Quality of life assessment as a predictor of survival in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>There are conflicting and inconsistent results in the literature on the prognostic role of quality of life (QoL) in cancer. We investigated whether QoL at admission could predict survival in lung cancer patients.</p> <p>Methods</p> <p>The study population consisted of 1194 non-small cell lung cancer patients treated at our institution between Jan 2001 and Dec 2008. QoL was evaluated using EORTC-QLQ-C30 prior to initiation of treatment. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression evaluated the prognostic significance of QoL.</p> <p>Results</p> <p>Mean age at presentation was 58.3 years. There were 605 newly diagnosed and 589 previously treated patients; 601 males and 593 females. Stage of disease at diagnosis was I, 100; II, 63; III, 348; IV, 656; and 27 indeterminate. Upon multivariate analyses, global QoL as well as physical function predicted patient survival in the entire study population. Every 10-point increase in physical function was associated with a 10% increase in survival (95% CI = 6% to 14%, p < 0.001). Similarly, every 10-point increase in global QoL was associated with a 9% increase in survival (95% CI = 6% to 11%, p < 0.001). Furthermore, physical function, nausea/vomiting, insomnia, and diarrhea (p < 0.05 for all) in newly diagnosed patients, but only physical function (p < 0.001) in previously treated patients were predictive of survival.</p> <p>Conclusions</p> <p>Baseline global QoL and physical function provide useful prognostic information in non-small cell lung cancer patients.</p

Application of Direct Renin Inhibition to Chronic Kidney Disease

Chronic kidney disease has serious implications with a high risk for progressive loss of renal function, increased cardiovascular events as well as a substantial financial burden. The renin-angiotensin-aldosterone system (RAAS) is activated in chronic kidney disease, especially in diabetes and hypertension, which are the leading causes of chronic kidney disease. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease the rate of progression of diabetic and non-diabetic nephropathy and are recommended therapy for chronic kidney disease. Key clinical trials supporting the use of ACE inhibitors and ARBs in chronic kidney disease are discussed. Recent developments in our understanding of RAAS biology and the use of direct renin inhibition are reviewed in the context of their potential impact on the prevention and management of chronic kidney disease. Despite the clinical success of ACE inhibitors and ARBs the rates of mortality and progression to renal failure remain high in these patient populations. ACE inhibitor or ARB monotherapy, in doses commonly used in clinical practice does not result in complete suppression of the RAAS. Aliskiren, a direct renin inhibitor, offers a novel approach to inhibit the RAAS in chronic kidney disease. High dose ARB therapy or combination therapies with ACE inhibitors and ARBs have shown beneficial effects on surrogate markers of chronic kidney disease. Early data based on urinary protein excretion rates as a surrogate marker for renal function suggest a possibly novel role for aliskiren alone or in combination with ARBs in chronic kidney disease

Pathogen Proteins Eliciting Antibodies Do Not Share Epitopes with Host Proteins: A Bioinformatics Approach

The best way to prevent diseases caused by pathogens is by the use of vaccines. The advent of genomics enables genome-wide searches of new vaccine candidates, called reverse vaccinology. The most common strategy to apply reverse vaccinology is by designing subunit recombinant vaccines, which usually generate an humoral immune response due to B-cell epitopes in proteins. A major problem for this strategy is the identification of protective immunogenic proteins from the surfome of the pathogen. Epitope mimicry may lead to auto-immune phenomena related to several human diseases. A sequence-based computational analysis has been carried out applying the BLASTP algorithm. Therefore, two huge databases have been created, one with the most complete and current linear B-cell epitopes, and the other one with the surface-protein sequences of the main human respiratory bacterial pathogens. We found that none of the 7353 linear B-cell epitopes analysed shares any sequence identity region with human proteins capable of generating antibodies, and that only 1% of the 2175 exposed proteins analysed contain a stretch of shared sequence with the human proteome. These findings suggest the existence of a mechanism to avoid autoimmunity. We also propose a strategy for corroborating or warning about the viability of a protein linear B-cell epitope as a putative vaccine candidate in a reverse vaccinology study; so, epitopes without any sequence identity with human proteins should be very good vaccine candidates, and the other way around

Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008

<p>Abstract</p> <p>Background</p> <p>Health-related quality of life and survival are two important outcome measures in cancer research and practice. The aim of this paper is to examine the relationship between quality of life data and survival time in cancer patients.</p> <p>Methods</p> <p>A review was undertaken of all the full publications in the English language biomedical journals between 1982 and 2008. The search was limited to cancer, and included the combination of keywords 'quality of life', 'patient reported-outcomes' 'prognostic', 'predictor', 'predictive' and 'survival' that appeared in the titles of the publications. In addition, each study was examined to ensure that it used multivariate analysis. Purely psychological studies were excluded. A manual search was also performed to include additional papers of potential interest.</p> <p>Results</p> <p>A total of 451 citations were identified in this rapid and systematic review of the literature. Of these, 104 citations on the relationship between quality of life and survival were found to be relevant and were further examined. The findings are summarized under different headings: heterogeneous samples of cancer patients, lung cancer, breast cancer, gastro-oesophageal cancers, colorectal cancer, head and neck cancer, melanoma and other cancers. With few exceptions, the findings showed that quality of life data or some aspects of quality of life measures were significant independent predictors of survival duration. Global quality of life, functioning domains and symptom scores - such as appetite loss, fatigue and pain - were the most important indicators, individually or in combination, for predicting survival times in cancer patients after adjusting for one or more demographic and known clinical prognostic factors.</p> <p>Conclusion</p> <p>This review provides evidence for a positive relationship between quality of life data or some quality of life measures and the survival duration of cancer patients. Pre-treatment (baseline) quality of life data appeared to provide the most reliable information for helping clinicians to establish prognostic criteria for treating their cancer patients. It is recommended that future studies should use valid instruments, apply sound methodological approaches and adequate multivariate statistical analyses adjusted for socio-demographic characteristics and known clinical prognostic factors with a satisfactory validation strategy. This strategy is likely to yield more accurate and specific quality of life-related prognostic variables for specific cancers.</p

Prognostic value of quality of life score in disease-free survivors of surgically-treated lung cancer

BACKGROUND: We aimed to evaluate the prognostic value of quality of life (QOL) for predicting survival among disease-free survivors of surgically-treated lung cancer after the completion of cancer treatment. METHODS: We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), the Quality of Life Questionnaire Lung Cancer Module (QLQ-LC13), Hospital Anxiety and Depression Scale (HADS), and Posttraumatic Growth Inventory (PTGI) to 809 survivors who were surgically-treated for lung cancer at two hospitals from 2001 through 2006. We gathered mortality data by linkage to the National Statistical Office through December 2011. We used Cox proportional hazard models to compute adjusted hazard ratios (aHRs) and 95 % confidence intervals (CIs) to estimate the relationship between QOL and survival. RESULTS: Analyses of QOL items adjusted for age, sex, stage, body mass index, and physical activity showed that scores for poor physical functioning, dyspnea, anorexia, diarrhea, cough, personal strength, anxiety, and depression were associated with poor survival. With adjustment for the independent indicators of survival, final multiple proportional hazard regression analyses of QOL show that physical functioning (aHR, 2.39; 95 % CI, 1.13–5.07), dyspnea (aHR, 1.56; 95 % CI, 1.01–2.40), personal strength (aHR, 2.36; 95 % CI, 1.31–4.27), and anxiety (aHR, 2.13; 95 % CI, 1.38–3.30) retained their independent prognostic power of survival. CONCLUSION: This study suggests that patient-reported QOL outcomes in disease-free survivors of surgically-treated lung cancer after the completion of active treatment has independent prognostic value for long-term survival

Administered circulating microparticles derived from lung cancer patients markedly improved angiogenesis, blood flow and ischemic recovery in rat critical limb ischemia.

We hypothesized that lung cancer patient's circulating microparticles (Lc-MPs) could promote angiogenesis, blood flow in ischemic zone and ischemic recovery in rat critical limb ischemia (CLI).This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access

The amino-terminal domain of GRK5 inhibits cardiac hypertrophy through the regulation of calcium-calmodulin dependent transcription factors

We have recently demonstrated that the amino-terminal domain of G protein coupled receptor kinase (GRK) type 5, (GRK5-NT) inhibits NFκB activity in cardiac cells leading to a significant amelioration of LVH. Since GRK5-NT is known to bind calmodulin, this study aimed to evaluate the functional role of GRK5-NT in the regulation of calcium-calmodulin-dependent transcription factors. We found that the overexpression of GRK5-NT in cardiomyoblasts significantly reduced the activation and the nuclear translocation of NFAT and its cofactor GATA-4 in response to phenylephrine (PE). These results were confirmed in vivo in spontaneously hypertensive rats (SHR), in which intramyocardial adenovirus-mediated gene transfer of GRK5-NT reduced both wall thickness and ventricular mass by modulating NFAT and GATA-4 activity. To further verify in vitro the contribution of calmodulin in linking GRK5-NT to the NFAT/GATA-4 pathway, we examined the effects of a mutant of GRK5 (GRK5-NTPB), which is not able to bind calmodulin. When compared to GRK5-NT, GRK5-NTPB did not modify PE-induced NFAT and GATA-4 activation. In conclusion, this study identifies a double effect of GRK5-NT in the inhibition of LVH that is based on the regulation of multiple transcription factors through means of different mechanisms and proposes the amino-terminal sequence of GRK5 as a useful prototype for therapeutic purposes