Overexpression of Fut 2, 4, and 8, and nuclear localization of Fut 4 in ovarian cancer cell lines induced by ascitic fluids from epithelial ovarian cancer patients.

Fucosyltransferases (Fut) regulate the fucosylation process associated with tumorogenesis in different cancer types. Ascitic fluid (AF) from patients diagnosed with advanced stage of epithelial ovarian cancer (EOC) is considered as a dynamic tumor microenvironment associated with poor prognosis. Previous studies from our laboratory showed increased fucosylation in SKOV-3 and OVCAR-3, cancer-derived cell lines, when these cells were incubated with AFs derived from patients diagnosed with EOC. In the present work we studied three fucosyltransferases (Fut 2, Fut 4, and Fut 8) in SKOV-3, OVCAR-3 and CAOV-3 cell lines in combination with five different AFs from patients diagnosed with this disease, confirming that all tested AFs increased fucosylation. Then, we demonstrate that mRNAs of these three enzymes were overexpressed in the three cell lines under treatment with AFs. SKOV-3 showed the higher overexpression of Fut 2, Fut 4, and Fut 8 in comparison with the control condition. We further confirmed, in the SKOV-3 cell line, by endpoint PCR, WB, and confocal microscopy, that the three enzymes were overexpressed, being Fut 4 the most overexpressed enzyme compared to Fut 2 and Fut 8. These enzymes were concentrated in vesicular structures with a homogeneous distribution pattern throughout the cytoplasm. Moreover, we found that among the three enzymes, only Fut 4 was located inside the nuclei. The nuclear location of Fut 4 was confirmed for the three cell lines. These results allow to propose Fut 2, Fut 4, and Fut 8 as potential targets for EOC treatment or as diagnostic tools for this disease.

Morbidity and mortality in hip surgery patients due to fracture during the COVID-19 pandemic.

BACKGROUND: The COVID-19 epidemic generated major changes in general surgical management protocols. The literature has reported high mortality rates for hip fracture surgery in patients with COVID-19. This study describes the morbidity and mortality in patients undergoing surgery due to hip fractures in 12 Colombian institutions between March and September 2020. METHODOLOGY: This was a retrospective observational descriptive study. Medical records of 12 hospitals were reviewed. Consecutive patients who underwent hip fracture surgery from March 6 to September 6, 2020, were included. Data collected were sociodemographic profile, type of fracture, surgical treatment, complications, and early (1 month) or mid-term (1-6 months) mortality associated or not with COVID-19. RESULTS: Five hundred twenty patients with hip fractures requiring surgery in the 12 institutions were included. 364 (70%) were women; mean age was 77.7 years (SD: 13.8), mean BMI was 25.1, 91.73% of patients had at least one comorbidity, 60.38% were classified as ASA II and 25.77% as ASA III. There were 267 (51.34%) pertrochanteric fractures, 227 (43.65%) femoral neck fractures, and 26 (5.0%) subtrochanteric fractures. 274 (52.69%) patients were treated with osteosynthesis, 244 (46.92%) with arthroplasty, and 2 (0.38%) with girdlestone. Surgery was performed less than 24 h after the fracture for 115 (22.11%) patients, between 24 and 72 h for 208 (40.0%) patients, and more than 72 h for 197 (37.88%) patients. One hundred six patients in total suffered a medical or surgical complication throughout the different follow-up stages, amongst the most frequent were respiratory failure, coronary events, surgical site infection, cutting-out and peri­implant fracture. 25 (4.8%) patients required attention in the Intensive Care Unit (ICU). 13 patients had COVID-19 throughout the follow-up period. 27 patients died due to any cause, and 3 of them had reported a positive COVID-19 test any time during follow-up period, of which one died during the first month, and two died between 1 and 6 months. Statistically significant associations were found between age older than 75 years old, ASA classification, ICU requirement, and death. CONCLUSION: 520 patients received surgical treatment for hip fracture during the first six months of the COVID-19 pandemic in 12 medical centers in Colombia. 21.10% suffered a complication during the early stage (30 days) and 4.77% during the midterm stage (1-6 months). 4.8% were admitted in the ICU during the early stage. All-cause death was 27 patients, early death was 11 (40.74%) and midterm death was 16 (59.25%). 13 patients were positive for COVID-19, 3 died, one (1/5=20%) on the first 30 days and the other two (2/8=25%) from month 1 to 6.

