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1.
Sep Purif Technol ; 294: 121180, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35573908

RESUMO

The outbreak of SARS-CoV-2 pandemic highlighted the worldwide lack of surgical masks and personal protective equipment, which represent the main defense available against respiratory diseases as COVID-19. At the time, masks shortage was dramatic in Italy, the first European country seriously hit by the pandemic: aiming to address the emergency and to support the Italian industrial reconversion to the production of surgical masks, a multidisciplinary team of the University of Bologna organized a laboratory to test surgical masks according to European regulations. The group, driven by the expertise of chemical engineers, microbiologists, and occupational physicians, set-up the test lines to perform all the functional tests required. The laboratory started its activity on late March 2020, and as of the end of December of the same year 435 surgical mask prototypes were tested, with only 42 masks compliant to the European standard. From the analysis of the materials used, as well as of the production methods, it was found that a compliant surgical mask is most likely composed of three layers, a central meltblown filtration layer and two external spunbond comfort layers. An increase in the material thickness (grammage), or in the number of layers, does not improve the filtration efficiency, but leads to poor breathability, indicating that filtration depends not only on pure size exclusion, but other mechanisms are taking place (driven by electrostatic charge). The study critically reviewed the European standard procedures, identifying the weak aspects; among the others, the control of aerosol droplet size during the bacterial filtration test results to be crucial, since it can change the classification of a mask when its performance lies near to the limiting values of 95 or 98%.

2.
Appl Environ Microbiol ; 88(7): e0220921, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35311511

RESUMO

Bacterial strains belonging to the genus Rhodococcus are able to degrade various toxic organic compounds and tolerate high concentrations of metal(loid)s. We have previously shown that Rhodococcus aetherivorans BCP1 is resistant to various levels of the two arsenic inorganic species, arsenite [As(III)] and arsenate [As(V)]. However, while arsenite showed toxic effects at concentrations as low as 5 mM, arsenate at 30 mM boosted the growth rate of BCP1 cells and was toxic only at concentrations of >100 mM. Since such behavior could be linked to peculiar aspects of its metabolism, the transcriptomic analysis of BCP1 cells exposed to 5 mM As(III) and 30 mM As(V) was performed in this work. The aim was to clarify the mechanisms underlying the arsenic stress response of the two growth phenotypes in the presence of the two different oxyanions. The results revealed that As(III) induced higher activity of reactive oxygen species (ROS)-scavenging enzymes than As(V) in relation to the expression of enzymes involved in cellular damage recovery and redox buffers/cofactors (ergothioneine, mycofactocin, and mycothiol). Further, As(III) downregulated pathways related to cell division, while both oxyanions downregulated genes involved in glycolysis. Notably, As(V) induced the expression of enzymes participating in the synthesis of metallophores and rearranged the central and energetic metabolism, also inducing alternative pathways for ATP synthesis and glucose consumption. This study, in providing transcriptomic data on R. aetherivorans exposed to arsenic oxyanions, sheds some light on the plasticity of the rhodococcal response to arsenic stress, which may be important for the improvement of biotechnological applications. IMPORTANCE Members of the genus Rhodococcus show high metabolic versatility and the ability to tolerate/resist numerous stress conditions, including toxic metals. R. aetherivorans BCP1 is able to tolerate high concentrations of the two inorganic arsenic oxyanions, arsenite [As(III)] and arsenate [As(V)]. Despite the fact that BCP1 intracellularly converts As(V) into As(III), this strain responds very differently to the presence of these two oxyanions in terms of cell growth and toxic effects. Indeed, while As(III) is highly toxic, exposure to specific concentrations of As(V) seems to boost cell growth. In this work, we investigated the transcriptomic response, ATP synthesis, glucose consumption, and H2O2 degradation in BCP1 cells exposed to As(III) and As(V), inducing two different growth phenotypes. Our results give an overview of the transcriptional rearrangements associated with the dual response of BCP1 to the two oxyanions and provide novel insights into the energetic metabolism of Rhodococcus under arsenic stress.


