Survivorship Care in Middle-Income Countries: A Guideline Development for Colombia Using Breast Cancer as a Model.

Cancer survival has significantly increased during the past few decades, making survivorship care a key element of cancer control and posing several challenges for long-term care in low- and middle-income countries (LMIC). Most survivorship care guidelines emphasize the potential role of primary care physicians and the need for comprehensive care, with a preference for patient-centered over disease-centered approaches. However, guidelines developed in high-income countries are not always suitable for LMIC, where a shortage of oncology workforce, deficient training in primary care, and low access to comprehensive centers frequently induce undertreatment and a lack of follow-up. Despite universal health insurance coverage, Colombia has fragmented cancer care with deficient survivorship care, given its focus on relapse surveillance without integration of supportive care and comorbidity management, in addition to unequal access for low-income populations and distant regions. Using the breast cancer framework, we describe the development of a guideline for survivorship care on the basis of a risk approach and the proper integration of oncology specialists and family physicians. We used a three-phase process to develop recommendations for disease control (disease-centered review), interventions aimed at improving patients' quality of life (patient-centered review), and care delivery (delivery model review). We deem our proposal suitable for middle-income countries, which represents an input for more standardized survivorship care in these settings.

A novel RYR1 variant in an infant with a unique fetal presentation of central core disease.

Ryanodine receptor type 1-related disorder (RYR1-RD) is the most common subgroup of congenital myopathies with a wide phenotypic spectrum ranging from mild hypotonia to lethal fetal akinesia. Genetic testing for myopathies is imperative as the diagnosis informs counseling regarding prognosis and recurrence risk, treatment options, monitoring, and clinical management. However, diagnostic challenges exist as current options are limited to clinical suspicion prompting testing including: single gene sequencing or familial variant testing, multi-gene panels, exome, genome sequencing, and invasive testing including muscle biopsy. The timing of diagnosis is of great importance due to the association of RYR1-RD with malignant hyperthermia (MH). MH is a hypermetabolic crisis that occurs secondary to excessive calcium release in muscles, leading to systemic effects that can progress to shock and death if unrecognized. Given the association of MH with pathogenic variants in RYR1, a diagnosis of RYR1-RD necessitates an awareness of medical team to avoid potentially triggering agents. We describe a case of a unique fetal presentation with bilateral diaphragmatic eventrations who had respiratory failure, dysmorphic facial features, and profound global hypotonia in the neonatal period. The diagnosis was made at several months of age, had direct implications on her clinical care related to anticipated need to long-term ventilator support, and ultimately death secondary an arrhythmia as a result of suspected MH. Our report reinforces the importance of having high suspicion for a genetic syndrome and pursuing early, rapid exome or genome sequencing as first line testing in critically ill neonatal intensive care unit patients and further evaluating the pathogenicity of a variant of uncertain significance in the setting of a myopathic phenotype.

The Clonal Relationship Between the Ductal and Lobular Components of Mixed Ductal-Lobular Carcinomas Suggested a Ductal Origin in Most Tumors.

The relationship between the ductal and lobular components of invasive ductolobular carcinomas (IDLC) has not been fully elucidated. In this study, the molecular alterations of both components were analyzed in a series of 20 IDLC that were selected, not only by morphologic criteria, but also by the loss of E-cadherin expression in the lobular component. We found that 80% of tumors shared alterations of driver genes in both components, being PIK3CA the most common alteration. In addition, 45% of IDLC carried CDH1 mutations in their lobular component that were absent in the ductal component. Fluorescent in situ hybridization analysis of the CDH1 gene excluded homozygous CDH1 loss as a frequent cause of E-cadherin loss in tumors without CDH1 mutations. In addition, no pathogenic mutations of catenin genes were detected in this series of tumors. In 25% of tumors, actionable mutations in PIK3CA , AKT1 , and ERBB2 were found in only 1 component. Altogether, our results confirm that most IDLC derive from invasive carcinoma of no special type, in which a population of cells lose E-cadherin and acquire a lobular phenotype. The frequency of CDH1 mutations in IDLC appears to be lower than in conventional invasive lobular carcinomas, suggesting the implication of alternative mechanisms of E-cadherin loss. Moreover, molecular heterogeneity between ductal and lobular areas suggests the need for molecular characterization of both components to guide targeted therapies.

Fetal and postnatal MRI findings of Blake pouch remnant causing obstructive hydrocephalus.