Reduced Number of Thymoma CTLA4-Positive Cells Is Associated With a Higher Probability of Developing Myasthenia Gravis.

BACKGROUND AND OBJECTIVES: Myasthenia gravis (MG) is an autoimmune disease associated with comorbid thymoma in 10%-15% of cases. Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) expressed by T cells downregulates T-cell-mediated immune response. Polymorphisms in the CTLA4 gene have been associated with the development of MG. In this context, we aimed to determine whether CTLA4 expression in the thymoma differs between patients with and without MG and whether CTLA4 gene polymorphisms are associated with these differences. METHODS: This is a retrospective study of all patients, with and without MG, surgically treated at our institution for thymoma between January 2010 and December 2020. Ten samples were obtained from normal thymuses as controls. The number of CTLA4-positive cells in paraffin-embedded thymoma samples was determined by immunohistochemistry. The presence of follicular-center and regulatory T-cell lymphocytes was determined by immunohistochemistry (B-cell lymphoma [BCL]-6 expression) and double immunofluorescence-based staining of CD4-FOXP3, respectively. We evaluated the association between thymic expression of CTLA4 and the development of MG. We also determined the association between CTLA4 expression and various clinical and prognostic characteristics of MG. We sequenced the CTLA4 gene and evaluated possible associations between CTLA4 polymorphisms and thymic CTLA4 expression. Finally, we assessed the potential association between these polymorphisms and the risk of MG. RESULTS: Forty-one patients with thymoma were included. Of them, 23 had comorbid MG (56.1%). On average, patients with MG had fewer CTLA4-positive cells in the thymoma than non-MG patients: 69.3 cells/mm2 (95% CIs: 39.6-99.1) vs 674.4 (276.0-1,024.0) cells/mm2; p = 0.001 and vs controls (200.74 [57.9-343.6] cells/mm2; p = 0.02). No between-group differences (MG vs non-MG) were observed in the number of cells positive for BCL6 or CD4-FOXP3. CTLA4 expression was not associated with differences in MG outcome or treatment refractoriness. Two polymorphisms were detected in the CTLA4 gene, rs231770 (n = 30 patients) and rs231775 (n = 17). MG was present in a similar proportion of patients for all genotypes. However, a nonsignificant trend toward a lower CTLA4-positive cell count was observed among carriers of the rs231775 polymorphism vs noncarriers: 77.9 cells/mm2 (95% CI: -51.5 to 207.5) vs 343.3 cells/mm2 (95% CI: 126.2-560.4). DISCUSSION: Reduced CTLA4 expression in thymoma may predispose to a higher risk of developing MG.

Results in mediastinal lymph node staging of surgical lung cancer: Data from the prospective cohort of the Spanish Video-Assisted Thoracic Surgery Group.

OBJECTIVES: The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS). METHODS: A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3 cm. RESULTS: The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3 cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44-0.79) and 0.71 (0.66-0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52-2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3 cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed. CONCLUSIONS: CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3 cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3 cm but does not vary significantly as a function of whether patients have undergone invasive testing.

New perspectives in the management of small cell lung cancer.

The treatment of small cell lung cancer (SCLC) is a challenge for all specialists involved. New treatments have been added to the therapeutic armamentarium in recent months, but efforts must continue to improve both survival and quality of life. Advances in surgery and radiotherapy have resulted in prolonged survival times and fewer complications, while more careful patient selection has led to increased staging accuracy. Developments in the field of systemic therapy have resulted in changes to clinical guidelines and the management of patients with advanced disease, mainly with the introduction of immunotherapy. In this article, we describe recent improvements in the management of patients with SCLC, review current treatments, and discuss future lines of research.

New horizons for uncommon mutations in non-small cell lung cancer: BRAF, KRAS, RET, MET, NTRK, HER2.

The 2004 discovery of EGFR mutations, followed by ALK rearrangements, ushered in a targeted therapy era for advanced non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with NSCLC. In the last decade, rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted strategies. Recent genome studies of lung adenocarcinoma have identified other possible therapeutic targets, including RET, NTRK fusions, c-MET alterations, and activating mutations in KRAS, BRAF, and HER2, all with frequencies greater than 1%. Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical development. This review updates the therapeutic arsenal that especially targets those genes.