Assuntos
Arsênio , Rhodococcus , Trifosfato de Adenosina/metabolismo , Arsênio/metabolismo , Arsênio/toxicidade , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Rhodococcus/metabolismo , Transcriptoma
3.
Sci Rep ; 11(1): 3921, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594175

RESUMO

The orthoquartzite Imawarì Yeuta cave hosts exceptional silica speleothems and represents a unique model system to study the geomicrobiology associated to silica amorphization processes under aphotic and stable physical-chemical conditions. In this study, three consecutive evolution steps in the formation of a peculiar blackish coralloid silica speleothem were studied using a combination of morphological, mineralogical/elemental and microbiological analyses. Microbial communities were characterized using Illumina sequencing of 16S rRNA gene and clone library analysis of carbon monoxide dehydrogenase (coxL) and hydrogenase (hypD) genes involved in atmospheric trace gases utilization. The first stage of the silica amorphization process was dominated by members of a still undescribed microbial lineage belonging to the Ktedonobacterales order, probably involved in the pioneering colonization of quartzitic environments. Actinobacteria of the Pseudonocardiaceae and Acidothermaceae families dominated the intermediate amorphous silica speleothem and the final coralloid silica speleothem, respectively. The atmospheric trace gases oxidizers mostly corresponded to the main bacterial taxa present in each speleothem stage. These results provide novel understanding of the microbial community structure accompanying amorphization processes and of coxL and hypD gene expression possibly driving atmospheric trace gases metabolism in dark oligotrophic caves.

4.
Tumour Biol ; 42(6): 1010428320925301, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32489146

RESUMO

A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast cancer. Ninety ER-positive, HER2 negative locally advanced breast cancer patients received letrozole (2.5 mg daily) and cyclophosphamide (50 mg daily) with/without Sorafenib (400 mg/bid daily) for 6 months before undergoing surgery. Ki67 expression and tumor size measured with caliber were determined at baseline, after 30 days of treatment and at the end of treatment. Patients were assigned to a clinical response category according to Response Evaluation Criteria in Solid Tumors, both at 30 days and before surgery and further classified as high-responder and low-responder according to the median variation of Ki67 values between biopsy and 30 days and between biopsy and surgery time. The predictive role of Ki67 and its changes with regard to clinical response and survival was analyzed. No differences in terms of survival outcomes emerged between the arms of treatment, while we observed a higher percentage of women with progression or stable disease in arm with the combination containing Sorafenib (20.5% vs 7.1%, p = 0.06). Clinical complete responders experienced a greater overall variation in Ki67 when compared with partial responders and patients with progressive/stable disease (66.7% vs 30.7%, p = 0.009). High responders showed a better outcome than low responders in terms of both disease-free survival (p = 0.009) and overall survival (p = 0.002). ΔKi67 score evaluated between basal and residual tumor at definitive surgery showed to be highly predictive of clinical complete response, and a potential parameter to be used for predicting disease-free survival and overall survival in luminal breast cancer treated with neoadjuvant endocrine-based therapy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/genética , Letrozol/administração & dosagem , Prognóstico , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem da Célula/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Letrozol/efeitos adversos , Terapia Neoadjuvante , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Resultado do Tratamento
5.
Appl Microbiol Biotechnol ; 104(6): 2747, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32047989

RESUMO

The published online version contains mistake in the author list for the author "M. Cappelletti" was incorrectly presented.

