Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25.

SummaryThe recently discovered mitochondrial calcium uniporter (MCU) promotes Ca2+ accumulation into the mitochondrial matrix [1, 2]. We identified in silico miR-25 as a cancer-related MCU-targeting microRNA family and demonstrate that its overexpression in HeLa cells drastically reduces MCU levels and mitochondrial Ca2+ uptake, while leaving other mitochondrial parameters and cytosolic Ca2+ signals unaffected. In human colon cancers and cancer-derived cells, miR-25 is overexpressed and MCU accordingly silenced. miR-25-dependent reduction of mitochondrial Ca2+ uptake correlates with resistance to apoptotic challenges and can be reversed by anti-miR-25 overexpression. Overall, the data demonstrate that microRNA targeting of mitochondrial Ca2+ signaling favors cancer cell survival, thus providing mechanistic insight into the role of mitochondria in tumorigenesis and identifying a novel therapeutic target in neoplasia

Indicazioni per uno Studio su Familiarit\ue0 e fattori di rischio del Sarcoma di Kaposi classico

Obiettivi: Dalle analisi dei dati degli studi precedenti effettuati in Sicilia sono emerse diverse indicazioni, per cui \ue8 stata avviata un\u2019indagine in Sicilia nel 2013 , grazie ad un finanziamento della LILT nazionale, intesa a: valutare la situazione immunologica ed ematochimica e la sieroprevalenza in persone a stretto contatto con i malati (parente di 1 grado o marito/moglie) o parenti affetti dalla stessa patologia; indagare alcuni fattori di rischio con un questionario;effettuare il follow-up dei malati ogni 6-12-18-24 mesi ; individuare un Centro di Riferimento in Sicilia per la diagnosi e cura di questo tumore raro. Materiali e Metodi: Sono stati arruolati 24 Casi (21M/3F) e 27 Controlli familiari (9M/18F), residenti in Sicilia e solo un caso di sesso maschile residente in Calabria. La casistica non include 3 casi maschi perch\ue9 arruolati per la seconda volta al follow-up ; inoltre 1 caso M e relativo controllo (moglie) \ue8 stato escluso in quanto affetto da altro tipo di Sarcoma. I controlli sono stati familiari consanguinei e/o non consanguinei ( moglie, marito, genero ecc..) di casi in cura presso le Universit\ue0 di Catania e Messina oppure gi\ue0 arruolati negli studi precedenti dalla LILT di Ragusa, alcuni dei quali deceduti. Risultati: Dal confronto tra Controlli HHV8 positivi (n\ub011) vs. Controlli HHV8 negativi (n\ub016) non sono state individuate differenze significative a eta\u2019, sesso, livello d\u2019istruzione, occupazione e varie esposizione ambientali (et\ue0 : >64 vs <=64 OR=1.13 , 95% CI=[0.19-6.66] p=0.897 ; sesso: F vs M OR=0.80, 95% CI=[0.15-4.16] p=0.786; Istruzione:Medie vs No/elementare OR=0.17 ,95% CI=[0.01-3.28] p=0.181/ Liceo/Laurea vs No/elementare OR=0.19, 95% CI=[0.01-2.86] p=0.1; Occupazione: lavori manuali vs inattivo/disoccupato OR=2.25, 95% CI=[0.22-22.66] p=0.480/ lavori impiegato vs inattivo/disoccupato OR=0.60, 95% CI=[0.05-7.71] p=0.692 / altro tipo lavoro vs inattivo/disoccupato ( OR=0.38, 95% CI=[0.02-7.86] p=0.513); Abita o lavora vicino alle acque : SI vs No OR=4.44 95% CI=[0.73-27.24] p=0.077 ; Contatto con animali: Si vs No OR=2.63 95% CI=[0.33-20.66] p=0.341; Contatto con terreno: Si vs No OR=1.3995% CI=[0.28-6.84] p=0.685 ). Dall\u2019analisi di alcuni parametri ematochimici , confrontando Controlli vs Casi , emerge che i casi mostrano un pi\uf9 basso livello serico sia per l\u2019Albumina che al rapporto Albumina/Globuline (Albumina: Controlli 61.48 (3.16) vs Casi 58.61 (5.24) P=0.0210; Alb/glob: Controlli 1.62 (0.25) vs Casi 1.45 (0.30) P=0.0359 ) Conclusione: Dal confronto casi vs controlli, fra i parametri emato-chimici risultano interessanti dati relativi al Quadro Sieroproteico. Inoltre dal confronto dei dati tra Controlli HHV8 positivi vs. Controlli HHV8 negativi si registrano grandi differenze, ma non significative relativamente alle attivit\ue0 lavorative, al contatto con gli animali, il suolo e l\u2019acqua . Tali indicazioni meriterebbero di essere investigate in studi pi\uf9 grandi con dati d\u2019esposizione pi\uf9 dettagliati . Inoltre a nostro parere, da questa indagine in Sicilia sul Sarcoma di Kaposi classico si possono trarre indicazioni per il disegno di uno studio utile per individuare anche cluster familiari, verificarne la sieroprevalenza per l\u2019HHV8 tenendo in conto eventuali difformit\ue0 al loro interno tra casi e controlli relativamente al sesso e all\u2019et\ue0