Blake pouch remnant, also known as Blake pouch cyst or persistent Blake pouch, is a posterior fossa embryologic anomaly that is often seen in isolation with most affected patients being asymptomatic. However, even in isolation, Blake pouch remnant can result in obstructive hydrocephalus requiring early neurosurgical intervention making it an important diagnosis for the fetal radiologist to consider. We present a rare case of a patient with prenatally diagnosed "inferior vermian hypoplasia" on fetal MRI that went on to develop progressive obstructive hydrocephalus in infancy secondary to what was determined to be a Blake pouch remnant.

Prenatal diagnosis of Proteus syndrome: Diagnosis of an AKT1 mutation from amniocytes.

Proteus syndrome is a mosaic genetic overgrowth disorder caused by a postzygotic, mosaic activating mutation in AKT1. Rare prenatal presentations include segmental tissue overgrowth, and skeletal and CNS anomalies. We present the first report of prenatally diagnosed and molecularly confirmed Proteus syndrome. Prenatal imaging identified megalencephaly, brain and eye malformations, focal soft tissue enlargement, and ambiguous genitalia. Exome sequencing performed on cultured amniocytes demonstrated an AKT1 pathogenic variant consistent with Proteus syndrome, and postnatal examination confirmed the diagnosis. Postnatal Sanger sequencing could not identify the AKT1 pathogenic variant. This case underscores the importance of prenatal exome sequencing on cultured amniocytes for mosaic overgrowth disorders, as well as provides additional information on the prenatal phenotype of Proteus syndrome, and highlights the impact of prenatal diagnosis on postnatal management.

Clinical failure of nanoparticles in cancer: mimicking nature's solutions.

The use of nanotechnology has become a promising approach in the treatment of cancer. However, most intravenously injected nanoparticles (NPs) do not effectively reach the tumor mass due to the biological barriers in the body. In an attempt to unify clinical criteria and basic research, we have collected the latest studies and described novel alternatives such as the use of NPs covered with cell membranes to increase NP delivery efficiency. Furthermore, we focus on the prospect of using the cell's natural messengers, exosomes, as vehicles to transport anti-cancer agents and we discuss the technical complications involved. Finally, we propose novel approaches to produce engineered exosomes which may overcome such technical limitations in order to achieve a proper anti-cancer nanotherapy.

Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients.

BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; P = 0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.

Fetal magnetic resonance imaging of skeletal dysplasias.

BACKGROUND: Fetal magnetic resonance imaging (MRI) is obtained for prenatal diagnosis and prognostication of skeletal dysplasias; however, related literature is limited. OBJECTIVE: The purpose of this study was to define the utility of fetal MRI for skeletal dysplasias and to report MRI findings associated with specific diagnoses. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board; informed consent was waived. Women referred for suspected fetal skeletal dysplasia who underwent MRI between January 2003 and December 2018 were included. Definitive diagnoses were determined by genetic testing, autopsy, physical examination and/or postnatal/postmortem imaging. Fetal MRI examinations and reports were reviewed. Descriptive statistics were used to summarize imaging findings. RESULTS: Eighty-nine women were referred for fetal MRI for possible skeletal dysplasia. Forty-three (48%) were determined to have a diagnosis other than skeletal dysplasia and nine were excluded for lack of specific skeletal dysplasia diagnosis. Thirty-seven cases of skeletal dysplasia with available fetal MRI and specific diagnosis were included for analysis. Diagnoses included achondrogenesis (n=2), achondroplasia (n=5), Boomerang dysplasia (n=1), campomelic dysplasia (n=2), Jeune syndrome (n=1), Kniest dysplasia (n=1), osteogenesis imperfecta (n=15) and thanatophoric dysplasia (n=10). A specific skeletal dysplasia diagnosis was mentioned in 17/37 (46%) of MRI imaging reports and correct for 14/17 (82%). MRI findings were reported for each specific skeletal dysplasia diagnosis. CONCLUSION: Fetal MRI is a useful diagnostic tool for skeletal dyplasias and excluded the diagnosis in nearly half of referred pregnancies. In addition to providing fetal lung volumes, fetal MRI demonstrates findings of the brain in achondroplasia and thanatophoric dysplasia, of the spine in achondroplasia and achondrogenesis, of the calvarium in osteogenesis imperfecta and thanatophoric dysplasia, and of the cartilage in Kniest dysplasia.

Crystalline morphology of thermoplastic starch/talc nanocomposites induced by thermal processing.

