KRAS mutation as a prognostic factor and predictive factor in advanced/metastatic non-small cell lung cancer: A systematic literature review and meta-analysis.

KRAS (Kirsten Rat Sarcoma) is the most common oncogenic mutation detected in patients with non-small cell lung cancer (NSCLC). However, the role of KRAS as either a prognostic factor or predictive factor (modifier of treatment effects) in NSCLC is not well established at this time. This systematic literature review (SLR) and meta-analysis synthesized the available evidence regarding the role of KRAS mutation as a predictive factor and/or prognostic factor of survival and response outcomes in patients with advanced/metastatic (stage IIIB-IV) NSCLC. Relevant clinical trials and observational studies were identified by searching MEDLINE, Embase and Cochrane Register of Controlled Trials. Meta-analyses were performed using data extracted from multivariable and univariable analyses from clinical studies to assess the empirical evidence of KRAS mutation status as a prognostic or/and predicitive factor. 43 selected studies were identified by the SLR and included in this meta-analysis. Pairwise meta-analyses of hazard ratios (HRs) reported in randomized controlled trials (RCTs) did not demonstrate a significant prognostic effect of mutant KRAS on overall survival (OS) (HR=1.10; 95% CI [0.88, 1.38]) or progression free survival (PFS) (HR=1.03; 95% CI [0.80, 1.33]). However, when conducting meta-analyses on HRs reported in observational studies, a statistically significant negative prognostic effect of mutant KRAS was observed (OS HR=1.71; 95% CI [1.07, 2.84]; PFS HR=1.18; 95% CI [1.02, 1.36]). Meta-analyses of objective response rate (ORR) in RCTs demonstrated a negative prognostic effect of mutant KRAS (RR=0.38; 95% CI [0.16, 0.63]). Limited data were available to evaluate the role of KRAS mutation as a predictive factor. In conclusion, this research offers evidence that KRAS mutation may be a negative prognostic factor for survival and response outcomes in patients with advanced/metastatic NSCLC, but further research is needed to address conflicting results on the importance of KRAS mutations as a predictive factor.

Online support groups for young women with breast cancer: a proof-of-concept study.

OBJECTIVE: This initial study examined a therapist-led, synchronous, online support group (OSG) with psycho-education (OSG + E) compared to self-help psycho-education (E). The study aims were to examine proof of concept-feasibility, acceptability, and usefulness-and to hone methods for a formal RCT. METHODS: One hundred five young breast cancer survivors (<50 years) post-treatment were randomized either to OSG + E or E. OSG + E received a therapist-led 10-week synchronous online intervention. E received a self-help workbook. Assessments were at baseline, 10 weeks, and 3 months, with willing OSG + E members completing post-study interviews. Researchers used inductive analysis, generating qualitative themes for feasibility, acceptability, and usefulness. We examined trajectories for one primary and two secondary quantitative outcomes and a combined moderator to discover who preferentially benefitted from the intervention. RESULTS: Qualitative analyses revealed that synchronous chat was at times challenging, but minimal technical coaching, structure, set topics, and professional facilitation enabled conversations that were focused and meaningful. A combined moderator indicated that generally more women benefitted from OSG + E relative to E and particularly those women in semi-rural and rural areas. CONCLUSIONS: This study suggests that therapist-led synchronous OSGs are feasible, acceptable, and useful for young breast cancer survivors and that a future RCT with a larger sample size, perhaps more focused on non-urban areas, is needed to establish its effectiveness.

Talking with text: communication in therapist-led, live chat cancer support groups.

CancerChatCanada is a pan-Canadian initiative with a mandate to make professionally led cancer support groups available to more people in Canada. Although online support groups are becoming increasingly popular, little is known about therapist-led, synchronous groups using live chat. The purpose of this study was to generate a rich descriptive account of communication experiences in CancerChatCanada groups and to gain an understanding of processes associated with previously-reported benefits. We used interpretive description to analyze interview segments from 102 patients, survivors and family caregivers who participated in CancerChatCanada groups between 2007 and 2011. The analysis yielded four inter-related process themes (Reaching Out From Home, Feeling Safe, Emotional Release, and Talking With Text) and one outcome theme (Resonance and Kinship). The findings extend previous research about text-only online support groups and provide novel insights into features of facilitated, live chat communication that are valued by group members.

Identification of camphor oxidation and reduction products in Pseudomonas putida: new activity of the cytochrome P450cam system.

P450 enzymes are known for catalyzing hydroxylation reactions of non-activated C-H bonds. For example, P450(cam) from Pseudomonas putida oxidizes (1R)-(+)-camphor to 5-exo-hydroxy camphor and further to 5-ketocamphor. This hydroxylation reaction proceeds via a catalytic cycle in which the reduction of dioxygen (O(2)) is coupled to the oxidation of the substrate. We have observed that under conditions of low oxygen, P. putida and isolated P450(cam) reduce camphor to borneol. We characterized the formation of borneol under conditions of low oxygen or when the catalytic cycle is shunted by artificial oxidants like m-chloro perbenzoic acid, cumene hydroperoxide, etc. We also tested the toxicity of camphor and borneol with P. putida and Escherichia coli. We have found that in P. putida borneol is less toxic than camphor, whereas in E. coli borneol is more toxic than camphor. We discuss a potental ecological advantage of the camphor reduction reaction for P. putida.