- Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting. [Journal Article]
- IJInt J Cancer 2019 Jul 22
- We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor …
We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression free survival at first-line (mPFS1) was 12 months. Pertuzumab as first-line conferred longer mPFS1 compared to other first-line treatments (16 vs 9 months, p=0.0001), regardless of IHC subtype. Median PFS in second-line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T-DM1 compared to other agents (7 vs 6 months, p=0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs) (p=0.17), while a trend emerged for tumors with one HR (p=0.05). Conversely, PFS2 gain was significant in HRs-negative tumors (p=0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T-DM1 in second-line following pertuzumab were significantly lower compared to pertuzumab-naïve patients(p=0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p=0.02 and p=0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment-related outcomes of HER2-positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor (ER) pathways in HER2-positive (mbc) patients. This article is protected by copyright. All rights reserved.
- Mitochondrial Heat Shock Response Induced by Ectromelia Virus is Accompanied by Reduced Apoptotic Potential in Murine L929 Fibroblasts. [Journal Article]
- AIArch Immunol Ther Exp (Warsz) 2019 Jul 19
- Poxviruses utilize multiple strategies to prevent activation of extrinsic and intrinsic apoptotic pathways for successful replication. Mitochondrial heat shock proteins (mtHsps), especially Hsp60 and…
Poxviruses utilize multiple strategies to prevent activation of extrinsic and intrinsic apoptotic pathways for successful replication. Mitochondrial heat shock proteins (mtHsps), especially Hsp60 and its cofactor Hsp10, are engaged in apoptosis regulation; however, until now, the influence of poxviruses on mtHsps has never been studied. We used highly infectious Moscow strain of ectromelia virus (ECTV) to investigate the mitochondrial heat shock response and apoptotic potential in permissive L929 fibroblasts. Our results show that ECTV-infected cells exhibit mostly mitochondrial localization of Hsp60 and Hsp10, and show overexpression of both proteins during later stages of infection. ECTV infection has only moderate effect on the electron transport chain subunit expression. Moreover, increase of mtHsp amounts is accompanied by lack of apoptosis, and confirmed by reduced level of pro-apoptotic Bax protein and elevated levels of anti-apoptotic Bcl-2 and Bcl-xL proteins. Taken together, we show a positive relationship between increased levels of Hsp60 and Hsp10 and decreased apoptotic potential of L929 fibroblasts, and further hypothesize that Hsp60 and/or its cofactor play important roles in maintaining protein homeostasis in mitochondria for promotion of cell survival allowing efficient replication of ECTV.
- Simultaneous bilateral rupture of the patellar ligament in chronic renal patient. A case report. [Case Reports]
- RBRev Bras Ortop 2013 Sep-Oct; 48(5):455-459
- The authors report a case of simultaneous bilateral rupture of the patellar ligament resulting of low-energy trauma in a patient with chronic renal failure.
The authors report a case of simultaneous bilateral rupture of the patellar ligament resulting of low-energy trauma in a patient with chronic renal failure.
- Injury of the knee ligaments associated with ipsilateral femoral shaft fractures. [Journal Article]
- RBRev Bras Ortop 2013 Sep-Oct; 48(5):438-440
- CONCLUSIONS: We highlight the difficulty of diagnosis at the time of admission and the need for systematic physical examination before and after surgical treatment of femoral fracture.
- Posterior cruciate ligament injury: characteristics and associations of most frequent injuries. [Journal Article]
- RBRev Bras Ortop 2013 Sep-Oct; 48(5):427-431
- CONCLUSIONS: Surgical treatment of PCL injuries in a center for orthopedic trauma care was mostly multiligament and mainly involving the ACL. A significant association was seen between the type of injury with mechanism of injury, presentation of the knee, if dislocated or reduced, and the presence of associated fracture.
- Landscape genomics to the rescue of a tropical bee threatened by habitat loss and climate change. [Journal Article]
- EAEvol Appl 2019; 12(6):1164-1177
- Habitat degradation and climate change are currently threatening wild pollinators, compromising their ability to provide pollination services to wild and cultivated plants. Landscape genomics offers …
Habitat degradation and climate change are currently threatening wild pollinators, compromising their ability to provide pollination services to wild and cultivated plants. Landscape genomics offers powerful tools to assess the influence of landscape modifications on genetic diversity and functional connectivity, and to identify adaptations to local environmental conditions that could facilitate future bee survival. Here, we assessed range-wide patterns of genetic structure, genetic diversity, gene flow, and local adaptation in the stingless bee Melipona subnitida, a tropical pollinator of key biological and economic importance inhabiting one of the driest and hottest regions of South America. Our results reveal four genetic clusters across the species' full distribution range. All populations were found to be under a mutation-drift equilibrium, and genetic diversity was not influenced by the amount of reminiscent natural habitats. However, genetic relatedness was spatially autocorrelated and isolation by landscape resistance explained range-wide relatedness patterns better than isolation by geographic distance, contradicting earlier findings for stingless bees. Specifically, gene flow was enhanced by increased thermal stability, higher forest cover, lower elevations, and less corrugated terrains. Finally, we detected genomic signatures of adaptation to temperature, precipitation, and forest cover, spatially distributed in latitudinal and altitudinal patterns. Taken together, our findings shed important light on the life history of M. subnitida and highlight the role of regions with large thermal fluctuations, deforested areas, and mountain ranges as dispersal barriers. Conservation actions such as restricting long-distance colony transportation, preserving local adaptations, and improving the connectivity between highlands and lowlands are likely to assure future pollination services.
