PARP inhibition: A promising therapeutic target in ovarian cancer.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

Nutritional surveillance in Tuscany: maternal perception of nutritional status of 8-9 y-old school-children.

INTRODUCTION: Overweight and obesity in the developmental age has become a public health problem. For this reason, prevention projects must be developed in advance with the aim to involve not only children, but their parents as well. Our objective is to evaluate the accuracy of the mothers' perceptions of adolescent nutritional status. METHODS: Cross-sectional study. We selected a statistical sample of 3,076 subjects (1,583 males, 1,493 females), 8-9 y-old school-children of 164 3rd-grade elementary school classes from throughout Tuscany, as well as their mothers. The mothers' information was gathered via self-administered questionnaires, while the children were given an eating behaviour survey under the supervision of qualified personnel. Mothers' education level (self-reported) height and weight were collected; children's height and weight were measured. The former were asked how they perceived their children's body image. RESULTS: A correlation exists between the mothers' perceptions of the nutritional state of their children via the silhouettes and the BMI classes of the children, which is equal to 80% with a kappa-Cohen for agreement equal to 0.58 (SE = 0.02; P < 0.0001). However, no correlation exists between the mothers' responses to the question "In your opinion, is your child ...?" and the child's actual BMI class (the exact percentage correlation is equal to 75%, with a kappa-Cohen for agreement equal to 0.43 SE = 0.014; P < 0.0001). DISCUSSION: Mothers have an accurate perception of the nutritional status of their children, correctly choosing the silhouette that corresponds to the child's BMI profile without variation by gender. We can assume that mothers in our sample have a good concept about healthy nutritional status.

Nutritional surveillance in Tuscany: eating habits at breakfast, mid-morning and afternoon snacks among 8-9 y-old children.

INTRODUCTION: The prevalence of overweight and obesity in children is rapidly increasing in many countries. For that it has been interesting to investigate the eating habits of 8-9 y-old Tuscany children by paying attention to their meals frequency per day and their food choices in total and in relation to children's Body Mass Index (BMI) classes. In addition we considered some environment factors that could affect the children eating behaviours, such as mother's BMI and their education level. METHODS: A statistical sample of 3076 (1583 males, 1493 females), 8-9 year-old school-children was collected; weight and height were measured using standardized personnel and instruments. BMI classes were calculated using Cole et al.'s cutoff for children and adolescents. In order to evaluate the consumption frequency of individual meals and various foods, a Food Frequency Questionnaire (FFQ) was used, which was completed by the children themselves at school. A self-administered questionnaire revealed the weight and height of parents and their educational levels. Three educational levels were established: high, medium and low. RESULTS: The results showed that 92.3% of children ate breakfast from 4-7 times a week, the vast majority at home, while only 3% declared consuming breakfast never or almost never The most preferred breakfast consisted of milk and biscuits for all children's BMI classes. 95.9% of children reported having midmorning snack at school; fruit juice and tea are the most frequently consumed liquid foods, and pizza, salami sandwiches and pre-packaged snacks are the most frequently consumed solid foods in all BMI classes. 93.6% ate afternoon snack for the most part at home, even if 12% of children reported consuming it elsewhere; fruit juice and tea with pizza, sandwiches and pre-packaged snacks are still the most highly consumed foods by all children's BMI classes. The consumption frequency of breakfast (P < 0.001), mid-morning (P < 0.05) and afternoon snack (P < 0.05) of 8-9 y-old Tuscany children decrease with increase the children's BMI classes. The same tendency may be noted for the consumption frequency of breakfast in relation to mother's BMI (P < 0.05) and their education level (P < 0.05). This data strengthens the thesis that some home environments can affect the children's eating behaviours. CONCLUSION: No substantial differences in food choices at the meals analyzed were determined among normal weight, overweight and obese children. Children of normal weight had a greater tendency to consume meals more regularly. Mother's BMI and their education level can have influence on children's eating behaviours.

Placental, lipid, and glucidic effects of mammalian target of rapamycin inhibitors: impact on fetal growth and metabolic disorders during pregnancy after solid organ transplantation.

BACKGROUND: Mammalian target of rapamycin inhibitors (mTORi) are a promising new family of immunosuppressive drugs. No teratogenic effects have been reported to date. Their lipid and glucidic effects should not be underestimated, however, especially during pregnancy. Moreover, mTORi may affect fetal growth by mTOR placental activity. OBJECTIVE: Our purpose was to highlight mTORi placental impact and metabolic implications to detect possible maternal or fetal effects and define management guidelines in pregnant women after solid organ transplantation. METHODS: A literature search was performed for articles from the Medline and Pubmed databases with the use of the following keywords: mTOR inhibitors, pregnancy, placental transport, lipid metabolism, glucose metabolism. RESULTS: mTOR works as a positive regulator of system A, system L, and taurine placental amino acid transporter activity, which are critical for the transport of amino acids to the fetus. Exposing trophoblast cells to rapamycin reduces system L activity; therefore, treatment with rapamycin in human pregnancies could alter fetal growth with intrauterine growth restriction (IUGR). Regarding the metabolic effects mTORi increase lipolysis, impair insulin's antilipolytic effect and reduce lipid storage, which may potentially contribute to dyslipidemia. Chronic rapamycin treatment reduces adipose tissue size and ß-cell mass/function, causes hyperlipidemia, severe insulin resistance, and glucose intolerance, and promotes hepatic gluconeogenesis. CONCLUSIONS: The studies on mTORi treatment in transplanted pregnant women have not focused to date on the potential metabolic and placental effects. Selection of women at high risk for metabolic disorders could be needed and consideration of switching to another immunosuppressive drug required if diabetes and abnormal blood lipids have been diagnosed in prepregnancy counseling. It seems to be mandatory to encourage prompt reporting of any additional cases of pregnancy during mTORi exposure to provide a better understanding of the placental effects and safety profile of these immunosuppressive drugs.