Preliminary results of a vaginal constraint for reducing G2 late vaginal complications after postoperative brachytherapy in endometrial cancer: a prospective analysis.

PURPOSE: To evaluate the preliminary results of the use of 68 Gy EQD2(α/ß=3 Gy) as a dose limit to the lowest dose in the most exposed 2 cm3 of the vagina in order to reduce G2 late vaginal problems in postoperative endometrial carcinoma (EC). METHODS: From November 2016 to October 2019, 69 postoperative EC patients receiving vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) were prospectively analyzed. The median EBRT dose was 45 Gy (range: 44-50.4 Gy), 1.8-2 Gy/day, 5 fractions(Fr)/week. VBT was administered with the following schedule: 1Fr of 7 Gy after EBRT and 2 daily Fr × 7.5 Gy in exclusive VBT. The dose was prescribed at 0.5 cm from the applicator surface with an active length of 2.5 cm; 56 patients were treated with vaginal cylinders (49-3.5 cm, 6-3 cm, and 1-2.5 cm) and 13 with the colpostat technique. The overall VBT dose was adjusted to meet the vaginal restriction of < 68 Gy EQD2(α/ß=3 Gy) at 2 cm3. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum, and the objective LENT-SOMA criteria for vagina. RESULTS: With a median follow-up of 31.0 months, no vaginal-cuff recurrences were found. Late toxicity: only 1G1(1.4%) rectal toxicity; 21G1(30.4%) and 3G2(4.3%) vaginal complications. Only one (1.4%) of 3 G2 manifested as vaginal shortening. CONCLUSIONS: In postoperative EC patients treated with VBT, only one developed G2 vaginal stenosis with the use of 68 Gy EQD2(α/ß=3 Gy) as a dose constraint. These preliminary results seem to indicate the value of this dose limit for reducing G2 vaginal stenosis. Nonetheless, these findings should be confirmed in a larger number of patients with longer follow-up.

Chronic toxicity and long-term outcome in intraoperative electron radiotherapy as boost followed by whole-breast irradiation.

PURPOSE: The administration of a dose boost to the tumor bed after breast-conserving surgery has proven to reduce local recurrence. Intra-operative electron radiotherapy (IOERT) offers an alternative method to deliver a boost with several advantages, such as direct visualization of the tumor bed, less inter- and intrafraction motion and a reduction in the number of medical appointments. The objective of our study is to assess chronic toxicity and long-term outcome for our patients after IOERT boost. MATERIAL AND METHODS: Forty-six patients treated at our institution between July 2013 and June 2020 with IOERT boost during Breast-Conserving Surgery and consecutive whole breast irradiation were prospectively analyzed. A 10-12 Gy boost was prescribed to 42 patients and 4 patients received a 20 Gy boost. An analysis for overall survival, local relapse and distant progression was performed. Acute and chronic toxicity was assessed by CTCAE 4.0. RESULTS: The median age was 64.5 years (40-90). The median follow-up was 62 months (4-86). We had no local recurrences but 2 patients (4.3%) presented a distant recurrence. Mean pathological tumor size was 16 mm (6-52). 84.8% (39) of the patients had invasive ductal carcinoma. 52.2% (24) presented histological grade II. 52.2% (24) were Luminal A like, 21.7% (10) Luminal B like, 13% (6) HER2 positive, 13% (6) triple negative. No Grade 3-4 chronic toxicity was observed. Grade 1-2 fibrosis was evidenced in 13% (6) of the patients, 4.3% (2) patients presented fat necrosis, 6.5% (3) presented seroma, 4.3% (2) had localized pain, 2.2% (1) presented localized hematoma and 2.2% (1) presented localized edema. CONCLUSIONS: IOERT boost in breast cancer treatment during BCS is a safe option with low chronic toxicity. The recurrence rates are comparable to published data and emphasize that IOERT as boost is an effective treatment.

LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells.

Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy.

Is one brachytherapy fraction of 7 Gy similar to more fractions after external beam irradiation in postoperative endometrial carcinoma?