6.
Appl Microbiol Biotechnol ; 104(6): 2675-2689, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31993702

RESUMO

Nowadays, the increase of the unconventional oil deposit exploitation and the amount of oil sands process-affected waters (OSPW) in tailing ponds emerges the importance of developing bio-monitoring strategies for the restoration of these habitats. The major constituents of such deposits are naphthenic acids (NAs), emerging contaminant mixtures with toxic and recalcitrant properties. With the aim of developing bio-monitoring strategies based on culture-independent approach, we identified genes coding for enzymes involved in NA degradation from Rhodococcus opacus R7 genome, after the evaluation of its ability to mineralize model NAs. R. opacus R7 whole-genome analysis unveiled the presence of pobA and chcpca gene clusters putatively involved in NAs degradation. Gene expression analysis demonstrated the specific induction of R7 aliA1 gene, encoding for a long-chain-fatty-acid-CoA ligase, in the presence of cyclohexanecarboxylic acid (CHCA) and hexanoic acid (HA), selected as representative compounds for alicyclic and linear NAs, respectively. Therefore, aliA1 gene was selected as a molecular marker to monitor the biodegradative potential of slurry-phase sand microcosms in different conditions: spiked with CHCA, in the presence of R. opacus R7, the autochthonous microbial community, and combining these factors. Results revealed that the aliA1-targeting culture-independent approach could be a useful method for bio-monitoring of NA degradation in a model laboratory system.


Assuntos
Biodegradação Ambiental , Ácidos Carboxílicos/metabolismo , Monitoramento Ambiental/métodos , Rhodococcus/genética , Microbiologia do Solo , Poluentes Químicos da Água/metabolismo , Marcadores Genéticos , Genoma Bacteriano , Rhodococcus/metabolismo
7.
Breast ; 46: 19-24, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31051411

RESUMO

BACKGROUND: Endocrine treatment with Tamoxifen and aromatase inhibitors (AIs) is a staple in the management of hormone receptor positive breast cancer (HR + BC). It has become clear that HR + BC carries a consistent risk of relapse up to 15 years post-diagnosis. While increasing evidence supports the use of extended adjuvant Tamoxifen over 5 years, controversial data are available on the optimal duration of extended AIs adjuvant treatment. We performed a meta-analysis to assess the real impact of extended adjuvant therapy with AIs on disease-free survival (DFS). METHODS: A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. Primary and secondary endpoints were Disease Free Survival (DFS) and overall survival (OS) respectively. A subgroup analysis was also performed to elucidate the impact of nodal involvement. RESULTS: The pooled analysis revealed a significant increase in DFS in the extended AIs group (hazard ratio (HR): 0.78, 95% CI: 0.68-0.90; P = 0.0006). The subgroup analysis according to nodal status showed a greater DFS benefit with extended AIs in patients with positive nodes (HR = 0.67 versus 0.80). Our analysis also demonstrated no improvement in OS with extended AIs (HR = 0.99, 95%CI: 0.87-1.12; P = 0.84). CONCLUSION: This work confirmed the efficacy of extended adjuvant treatment with AIs for HR + early breast cancer, with a 22% increase in DFS, but no impact on OS. Greater efficacy was observed in women with positive nodal status.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/administração & dosagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/metabolismo , Resultado do Tratamento
8.
Mucosal Immunol ; 8(4): 863-73, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25465099

RESUMO

Allergic asthma is a chronic, inflammatory lung disease. Some forms of allergic asthma are characterized by T helper type 2 (Th2)-driven eosinophilia, whereas others are distinguished by Th17-driven neutrophilia. Stimulation of Toll-like receptor 4 (TLR4) on hematopoietic and airway epithelial cells (AECs) contributes to the inflammatory response to lipopolysaccharide (LPS) and allergens, but the specific contribution of TLR4 in these cell compartments to airway inflammatory responses remains poorly understood. We used novel, conditionally mutant Tlr4(fl/fl) mice to define the relative contributions of AEC and hematopoietic cell Tlr4 expression to LPS- and allergen-induced airway inflammation. We found that Tlr4 expression by hematopoietic cells is critical for neutrophilic airway inflammation following LPS exposure and for Th17-driven neutrophilic responses to the house dust mite (HDM) lysates and ovalbumin (OVA). Conversely, Tlr4 expression by AECs was found to be important for robust eosinophilic airway inflammation following sensitization and challenge with these same allergens. Thus, Tlr4 expression by hematopoietic and airway epithelial cells controls distinct arms of the immune response to inhaled allergens.