PHD finger protein 20-like protein 1 (PHF20L1) in ovarian cancer: from its overexpression in tissue to its upregulation by the ascites microenvironment.

BACKGROUND: Ovarian cancer is the most aggressive gynecological malignancy. Transcriptional regulators impact the tumor phenotype and, consequently, clinical progression and response to therapy. PHD finger protein 20-like protein 1 (PHF20L1) is a transcriptional regulator with several isoforms, and studies on its role in ovarian cancer are limited. We previously reported that PHF20L1 is expressed as a fucosylated protein in SKOV-3 cells stimulated with ascites from patients with ovarian cancer. METHODS: We decided to analyze the expression of PHF20L1 in ovarian cancer tissues, determine whether a correlation exists between PHF20L1 expression and patient clinical data, and analyze whether ascites can modulate the different isoforms of this protein. Ovarian cancer biopsies from 29 different patients were analyzed by immunohistochemistry, and the expression of the isoforms in ovarian cancer cells with or without exposure to the tumor microenvironment, i.e., the ascitic fluid, was determined by western blotting assays. RESULTS: Immunohistochemical results suggest that PHF20L1 exhibits increased expression in sections of tumor tissues from patients with ovarian cancer and that higher PHF20L1 expression correlates with shorter progression-free survival and shorter overall survival. Furthermore, western blotting assays determined that protein isoforms are differentially regulated in SKOV-3 cells in response to stimulation with ascites from patients with epithelial ovarian cancer. CONCLUSION: The results suggest that PHF20L1 could play a relevant role in ovarian cancer given that higher PHF20L1 protein expression is associated with lower overall patient survival.

Study protocol for an observational cohort evaluating incidence and clinical relevance of perioperative elevation of high-sensitivity troponin I and N-terminal pro-brain natriuretic peptide in patients undergoing lung resection.

INTRODUCTION: Myocardial injury after non-cardiac surgery has been defined as myocardial injury due to ischaemia, with or without additional symptoms or ECG changes occurring during or within 30 days after non-cardiac surgery and mainly diagnosed based on elevated postoperative cardiac troponin (cTn) values. In patients undergoing thoracic surgery for lung resection, only postoperative cTn elevations are seemingly not enough as an independent predictor of cardiovascular complications. After lung resection, troponin elevations may be regulated by mechanisms other than myocardial ischaemia. The combination of perioperative natriuretic peptide measurement together with high-sensitivity cTns may help to identify changes in ventricular function during thoracic surgery. Integrating both cardiac biomarkers may improve the predictive value for cardiovascular complications after lung resection. We designed our cohort study to evaluate perioperative elevation of both high-sensitivity troponin I (hs-TnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients undergoing lung resection and to establish a risk score for major cardiovascular postoperative complications. METHODS AND ANALYSIS: We will conduct a prospective, multicentre, observational cohort study, including 345 patients undergoing elective thoracic surgery for lung resection. Cardiac biomarkers such as hs-TnI and NT-proBNP will be measured preoperatively and at postoperatively on days 1 and 2. We will calculate a risk score for major cardiovascular postoperative complications based on both biomarkers' perioperative changes. All patients will be followed up for 30 days after surgery. ETHICS AND DISSEMINATION: All participating centres were approved by the Ethics Research Committee. Written informed consent is required for all patients before inclusion. Results will be disseminated through publication in peer-reviewed journals and presentations at national or international conference meetings. TRIAL REGISTRATION NUMBER: NCT04749212.

Clinical characteristics and outcomes of thymoma-associated myasthenia gravis.