PURPOSE: To determine whether brachytherapy with a single hypofractionated dose of 7 Gy provides the similar vaginal-cuff relapses and safety profile in terms of complications compared to schedules of 2 or 3 fractions of lower doses in patients treated previously with external beam irradiation in postoperative endometrial carcinoma. METHODS/MATERIAL: From June 2003 to December 2016, 325 patients were treated with 3 different schedules of high-dose-rate brachytherapy after external beam irradiation for postoperative endometrial carcinoma. The patients were divided into 3 groups: Group-1: 125 patients were treated with 3 fractions of 4-6 Gy per fraction (3 fractions/week) between 2003 and 2008; Group-2: 93 patients were treated with 2 consecutive daily fractions of 5-6 Gy between 2008 and 2011; Group-3: 107 patients received a single fraction of 7 Gy between 2011 and 2016. Bladder and rectum complications were assessed using RTOG scores and with the objective scores of LENT-SOMA for the vagina. STATISTICS: the chi-square test. RESULTS: The mean follow-up of Groups 1, 2 and 3 was 95, 67 and 51 months, respectively. Three patients in Group-1, 2 in Group-2, 1 in Group-3 developed vaginal-cuff relapse (p = 0.68). No differences were found in late toxicity among the three groups. CONCLUSIONS: One single dose of 7 Gy is safe and effective and may be the best treatment schedule with a similar incidence of vaginal-cuff relapses, complications and patient comfort with less hospital attendance.

Are endometrial cancer radiotherapy results age related?

OBJECTIVE: To analyze the impact of age on radiotherapy results based on cancer-specific survival (CSS), vaginal-cuff relapses (VCR) and complications analysis in 438 patients with endometrial carcinoma (EC) receiving postoperative radiotherapy (PRT) divided into three age groups for analysis. MATERIALS AND METHODS: From 2003 to 2015, 438 patients with EC were treated with PRT and divided into three age groups: Group-1: 202 patients < 65 years; Group-2: 210 patients ≥ 65 and < 80 years; Group-3: 26 patients ≥ 80 years. Vaginal toxicity was assessed using the objective LENT-SOMA criteria and RTOG scores were recorded for the rectum, bladder, and small bowel. STATISTICS: Chi square and Student's t tests, Kaplan-Meier survival study for analysis of CSS. RESULTS: The mean follow-up was 5.6 years in Group-1, 5.6 years in Group-2 and 6.3 years in Group-3 (p = 0.38). No differences were found among the groups in distribution of stage, grade, myometrial invasion, Type 1 vs. 2 EC and VLSI (p = 0.97, p = 0.52, p = 0.35, p = 0.48, p = 0.76, respectively). There were no differences in rectal, bladder and vagina late toxicity (p = 0.46, p = 0.17, p = 0.75, respectively). A better CSS at 5 years was found in Group-1 (p = 0.006), and significant differences were found in late severe small bowel toxicity in Group-3 (p = 0.005). VCR was increased in Group-3 (p = 0.017). CONCLUSIONS: Patients ≥ 65 years had a worse outcome in comparison to younger patients. Late vaginal, rectal and bladder toxicities were similar in the three groups, although an increase of severe late small bowel toxicity led to IMRT in patients ≥ 80 years. Further larger studies are needed including quality of life analysis in patients ≥ 80 years.

[Cardiovascular risk and cardiovascular events in the general population of the sanitary area of Toledo. RICARTO Study]. / Justificación, objetivos y diseño metodológico del estudio RICARTO (RIesgo CARdiovascular y eventos cardiovasculares en la población general del área sanitaria de TOledo).

INTRODUCTION: The main aim of this study is to ascertain the prevalence of cardiovascular risk factors (CVRF), target organ damage (TOD), cardiovascular disease (CVD), as well as life habits (physical exercise, alcohol consumption, and Mediterranean diet) in the population of a Health Area in Toledo, Spain, to assess cardiovascular risk (CVR). MATERIAL AND METHODS: Epidemiological and observational study that will analyse a sample from the general population aged 18 years or older, randomly selected from a database of health cards, and stratified by age and gender. Clinical history, physical examination, and complementary tests will be performed. Aliquots of whole blood and serum samples will be stored at a temperature of-85°C to evaluate future genetic studies. CVR will be estimated by using SCORE project scales calibrated for Spanish population and the Framingham Heart Study scale. When the estimated sample size has been achieved and after a minimum follow-up of 5 years, a final visit will performed in which CVRF, TOD, CVD, CVRF control, and fatal and non-fatal outcomes will be evaluated. DISCUSSION: The RICARTO study is aimed to assess the prevalence of the main CVRF, TOD and CVD in order to determine the CVR in the general population of a health area of Toledo. An analysis will be repeated on the final sample after at least 5 years of follow-up to ascertain the incidence of CV outcomes and the temporal trends of life style, as well as the prevalence of CVRF, TOD, and CVD.

