Pathology and genetics of tumours of the urinary system and male genital organs

EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016.

https://uroweb.org/wp-content/uploads/Babjuk-M-et-al.-Eur-Urol-2013-644639.-EAU-Guidelines-on-non-muscle-invasive-urothelial-carcinoma-of-the-bladder-updqte-2013.pdf

EAU Guidelines on Non–Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2013

Metastatic spread of cancer continues to be the greatest barrier to cancer cure. Understanding the molecular mechanisms of metastasis is crucial for the design and effective use of novel therapeutic strategies to combat metastases. One class of molecules that has been repeatedly implicated in metastasis is the matrix metalloproteinases (MMPs). In this review, we re-examine the evidence that MMPs are associated with metastasis and that they make a functional contribution to the process. Initially, it was believed that the major role of MMPs in metastasis was to facilitate the breakdown of physical barriers to metastasis, thus promoting invasion and entry into and out of blood or lymphatic vessels (intravasation, extravasation). However, recent evidence suggests that MMPs may have a more complex role in metastasis and that they may make important contributions at other steps in the metastatic process. Studies using intravital videomicroscopy, as well as experiments in which levels of MMPs or their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are manipulated genetically or pharmacologically, suggest that MMPs are key regulators of growth of tumors, at both primary and metastatic sites. On the basis of this evidence, a new view of the functional role of MMPs in metastasis is presented, which suggests that MMPs are important in creating and maintaining an environment that supports the initiation and maintenance of growth of primary and metastatic tumors. Further clarification of the mechanisms by which MMPs regulate growth of primary and metastatic tumors will be important in the development of novel therapeutic strategies against metastases.

/pdf/changing-views-of-the-role-of-matrix-metalloproteinases-in-17khjxc5wu.pdf

Changing Views of the Role of Matrix Metalloproteinases in Metastasis

2458 Despite dramatic improvements in treatment over the past 40 years, acute lymphoblastic leukemia (ALL) remains one of the most common causes of death from disease in childhood. Glucocorticoids are among the most effective agents used in the treatment of lymphoid malignancies, and patient response to treatment is an important determinant of long-term outcome in childhood ALL. In spite of its clinical significance, the molecular basis of glucocorticoid resistance is still poorly understood. The aim of this study was to develop an experimental model system to define clinically relevant mechanisms of glucocorticoid resistance in childhood ALL. An in vivo model of childhood ALL has been developed in our laboratory, using patient biopsies established as xenografts in immune-deficient nonobese diabetic severe-combined immunodeficient (NOD/SCID) mice. This model is highly representative of the human disease (Lock et al., Blood, 99: 4100-4108, 2002). The in vivo responses of these xenografts to the glucocorticoid dexamethasone (DEX) correlated significantly with patient outcome (p 1 μM) in xenografts from six patients, five of whom died of their disease. In contrast, four DEX-sensitive xenografts (IC50 values 2-fold in sensitive xenografts within 8 hours of treatment. In contrast, Bim induction was dramatically attenuated in DEX-resistant xenografts. These results have identified a clinically significant and novel mechanism of glucocorticoid resistance in childhood ALL, which occurs downstream of receptor-ligand interactions, but upstream of the signalling pathway resulting in Bim induction and apoptosis.

Novel mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia.

Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors.

/pdf/epigenetic-regulation-of-gfi1-in-endocrine-related-cancers-a-omngi9fs4h.pdf

Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: a Role Regulating Tumor Growth.

Objective
Determining the prevalence of symptoms suggestive of overactive bladder (OAB) in a Spanish population and evaluate the impact of these symptoms on well-being and labour productivity in this population.

Prevalencia y caracterización de la vejiga hiperactiva detectada en una población de Madrid con el cuestionario OAB-V3 autoadministrado en atención primaria

Wet age-related macular degeneration is associated with chronic ischemia and inflammation that upregulate several inflammatory cytokines and growth factors, particularly vascular endothelial growth factor and fibroblast growth factor which promote the growth of choroidal neovascularization. Only with the introduction of drugs that directly inhibit the actions of vascular endothelial growth factor have ophthalmologists been able to offer patients with wet age-related macular degeneration reasonable hope for improvement of vision. However, intravitreal administration of anti-vascular endothelial growth factor drugs could be associated with unexpected ocular and systemic side effects. We present consecutive case series of 64 eyes of 64 patients with wet age-related macular degeneration treated with a single intravitreal injection of Dobesilate, a synthetic fibroblast growth factor inhibitor. The end points were the improvement from baseline visual acuity and normalization of retinal histology at 1 month. Intravitreal Dobesilate injection results in a significant improvement in functional and anatomic outcomes from the first month after injection. There were no cases of treatment-associated complications.

Clinical Efficacy of Intravitreal Injection of Dobesilate for Reversing Choroidal Angiogenesis in Age-Related Macular Degeneration

428 morin, quercetin, rutin, gallic acid and resveratrol (polyphenols in mediterranean diet) inhibit mmp-9 expression and in vitro invasiveness in mb-49 (murine bladder) cancer cell line

We present two cases of urologic malignancies, transitional cell carcinoma of the bladder and renal cell carcinoma respectively, closely associated to progressive systemic sclerosis. The relationship between such neoplasms and immune disorders is thereof reviewed. Cancer may develop in a context of diminished immunological surveillance. Conversely, autoimmunity can also be secondary to neoplasia and somehow understood as paraneoplastic. Anyway, the cases here reported could be regarded as unusual associations that may reproduce the still unclear connections between immunity and neoplasia.

Javier C. Angulo

Papers

Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: a Role Regulating Tumor Growth.

Prevalencia y caracterización de la vejiga hiperactiva detectada en una población de Madrid con el cuestionario OAB-V3 autoadministrado en atención primaria

Clinical Efficacy of Intravitreal Injection of Dobesilate for Reversing Choroidal Angiogenesis in Age-Related Macular Degeneration

428 morin, quercetin, rutin, gallic acid and resveratrol (polyphenols in mediterranean diet) inhibit mmp-9 expression and in vitro invasiveness in mb-49 (murine bladder) cancer cell line

Urologic malignancies and progressive systemic sclerosis.