Assuntos
Asma/genética , Asma/imunologia , Eosinófilos/metabolismo , Expressão Gênica , Neutrófilos/metabolismo , Receptor 4 Toll-Like/genética , Animais , Asma/metabolismo , Asma/patologia , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Eosinófilos/imunologia , Eosinófilos/patologia , Células Epiteliais/metabolismo , Imunidade Inata , Lipopolissacarídeos/imunologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Knockout , Neutrófilos/imunologia , Neutrófilos/patologia , Pyroglyphidae/imunologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Receptor 4 Toll-Like/metabolismo
9.
Br J Cancer ; 112(1): 52-60, 2015 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-25461806

RESUMO

PURPOSE: To assess whether the combination of letrozole, metronomic cyclophosphamide and sorafenib (LCS) is well tolerated and shows activity in primary breast cancer (BC). METHODS: Thirteen oestrogen receptor-positive, postmenopausal, T2-4, N0-1 BC patients received the LCS combination for 6 months. In these patients we examined the pharmacokinetics of sorafenib and cyclophosphamide, toxicity of the regimen, the clinical response to therapy and changes in the levels of biologically relevant biomarkers. RESULTS: Adequate plasma concentrations of sorafenib were achieved in patients when it was dosed in combination with L+C. The mean plasma concentrations of C were consistently lower following administration of LCS, compared with administration of L+C only. The most common drug-related grade 3/4 adverse events were skin rash (69.3%), hand-foot skin reaction (69.3%) and diarrhoea (46.1%). According to RECIST Criteria, a clinical complete response was observed in 6 of 13 patients. A significant reduction in tumour size, evaluated with MRI, was also observed between baseline and 14 days of treatment in all 13 patients (P=0.005). A significant reduction in SUV uptake, measured by (18)FDG-PET/CT, was observed in all patients between baseline and 30 days of treatment (P=0.015) and between baseline and definitive surgery (P=0.0002). Using modified CT Criteria, a response was demonstrated in 8 out of 10 evaluable patients at 30 days and in 11 out of 13 evaluable patients at the definitive surgery. A significant reduction in Ki67 expression was observed in all patients at day 14 compared with baseline (P<0.00001) and in 9 out of 13 patients at the definitive surgery compared with baseline (P<0.03). There was also a significant suppression of CD31 and VEGF-A expression in response to treatment (P=0.01 and P=0.007, respectively). CONCLUSIONS: The LCS combination is feasible and tolerable. The tumour response and target biomarker modulation indicate that the combination is clinically and biologically active.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Administração Metronômica , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/farmacocinética , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Niacinamida/farmacocinética , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Nitrilas/farmacocinética , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto , Sorafenibe , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Triazóis/farmacocinética
10.
Gynecol Obstet Fertil ; 42(11): 779-86, 2014 Nov.
Artigo em Francês | MEDLINE | ID: mdl-25444700

RESUMO

OBJECTIVES: In order to maintain the benefits of perineal reeducation, patients with stress urinary incontinence need to perform self-retraining exercises of the perineal muscles at home. The aim of this randomized prospective multicentric study is to assess the effectiveness of GYNEFFIK(®), a perineal electrostimulator, during this home-care phase. PATIENTS AND METHODS: Two parallel groups of women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI), improved by physiotherapy, have followed a self-reeducation program, either with electrostimulation sessions (GYNEFFIK(®) or home perineal electrostimulation [HPES] arm) or with usual care (UC) only, without electrostimulation. The comparison of the two groups was based on the rate of women in which the benefit of the initial perineal reeducation was maintained (defined as the ICIQ and Ditrovie scales' score not worsening) at 2, 4 and 6 months. RESULTS: A total of 161 patients were analyzed (76 in the HPES arm and 85 in the UC arm). The therapeutic benefit of the initial perineal reeducation at the last available measure (6 months for a wide majority of patients) was maintained in 81.6% in the HPES arm versus 62.4% in the UC arm (P=0.007). This significant difference reflects a significant improvement both in clinical symptomatology and in quality of life. ICIQ score was improved in 44% of patients of HPES arm while it was improved in 14% of patients of UC arm (P<0.001) and daily number of urine leakage decreased of 1.2 leakage in the HPES arm versus 0.1 leakage in UC arm (P<0.05). Likewise, improvement of quality of life was superior in the HPES arm (48% improvement of Ditrovie score versus 19% in the UC group ; P<0.05). DISCUSSION AND CONCLUSION: Investigator global impression was more favorable in the HPES arm (clinical improvement in 83% of patients versus 68% in the UC arm). At the last measure (i.e. endpoint), the benefit of initial physiotherapy was considered maintained or improved in all patients of the HPES arm while it was reported as worsened in 16.5% of the UC group. Using GYNEFFIK(®) favorably impacts quality of life, particularly physical activity and vitality and decreases emotional consequences of UI (i.e. anxiety and depression score as assessed by HAD scale).