[Characteristics and cardiovascular events in a general population included in the RICARTO (RIesgo CARdiovascular TOledo) study: Data from the first 1,500 individuals included in the study]. / Características de la población general incluida en el estudio RICARTO (RIesgo CARdiovascular y eventos cardiovasculares en la población general del área sanitaria de TOledo): resultados con los primeros 1.500 individuos incluidos en el estudio.

INTRODUCTION: The aim of this study was to assess cardiovascular risk (CVR) by investigating the prevalence of CVR factors (CVRF), target organ damage (TOD), and cardiovascular disease (CVD) in general population of the health area of Toledo, Spain. MATERIAL AND METHODS: Epidemiological and observational study that analysed a sample from the general population aged 18years or older, randomly selected from a database of health cards stratified by age and gender. Clinical history, physical examination, and complementary tests were performed. Total blood and serum samples were frozen at -85°C to evaluate genetic studies in the future. Standard statistical analysis was performed. CVR was assessed by the SCORE scale calibrated for the Spanish population, and the Framingham Heart Study scale. RESULTS: A total of 1,500 individuals (mean age 49.1±15.8years, 55.6% women) were included. Prevalences: dyslipidaemia 56.9% (95% confidence interval [95% CI]: 54.3-59.4), hypertension 33.0% (95%CI: 30.6-35.4), diabetes mellitus 8.6% (95%CI: 7.17-10.1), smoking 24.2% (95%CI; 122.0-26.4), obesity 25.3% (95%CI; 23.1-27.5), and sedentary life-style 39.4% (95%CI; 36.9-41.8). No CVRF was reported in 21.1% of cases, and 18.6% had 3-5 CVRF. TOD: electrocardiographic left ventricular hypertrophy, 4.3%, peripheral artery disease, 10.1% (Doppler ultrasound), and 15.3% (oscillometric device), microalbuminuria, 4.3%, sub-clinical renal disease, 3.2%, and nephropathy in 3.8% (CKD-EPI). At least one CVD was reported in 9.2% of cases. A low CVR (SCORE) was present in 44.6% of individuals. CONCLUSIONS: Dyslipidaemia was found in 60% of individuals, 40% had a sedentary life-style, 30% with hypertension, 20% smoked, 20% obesity, and almost 10% with diabetes. More than a half of individuals have a moderate-high-very high risk. The prevalence of TOD and CVD are significant.

Activation of CK1ɛ by PP2A/PR61ɛ is required for the initiation of Wnt signaling.

This corrects the article DOI: 10.1038/onc.2016.209.

Activation of CK1ɛ by PP2A/PR61ɛ is required for the initiation of Wnt signaling.

Canonical Wnt signaling induces the stabilization of ß-catenin, its translocation to the nucleus and the activation of target promoters. This pathway is initiated by the binding of Wnt ligands to the Frizzled receptor, the association of the LRP5/6 co-receptor and the formation of a complex comprising Dvl-2, Axin and protein kinases CK1α, ɛ, γ and GSK3. Among these, activation of CK1ɛ, constitutively bound to LRP5/6 through p120-catenin, is required for the association of the rest of the components. We describe here that CK1ɛ is activated by the PP2A/PR61ɛ phosphatase. Binding of Wnt ligands promotes the interaction of LRP5/6-associated CK1ɛ with Frizzled-bound PR61ɛ regulatory subunit, facilitating the access of PP2A catalytic subunit to CK1ɛ and its activation, what enables the recruitment of Dvl-2 to the receptor complex and the initiation of the Wnt pathway. Our results uncover the mechanism of activation of the canonical Wnt pathway by its ligands.

Vaginal-cuff control and toxicity results of a daily HDR brachytherapy schedule in endometrial cancer patients.

