Epidemiology: Extent of the Problem

Peritoneal carcinomatosis (PC) most commonly represents local or regional evolution of an abdominal carcinoma. Sometimes it can be synchronous with the primary tumor (primary carcinomatosis) but more often is present as recurrent disease (metachronous or secondary) after first-line treatment of the originating tumor. Patients with tumors from colon, ovary, and stomach cancer are more likely to present with PC during their clinical course. Less frequently, other abdominal malignancies, such as uterus, pancreas, small bowel, biliary, or urinary tract, can involve the peritoneum. Tumors originating from the peritoneum itself are definitely rarer: mesothelioma, pseudomyxoma peritonei (PMP), primitive peritoneal carcinoma, and desmoplastic small-round-cell tumor. PC from extra-abdominal tumors, such as lung, breast, melanoma, or peritoneal sarcomatosis, is exceptional, and few epidemiological data are available on them. Statistical analysis of worldwide cancer incidence, prevalence, and mortality rate is available on GLOBOCAN 2012 [1]. In Italy, most epidemiological data are available in the reports from the Italian Association of Tumor Registries (AIRTUM) [2], which collects data regarding incidence, prevalence, and mortality rates from all local and regional tumor registries, covering at least 34% of total population. This data is considered a high-quality regional coverage by and international ranking system (GLOBOCAN 2012 rate B)

Maternal smoking in pregnancy and birth defects:a systematic review based on 173 687 malformed cases and 11.7 million controls

BACKGROUND: There is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations are associated with smoking. METHODS: Observational studies published 1959–2010 were identified (Medline), and included if they reported the odds ratio (OR) for having a non-chromosomal birth defect among women who smoked during pregnancy compared with non-smokers. ORs adjusted for potential confounders were extracted (e.g. maternal age and alcohol), otherwise unadjusted estimates were used. One hundred and seventy-two articles were used in the meta-analyses: a total of 173 687 malformed cases and 11 674 332 unaffected controls. RESULTS: Significant positive associations with maternal smoking were found for: cardiovascular/heart defects [OR 1.09, 95% confidence interval (CI) 1.02–1.17]; musculoskeletal defects (OR 1.16, 95% CI 1.05–1.27); limb reduction defects (OR 1.26, 95% CI 1.15–1.39); missing/extra digits (OR 1.18, 95% CI 0.99–1.41); clubfoot (OR 1.28, 95% CI 1.10–1.47); craniosynostosis (OR 1.33, 95% CI 1.03–1.73); facial defects (OR 1.19, 95% CI 1.06–1.35); eye defects (OR 1.25, 95% CI 1.11–1.40); orofacial clefts (OR 1.28, 95% CI 1.20–1.36); gastrointestinal defects (OR 1.27, 95% CI 1.18–1.36); gastroschisis (OR 1.50, 95% CI 1.28–1.76); anal atresia (OR 1.20, 95% CI 1.06–1.36); hernia (OR 1.40, 95% CI 1.23–1.59); and undescended testes (OR 1.13, 95% CI 1.02–1.25). There was a reduced risk for hypospadias (OR 0.90, 95% CI 0.85–0.95) and skin defects (OR 0.82, 0.75–0.89). For all defects combined the OR was 1.01 (0.96–1.07), due to including defects with a reduced risk and those with no association (including chromosomal defects). CONCLUSIONS: Birth defects that are positively associated with maternal smoking should now be included in public health educational materials to encourage more women to quit before or during pregnancy

Thymosin \u3b11 represents a potential potent single-molecule-based therapy for cystic fibrosis

Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity. The most common mutation, p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activity but is prematurely degraded. Because of the inherent complexity of the pathogenetic mechanisms involved in CF, which include impaired chloride permeability and persistent lung inflammation, a multidrug approach is required for efficacious CF therapy. To date, no individual drug with pleiotropic beneficial effects is available for CF. Here we report on the ability of thymosin alpha 1 (T\u3b11)-a naturally occurring polypeptide with an excellent safety profile in the clinic when used as an adjuvant or an immunotherapeutic agent-to rectify the multiple tissue defects in mice with CF as well as in cells from subjects with the p.Phe508del mutation. T\u3b11 displayed two combined properties that favorably opposed CF symptomatology: it reduced inflammation and increased CFTR maturation, stability and activity. By virtue of this two-pronged action, T\u3b11 has strong potential to be an efficacious single-molecule-based therapeutic agent for CF

Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy

The discovery that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis of cancer cells without causing toxicity in mice has led to the in-depth study of pro-apoptotic TRAIL receptor (TRAIL-R) signalling and the development of biotherapeutic drug candidates that activate TRAIL-Rs. The outcome of clinical trials with these TRAIL-R agonists has, however, been disappointing so far. Recent evidence indicates that many cancers, in addition to being TRAIL resistant, use the endogenous TRAIL–TRAIL-R system to their own advantage. However, novel insight on two fronts — how resistance of cancer cells to TRAIL-based pro-apoptotic therapies might be overcome, and how the pro-tumorigenic effects of endogenous TRAIL might be countered — gives reasonable hope that the TRAIL system can be harnessed to treat cancer. In this Review we assess the status quo of our understanding of the biology of the TRAIL–TRAIL-R system — as well as the gaps therein — and discuss the opportunities and challenges in effectively targeting this pathway