BACKGROUND AND PURPOSE: Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, it is not clear whether thymoma recurrence or unresectable lesions entail a worse prognosis of MG. METHODS: This multicenter study was based on data from a Spanish neurologist-driven MG registry. All patients were aged >18 years at onset and had anti-acetylcholine receptor antibodies. We compared the clinical data of thymomatous and nonthymomatous patients. Prognosis of patients with recurrent or nonresectable thymomas was assessed. RESULTS: We included 964 patients from 15 hospitals; 148 (15.4%) had thymoma-associated MG. Median follow-up time was 4.6 years. At onset, thymoma-associated MG patients were younger (52.0 vs. 60.4 years, p < 0.001), had more generalized symptoms (odds ratio [OR]: 3.02, 95% confidence interval [CI]: 1.95-4.68, p < 0.001) and more severe clinical forms according to the Myasthenia Gravis Foundation of America (MGFA) scale (OR: 1.6, 95% CI: 1.15-2.21, p = 0.005). Disease severity based on MGFA postintervention status (MGFA-PIS) was higher in thymomatous patients at 1 year, 5 years, and the end of follow-up. Treatment refractoriness and mortality were also higher (OR: 2.28, 95% CI: 1.43-3.63, p = 0.001; hazard ratio: 2.46, 95% CI: 1.47-4.14, p = 0.001). Myasthenic symptoms worsened in 13 of 27 patients with recurrences, but differences in long-term severity were not significant. Fifteen thymomatous patients had nonresectable thymomas with worse MGFA-PIS and higher mortality at the end of follow-up. CONCLUSIONS: Thymoma-associated MG patients had more severe myasthenic symptoms and worse prognosis. Thymoma recurrence was frequently associated with transient worsening of MG, but long-term prognosis did not differ from nonrecurrent thymoma. Patients with nonresectable thymoma tended to present severe forms of MG.

Ascites from Ovarian Cancer Induces Novel Fucosylated Proteins.

Ovarian cancer is considered to be the most lethal type of gynecological cancer. During the advanced stages of ovarian cancer, an accumulation of ascites is observed. Fucosylation has been classified as an abnormal post-translational modification that is present in many diseases, including ovarian cancer. Ovarian cancer cells that are cultured with ascites stimulation change their morphology; concomitantly, the fucosylation process is altered. However, it is not known which fucosylated proteins are modified. The goal of this work was to identify the differentially fucosylated proteins that are expressed by ovarian cancer cell lines that are cultured with ovarian cancer patients' ascites. Aleuria aurantia lectin was used to detect fucosylation, and some changes were observed, especially in the cell membrane. Affinity chromatography and mass spectrometry (MALDI-TOF) were used to identify 6 fucosylated proteins. Four proteins (Intermediate filament family orphan 1 [IFFO1], PHD finger protein 20-like protein 1 [PHF20L1], immunoglobulin gamma 1 heavy chain variable region partial [IGHV1-2], and Zinc finger protein 224 [ZNF224]) were obtained from cell cultures stimulated with ascites, and the other two proteins (Peregrin [BRPF1] and Dystrobrevin alpha [DTNA]) were obtained under normal culture conditions. The fucosylated state of some of these proteins was further analyzed. The experimental results show that the ascites of ovarian cancer patients modulated the fucosylation process. The PHD finger protein 20-like protein 1, Zinc finger protein 224 and Peregrin proteins colocalize with fucosylation at different levels.

Biological and toxicological evaluation of Rhus trilobata Nutt. (Anacardiaceae) used traditionally in mexico against cancer.

BACKGROUND: Rhus trilobata Nutt. (Anacardiaceae) (RHTR) is a plant of Mexico that is traditionally used as an alternative treatment for several types of cancer. However, the phytochemical composition and potential toxicity of this plant have not been evaluated to support its therapeutic use. Therefore, this study aimed to evaluate the biological activity of RHTR against colorectal adenocarcinoma cells, determine its possible acute toxicity, and analyze its phytochemical composition. METHODS: The traditional preparation was performed by decoction of stems in distilled water (aqueous extract, AE), and flavonoids were concentrated with C18-cartridges and ethyl acetate (flavonoid fraction, FF). The biological activity was evaluated by MTT viability curves and the TUNEL assay in colorectal adenocarcinoma (CACO-2), ovarian epithelium (CHO-K1) and lung/bronchus epithelium (BEAS-2B) cells. The toxicological effect was determined in female BALB/c mice after 24 h and 14 days of intraperitoneal administration of 200 mg/kg AE and FF, respectively. Later, the animals were sacrificed for histopathological observation of organs and sera obtained by retro-orbital bleeding for biochemical marker analysis. Finally, the phytochemical characterization of AE and FF was conducted by UPLC-MSE. RESULTS: In the MTT assays, AE and FF at 5 and 18 µg/mL decreased the viability of CACO-2 cells compared with cells treated with vehicle or normal cells (p ≤ 0.05, ANOVA), with changes in cell morphology and the induction of apoptosis. Anatomical and histological analysis of organs did not reveal important pathological lesions at the time of assessment. Additionally, biochemical markers remained normal and showed no differences from those of the control group after 24 h and 14 days of treatment (p ≤ 0.05, ANOVA). Finally, UPLC-MSE analysis revealed 173 compounds in AE-RHTR, primarily flavonoids, fatty acids and phenolic acids. The most abundant compounds in AE and FF were quercetin and myricetin derivates (glycosides), methyl gallate, epigallocatechin-3-cinnamate, ß-PGG, fisetin and margaric acid, which might be related to the anticancer properties of RHTR. CONCLUSION: RHTR exhibits biological activity against cancer cells and does not present adverse toxicological effects during its in vivo administration, supporting its traditional use.

