Caracterización de los pacientes trasplantados por Cirrosis Criptogénica. Estudio comparativo de la evolución post-trasplante hepático de las Cirrosis secundarias a EHDG y las Cirrosis Enólicas

Nuestro objetivo es comparar la evolución post-trasplante hepático de los pacientes con cirrosis por una enfermedad hepática por depósito de grasa (EHDG) y los pacientes trasplantados por cirrosis enólica desde el punto de vista de supervivencia y complicaciones metabólicas y desarrollo de complicaciones cardiovascular con un seguimiento post-trasplante a medio plazo. Se estudiaron retrospectivamente los pacientes sometidos a TH por Cirrosis Criptogénica en nuestro centro, desde el 1 de enero de 1997 hasta el 31 de diciembre de 2006 (caracterizando aquellos con fenotipo de EHDG subyacente). La mayoría de pacientes trasplantados por CC en nuestro centro corresponden a una cirrosis secundaria a EHDG. La prevalencia de CHC es mayor en estos pacientes que en los TH por OH. El desarrollo de complicaciones metabólicas, enfermedad cardiovascular y supervivencia al 5º año post-TH fue similar a los pacientes trasplantados por cirrosis OH.El nostre objectiu és comparar l'evolució post-trasplantament hepàtic dels pacients amb cirrosi per una malaltia hepàtica per depòsit de greix (EHDG) i els pacients trasplantats per cirrosi enòlica des del punt de vista de supervivència i complicacions metabòliques i desenrotllament de complicacions cardiovasculars amb un seguiment post-trasplantament a mitjà termini. Es van estudiar retrospectivament els pacients sotmesos a TH per Cirrosi Criptogénica en el nostre centre, des de l'1 de gener de 1997 fins al 31 de desembre de 2006 (caracteritzant aquells amb fenotip d'EHDG subjacent) . La majoria de pacients trasplantats per CC en el nostre centre corresponen a una cirrosi secundària a EHDG. La prevalença de CHC és major en estos pacients que en els TH per OH. El desenrotllament de complicacions metabòliques, malaltia cardiovascular i supervivència al 5t any post-TH va ser semblant als pacients trasplantats per cirrosi OH.

Surgical management of parathyroid carcinoma : A case report Manejo quirúrgico de carcinoma de paratiroides: A propósito de un caso

Introduction: Parathyroid carcinoma should be taken into consideration among the differential diagnosis of primary hyperparathyroidism, even though it is one of the less common malignant tumours in the world, because an early diagnosis is essential for the treatment and the prognosis of the patient. Case Report: We present the case of a patient whose symptoms were compatible with hyperfunction of parathyroid gland. Due to the malignant disease suspicion and the non-invasion of adjacent tissue, he was treated with a parathyroidectomy. Conclusion: This type of treatment supposes a lower morbidity without decrease in overall survival, according to bibliography

"Primary Squamous Cell Carcinoma of the Vagina: HPV Detection, p16INK4A Overexpression and Clinicopathological Correlations"

International audienceAim: To determine the role of HPV in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinico-pathological significance. Methods: All cases of SCCVa diagnosed over a 15 year period from two hospitals in Barcelona, Spain (n=32) were retrieved. Patients with a history of carcinoma of the cervix diagnosed less than 5 years before were excluded. HPV was detected and typed by PCR using the SPF10 primers. Immunohistochemistry for p16 and p53 was performed. Results: HPV was detected in 25 cases (78.1%). HPV16 was the most prevalent type. Patients with HPV-positive tumours were frequently associated with a history of carcinoma or intraepithelial neoplasia of the cervix or vulva diagnosed more than 5 years before (56% vs. 0%; p=0.01). HPV-positive tumours were more frequently of non-keratinizing, basaloid or warty type than HPV-negative neoplasms (84% vs. 14.3%; p<0.001), and almost constantly showed diffuse positive staining for p16INK4a (96%, vs. 14.3%; p<0.001). The sensitivity and specificity of p16 to identify HPV-positive tumours were 96% and 85.7% respectively. Conclusions: A high number of SCCVs are related to HPV infection and may be identified by immunostaining for p16. HPV-positive tumours tend to affect women with history of cervical neoplasm

Low-Density Lipoprotein Receptor Is a Key Driver of Aggressiveness in Thyroid Tumor Cells

We previously described the role of low-density lipoprotein (LDL) in aggressiveness in papillary thyroid cancer (PTC). Moreover, the MAPK signaling pathway in the presence of BRAF V600E mutation is associated with more aggressive PTC. Although the link between MAPK cascade and LDL receptor (LDLR) expression has been previously described, it is unknown whether LDL can potentiate the adverse effects of PTC through it. We aimed to investigate whether the presence of LDL might accelerate the oncogenic processes through MAPK pathway in presence or absence of BRAF V600E in two thyroid cell lines: TPC1 and BCPAP (wild-type and BRAF V600E, respectively). LDLR, PI3K-AKT and RAS/RAF/MAPK (MEK)/ERK were analyzed via Western blot; cell proliferation was measured via MTT assay, cell migration was studied through wound-healing assay and LDL uptake was analyzed by fluorometric and confocal analysis. TPC1 demonstrated a time-specific downregulation of the LDLR, while BCPAP resulted in a receptor deregulation after LDL exposition. LDL uptake was increased in BCPAP over-time, as well as cell proliferation (20% higher) in comparison to TPC1. Both cell lines differed in migration pattern with a wound closure of 83.5 ± 9.7% after LDL coculture in TPC1, while a loss in the adhesion capacity was detected in BCPAP. The siRNA knockdown of LDLR in LDL-treated BCPAP cells resulted in a p-ERK expression downregulation and cell proliferation modulation, demonstrating a link between LDLR and MAPK pathway. The modulation of BRAF-V600E using vemurafenib-impaired LDLR expression decreased cellular proliferation. Our results suggest that LDLR regulation is cell line-specific, regulating the RAS/RAF/MAPK (MEK)/ERK pathway in the LDL-signaling cascade and where BRAF V600E can play a critical role. In conclusion, targeting LDLR and this downstream signaling cascade, could be a new therapeutic strategy for PTC with more aggressive behavior, especially in those harboring BRAF V600E