Breast carcinoma survival in Europe and the United States.

BACKGROUND: Breast carcinoma survival rates were found to be higher in the U.S. than in Europe. METHODS: Multiple regression analysis of breast carcinoma survival rates among women diagnosed between 1990 and 1992 was performed using clinical data from population-based case series from the Surveillance, Epidemiogy, and End Results (SEER) program (13,172 women) and the European Concerted Action on survival and Care of Cancer Patients (EUROCARE) project (4478 women). RESULTS: Early-stage tumors (T1N0M0) were more frequent in the SEER data (41% of cases) than in the EUROCARE data (29%). In the SEER data, early tumors were more frequent in women age > or = 65 years (43%) than in younger women (38%), whereas the reverse was true in the European data (25% vs. 31%). In both case series, > 90% of women underwent surgery and 81-82% underwent lymphadenectomy, but the number of axillary lymph nodes evaluated was higher in the SEER data than in the EUROCARE data. The 5-year survival rate was higher in the U.S. case series (89%) than in the European series (79%). This differential was observed for each stage category evaluated: early (T1N0M0), large lymph node-negative (T2-3N0M0), lymph node-positive (T1-3N+M0), locally advanced (T4M0), and metastatic (M1) tumors. The overall relative excess risk (RER) of death was significantly higher (RER, 1.37; 95% confidence interval [95% CI], 1.25-1.50) among European women compared with U.S. women (referent group). Adjustment for stage, age, surgery, and the number of lymph nodes evaluated explained most of the excess risk (RER, 1.07; 95% CI, 0.98-1.17). CONCLUSIONS: Transatlantic differences in the 5-year survival rates for women diagnosed with breast carcinoma between 1990 and 1992 were attributable mainly to differences in stage of disease. Resources should be invested to achieve earlier diagnosis of breast carcinoma in Europe, especially for elderly women

Housing Reloaded. The European Large Scale Heritage

miR-224 has recently emerged as a driver oncomiR in sporadic colorectal carcinogenesis, but its pathogenetic role is still controversial. A large phenotypical and molecularly characterized series of preinvasive and invasive colorectal lesions was investigated for miR-224 expression by qRT-PCR and in situ hybridization. The caspase-3 and caspase-7 status was also assessed and correlated to miR-224 dysregulation. miR-224 was significantly upregulated during the adenoma-carcinoma sequence and in the context of inflammatory bowel disease dysplastic lesions, whereas its expression was significantly downregulated among BRAF-mutated tumors and in the presence of a DNA mismatch repair deficiency. miR-224 targets caspase-3 and caspase-7 in colorectal cancer, and this inverse relation was already evident from the earliest phases of transformation in intestinal mucosa. The miR-224/caspases axis may represent an interesting field of study for innovative biomarkers/therapeutics for BRAF-mutated/DNA mismatch repair-deficient tumors. Copyright \ua9 2018 The Authors. Published by Elsevier Inc. All rights reserved

Italian multicentricepidemiological case control strudy on risk factors for childhood leukemia,non hodgkin limphoma and neuroblastoma:study population and prevalence of risk factors in Italy

