Browsing by Subject "Breast Cancer"

Now showing 1 - 5 of 5
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    Combined expression levels of KDM2A and KDM2B correlate with nucleolar size and prognosis in primary breast carcinomas
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Nicola, Igor De; Guerrieri, Ania Naila; Penzo, Marianna; Ceccarelli, Claudio; Leo, Antonio De; Treré, Davide; Montanaro, Lorenzo
    Ribosome biogenesis is a fine-tuned cellular process and its deregulation is linked to cancer progression: tumors characterized by an intense ribosome biogenesis often display a more aggressive behavior. Ribosomal RNA (rRNA) synthesis is controlled at several levels, the higher one being the epigenetic regulation of the condensation of chromatin portions containing rRNA genes. KDM2A and KDM2B (Lysine (K)-specific demethylase 2A/B) are histone demethylases modulating the accessibility of ribosomal genes, thereby regulating their transcription. Both enzymes are able to demethylate lysins at relevant sites (e.g. K4, K36) on histone H3. We previously demonstrated that KDM2B is one of the factors regulating ribosome biogenesis in human breast cancer. In this study we aimed to define the combined contribution of KDM2A and KDM2B to breast cancer outcome. KDM2A and KDM2B mRNA levels, nucleolar area as a marker of ribosome biogenesis, and patients' prognosis were retrospectively assessed in a series of primary breast carcinomas. We observed that tumors characterized by reduced levels of both KDM2A and KDM2B displayed a particularly aggressive clinical behavior and increased nucleolar size. Our results suggest that KDM2A and KDM2B may cooperate in regulating ribosome biogenesis thus influencing the biological behavior and clinical outcome of human breast cancers.
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    Evaluating Trastuzumab in the treatment of HER2 positive breast cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Jaques, Ryan; Xu, Sam; Matsakas, Antonios
    The transmembrane oncoprotein HER2 is encoded by ERBB2 gene and overexpressed in around 20% of invasive breast cancers. It can be specifically targeted by Trastuzumab (Herceptin ® ), a humanised IgG1 antibody. Trastuzumab has been regarded as one of the most effective therapeutic drugs targeted to HER2 positive cancers. However, there are drawbacks, notably cardiotoxicity and resistance, which have raised awareness in clinical use. Therefore, understanding the mechanism of action is vital to establish improved therapeutic strategies. Here we evaluate Trastuzumab application in the treatment of HER2 positive breast cancer, focusing on its mechanistic actions and clinical effectiveness. Alternative therapies targeting the HER2 receptor and its downstream anomalies will also be discussed, as these could highlight further targets that could be key to improving clinical outcomes.
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    HtrA1 loss is related to aggressive behavior parameters in sentinel node positive breast cancer
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Franco, Renato; Collina, Francesca; Di Bonito, Maurizio; Botti, Gerardo; Montanaro, Donatella; Di Maio, Luigi; Vincenz, Bruno; Landi, Gabriella; D’Aiuto, Massimiliano; Caraglia, Michele; Baldi, Alfonso
    Aim: HtrA1, a member of the High Temperature Requirement Factor A family of oxidative stress-response proteases seems to play a role as a tumor suppressor, being down-regulated in a series of human cancers during their progression. Particularly, low HtrA1 mRNA levels have been observed in breast cancer patients with more aggressive clinical features. These have been shown to relate to a longer disease free and overall survival, with more pronounced effects in axillary nodes positive patients. Subjects and Methods: We have analyzed for immunohistochemical HtrA1 expression a series of 66 sentinel node positive breast cancers through Tissue Micro Array technology. Results: HtrA1 was absent to low in 29 cases, medium in 19 cases and high in 18 cases. Our data revealed a positive significant relation between HtrA1 expression level and estrogen (p=0,002) and progestinic receptor expression (p=0.003) and a negative correlation with histological grading (p=0.028), proliferation index (p=0.05), common BC histotypes (p=0.040), luminal A and B subtypes (p=0.001), metastasis development (p<0.0001) and local relapse (p<0.0001). Finally, no correlation was recorded between HtrA1 expression level and breast cancer histology type and metastasis to non sentinel nodes. Interestingly HtrA1 loss in SLN metastasis was able to predict positive non sentinel nodes (p=0.001). Conclusions: Low HtrA1 expression is significantly related to breast cancer poor prognosis parameters, and HtrA1 loss in sentinel nodes is related to metastasis of non sentinel nodes, offering a further marker useful for BC prognostic stratification.
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    Promesas biotecnológicas. Determinismo genético, cáncer y maternidad por sustitución: un análisis crítico
    (Universidad de Murcia. Servicio de Publicaciones, 2017) Pérez Sedeño, Eulalia
    La biotecnología, sobre todo a partir del desciframiento del genoma humano, ha ofrecido muchas promesas, en su mayoría aún sin cumplir. Mediante el análisis feminista de algunas de estas promesas y el del caso de la maternidad por sustitución, veremos cómo los objetivos, fines e imaginarios de estas biotecnologías afectan de manera desigual a las mujeres y pueden ayudar a perpetuar las desigualdades existentes y el papel subordinado de las mujeres en nuestras sociedades. Análisis de este tipo pueden alertar al res- pecto y ayudar a minimizar los daños.
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    The role of TF- and Tn-antigens in breast cancer metastasis
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Kölbl, Alexandra C.; Jeschke, Udo; Friese, Klaus; Andergassen, Ulrich
    Almost 40 years ago, researchers found that the Thomsen-Friedenreich (TF) and the Thomsen nouvelle (Tn) antigens could be detected in carcinoma, but not in healthy tissue. A short time after that it became clear that TF and Tn are precursor molecules of the MN-blood group antigens. In normal tissue TF and Tn are coated by glycosyl structures, thereby forming the glycoproteins which are known to account for the MN-blood group antigens, but in malignant tissue these molecules are uncovered. TF, which has an additional Galectin-residue compared to Tn, is correlated with a more favourable prognosis for patients. On the contrary, patients with Tn-bearing tissues have a worse prognosis for overall and progression-free survival. It is known that TF and Tn are involved in the adhesion of tumour cells to the endothelium via a mechanism recruiting Galectin-3 and MUC-1, which is the first step in metastasis formation. Furthermore, it became clear that this pathway can be blocked by a growing number of molecules, thereby creating ways of therapeutical intervention.