BackgroundA frequent manifestation of advanced NSCLC is malnutrition, even though there are many studies which relate it with a poor survival, its relation with toxicity has not yet been consistently reported. The aim of this study was to associate malnutrition and albumin serum levels with the occurrence of chemotherapy-induced toxicity in cisplatin plus paclitaxel chemotherapy-treated NSCLC.MethodsWe prospectively evaluated 100 stage IV NSCLC patients treated with paclitaxel (175 mg/m2) and cisplatin (80 mg/m2). Malnutrition was assessed using SGA prior treatment. Neutrophil Lymphocyte Ratio (NLR) and the Platelet Lymphocyte Ratio (PLR) were used to determine the presence of systemic inflammatory response (SIR) and were related to the development of toxicity. Toxicity was graded according to NCI CTCAE version 3.0 after two chemotherapy cycles.ResultsMedian age was 58 ± 10 years, 51% of patients were malnourished, 50% had albumin ≤3.0 mg/mL. NLR ≥ 5 was associated with basal hypoalbuminemia (mean ranks, 55.7 vs. 39 p = 0.006), ECOG = 2 (47.2 vs. 55.4 p = 0.026) and PLR ≥ 150 were significantly related with a basal body mass index ≤20 (56.6 vs. 43.5; p = 0.02) and hypoalbuminemia (58.9 vs. 41.3; p = 0.02). Main toxicities observed after 2 cycles of chemotherapy were alopecia (84%), nausea (49%), neuropathy (46%), anemia (33%), lymphopenia (31%), and leukopenia (30%). Patients malnourished and with hypoalbuminemia developed more chemotherapy-induced toxicity overall when compared with those without malnutrition (31 vs 22; p = 0.02) and normal albumin (mean ranks, 62 vs 43; p = 0.002), respectively. Hypoalbuminemia was associated with anemia (56 vs 47; p = 0.05), fatigue (58 vs 46; p = 0.01), and appetite loss (57.1 vs 46.7; p = 0.004) compared with normal albumin. PLR ≥ 150 was related with the development of toxicity grade III/IV (59.27 vs. 47.03 p = 0.008) and anemia (37.9 vs 53.8 p = 0.004).ConclusionSIR parameters were associated with malnutrition, weight loss and hypoalbuminemia. Chemotherapy-induced toxicity in NSCLC patients treated with paclitaxel and cisplatin was associated with malnutrition and hypoalbuminemia. Early nutritional assessment and support might confer beneficial effects.
BackgroundCentral nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), serum CEA levels, and EGFR and HER2 tissue-expression in brain metastasis (BM) and overall survival (OS) in patients with advanced NSCLC.MethodsIn a prospective manner, we studied 293 patients with NSCLC in IIIB-IV clinical stage. They received standard chemotherapy. CEA was measured prior to treatment; EGFR and HER2 were evaluated by immunohistochemistry. BM development was confirmed by MRI in symptomatic patients.ResultsBM developed in 27, and 32% of patients at 1 and 2 years of diagnosis with adenocarcinoma (RR 5.2; 95% CI, 1.002–29; p = 0.05) and CEA ≥ 40 ng/mL (RR 11.4; 95% CI, 1.7–74; p < 0.01) as independent associated factors. EGFR and HER2 were not statistically significant. Masculine gender (RR 1.4; 95% CI, 1.002–1.9; p = 0.048), poor performance status (RR 1.8; 95% CI, 1.5–2.3; p = 0.002), advanced clinical stage (RR 1.44; 95% CI, 1.02–2; p = 0.04), CEA ≥ 40 ng/mL (RR 1.5; 95% CI, 1.09–2.2; p = 0.014) and EGFR expression (RR 1.6; 95% CI, 1.4–1.9; p = 0.012) were independent associated factors to worse OS.ConclusionHigh CEA serum level is a risk factor for BM development and is associated with poor prognosis in patients with advanced NSCLC. Surface expression of CEA in tumor cells could be the physiopathological mechanism for invasion to CNS.
How episodic memories decay is an unresolved question in cognitive neuroscience. The role of short-term mechanisms regarding the decay of episodic memories is circumscribed to set the maximum recall from which a monotonic decay occurs. However, this sequential view from the short to the long-term is not compulsory, as short-term dependent memory gains (like recency effects when memorizing a list of elements; serial-position effects) may not be translated into long-term memory differences. Moreover, producing memorable events in the laboratory faces important challenges, such as recreating realistic conditions with elevated recall, or avoiding spontaneous retrievals during memory retention (sociocultural hooks). Here we propose the use of magic to enhance the study of memory. We designed a sequence of magic tricks performed live on stage to evaluate the interaction between memory decay and serial-position effects of those tricks. The audience was asked to freely recall the tricks at four different timepoints: just after the show, 10 days, 1.5 months and 4.5 months. We discovered serial-position differences after the show that were no longer present later on, suggesting that short-term memory gains do not translate into the long-term. Illustrating the power of naturalistic stimuli to study long-term memory while interrogating the interaction between short-term and long-term mechanisms, this work is, to our knowledge, the first scientific study of the memorability of magic tricks.
The present study was designed to detect changes in p53 and MDM2 protein expression patterns in plasma from lung cancer patients. The largest p53 protein expression was observed in adenocarcinoma patients; however, mutant p53 was not increased in any cancer sample. A significant increase in the 57-kDa MDM2 isoform was observed in adenocarcinoma patients with low protein expression of the 90-kDa isoform. Our findings suggest that p53 accumulation could be due to a decrease in full-length MDM2 isoform together with an increase of the 57-kDa MDM2 isoform that was unable to stimulate p53 degradation.
Methods: Blood, plasma and serum samples were spiked with known quantities of human DNA. To optimize the yield of DNA, we investigated the effects of changes in the blood collection and processing, storage and DNA extraction protocols. We compared two DNA purification methods, the QIAamp blood DNA kit (QIAGEN) (with and without proteinase K pre-digestion) and phenol/chloroform DNA extraction after heat denaturation (5 minutes at 95˚C). Extracted DNA was quantified using the PicoGreen assay and its quality was checked by conventional PCR analysis for the p53 gene. Results: Using the standard QIAamp protocol, the efficiency of DNA extraction from serum was 13.8 ± 5.9% (Mean ± SD). Pre-incubation with proteinase K (0.4 mg/ml, QIAGEN) at 37˚C for 2 hours significantly increased the DNA recovery (p<0.0001, unpaired t-test), but longer incubation time and incubation at 50˚C did not improve the DNA yield further. Further improvements in the efficiency of the QIAamp protocol were obtained by increasing the volume of elution buffer, but reloading the columns and using different buffers did not improve the yield. Using the phenol/chloroform extraction method after heat denaturation, the efficiency of DNA extraction was 52.7 ± 4.6% (Mean ± SD), which is significantly better than the QIAamp protocol (p<0.0001, unpaired t-test). Delays in processing blood samples reduced the DNA yield. Importantly, all the recovered DNA was of quality suitable for PCR analysis. Conclusions: We recommend that blood samples are held on ice for no more than 1 hour before plasma/serum separation by double spin. Because of its higher efficiency, low-cost and good quality products for PCR analysis, we prefer the phenol/chloroform circulating DNA isolation method with heat denaturation.
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