A structural study about the changes induced by plasticization of native corn starch was carried out in this work. The influence of talc nanoparticles presence during starch thermal processing was also evaluated. Macroscopic observation of the granules appearance evolution during melt-mixing and thermo-compression was supported by a theoretical description related to these processing methods. Melt-mixing induced a polymorphic transformation from A- to Vh-type and a reduction in the degree of crystallinity. Homogenous appearance of the plasticized starch was in accordance to the disruption of granules integrity, evidenced by SEM. This observation agreed to the distinctive XRD pattern of plasticized starch from unprocessed granules. Talc incorporation did not require the adjustment of processing parameters in order to obtain a homogenous thermoplastic material, with an adequate particles distribution within the matrix. Regardless talc presence, plasticized starch presented a Vh-type crystalline structure. Thermo-compression led to particles alignment promoted by talc laminar morphology.

Low performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. METHODS: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used. RESULTS: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (P < 0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (P = 0.038). CONCLUSION: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.

Decreased rectal meconium signal on MRI in fetuses with open spinal dysraphism.

OBJECTIVE: To evaluate rectal meconium signal in fetuses with open spinal dysraphism and correlate findings with postnatal exam. METHODS: This is a single-institution Institutional Review Board-approved Health Insurance Portability and Accountability Act (HIPAA) compliant retrospective analysis of fetal MRIs of open spinal dysraphism from 2004 to 2016. Fetuses with diagnostic T1-weighted images and postnatal follow-up at our institution were included. RESULTS: A total of 115 fetuses (average gestational age 23.9 ± 3.6 weeks) met inclusion criteria. Of these, 80% (92/115) had T1 hyperintense rectal meconium signal. Average height of the meconium column, measured from the base of the bladder to its most inferior extent, was 9.2 ± 4.3 mm in fetuses ≥20-week gestational age and 11.1 ± 4.4 mm in fetuses ≥23-week gestational age (n = 110) . None had bowel dilation. One of 115 fetuses had a simple form of anorectal malformation allowing complete repair in the neonatal period, but this fetus had a normal meconium column height on fetal MRI of 22 mm. The remaining 23/115 fetuses with lack of normal rectal meconium signal were born without evidence of anorectal malformation. CONCLUSION: Decreased or absent T1-hyperintense rectal meconium signal in fetuses with open spinal dysraphism does not correlate with imperforate anus postnatal and may be a reflection of neurogenic bowel in this patient population.

Activating Transcription Factor 4 Modulates TGFß-Induced Aggressiveness in Triple-Negative Breast Cancer via SMAD2/3/4 and mTORC2 Signaling.

Purpose: On the basis of the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFß1. ATF4 is overexpressed in patients with triple-negative breast cancer (TNBC), but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on patients with breast cancer survival and TNBC aggressiveness, and the relationships between TGFß and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature.Experimental Design: Patient survival data were determined by Kaplan-Meier analysis. Relationship between TGFß and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and in vivo using patient-derived xenografts (PDX).Results: ATF4 overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFß was identified. ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFß/SMAD and mTOR/RAC1-RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2,509 patients with breast cancer.Conclusions: ATF4 may represent a valuable prognostic biomarker and therapeutic target in patients with TNBC, and we identified a cell signaling pathway-based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer. Clin Cancer Res; 24(22); 5697-709. ©2018 AACR.

Congenital aqueduct stenosis: Progressive brain findings in utero to birth in the presence of severe hydrocephalus.

PURPOSE: To evaluate the effects of progressive hydrocephalus on the developing brain in a cohort of fetuses diagnosed with congenital aqueduct stenosis by comparing prenatal magnetic resonance imaging and postnatal imaging. METHODS: This IRB approved single center retrospective review of prenatally diagnosed children with congenital aqueduct stenosis interrogated changes in the brain between prenatal and postnatal imaging and analyzed statistics using SAS software package version 9.3. RESULTS: Thirty fetuses imaged at a mean gestational age of 26 weeks had aqueduct obstruction confirmed by postnatal imaging. Progressive hydrocephalus required shunting in all but one patient (97%). Those patients with increasing hydrocephalus showed increase in ventricular rupture (60%), loss of septal leaflets (47%), and reduction in white matter and corpus callosum volume (43%). Cerebellar ectopia developed in 27% with 6% meeting the criteria for Chiari I malformation. CONCLUSION: Hydrocephalus in the fetus results in enlarging ventricular rupture, loss of the septum pellucidum leaflets, volume reduction of brain parenchyma including corpus callosum, and risk for Chiari I anomaly. Given advances in fetal surgery and imaging in the last 3 decades, there may be cause to revisit the idea of in utero cerebral spinal fluid diversion as a means to potentially ameliorate progressive loss of the developing brain.