Copas de doble movilidad cementadas: sobrevida, indicaciones y medición de la calidad de vida / Cemented double mobility cups: Survival, indications and measurement of quality of life

Introducción Las copas de doble movilidad son implantes en que se introduce una cabeza protésica en un núcleo de polietileno, el cual posteriormente se articula con una copa metálica implantada en el acetábulo. Este tipo de diseño desarrollado en Francia desde la década de 1970ha demostrado disminuir el riesgo de luxación en un remplazo total de cadera. Estas copas han sido utilizadas históricamente de forma no cementada. No obstante, actualmente se pueden utilizar copas cementadas. Los objetivos de este estudio son determinar la sobrevida de las copas de doble movilidad cementadas y medir la calidad de vida de los pacientes. Materiales y métodos Se realiza un estudio multicéntrico retrospectivo, cuya indicación para la cirugía sea fracturas (61,5%), artrosis (34,6%) o tumores (3,8%). El análisis se realizó con los pacientes operados entre los años 2011-2013 y se encontraron 82 caderas operadas con copas de doble movilidad cementadas con un promedio de edad de 76 años. Resultados Se revisó una copa de doble movilidad por infección; por tanto, se obtuvo una sobrevida del 97,6% con un promedio de tiempo de seguimiento de 33,7 (29,7-37,7) meses con un IC 95%, y un promedio en la escala de Oxford de 38,2 (34,8-41,7) con un IC 95%. Discusión Se pudo concluir que la tasa de sobrevida es óptima para el tiempo de seguimiento y el puntaje promedio en la escala de Oxford es bueno si se tienen en cuenta las comorbilidades y la media de edad de los pacientes. Nivel de evidencia clínica. Nivel IV.

Background The dual mobility cups are implants where a prosthetic head is introduced into a polyethylene core, which is subsequently articulated with a metal cup to be implanted in the acetabulum. This type of design developed in France since the seventies has shown to decrease the risk of dislocation in total hip replacement. These cups have been used historically cementless, however now can be use cemented. The objectives are to determine the survival of double cemented mobility cups and to measure the quality of life of patients. Materials and methods A retrospective multicenter study was made. Patients who underwent primary surgery and whose indication for surgery is fractures (61.5%), osteoarthritis (34.6%) or tumors (3.8%) were included. The analysis was performed with patients operated between 2011 and 2013. Results The study was based in 82 hips operated with dual mobility cemented cups with a patient's average age of 76 (13.4) years old. A dual mobility cup was checked for infection therefore obtaining a survival rate of 97.6% and an average follow up of 33.7 months with 95% CI (29,7-37,7) and an average in the Oxford scale of 38.2 with 95% CI (34,8-41,7) Discussion It was concluded that the survival rate is optimal taking into account the follow up time and the average score on Oxford scale were good considering comorbidities and the average age of patients. Evidence level. IV.

Mediastinal staging by videomediastinoscopy in clinical N1 non-small cell lung cancer: a prospective multicentre study.

