Background: The prognosis of early stage non-small cell lung cancer (NSCLC) is quite disappointing and the benefits of adjuvant therapy are relatively small. Thus, there is an urgent need to identify novel prognostic and predictive biomarkers. Lung adenocarcinoma has distinct clinical–pathological characteristics and novel therapeutic strategies are under active evaluation in the adjuvant setting. Here, we investigated the prognostic impact of circulating tumor cells (CTCs) and gene and miRNA tissue expression in resectable NSCLC. Patients and methods: We assessed the association between CTC subpopulations and the outcome of resected early stage lung adenocarcinoma (ADC) patients at three different time-points (CTC1-3) (before surgery, after one month, and after six months) in comparison to squamous cell carcinoma (SCC). Furthermore, gene and miRNA tissue expression, immunoprofiling, and epithelial-to-mesenchymal transition (EMT) markers were correlated with outcome. Results: ADC (n = 47) and SCC (n = 50) revealed different tissue expression profiles, resulting in the presence of different CTC subpopulations. In ADC, miR-155 correlated with AXL and IL6R expression, which were related to the presence of EMT CTC1 (p = 0.014 and p = 0.004). In the multivariate analysis, CTC2 was an independent prognostic factor for relapse-free survival, and CTC3 and AXL were independent prognostic for overall survival only in ADC. Neither the surgery nor the adjuvant treatment influenced the prognosis of these patients. Conclusions: Our study elucidate the prognostic impact of tissue AXL expression and the presence of CTCs after surgery in adenocarcinoma patients. Tissue AXL expression and CTC EMT activation could potentially represent biomarkers for the stratification of ADC patients that might benefit from new adjuvant therapies.
Low dose computed tomography (LDCT) screening, together with the recent advances in targeted and immunotherapies, have shown to improve non-small cell lung cancer (NSCLC) survival.Furthermore, screening has increased the number of early stage-detected tumors, allowing for surgical resection and multimodality treatments when needed. The need for improved sensitivity and specificity of NSCLC screening has led to increased interest in combining clinical and radiological data with molecular data. The development of biomarkers is poised to refine inclusion criteria for LDCT screening programs.Biomarkers may also be useful to better characterize the risk of indeterminate nodules found in the course of screening or to refine prognosis and help in the management of screening detected tumors. The clinical implications of these biomarkers are still being investigated and whether or not biomarkers will be included in further decision-making algorithms in the context of screening and early lung cancer management still needs to be determined. However, it seems clear that there is much room for improvement even in early stage lung cancer disease-free survival (DFS) rates; thus, biomarkers may be the key to refine risk-stratification and treatment of these patients. Clinicians' capacity to register, integrate, and analyze all the available data in both high risk individuals and early stage NSCLC patients will lead to a better understanding of the disease's mechanisms, and will have a direct impact in diagnosis, treatment, and follow up of these patients. In this review, we aim to summarize all the available data regarding the role of biomarkers in LDCT screening and early stage NSCLC from a multidisciplinary perspective. We have highlighted clinical implications, the need to combine risk stratification, clinical data, radiomics, molecular information and artificial intelligence in order to improve clinical decision-making, especially regarding early diagnostics and adjuvant therapy. We also discuss current and future perspectives for biomarker implementation in routine clinical practice.
Detection of CTCs 1 month after radical resection might be a useful marker to predict early recurrence in Stage I-III NSCLC. The SUVmax value of the primary tumour on preoperative PET scans was associated with the presence of CTC 1 month after the operation.
Objective Retinal degenerations are a class of devastating blinding diseases that are characterized by photoreceptor dysfunction and death. In this study, we tested whether grape consumption, in the form of freeze-dried grape powder (FDGP), improves photoreceptor survival in a mouse model of retinal degeneration. Methods Retinal degeneration was induced in mice by acute oxidative stress using subretinal injection of paraquat and comparisons were to equivalent volumes of injected saline. The grape-supplemented diet was made by formulating base mouse chow with FDGP, corresponding to 3 daily human servings of grapes, and a control diet was formulated with equivalent sugar composition as FDGP (0.68% glucose/0.68% fructose mixture). Mice were placed on the diets at weaning for 5 weeks prior to oxidative stress injury until analysis at 2 weeks post-injection. Retinal function was measured using electroretinography, thickness of the photoreceptor layer was measured using optical coherence tomography, and rows of photoreceptor nuclei were counted on histological sections. Results In mice fed the control diet, oxidative stress significantly reduced photoreceptor layer thickness and photoreceptor numbers. In contrast, retina thickness and photoreceptor numbers were not reduced by oxidative stress in mice on the grape-supplemented diet, indicating significantly higher photoreceptor survival after injury than mice on the control diet. Furthermore, mice on the grape diet showed preservation of retina function after oxidative stress injury compared with mice on the control diet. Conclusions A diet supplemented with grapes rescued retinal structure and function in an oxidative stress-induced mouse model of retinal degeneration, which demonstrates the beneficial effect of grapes on photoreceptors.
Rab-related small GTP-binding proteins are known to be involved in the regulation of the vesicular transport system in eukaryotic cells. We report the characterization of a previously isolated full-length cDNA PpRab1 from Pinus pinaster. Amino acid sequence analysis revealed the presence of G1-G5 conserved domains of the GTPase Ras superfamily and a double cysteine motif in the C-terminal, characteristic of Rab proteins. The PpRab1 protein shows high sequence similarity to several Rab1 GTP-binding proteins in plants. Phylogenetic analysis showed that, within the Ras superfamily, PpRab1 is more closely related to the Rab family and within this, PpRab1 protein was found to cluster with Arabidopsis subfamily AtRABE, whose members are known to regulate ER-to-Golgi membrane trafficking steps. PpRab1 transcripts were expressed at constitutively high levels for the initial stages of zygotic embryo development, and then their relative abundance decreased as embryo matures. The PpRab1 transcript is not embryo-specific as it was found in roots, cotyledons and hypocotyls. An increase in PpRab1 expression level was observed when seeds are germinated and collected at successive time points of development. In situ RT-PCR analysis revealed an expression signal in early zygotic embryos. In view of the proposed roles of Rab1 GTP-binding protein, the possible function of the protein encoded by PpRab1 in embryogenesis is discussed.
Abstract:The contraceptive vaginal ring (CVR) is a combined hormonal contraceptive method, containing ethinyl estradiol and etonogestrel, that works by inhibiting ovulation. It differs from combined oral contraceptives (COCs) in the route of administration, which is vaginal, and the frequency of administration, which is monthly. The efficacy of the CVR is similar to that of COCs but compliance appears to be better in typical users. The CVR enables appropriate control of the menstrual cycle, with a similar side effect profile to COCs, while achieving good user acceptance. Different studies have established noncontraceptive beneficial effects of the CVR; for example, it can be useful for treating dysmenorrhea or excess menstrual bleeding. Recent epidemiological studies have confirmed that the risk of venous thromboembolism with the CVR is similar to that of COCs, including COCs that contain levonorgestrel.
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