PURPOSE: To analyze the vaginal-cuff local control (VCC) and toxicity in postoperative endometrial carcinoma patients (EC) underwent high-dose-rate brachytherapy (HDR-BT) administered daily. MATERIALS AND METHODS: 154 consecutive patients received postoperative HDR-BT for EC from January 2007 to September 2011. FIGO-staging I-IIIC2 patients were divided into two groups according to risk classification: Group 1 (94/154) included high-risk or advanced disease patients and Group 2 (60/154) included intermediate-risk EC patients. Group 1 underwent external beam irradiation (EBI) plus HDR-BT (2 fractions of 5 Gy) and Group 2 underwent HDR-BT alone (4 fractions of 5 Gy). Toxicity evaluation was done with RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. RESULTS: With a median follow-up of 46.7 months (36.6-61 months) only two patients developed vaginal-cuff recurrence in Group 1 (2.1 %) and none in group 2 (0 %). Early toxicity in Group 1 appeared 5.3 % in rectum, 7.5 % in bladder (G1-G2) and 2.1 % in vagina (G1); late toxicity was present in 7.3 % in rectum (all G1-G2 but 1 G3) and in 27.7 % in vagina (all G1-G2 but one G4). In Group 2, 6.7 % developed acute G1-G2 bladder and 6.6 % acute vaginal (G1-G2) toxicity. No late rectal or bladder toxicity was observed; 21.7 % of G1-G2 presented late problems in vagina. CONCLUSIONS: The present HDR-BT schedule of 2 fractions of 5 Gy after EBI and 4 fractions of 5 Gy administered daily showed excellent results in terms of VCC and toxicity.

Reprogramming human B cells into induced pluripotent stem cells and its enhancement by C/EBPα.

B cells have been shown to be refractory to reprogramming and B-cell-derived induced pluripotent stem cells (iPSC) have only been generated from murine B cells engineered to carry doxycycline-inducible Oct4, Sox2, Klf4 and Myc (OSKM) cassette in every tissue and from EBV/SV40LT-immortalized lymphoblastoid cell lines. Here, we show for the first time that freshly isolated non-cultured human cord blood (CB)- and peripheral blood (PB)-derived CD19+CD20+ B cells can be reprogrammed to iPSCs carrying complete VDJH immunoglobulin (Ig) gene monoclonal rearrangements using non-integrative tetracistronic, but not monocistronic, OSKM-expressing Sendai Virus. Co-expression of C/EBPα with OSKM facilitates iPSC generation from both CB- and PB-derived B cells. We also demonstrate that myeloid cells are much easier to reprogram than B and T lymphocytes. Differentiation potential back into the cell type of their origin of B-cell-, T-cell-, myeloid- and fibroblast-iPSCs is not skewed, suggesting that their differentiation does not seem influenced by 'epigenetic memory'. Our data reflect the actual cell-autonomous reprogramming capacity of human primary B cells because biased reprogramming was avoided by using freshly isolated primary cells, not exposed to cytokine cocktails favoring proliferation, differentiation or survival. The ability to reprogram CB/PB-derived primary human B cells offers an unprecedented opportunity for studying developmental B lymphopoiesis and modeling B-cell malignancies.

Data from proteomic characterization of the role of Snail1 in murine mesenchymal stem cells and 3T3-L1 fibroblasts differentiation.

The transcription factor (TF) Snail1 is a major inducer of the epithelial-mesenchymal transition (EMT) during embryonic development and cancer progression. Ectopic expression of Snail in murine mesenchymal stem cells (mMSC) abrogated their differentiation to osteoblasts or adipocytes. We used either stable isotopic metabolic labeling (SILAC) for 3T3-L1 cells or isobaric labeling with tandem mass tags (TMT) for mMSC stably transfected cells with Snail1 or control. We carried out a proteomic analysis on the nuclear fraction since Snail is a nuclear TF that mediates its effects mainly through the regulation of other TFs. Proteomics data have been deposited in ProteomeXchange via the PRIDE partner repository with the dataset identifiers PXD001529 and PXD002157 (Vizcaino et al., 2014) [1]. Data are associated with a research article published in Molecular and Cellular Proteomics (Pelaez-Garcia et al., 2015) [2].

Recommendations of the Spanish Brachytherapy Group of SEOR for HDR endoluminal treatments. Part 1: Oesophagus.

The endoesophageal brachytherapy technique provides good results in the treatment of oesophageal cancer, when indicated. In a consensus meeting, the Spanish Brachytherapy Group of SEOR and the Spanish Society of Medical Physics (SEFM) agreed on the indications, dose, fractionation schedule, prescription and reporting to be performed in endoesophageal brachytherapy. The results of this consensus are presented here as recommendations for medical practice.

Regulation of the protein stability of EMT transcription factors.

The epithelial to mesenchymal transition (EMT) consists of a rapid change of cell phenotype, characterized by the loss of epithelial characteristics and the acquisition of a more invasive phenotype. Transcription factors regulating EMT (Snail, Twist and Zeb) are extremely labile proteins, rapidly degraded by the proteasome system. In this review we analyze the current mechanisms controlling degradation of EMT transcription factors, focusing on the role of new E3 ubiquitin-ligases involved in EMT. We also summarize the regulation of the stability of these EMT transcription factors, specially observed in different stress conditions, such as hypoxia, chemotherapeutic drugs, oxidative stress or γ-irradiation.