Assuntos
Terapia por Estimulação Elétrica/métodos , Períneo , Incontinência Urinária/terapia , Vagina , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Incontinência Urinária/psicologia , Incontinência Urinária por Estresse/terapia
11.
Genome Announc ; 2(4)2014 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-25146139

RESUMO

Rhodococcus opacus strain R7 (CIP107348) degrades several mono- and polycyclic aromatic hydrocarbons. Here, we present the high-quality draft genome sequence of strain R7, consisting of 10,118,052 bp, with a G+C content of 67.0%, 9,602 protein-coding genes, and 62 RNAs genes.

12.
Placenta ; 35(7): 431-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24819155

RESUMO

INTRODUCTION: Circulating endothelial progenitor cells (EPCs) may play a crucial role during pregnancy by sustaining adequate placentation and fetal growth. Unambiguous demonstration of EPC increase during pregnancy has been hampered so far by lack of standardized methods for EPC quantification. In this study we used the currently most accepted phenotype for EPC detection for investigating whether maternal circulating EPCs might increase during normal pregnancy and whether they may fail to increase in pregnancy complicated by idiopathic intrauterine growth restriction (IUGR), a leading cause of perinatal mortality and morbidity characterized by insufficient placental perfusion. METHODS: Twenty-one non-pregnant women, 44 women during healthy pregnancy progression (9, 13 and 22 women in the first, second and third trimester, respectively) and 11 with pregnancy complicated by idiopathic IUGR were recruited in a cross-sectional study. EPCs in maternal blood were identified as CD45(dim)/CD34+ / KDR+ cells by flow cytometry. Plasmatic cytokines were measured by ELISA. RESULTS: We observed a significant and progressive increase of EPCs in normal pregnancy, yet detectable in early pregnancy but even more pronounced in the third trimester. The increase of EPCs was impaired in IUGR-complicated pregnancies at comparable gestational age. The circulating levels of placental growth-factor and stromal-derived-factor-1 were significantly lower in IUGR than normal pregnancies, possibly contributing to EPC impairment. CONCLUSIONS: EPC count in maternal circulation may have a great potential as a novel biomarker for pregnancy monitoring and may represent the target of novel therapeutic strategies designed to prevent adverse pregnancy outcomes often occurring in IUGR.


Assuntos
Células Progenitoras Endoteliais/patologia , Retardo do Crescimento Fetal/sangue , Adulto , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Quimiocina CXCL12/sangue , Estudos Transversais , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Fator de Crescimento Placentário , Gravidez , Proteínas da Gravidez/sangue , Valores de Referência
13.
Br J Cancer ; 110(9): 2209-16, 2014 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-24722179