Background Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case/control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descriptive information. Methods The study was carried out in 14 Italian regions (78.3% of Italian population aged 0?10). It included leukaemia, NHL and neuroblastoma cases incident in 0?10 year olds in 1998-2001,registered by the Italian Association of Paediatric Haematology and Oncology (AIEOP)(accrual over 95% of estimated incidence). Two controls for each leukaemia case were randomly sampled from the Local Health Authorities rolls, matched by gender, birthdate and residence. The same controls were used in NHL and neuroblastoma studies. Parents were interviewed at home on: physical agents (ELF-MF and ionizing radiation), chemicals (smoking, solvents, traffic, insecticides), occupation, medical and personal history of children and parents, infectious diseases, immunizations and associated factors. Occupational exposure was collected using job specific modules. ELF-MF was measured in the main rooms (spot measurement) and close to child?s bed (48 hours measurement). Results The study included: 683 leukaemia cases (87% ALL, 13% AnLL), 97 NHL, 155 neuroblastomas, and 1044 controls.ELF-MF long term measurements were obtained for 61.1% of controls and 81.6% of leukaemia cases; 8.8% of controls were exposed at over 0.1 microTesla (\u3bcT), 3.5% and 2.1% at respectively over 0.2 and 0.3 \u3bcT. 25% of controls? fathers had smoked over 10 cigarettes/day during the year of conception, varying according to education and region. Maternal smoking was less common (71.4% did not smoke in pregnancy). Maternal passive smoking during pregnancy was reported by 31.2% of controls; the child?s passive smoking for 28.6%. Occupational exposure to solvents was estimated in 18.3% of controls? fathers and 7.7% of mothers. Contact with public was more frequent among mothers (36.1%) than fathers (23.4%). Conclusions SETIL represents a data source on exposure of Italian children to a broad array of potential carcinogenic factors

Risk of neuroblastoma, maternal characteristics and perinatal exposures: The SETIL study.

Neuroblastoma (NB) is the most common extra-cranial paediatric solid tumour. Incidence peaks in infancy, suggesting a role of in-utero and neonatal exposures but its aetiology is largely unknown. The aim of the present study is to evaluate the association between maternal characteristics and perinatal factors with the risk of NB, using data from the SETIL database.SETIL is a large Italian population-based case-control study established to evaluate several potential cancer risk factors in 0-10 year olds. Information about maternal characteristics, reproductive history, environmental and occupational exposures during pregnancy, as well as newborns' characteristics were obtained using a structured questionnaire. Extremely low frequency magnetic field (ELF-MF) home exposure was measured. The study included 1044 healthy controls and 153 NB cases, diagnosed between 1998 and 2001.A twofold risk was associated to exposure in pregnancy to chemical products for domestic work and to hair dye. The risk associated with the latter was higher among 0-17 month old children (OR=5.5, 95\%CI: 1.0-29.3). Risk was increased for children whose mothers had suffered work related exposure in the preconception period to solvents (OR=2.0 95\%CI: 1.0-4.1) and in particular to aromatic hydrocarbons (OR=9.2, 95\%CI: 2.4-34.3). No association was observed with ELF-MF exposure. A higher risk was found among children with congenital malformations (OR=4.9, 95\%CI: 1.8-13.6) or neurofibromatosis (2 cases and 0 controls, p=0.016).Our study suggests maternal exposure to hair dyes and aromatic hydrocarbons plays a role and deserves further investigation. The association with congenital malformations might also be explained by over-diagnosis. External exposure, in particular during and before pregnancy might contribute to NB occurrence

Childhood cancer survival in Europe.

BACKGROUND: EUROCARE-3 collected data from 45 population-based cancer registries in 20 countries on 24 620 European children aged from 0 to 14 years diagnosed with malignancy in the period 1990-1994. METHODS: Five-year survival between countries was compared for all malignancies and for the major diagnostic categories, adjusting for age, and estimated average European survival weighting for differences in childhood populations. RESULTS: For all cancers combined, survival variation was large (45% in Estonia to 90% in Iceland), and was generally low (60-70%) in eastern Europe and high (> or =75%) in Switzerland, Germany and the Nordic countries (except Denmark). The Nordic countries had the highest survival for four of the seven major tumour types: nephroblastoma (92%), acute lymphoid leukaemia (85%), CNS tumours (73%) and acute non-lymphocytic leukaemia (62%). The eastern countries had lowest survival: 89% for Hodgkin's disease, 71% for nephroblastoma, 68% for acute lymphoid leukaemia, 61% for non-Hodgkin's lymphoma, 57% for central nervous system (CNS) tumours and 29% for acute non-lymphocytic leukaemia. CONCLUSIONS: The Nordic countries represent a survival gold standard to which other countries can aspire. Since most childhood cancers respond well to treatment, survival differences are attributable to differences in access (including referral and timely diagnosis) and use of modern treatments; however, the obstacles to access and application of standard treatments probably vary markedly with country

EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century.

No abstract availabl

Erratum to: Survival prediction in high-grade gliomas using CT perfusion imaging

Erratum to: J Neurooncol (2015) 123:93\u2013102 DOI 10.1007/s11060-015-1766-5 Three participants were missing in the Appendix (listing the members of the PERNO study group) in the original publication. They are included in the complete list in the Appendix below