A Small Molecule SMAC Mimic LBW242 Potentiates TRAIL- and Anticancer Drug-Mediated Cell Death of Ovarian Cancer Cells

BACKGROUND: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (SMAC) has been described to sensitize for apoptosis. We have explored the pro-apoptotic activity of LBW242, a mimic of SMAC/DIABLO, on ovarian cancer cell lines (A2780 cells and its chemoresistant derivative A2780/ADR, SKOV3 and HEY cells) and in primary ovarian cancer cells. The effects of LBW242 on ovarian cancer cell lines and primary ovarian cancer cells was determined by cell proliferation, apoptosis and biochemical assays. PRINCIPAL FINDINGS: LBW242 added alone elicited only a moderate pro-apoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or anticancer drugs in inducing apoptosis of both ovarian cancer cell lines and primary ovarian cancer cells. Mechanistic studies show that LBW242-induced apoptosis in ovarian cancer cells is associated with activation of caspase-8. In line with this mechanism, c-FLIP overexpression inhibits LBW242-mediated apoptosis. CONCLUSION: LBW242 sensitizes ovarian cancer cells to the antitumor effects of TRAIL and anticancer drugs commonly used in clinic. These observations suggest that the SMAC/DIABLO mimic LBW242 could be of value for the development of experimental strategies for treatment of ovarian cancer

The Mutyh Base Excision Repair Gene Influences the Inflammatory Response in a Mouse Model of Ulcerative Colitis

BACKGROUND: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/-) mice to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS). The Mutyh(-/-) phenotype was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh(-/-) mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh(-/-) mice. Lymphoid hyperplasia and a significant reduction in Foxp3(+) regulatory T cells were observed only in Mutyh(-/-) mice. CONCLUSIONS: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response

Balancing repair and tolerance of DNA damage caused by alkylating agents

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity

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

7noreservedOverweight 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. 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. 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). 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.mixedLAZZERI, G.; CASORELLI, A.; GIALLOMBARDO, D.; GRASSO, A.; GUIDONI, C.; MENONI, E.; GIACCHI, M.Lazzeri, G.; Casorelli, A.; Giallombardo, D.; Grasso, A.; Guidoni, C.; Menoni, E.; Giacchi, M

Corrigendum to “Bartholin gland cancer” (Bartholin gland cancer (2017) 117 (1–11), (S1040842816302645) (10.1016/j.critrevonc.2017.06.005))

The authors regret that the name and surname of Claudia Marchetti did not appear in the correct order. The authors would like to apologise for any inconvenience caused

Manuale pratico di oncologia. Fondamenti per il medico non oncologo- Costanzo Francesco; Cognetti Francesco; Benedetti Panici Pierluigi

Benedetti Panici P, Di Donato V., Fischetti M, Lo Prete E, Musella A, Plotti F, Casorelli A, Bellati F (2011). Capitoli: Carcinoma Dell' Endometrio.. arcinoma Epiteliale Dell’ovaio In: -. Manuale Pratico Di Oncologia Fondamenti Per Il Medico Non Oncologo