Hepatocellular carcinoma after sustained virological response with interferon-free regimens in HIV/hepatitis C virus-coinfected patients.

OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (P < 0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (P = 1.0). CONCLUSION: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.

1-(Benzenesulfonyl)-1,5-dihydro-4,1-benzoxazepine as a new scaffold for the design of antitumor compounds.

AIM: Bozepinib is a potent and selective anticancer compound which chemical structure is made up of a benzofused seven-membered ring and a purine moiety. We previously demonstrated that the purine fragment does not exert antiproliferative effect per se. METHODOLOGY: A series of 1-(benzenesulfonyl)-4,1-benzoxazepine derivatives were synthesized in order to study the influence of the benzofused seven-membered ring in the biological activity of bozepinib by means of antiproliferative, cell cycle and apoptosis studies. RESULTS & CONCLUSION: Our results show that the methyleneoxy enamine sulfonyl function is essential in the antitumor activity of the structures and thus, it is a scaffold suitable for further modification with a view to obtain more potent antitumor compounds.

Real-life experience with sorafenib for the treatment of hepatocellular carcinoma in HIV-infected patients.

OBJECTIVE: To report the real-life results of sorafenib use in a cohort of HIV-infected patients with hepatocellular carcinoma (HCC). METHODS: The GEHEP-002 cohort (ClinicalTrials.gov ID: NCT02785835) has recruited 302 HCC cases diagnosed in HIV-infected patients from 32 centers from Spain. RIS-HEP12 study included 44 (14%) cases that have received at least one dose of sorafenib. The overall survival after the start of treatment was the main efficacy outcome. Permanent discontinuation due to adverse events was the primary safety end point. RESULTS: Reasons for sorafenib use are HCC recurrence after previous curative therapy (n = 7), progression following transarterial chemoembolization (n = 6) and first treatment against HCC (n = 31). Nineteen (43%) patients harbored Child-Pugh B cirrhosis. Barcelona-Clinic Liver Cancer stage was A 3 (7%), B 6 (14%), C 30 (68%) and D 5 (11%). All patients were on antiretroviral therapy (ART). The median (Q1-Q3) duration of sorafenib treatment was 70 (31-158) days. Median survival was 7.2 months, whereas the median (Q1-Q3) duration of overall survival after the start of treatment was 4 (2-9.7) months. Twenty-six (59%) patients had any grade adverse events and 19 (43%) suffered a decompensation. Discontinuation due to adverse events occurred in 17 (38.6%) patients. There were no modifications or discontinuations of ART. CD4 cell counts and HIV viral load remained stable. CONCLUSION: The efficacy of sorafenib under real-life conditions in HIV-infected patients seems lower than that reported in the registration clinical trial. On the contrary, the tolerability of sorafenib appears to be similar to what is seen in patients without HIV infection. Sorafenib does not seem to modify the efficacy of ART.

RNASeq analysis reveals biological processes governing the clinical behaviour of endometrioid and serous endometrial cancers.

BACKGROUND: Endometrial carcinoma comprises a group of tumours with distinct histologic and molecular features and clinical behaviour. Here, we sought to define the biological processes that govern the clinical behaviour of endometrial cancers. METHODS: Sixteen prototype genes representative of different biological processes that would likely play a role in endometrial and other hormone-driven cancers were defined. RNA-sequencing gene expression data from 323 endometrial cancers from The Cancer Genome Atlas (TCGA) were used to determine the transcription module of each prototype gene. The expression of prototype genes and modules and their association with outcome was assessed in univariate and multivariate survival analyses. The association of MSH6 expression with outcome was validated in an independent cohort of 243 primary endometrial cancers using immunohistochemistry. RESULTS: We observed that the clinical behaviour of endometrial cancers as a group was associated with hormone receptor signalling, PI3K pathway signalling and DNA mismatch repair processes. When analysed separately, in endometrioid carcinomas, hormone receptor, PI3K and DNA mismatch repair modules were significantly associated with outcome in univariate analysis, whereas the clinical behaviour of serous cancers was likely governed by apoptosis and Wnt signalling. Multivariate survival analysis revealed that MSH6 gene expression was associated with outcome of endometrial cancer patients independently from traditional prognostic clinicopathologic parameters, which was confirmed in an independent cohort at the protein level. CONCLUSION: Endometrioid and serous endometrial cancers are underpinned by distinct molecular pathways. MSH6 expression levels may be associated with outcome in endometrial cancers as a group.

The effect of the synthetic route on the structural, textural, morphological and catalytic properties of iron(iii) oxides and oxyhydroxides.