Caracterización de los pacientes trasplantados por Cirrosis Criptogénica. Estudio comparativo de la evolución post-trasplante hepático de las Cirrosis secundarias a EHDG y las Cirrosis Enólicas

Nuestro objetivo es comparar la evolución post-trasplante hepático de los pacientes con cirrosis por una enfermedad hepática por depósito de grasa (EHDG) y los pacientes trasplantados por cirrosis enólica desde el punto de vista de supervivencia y complicaciones metabólicas y desarrollo de complicaciones cardiovascular con un seguimiento post-trasplante a medio plazo. Se estudiaron retrospectivamente los pacientes sometidos a TH por Cirrosis Criptogénica en nuestro centro, desde el 1 de enero de 1997 hasta el 31 de diciembre de 2006 (caracterizando aquellos con fenotipo de EHDG subyacente). La mayoría de pacientes trasplantados por CC en nuestro centro corresponden a una cirrosis secundaria a EHDG. La prevalencia de CHC es mayor en estos pacientes que en los TH por OH. El desarrollo de complicaciones metabólicas, enfermedad cardiovascular y supervivencia al 5º año post-TH fue similar a los pacientes trasplantados por cirrosis OH.El nostre objectiu és comparar l'evolució post-trasplantament hepàtic dels pacients amb cirrosi per una malaltia hepàtica per depòsit de greix (EHDG) i els pacients trasplantats per cirrosi enòlica des del punt de vista de supervivència i complicacions metabòliques i desenrotllament de complicacions cardiovasculars amb un seguiment post-trasplantament a mitjà termini. Es van estudiar retrospectivament els pacients sotmesos a TH per Cirrosi Criptogénica en el nostre centre, des de l'1 de gener de 1997 fins al 31 de desembre de 2006 (caracteritzant aquells amb fenotip d'EHDG subjacent) . La majoria de pacients trasplantats per CC en el nostre centre corresponen a una cirrosi secundària a EHDG. La prevalença de CHC és major en estos pacients que en els TH per OH. El desenrotllament de complicacions metabòliques, malaltia cardiovascular i supervivència al 5t any post-TH va ser semblant als pacients trasplantats per cirrosi OH.

Cholesterol and 27-hydroxycholesterol promote thyroid carcinoma aggressiveness

Cholesterol mediates its proliferative and metastatic effects via the metabolite 27-hydroxycholesterol (27-HC), at least in breast and endometrial cancer. We determined the serum lipoprotein profile, intratumoral cholesterol and 27-HC levels in a cohort of patients with well-differentiated papillary thyroid carcinoma (PTC; low/intermediate and high risk), advanced thyroid cancers (poorly differentiated, PDTC and anaplastic thyroid carcinoma, ATC) and benign thyroid tumors, as well as the expression of genes involved in cholesterol metabolism. We investigated the gene expression profile, cellular proliferation, and migration in Nthy-ori 3.1 and CAL-62 cell lines loaded with human low-density lipoprotein (LDL). Patients with more aggressive tumors (high-risk PTC and PDTC/ATC) showed a decrease in blood LDL cholesterol and apolipoprotein B. These changes were associated with an increase in the expression of the thyroid's LDL receptor, whereas 3-hydroxy-3-methylglutaryl-CoA reductase and 25-hydroxycholesterol 7-alpha-hydroxylase were downregulated, with an intratumoral increase of the 27-HC metabolite. Furthermore, LDL promoted proliferation in both the Nthy-ori 3.1 and CAL-62 thyroid cellular models, but only in ATC cells was its cellular migration increased significantly. We conclude that cholesterol and intratumoral accumulation of 27-HC promote the aggressive behavior process of PTC. Targeting cholesterol metabolism could be a new therapeutic strategy in thyroid tumors with poor prognosis

LDL, HDL and endocrine-related cancer : From pathogenic mechanisms to therapies

Cholesterol is essential for a variety of functions in endocrine-related cells, including hormone and steroid production. We have reviewed the progress to date in research on the role of the main cholesterol-containing lipoproteins; low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and their impact on intracellular cholesterol homeostasis and carcinogenic pathways in endocrine-related cancers. Neither LDL-cholesterol (LDL-C) nor HDL-cholesterol (HDL-C) was consistently associated with endocrine-related cancer risk. However, preclinical studies showed that LDL receptor plays a critical role in endocrine-related tumor cells, mainly by enhancing circulating LDL-C uptake and modulating tumorigenic signaling pathways. Although scavenger receptor type BI-mediated uptake of HDL could enhance cell proliferation in breast, prostate, and ovarian cancer, these effects may be counteracted by the antioxidant and anti-inflammatory properties of HDL. Moreover, 27-hydroxycholesterol a metabolite of cholesterol promotes tumorigenic processes in breast and epithelial thyroid cancer. Furthermore, statins have been reported to reduce the incidence of breast, prostate, pancreatic, and ovarian cancer in large clinical trials, in part because of their ability to lower cholesterol synthesis. Overall, cholesterol homeostasis deregulation in endocrine-related cancers offers new therapeutic opportunities, but more mechanistic studies are needed to translate the preclinical findings into clinical therapies