Browsing by Subject "Bone metastasis"
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- PublicationOpen AccessBone morphogenetic proteins and their receptor signaling in prostate cancer(Murcia : F. Hernández, 2007) Ye, L.; Lewis-Russell, J.M.; Kynaston, H.G.; Jiang, W.G.Bone morphogenetic proteins (BMPs) belong to the TGF-ß superfamily and are vital bone inductive factors. BMPs also play important roles during embryonic development and the postnatal homeostasis of various organs and tissues, by controlling cellular differentiation, proliferation and apoptosis. Prostate cancer is the most common cancer in men in Western countries, with a high incidence of bone metastasis. Once bony metastasis developed, the condition is incurable, and contributes significant disease specific morbidity and mortality. However, the mechanisms underlying the development of bone metastasis remain unclear. BMPs have been implicated in the development of both primary and secondary tumors, particularly skeletal metastasis. Aberrations in BMPs signaling have also been identified in various neoplasms. Recently studies have also suggested a pivotal role in bone metastasis for Noggin, which is a BMP antagonist. In this review, we discuss the current knowledge of BMPs signaling, abnormalities which have been identified and their involvement in tumour progression, and particularly in the development of bone metastasis in prostate cancer.
- PublicationOpen AccessEstrogen-deficient osteoporosis enhances the recruitment and activity of osteoclasts by breast cancer cells(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Salamanna, Francesca; Pagani, Stefania; Maglio, Melania; Borsari, Veronica; Giavaresi, Gianluca; Martelli, Alberto M.; Buontempo, Francesca; Fini, MilenaTo reduce the burden of bone metastases, the pathophysiology of the metastatic niche should be elucidated and targeted. The aim of the present study was to assess the effect of tumor cells on osteoclast (OC) recruitment and activity in the presence of altered bone remodelling. Peripheral blood mononuclear cells (PBMC) were isolated from healthy and ovariectomized (OVX) rats and co-cultured with MRMT-1 rat breast carcinoma cells or with their conditioned medium for 1 and 2 weeks. Alamar Blue viability test, synthesis of cathepsin K, transforming growth factor-beta 1 (TGFβ1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), metalloproteinase (MMP)-7, MMP-9, FITC-conjugate phalloidin staining and tartrate-resistant acid phosphatase (TRAP) staining were evaluated. The results indicate that breast carcinoma cells induced different responses in PBMC derived from rats affected by estrogen deficiency osteoporosis (OP) in comparison with healthy ones, with a significant increase in proliferation rate, OC differentiation, synthesis of TNF-α, MMP-7 and MMP-9. The data support the “proof of concept” that OP due to estrogen deficiency might offer a receptive site for cancer cells to form bone metastases.
- PublicationOpen AccessReceptor activator of nuclear factor-kappa B ligand (RANKL) stimulates bone-associated tumors through functional RANK expressed on bone-associated cancer cells?(Murcia : F. Hernández, 2009) Mori, K.; Ando, K.; Heymann, D.; Rédini, F.Primary and secondary bone tumors clearly deteriorate quality of life and the activity of daily living of patients. These undesirable diseases become a major social and economic burden. As both primary and secondary bone tumors develop in the unique bone tissue, it is therefore necessary to understand bone cell biology in tumor bone environment. Recent findings of the Receptor Activator of Nuclear Factor-kB ligand (RANKL)/RANK/osteoprotegerin (OPG) molecular triad, the key regulators of bone remodeling, opened new era of bone research. Although RANK is an essential receptor for osteoclast formation, activation and survival, functional RANK expression has been recently identified on several bone-associated tumor cells. When RANK is expressed on secondary bone tumor cells, it is implicated in tumor cell migration, whereas this is not the case for primary bone tumors. In any case, RANK is not involved in RANK-positive cell proliferation or death. In two models of bone metastases secondary to melanoma or prostate carcinoma, in vivo neutralization of RANKL by OPG resulted in complete protection from paralysis, due to metastases of vertebral body, and a marked reduction in tumor burden in bones, but not in other organs. OPG also decreased tumor formation and tumor burden in a mouse model of primary bone tumor, osteosarcoma. In all these models, tumor cells express RANK. These data revealed that local differentiation factors, such as RANKL, play an important role in cell migration in a metastatic tissue-specific manner. These findings substantiate the novel direct role of RANKL/RANK in bone-associated tumors, and its capability of representing new therapeutic targets.
- PublicationOpen AccessUso del ácido Zoledrónico en el tratamiento del Mieloma Múltiple(Murcia: Servicio de publicaciones de la Universidad de Murcia, 2013) Hernández Cano, Rosa Mª; Lorenzo Hernández, Mª Piedad; Soria Suárez, Mª IsabelEl objetivo principal del estudio del caso clínico fue determinar si el uso de los bifosfonatos en el tratamiento del Mieloma Múltiple es efectivo para conseguir disminución del dolor en el paciente y para valorar la disminución de hipercalcemia. Para ello se ha estudiado un caso clínico de una paciente sometida a tratamiento de quimioterapia y coadyuvado con tratamiento con Zometa en el Hospital Comarcal de Baza (Granada), durante las primeras sesiones del tratamiento, obteniéndose resultados favorables ya que se evidenció disminución en la incidencia de hipercalcemia y reducción del dolor. Tras una exhaustiva valoración del paciente, se seleccionaron 3 diagnósticos de enfermería, y se planificaron las intervenciones más apropiadas para cada uno de ellos, utilizando la taxonomía NANDA, NIC y NOC. Durante el tratamiento de la paciente se observaron variaciones en la temperatura corporal poco significativas y náuseas en las primeras sesiones; así como disminución del dolor que conllevó a un menor uso de analgésicos, normalización de cifras de calcio sérico y un aumento en su calidad de vida. Las conclusiones del estudio determinaron un efecto positivo en la administración del Ácido Zoledrónico, ya que se obtuvieron los resultados previstos y los efectos secundarios fueron mínimos, sin necesidad de interrumpir el tratamiento.