated in poorly differentiated squamous cell carcinomas of various organs. Furthermore, TSG101 is also expressed in the tissue of squamous metaplasia, and the expression of TSG101 is positively related to that of cytokeratin. In addition, while TSG101 is down regulated, the expressions of p21Cip1/WAF1, p14ARF and MDM2 are also decreased ehereas that of p53 is conversely increased. Phospho-Rb and E-Cadherin were found to be down regulated in advanced cancers, but we failed to find their correlation with TSG101 on cell proliferation and tumor metastasis. Taken together, we hypothesize that TSG101 expression may influence and promote cell differentiation by regulating keratin expression, being involved in the MDM2-p53 circuit and interacting with p21Cip1/WAF1. Besides, by the integration of the studies of TSG101, keratin 10, and Rb protein expression, we infer that TSG101 may indirectly suppress expression of Rb by up-regulating keratin 10 in epithelial cells. The detailed mechanisms of the observation require further investigation. Nevertheless, our results have provided evidences to support the role of TSG101 on differentiation of squamous epithelial cells in addition to tumorigenesis.
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Über das Carcinom des äusseren OhresLangguth, Hugo. January 1896 (has links)
Thèse : Médecine : Strasbourg : 1896. / Numéro d'ordre : 22.
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The prognostic significance of DJ-1 in patients with renal cell carcinoma of clear cell typeLee, Wing-sang. January 2009 (has links)
Thesis (M. Med. Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 67-76).
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Studies of FRMD4A in two models of squamous cell carcinomaGoldie, Stephen John January 2013 (has links)
No description available.
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Characterisation of calcium-sensing receptor signalling and feedback regulation in endogenous expression systemsMcCormick, Wanda Denise January 2008 (has links)
No description available.
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