RESUMO

BACKGROUND: Although Trastuzumab has improved survival of HER2+ breast cancer patients, resistance to the agent pre-exists or develops through the course of therapy. Here we show that a specific metabolism and autophagy-related cancer cell phenotype relates to resistance of HER2+ breast cancer to Trastuzumab and chemotherapy. METHODS: Twenty-eight patients with locally advanced primary breast cancer were prospectively scheduled to received one cycle of Trastuzumab followed by a new biopsy on day 21, followed by taxol/Trastuzumab chemotherapy for four cycles before surgery. FDG PET/CT scan was used to monitor tumour response. Tissue samples were immunohistochemically analysed for metabolism and autophagy markers. RESULTS: In pre-Trastuzumab biopsies, the LC3A+/HER2+ cell population was correlated with HIF1α expression (P=0.01), while GLUT1 and LC3B expression were correlated with Ki67 proliferation index (P=0.01 and P=0.01, respectively). FDG PET tumour dimensions before therapy were correlated with LC3B expression (P=0.005). Administration of Trastuzumab significantly reduced clinical and PET-detected tumour dimensions (P<0.01). An inverse association of tumour response with the percentage of cells expressing HIF1α at baseline was documented (P=0.01). Administration of Trastuzumab resulted in a decrease of the proliferation index (P=0.004), GLUT1 (P=0.04) and HER2 (P=0.01) expression. In contrast, the percentage of LC3A+/HER2+ cells was increased (P=0.01). High baseline HIF1α expression was the only parameter associated with poorer pathological response to preoperative chemotherapy (P=0.001). CONCLUSIONS: As the HER2+/LC3A+ phenotype, which often overexpresses HIF1α, is a major subpopulation increasing after therapy with Trastuzumab, LC3A- and HIF1α-targeting therapies should be investigated for the augmentation of anti-HER2 therapy efficacy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Autofagia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Proteínas Associadas aos Microtúbulos , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Estudos Retrospectivos , Trastuzumab
14.
Genome Announc ; 1(5)2013 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-24158549

RESUMO

Rhodococcus sp. strain BCP1 cometabolizes chlorinated compounds and mineralizes a broad range of alkanes, as it is highly tolerant to them. The high-quality draft genome sequence of Rhodococcus sp. strain BCP1, consisting of 6,231,823 bp, with a G+C content of 70.4%, 5,902 protein-coding genes, and 58 RNA genes, is presented here.

15.
Br J Cancer ; 108(8): 1587-92, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23579222

RESUMO

BACKGROUND: The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response (pathCR) and assess Ki-67 expression as an early predictor of response. PATIENTS AND METHODS: This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer (clinical stage ≥ T2, N0-1), from three sequential cohorts (cohort A of 40, cohort B of 40 and cohort C of 40 patients, respectively) based on different duration of the neoadjuvant letrozole. Biological markers such as ER, progesterone receptor, HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery. RESULTS: A total of 89 patients (75.4%) achieved an objective response with 44 (37.3%) clinical CRs and 45 (38.1%) partial responses. The clinical CRs were significantly observed in cohort C (23 out of 40 patients, 57.5%) and B (16 out of 38 patients, 42.1%) compared with cohort A (5 out of 40 patients, 12.5%) (P-value for trend <0.001). Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts. The pathCR rate was significantly more frequent in cohort C (7 out of 40 patients, 17.5%) than in cohort A (1 out of 40 patients, 2.5%) and B (2 out of 40 patients, 5.0%) (P-value for trend <0.04). CONCLUSION: One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Nitrilas/administração & dosagem , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Triazóis/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Estudos de Coortes , Esquema de Medicação , Feminino , Humanos , Antígeno Ki-67/biossíntese , Antígeno Ki-67/metabolismo , Letrozol , Terapia Neoadjuvante , Nitrilas/efeitos adversos , Triazóis/efeitos adversos
16.
Placenta ; 34(1): 35-41, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23182380