Madres y padres de adolescentes urbanos: percepciones y expectativas de la atención en salud sexual y reproductiva para sus hijos / Parental perceptions and expectations about sexual and reproductive health care for urban adolescents

Studies have reported which expectations and demands adolescents have for more accessible sexual and reproductive health (SRH) services. However, there is limited information regarding parents’ requirements and demands for SRH services their adolescents need. Aim: To explore the knowledge of parents regarding SRH needs of their adolescent daughters and sons and what they demand from primary health care services (PHCS). Material and Methods: A quali-quantitative, descriptive, cross-sectional study was performed. Nine fathers and 24 mothers were interviewed to design a survey. In the quantitative phase, 125 mothers voluntarily, anonymously and confidentially were interviewed. All participants were users of PHCS of urban communities in the Metropolitan Area showing a high percentage of births by adolescents’ mothers. Data analysis was descriptive and analytical. Results: Interviews served as input to design the questionnaire. Seventy seven percent (77,6%) of interviewed mothers knew that their sons/daughters, regardless of their gender, had concern about sexuality; their main fear was adolescent pregnancy. Seventy six percent (76%) was aware that their sons/daughters might request attention in SRH clinics and 97% agreed that they should require these services during early adolescence. The most desirable features of such services were identified. Conclusions: Parents recognize that they would prefer their sons/daughters postponed sexual initiation; however, they are aware that pregnancy prevention is needed. Mothers approve SRH services. They agree that counseling to prevent pregnancies and sexual transmitted diseases (STD) and AIDS was an important issue. They require support for themselves and their sons/daughters.

[Parental perceptions and expectations about sexual and reproductive health care for urban adolescents]. / Madres y padres de adolescentes urbanos: percepciones y expectativas de la atención en salud sexual y reproductiva para sus hijos.

UNLABELLED: Studies have reported which expectations and demands adolescents have for more accessible sexual and reproductive health (SRH) services. However, there is limited information regarding parents' requirements and demands for SRH services their adolescents need. AIM: To explore the knowledge of parents regarding SRH needs of their adolescent daughters and sons and what they demand from primary health care services (PHCS). MATERIAL AND METHODS: A quali-quantitative, descriptive, cross-sectional study was performed. Nine fathers and 24 mothers were interviewed to design a survey. In the quantitative phase, 125 mothers voluntarily, anonymously and confidentially were interviewed. All participants were users of PHCS of urban communities in the Metropolitan Area showing a high percentage of births by adolescents' mothers. Data analysis was descriptive and analytical. RESULTS: Interviews served as input to design the questionnaire. Seventy seven percent (77,6%) of interviewed mothers knew that their sons/daughters, regardless of their gender, had concern about sexuality; their main fear was adolescent pregnancy. Seventy six percent (76%) was aware that their sons/daughters might request attention in SRH clinics and 97% agreed that they should require these services during early adolescence. The most desirable features of such services were identified. CONCLUSIONS: Parents recognize that they would prefer their sons/daughters postponed sexual initiation; however, they are aware that pregnancy prevention is needed. Mothers approve SRH services. They agree that counseling to prevent pregnancies and sexual transmitted diseases (STD) and AIDS was an important issue. They require support for themselves and their sons/daughters.

[Lipid profile in patients admitted with acute coronary syndrome in Spain: data from Toledo health care area between 2005 and 2008]. / Perfil lipídico en pacientes ingresados por síndrome coronario agudo en España: datos del área sanitaria de Toledo entre los años 2005 y 2008.

INTRODUCTION AND OBJECTIVES: To evaluate the lipid profile of patients admitted with acute coronary syndrome in Toledo (Spain) between 2005 and 2008. METHODS: Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride levels were evaluated. Descriptive analyses and means comparison were performed. RESULTS: 1,381 patients of 3,986 admitted with acute coronary syndrome had a complete lipid profile. The mean age was 67.8±12.9 years (72.4% men). A first event was present in 76.3%. The mean total cholesterol (±SD) was 180.0±43.4, LDL-cholesterol 115±38.0, HDL-cholesterol 44.1±12.3, and triglyceride 145.3±92.4mg/dL, with statistically significant differences between men and women in LDL-cholesterol (116.3±37.8 vs 111.6±38.5mg/dL; p=0.04) and HDL-cholesterol (42.3±11.6 vs 48.4±13.2mg/dL; p=0.0001). In first or recurrent events were found, respectively, total cholesterol 179.1±43.1 and 174.5±44.1 (p<0.05), LDL-cholesterol 116.5±38.4 and 110±36.5 (p=0.007), HDL-cholesterol 44.1±12.2 and 44.2±12.9 (p<0.05), and triglyceride 141.2±81.7 and 158.5±119.7 (p=0.03). Optimal levels of LDL-cholesterol and HDL-cholesterol were found in 14.1 and 11.6% of patients with recurrent episodes, respectively. CONCLUSIONS: While most patients admitted with first episode of acute coronary syndrome to the Toledo Health Area have a lipid profile according to current guidelines, only 10% of those with recurrent acute coronary syndrome presented optimal LDL-cholesterol and HDL-cholesterol levels, which suggest the need to be more aggressive in the lipids control.