A variety of iron(iii) oxides and oxyhydroxides were synthesised and characterised using three distinct methods of preparation: microemulsion, precipitation and sol-gel. The results clearly showed that the structure, textural properties, crystal morphology and catalytic performance of the phases obtained were highly dependent on the chemical routes used for the synthesis. Precipitation and microemulsion methods allowed obtaining mesoporous nanostructured iron(iii) oxides with mean particle sizes of 4 nm (amorphous hematite) and 7 nm (ferrihydrite), which exhibited a high surface area (291.4 m(2) g(-1) and 192.3 m(2) g(-1), respectively) and a very good catalytic behaviour in the advanced oxidation of highly non-biodegradable wastewaters. The different conditions employed in the synthesis of these materials through the sol-gel method yielded two goethites with practically the same catalytic properties, but dissimilar morphologies and texture. When soft agitation and slow addition of the precipitating agent were used, the resulting material (G1) was made up of shorter and finer particles, markedly acicular, with an average length of 400 ± 50 nm and width of 15 ± 5 nm. However, vigorous agitation and rapid addition of the precipitating agent led to the formation of longer and coarser particles, moderately acicular, the average length and width being 950 ± 100 nm and 140 ± 20 nm, respectively. The use of the sol-gel technique also resulted in the formation of a solid consisting of a mixture of hematite as the main crystalline phase and goethite particles dispersed among the hematite particles. This solid presented a low specific surface area (13.2 m(2) g(-1)) and lower catalytic activity. Therefore, precipitation and microemulsion proved to be the most suitable techniques to synthesise catalytically active disordered iron(iii) oxide nanoparticles, due to the presence of highly reactive non-stoichiometric iron(iii) ions, a higher surface area and smaller particle sizes.

Congenital overinflation: prenatal MRI and US findings and outcomes.

OBJECTIVE: The purpose is to describe fetal MR and US findings of congenital overinflation (CO) and to correlate with postnatal outcome. METHODS: Two radiologists reviewed fetal MR and US images in 25 fetuses diagnosed with CO. Lesion size, appearance, location, and presence of hydrops were documented. Chart review was performed for pregnancy outcome, postnatal imaging, interventions, histopathology, and clinical outcome. RESULTS: All lesions demonstrated primarily homogeneous increased echogenicity and MR signal with absent pulmonary vascular distortion. A tubular cystic hilar structure was consistent with a dilated bronchus (68% MR, 25% US). The right lower (32%) and left lower (23%) lobes were most commonly involved. Two cases with central bronchial obstruction resulted in perinatal demise. Of 23 live births, 17 were asymptomatic, 1 symptomatic, and 5 lost to follow-up. Postnatal CT was performed in 17 of 18 patients confirming CO. Histopathology in nine patients revealed bronchial anomalies with hyperinflated (n = 7) or polyalveolar lung (n = 2). Nine patients were observed and remained asymptomatic. CONCLUSIONS: Fetal MR and US demonstrate a consistent pattern of imaging findings in fetuses with CO. Many cases are asymptomatic and can be managed with nonsurgical conservative therapy. CO because of central bronchial obstruction is associated with a guarded prognosis. © 2016 John Wiley & Sons, Ltd.

Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells.

Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Here we show that low adherent breast and colon cancer cells subpopulations have stem-like properties. Our results demonstrate that trypsin-sensitive (TS) breast and colon cancer cells subpopulations show increased ALDH activity, higher ability to exclude Hoechst 33342, enlarged proportion of cells with a cancer stem-like cell phenotype and are enriched in sphere- and colony-forming cells in vitro. Further studies in MDA-MB-231 breast cancer cells reveal that TS subpopulation expresses higher levels of SLUG, SNAIL, VIMENTIN and N-CADHERIN while show a lack of expression of E-CADHERIN and CLAUDIN, being this profile characteristic of the epithelial-to-mesenchymal transition (EMT). The TS subpopulation shows CXCL10, BMI-1 and OCT4 upregulation, differing also in the expression of several miRNAs involved in EMT and/or cell self-renewal such as miR-34a-5p, miR-34c-5p, miR-21-5p, miR-93-5p and miR-100-5p. Furthermore, in vivo studies in immunocompromised mice demonstrate that MDA-MB-231 TS cells form more and bigger xenograft tumors with shorter latency and have higher metastatic potential. In conclusion, this work presents a new, non-aggressive, easy, inexpensive and reproducible methodology to isolate prospectively cancer stem-like cells for subsequent biological and preclinical studies.