A quarter of patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) based on positron emission tomography-computed tomography (PET-CT) imaging have occult mediastinal nodal involvement (N2 disease). In a prospective study, endosonography alone had an unsatisfactory sensitivity (38%) in detecting N2 disease. The current prospective multicentre trial investigated the sensitivity of preoperative mediastinal staging by video-assisted mediastinoscopy (VAM) or VAM-lymphadenectomy (VAMLA).Consecutive patients with operable and resectable (suspected) NSCLC and cN1 after PET-CT imaging underwent VAM(LA). The primary study outcome was sensitivity to detect N2 disease. Secondary endpoints were the prevalence of N2 disease, negative predictive value (NPV) and accuracy of VAM(LA).Out of 105 patients with cN1 on imaging, 26% eventually developed N2 disease. Invasive mediastinal staging with VAM(LA) had a sensitivity of 73% to detect N2 disease. The NPV was 92% and accuracy 93%. Median number of assessed lymph node stations during VAM(LA) was 4 (IQR 3-5), and in 96%, at least three stations were assessed.VAM(LA) has a satisfactory sensitivity of 73% to detect mediastinal nodal disease in cN1 lung cancer, and could be the technique of choice for pre-resection mediastinal lymph node assessment in this patient group with a one in four chance of occult-positive mediastinal nodes after negative PET-CT.

Surgical treatment of lung cancer with synchronous adrenal metastases: Adrenalectomy first. / Tratamiento quirúrgico de metástasis suprarrenal sincrónica de cáncer de pulmón: adrenalectomía primero.

INTRODUCTION: The aim of this study is to present our patients with lung cancer and synchronous adrenal metastases treated with a reversal approach: starting with adrenalectomy and doing the lung resection second. METHODS: A total of 108 laparoscopic adrenalectomies were performed, and we analyze a consecutive serie of 10 patients with isolated adrenal synchronous metastases from the lung, surgically treated in a sequential way. All patients underwent staging mediastinoscopy, and patients with positive lymph nodes were primary treated with chemotherapy. We analyze: postoperative morbidity, length of stay, time between the 2surgeries, suvival free progression and global survival. Survival analysis was performed by the Kaplan-Meier method. RESULTS: Mean age: 56.8 (41-73) years old. Of the total, 8 patients were surgically performed by laparoscopy. Metastases average size: 5.9 (3-10) cm. Days between the 2surgeries were 28 (12-35) days. No morbidity after adrenalectomy. Length of stay was 4.3 (3-5) days. Disease-free survival at 2 years was 60%, the 5-year overall survival was 30%, with a median survival of 41.5 (0-98) months. CONCLUSIONS: Adrenalectomy involves no significant morbidity and can be performed safely without delaying lung surgery, and allows us to operate the primary lung tumor successfully as long as we ensure complete resection of the adrenal gland. A multidisciplinary oncology committee must individualize all cases and consider this therapeutic approach in all patients with resectable primary tumor and resectable adrenal metastases.

The translational blocking of α5 and α6 integrin subunits affects migration and invasion, and increases sensitivity to carboplatin of SKOV-3 ovarian cancer cell line.

Epithelial ovarian cancer is the most lethal gynecologic malignancy. Integrins, overexpressed in cancer, are involved in various processes that favor the development of the disease. This study focused on determining the degree of involvement of α5, α6 and ß3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the α5, α6 and ß3 integrins was blocked using morpholines, generating morphant cells for these proteins, which were corroborated by immunofluorescence assays. WST-1 proliferation assay showed that silencing of α5, α6, and ß3 integrins does not affect the survival of morphants. Wound healing and transwell chamber assays showed that blocking α5 and α6 integrins decrease, in lesser and greater level respectively, the migratory and the invasive capacity of SKOV-3 cells. Finally, blocking α5 and α6 integrins partially sensitized the cells response to carboplatin, while blocking integrin ß3 generated resistance to this drug. Statistical analyses were performed with the GraphPad Prism 5.0 software employing one way and two-way ANOVA tests; data are shown as average±SD. Results suggest that α5 and α6 integrins could become good candidates for chemotherapy targets in EOC.

Proteomic identification of fucosylated haptoglobin alpha isoforms in ascitic fluids and its localization in ovarian carcinoma tissues from Mexican patients.