Three or four fractions per week in postoperative high-dose-rate brachytherapy for endometrial carcinoma. The long-term results on vaginal relapses and toxicity.

BACKGROUND: High-dose-rate brachytherapy (HDR-BT) is an accepted part of treatment for endometrial carcinoma and is usually performed in 1-2 fractions per week using different total doses and doses per fraction. To reduce the overall treatment time, HDR-BT was administered with a 3-4 days/week schedule. PATIENTS AND METHODS: From June 2003 to December 2008, 164 patients with stage I-IIIc endometrial carcinoma were treated with HDR-BT (4-5 Gy per fraction). The patients were divided into two groups; Group 1 (40/164 patients) was treated with HDR-BT alone (6 fractions; 4 fractions/week) and Group 2 (124/164 patients) was treated with both (External Beam Radiotherapy [EBRT] + HDR-BT: 3 fractions/week). Complications were analyzed using RTOG scores for rectum and bladder and the objective scores of LENT-SOMA for vaginal complications. RESULTS: The mean followup was 48 months. In Group 1, 35 % of patients underwent treatment in ≤10 days and 65 % in >10 days. In Group 2, 53.2 % received treatment in ≤5 days and in 46.8 % in >5 days. Vaginal relapse was observed in only two patients (1.2 %), both having received adjuvant EBRT + HDR-BT. Acute vaginal toxicity appeared in 8.5 % and late vaginal toxicity in 20.7 % of patients with 13.4 % being G1, 6.7 % G2 and only 0.6 % being G4. No statistically significant differences were found in complications in either brachytherapy group regardless of the overall time. CONCLUSION: In our series, three fractions given in 3-5/days after EBRT or six fractions in 10 days, is a safe regimen in terms of complications and local control.

Snail1 controls TGF-ß responsiveness and differentiation of mesenchymal stem cells.

The Snail1 transcriptional repressor plays a key role in triggering epithelial-to-mesenchymal transition. Although Snail1 is widely expressed in early development, in adult animals it is limited to a subset of mesenchymal cells where it has a largely unknown function. Using a mouse model with inducible depletion of Snail1, here we demonstrate that Snail1 is required to maintain mesenchymal stem cells (MSCs). This effect is associated to the responsiveness to transforming growth factor (TGF)-ß1 that shows a strong Snail1 dependence. Snail1 depletion in conditional knockout adult animals causes a significant decrease in the number of bone marrow-derived MSCs. In culture, Snail1-deficient MSCs prematurely differentiate to osteoblasts or adipocytes and, in contrast to controls, are resistant to the TGF-ß1-induced differentiation block. These results demonstrate a new role for Snail1 in TGF-ß response and MSC maintenance.

Role of vitamin D receptor activators in peritoneal dialysis.

Chronic kidney disease (CKD), including patients on peritoneal dialysis (PD), is linked to an important increase in mortality risk. Within the new systemic term CKD-MBD, alterations in vitamin D metabolism are also included. Many adverse events have been associated with vitamin D deficiency or lack of vitamin D receptor (VDR) activation both in the general population and CKD patients, and these associations seem to be maintained in PD patients. Particularities of PD in vitamin D metabolism, calcium balance, low PTH levels and the high prevalence of adynamic bone disease are discussed. We also review the associations of clinical or survival benefits with vitamin D supplementation, VDR or selective VDR activation, although they are low-graded and most of them obtained from HD databases. Nevertheless, we think that the combined approach to secondary hyperparathyroidism seems also to be appropriate in PD patients, and vitamin D (native plus VDR or selective VDR activation) seem an important part of the required integral approach. The later may provide additional benefits but definitive prove is still lacking.