- Multielemental analysis in Nerium Oleander L. leaves as a way of assessing the levels of urban air pollution by heavy metals. [Journal Article]
- ARAppl Radiat Isot 2019 Jun 19; 152:18-24
- In this study, Nerium oleander L. leaves were used as biomonitors to evaluate environmental pollutants levels in a sub-region in the Metropolitan Area of Rio de Janeiro City (Brazil) through X-ray Fl…
In this study, Nerium oleander L. leaves were used as biomonitors to evaluate environmental pollutants levels in a sub-region in the Metropolitan Area of Rio de Janeiro City (Brazil) through X-ray Fluorescence (XRF). Control samples were collected in a rural zone next to the Parque Estadual da Pedra Branca/RJ. The samples were collected during all seasons of 2015 (summer, fall, winter and spring). The concentration of 13 elements (S, Cl, K, Ca, Mn, Fe, Cu, Zn, Br, Rb, Sr, Ba and Pb) was determined. Most of the elements showed, during all seasons, median concentrations of sampling sites higher than the results obtained from the control sites. The principal component analysis (PCA) showed the grouping of the elements in two main factors that can be associated to emission sources of these elements. The elements Cl, K, Ca, Cu, Rb and Sr can be associated as a possible influence from the soil (root uptake and/or resuspension). On the other hand, the elements Fe, Cu, Zn, and Pb can be associated to vehicle and industry emission sources. The study showed that the XRF technique applied to Nerium oleander L. leaves is efficient to environmental pollution analysis in Metropolitan Regions since it is precise, fast and low-cost, besides allowing the monitoring of pollution levels over time.
- Depression is associated with poor control of symptoms in asthma and rhinitis: A population-based study. [Journal Article]
- RMRespir Med 2019 Jun 30; 155:6-12
- CONCLUSIONS: Our results suggest that rhinitis exacerbations, particularly in non-atopic subjects, and low asthma control are strongly related to the presence of depressed mood in adults from the general population.
- Deficiency of Selected Cathepsins Does Not Affect the Inhibitory Action of ECTV on Immune Properties of Dendritic Cells. [Journal Article]
- IIImmunol Invest 2019 Jun 26; :1-17
- Ectromelia virus (ECTV), an orthopoxvirus, undergoes productive replication in conventional dendritic cells (cDCs), resulting in the inhibition of their innate and adaptive immune functions. ECTV rep…
Ectromelia virus (ECTV), an orthopoxvirus, undergoes productive replication in conventional dendritic cells (cDCs), resulting in the inhibition of their innate and adaptive immune functions. ECTV replication rate in cDCs is increased due to downregulation of the expression of cathepsins - cystein proteases that orchestrate several steps during DC maturation. Therefore, this study was aimed to determine if downregulation of cathepsins, such as B, L or S, disrupts cDC capacity to induce activating signals in T cells or whether infection of cDCs with ECTV further weakens their functions as antigen-presenting cells. Our results showed that cDCs treated with siRNA against cathepsin B, L and S synthesize similar amounts of pro-inflammatory cytokines and exhibit comparable ability to mature and stimulate alloreactive CD4+ T cells, as untreated wild type (WT) cells. Moreover, ECTV inhibitory effect on cDC innate and adaptive immune functions, observed especially after LPS treatment, was comparable in both cathepsin-silenced and WT cells. Taken together, the absence of cathepsins B, L and S has minimal, if any, impact on the inhibitory effect of ECTV on cDC immune functions. We assume that the virus-mediated inhibition of cathepsin expression in cDCs represents more a survival mechanism than an immune evasion strategy.
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- Determination of opiates in whole blood using microextraction by packed sorbent and gas chromatography-tandem mass spectrometry. [Journal Article]
- JCJ Chromatogr A 2019 May 15
- In Portugal, and worldwide, the abuse of psychoactive substances is increasing, with a significant incidence of deaths related to their consumption. Opiates are one of the most prevalent group of sub…
In Portugal, and worldwide, the abuse of psychoactive substances is increasing, with a significant incidence of deaths related to their consumption. Opiates are one of the most prevalent group of substances in that context, and they are responsible for a significant impact of the mentioned harms. Therefore, it becomes necessary to equip labs with faster and effective methods to identify and quantify these substances. This work describes the development and validation of a novel analytical method for the simultaneous determination of morphine, codeine and 6-monoacetylmorphine in blood samples by gas chromatography-tandem mass spectrometry (GC-MS/MS), using microextraction by packed sorbent (MEPS) for sample preparation. Before the MEPS procedure, a precipitation step with acetonitrile was performed. The MEPS parameters were optimized using the fractional factorial planning (2k-1) and surface response methodology. The final optimized conditions were: number of strokes (20), amount of formic acid in the washing solution (3.36%), number of washes of the sorbent (1), amount of ammonium hydroxide in the elution solution (2.36%) and number of elution cycles (11). After the extraction procedure, the analytes were derivatized with MSTFA with 5% TMS. Using a sample volume of 250 μL, the method was validated according to internationally accepted standards. The method proved to be linear in the range of 5-1000 ng/mL with coefficients of determination greater than 0.99 for all analytes. Intra-and inter-day precision and accuracy were in accordance with the above-mentioned criteria, presenting coefficients of variation ≤15% and relative errors within a range of ± 15% of the theoretical concentration. The absolute recoveries ranged from 6 to 23%. The validated method was applied to the analysis of real samples, being an advantageous tool for the detection of those substances in blood. This is the first time that GCMS/MS with MEPS was used for the determination of these compounds in biological fluids.