The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16–1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26–2.02) and in studies using PCR (HR 1.40; 95% CI 1.18–1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86–1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR

A non-invasive, improved RIA and overt observation in the study of singleton Apennines wolf (Canis lupus) reproductive behaviour

Abstract. The analysis of fecal hormones allows a close but non-invasive monitoring of animals avoiding the stress of restraint/capture, which in turn can upset animals’ hormonal profile. Steroid hormone progesterone was analysed in three singleton, female grey wolves of different age, belonging to the endangered species of the Apennines’ Canis lupus. The analysis was carried out during the breeding season by using an improved radioimmunoassay on samples collected on the field. To reduce the stress to animals and danger to people, the overt observations were carried out by operators who were already familiar with the animals, saving the money of a camera-monitoring-system. Concurrently, a male and a female gray wolves housed together were monitored as a control. The results indicated the importance of dehydration of fecal samples before the extraction with petroleum ether, which was shown to be more efficient than diethyl ether, and that pre-treatment with methanol greatly enhances extraction (p<0.01). Females of Apennines’ grey wolf showed the first sign of oestrus by a vaginal blood loss, that was easily detected on the ground; the analysis carried out on fecal samples revealed a rapidly declining luteal phase, with P4 metabolites reaching the basal values of a non-cyclic female. In the matter of welfare, behavioural observations on Apennines’ grey wolf showed that unpaired animals, although familiar with the operators, failed to display a sexual social behavior during the reproductive season, that is the behavioural signs were hidden in overt observational situation. [...