BACKGROUND: Ovarian cancer is the most lethal gynecologic disease due to delayed diagnosis, and ascites production is a characteristic of patients in advanced stages. The aim of this study was to perform the proteomic analysis of ascitic fluids of Mexican patients with ovarian carcinoma, in order to detect proteins with a differential expression pattern in the continuing search to identify biomarkers for this disease. METHODS: Samples were collected from 50 patients from the Instituto Nacional de Cancerología of México under informed consent and with approval of the bioethics and scientific committees. After elimination of abundant proteins (Albumin/IgGs) samples were processed for 2D electrophoresis and further protein identification by Mass Spectrometry (MALDI-TOF). Molecules of interest were followed by western blot and lectin binding assays, and their tissue location by histo-immunofluorescence and confocal analysis. RESULTS AND DISCUSSION: An area with a differential expression pattern among samples was located in the 2D gels. Identified proteins were 6 alpha 1 isoforms and 1 alpha 2 isoform of Haptoglobin, and 2 isoforms of Transthyretin. While Transthyretin isoforms were constitutively expressed in all samples, clear differences in the expression pattern of Haptoglobin alpha isoforms were found. Moreover, increased levels of fucosylation of Haptoglobin alpha isoforms analyzed in 40 samples by Aleuria aurantia lectin binding by 1D overlay assay showed a positive correlation with advanced stages of the disease. Tissue detection of Haptoglobin and its fucosylated form, by histo-immunofluorescence in biopsies of ovarian cancer, also showed a correlation with ovarian cancer progression. Moreover, results show that fucosylated Haptoglobin is produced by tumor cells. CONCLUSIONS: Increased numbers of highly fucosylated Haptoglobin alpha isoforms in ascitic fluids and the presence of fucosylated Haptoglobin in tumor tissues of ovarian cancer Mexican patients associated with advanced stages of the disease, reinforce the potential of fucosylated Haptoglobin alpha isoforms to be characterized as biomarkers for disease progression.

Diseño e implementación del sistema integrado de información para la E.S.E. Hospital San Rafael de Fusagasugá 2004 / Design and implementation of the integrated system of information for the E.S.E. Hospital San Rafael of Fusagasuga 2004

La E.S.E. Hospital San Rafael de Fusagasuga en Cundinamarca, presta servicios en los niveles I, II y algunos del III nivel de atención, para alrededor de 200.000 y 300.000 usuarios potenciales de la región del Sumapaz, los cuales pertenecen a diversos regímenes de salud y poseen diferentes beneficios de atención. Dentro de los problemas actuales del Hospital se encuentra que los procesos y procedimientos están desactualizados, y que se tiene un sistema de información insuficiente y desintegrado, lo que lleva a la inadecuada gestión dentro de las áreas, ineficiente prestación de los servicios de salud, aumento de las glosas y de los costos operativos; todo ello se traduce en insatisfacción de los usuarios por múltiples razones entre ellas, la insuficiente información acerca de los trámites concernientes a la atención, los largos períodos de espera en asignación de citas y consecución de documentos, además de los excesivos filtros para acceder a los servicios. Por otro lado, se hace necesario que la administración del Hospital tenga conocimiento de las necesidades tanto internas como las de la población, mediante indicadores que reflejen la situación real de la organización y de la comunidad, para poder destinar los recursos al fortalecimiento de los servicios más requeridos por la población, a la implementación de medidas de control de la gestión en las diferentes áreas, a la redefinición de funciones de su personal; finalmente esto será un gran aporte para la región, ya que con la adecuada intervención del sector salud se contribuye al mejoramiento de la calidad de vida de la población. Por lo tanto se propone realizar el montaje y puesta en marcha del sistema integrado de información para la E.S.E. Hospital San Rafael de Fusagasugá en un término de dieciocho meses, por medio del diseño e implementación de un software modular, con un costo aproximado de seiscientos veinte millones de pesos. Paralelamente se desarrollarán los proyectos de definición y doc.

Presión Arterial en niños escolares de la ciudad de Quito

Se realizó un estudio transversal en niños escolares de la Ciudad de Quito, para medir la presión arterial sistólica, mediante el método auscultatorio con mangos pediátricos adecuados y tensiómetros de mercurio precalibrados. Se tomó la presión a 225 niños varones y mujeres entre seis y doce años, observándose un comportamiento irregular en los grupos de edad, pero generalmente con una tendencia a aumentar la presión en relación directa a la edad. Además se pudo observar que la presión en relación directa a la edad. Además se pudo observar que la presión arterial es mayor en varones que en mujeres. Los valores de presión arterial en niños de Quito (2818 m. s.n.m.) es menor que en otras poblaciones estudiadas en E.E.U.U. y México. Se exponen curvas promedio, cuadros percentilares, curvas comparativas de presión arterial, elaboradas en base a las variables de peso, talla, edad, y sexo.