ABSTRACT
BACKGROUND AND AIMS: Epidemiological data demonstrate that HCC is prevalent in men compared to women. Herein, we examined the effect of gonadectomy in a murine model that spontaneously develops HCC. ANIMALS AND METHODS: Thirty-two male and 26 female HBV transgenic mice [Tg (Alb-1 HBV) Bri 44] underwent surgical castration or sham operation. At the 18th month, serum samples were collected and all mice were sacrificed. Liver weight and volume were evaluated, each liver was cut into 1.5-mm-thick consecutive slices and nodules were examined on freshly isolated tissue. Consecutive histological sections obtained from each liver slice were evaluated to confirm the diagnosis of HCC. RESULTS: Sham-operated females showed a significantly lower neoplastic growth compared to sham-operated males. This difference disappeared when females underwent gonadectomy. In males, neoplastic growth was not influenced by gonadectomy. Testosterone and estradiol levels were profoundly modified by gonadectomy in both males and females. The testosterone/estradiol ratio in gonadectomized females increased 4.5-fold compared to that in sham-operated females, becoming more similar to the ratio observed in castrated and sham-operated male mice. CONCLUSIONS: HCC growth in our experimental model was not simply influenced by the levels of testosterone or estradiol, taken singularly, but depended on their ratio.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/surgery , Castration , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms, Experimental/surgery , Animals , Carcinoma, Hepatocellular/pathology , Disease Models, Animal , Disease Progression , Estradiol/blood , Female , Liver/pathology , Liver Neoplasms, Experimental/pathology , Male , Mice , Mice, Transgenic , Organ Size , Testosterone/bloodABSTRACT
BACKGROUND/AIMS: Extreme preterm birth, <28 weeks of gestation, represents a public health concern with major economic implications, being the leading cause of neonatal mortality and morbidity. METHODS: A single-centre retrospective cohort study was carried out to assess the role of caesarean section and to identify perinatal factors affecting neonatal survival and psychomotor development in these infants. 57 cases with complete maternal, obstetrical and neonatological information were selected for this study and neurological development was assessed for at least 18 months of life. RESULTS: Infant survival and neurological morbidity rates were directly and inversely correlated to birth weights and gestational age at birth, respectively. In multivariate analysis only extreme prematurity (Subject(s)
Infant, Extremely Low Birth Weight
, Psychomotor Disorders/etiology
, Adult
, Birth Weight
, Cohort Studies
, Delivery, Obstetric/methods
, Female
, Gestational Age
, Humans
, Infant, Newborn
, Infant, Premature
, Male
, Pregnancy
, Retrospective Studies
, Survival Analysis
ABSTRACT
A vaccine against Hepatitis C virus (HCV) is urgently needed due to the unsatisfactory clinical response to current therapies. We evaluated the immunological properties of a chimeric Cucumber mosaic virus (CMV), a plant virus engineered to express on its surface a synthetic peptide derived from many HVR1 sequences of the HCV envelope protein E2 (R9 mimotope). Evidence was obtained that the chimeric R9-CMV elicits a specific humoral response in rabbits. Furthermore, in patients with chronic HCV infection, purified preparations of R9-CMV down-modulated the lymphocyte surface density of CD3 and CD8, and induced a significant release of interferon (IFN)-gamma, interleukin (IL)-12 p70 and IL-15 by lymphomonocyte cultures. Finally, an R9 mimotope-specific CD8 T-cell response, as assessed by intracellular IFN-gamma production, was achieved in the majority of the patients studied. Our results open up new prospects for the development of effective vaccines against HCV infection. Moreover, the wide edible host range of CMV makes the production of an edible vaccine conceivable.