RESUMO

INTRODUCTION: The state of activation of dendritic cells (DCs) at the feto-maternal interface critically contributes to optimal decidual immune responses needed to support fetal-placental development. We recently demonstrated that during healthy pregnancy also peripheral blood DCs (PBDCs), which are easily accessible, are activated as well. In this study, to investigate a possible involvement of DCs in intrauterine growth restriction (IUGR), we evaluated whether PBDCs in pregnancy complicated by IUGR may be altered compared with PBDCs in healthy pregnancy. METHODS: PBDCs from 12 pregnant women with primary IUGR, 21 healthy pregnant and 19 nonpregnant women were analyzed by flow cytometric analysis of whole-blood samples collected at a single time point. RESULTS: The number of plasmacytoid PBDCs was significantly reduced in women with IUGR pregnancy. Myeloid and plasmacytoid PBDCs in IUGR lacked the state of activation (assessed as CD80, CD86, CD40 expression) and the shift to a proinflammatory pattern of cytokine production occurring during healthy pregnancy. DISCUSSION: To our knowledge, this is the first study investigating the state of PBDC activation in IUGR pregnancy. Our results are in accordance with a previous study reporting a lower expression of activation and maturation markers by decidual DCs in IUGR placentas. CONCLUSIONS: The reduced activation of PBDCs in IUGR pregnancy may possibly reflect a reduced activation of decidual DCs. If confirmed at the feto-maternal interface, the alterations of DCs described in IUGR pregnancy have the potential to negatively impact on vascular development during gestation. These observations may therefore broaden our understanding of IUGR pathogenesis.


Assuntos
Células Dendríticas/imunologia , Células Dendríticas/patologia , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/imunologia , Adulto , Contagem de Células Sanguíneas , Células Sanguíneas/imunologia , Células Sanguíneas/patologia , Estudos de Casos e Controles , Citocinas/sangue , Regulação para Baixo/imunologia , Feminino , Retardo do Crescimento Fetal/patologia , Humanos , Recém-Nascido , Mediadores da Inflamação/sangue , Masculino , Gravidez
17.
Appl Microbiol Biotechnol ; 96(6): 1395-409, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23093177

RESUMO

Chloroform (CF) is largely produced by both anthropogenic and natural sources. It is detected in ground and surface water sources and it represents the most abundant halocarbon in the atmosphere. Microbial CF degradation occurs under both aerobic and anaerobic conditions. Apart from a few reports describing the utilization of CF as a terminal electron acceptor during growth, CF degradation was mainly reported as a cometabolic process. CF aerobic cometabolism is supported by growth on short-chain alkanes (i.e., methane, propane, butane, and hexane), aromatic hydrocarbons (i.e., toluene and phenol), and ammonia via the activity of monooxygenases (MOs) operatively divided into different families. The main factors affecting CF cometabolism are (1) the inhibition of CF degradation exerted by the growth substrate, (2) the need for reductant supply to maintain MO activity, and (3) the toxicity of CF degradation products. Under anaerobic conditions, CF degradation was mainly associated to the activity of methanogens, although some examples of CF-degrading sulfate-reducing, fermenting, and acetogenic bacteria are reported in the literature. Higher CF toxicity levels and lower degradation rates were shown by anaerobic systems in comparison to the aerobic ones. Applied physiological and genetic aspects of microbial cometabolism of CF will be presented along with bioremediation perspectives.


Assuntos
Bactérias/metabolismo , Clorofórmio/metabolismo , Aerobiose , Biodegradação Ambiental , Recuperação e Remediação Ambiental
18.
Neurosurg Rev ; 35(2): 245-53; discussion 253, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22009492

RESUMO

Spinal synovial cysts are cystic dilatations of the synovial membrane that may arise at all levels of the spine. We describe our experience, paying attention to diagnosis, surgical treatment, and long-term follow-up. Between 1995 and 2007, 18 patients were surgically treated. Of these, three patients were excluded from the study because they presented spinal instability at pre-operative assessment. All patients were evaluated pre-operatively with CT, MRI, and dynamic X-rays, and underwent surgery for removal of the cyst by hemilaminectomy and partial arthrectomy. All patients were evaluated with early MRI and had a minimum 2-year follow-up by dynamic X-rays. None of the patients required instrumented fusion due to the absence of radiological signs of instability on the pre-operative dynamic tests. In all patients, there was an immediate resolution of the symptoms, with evidence of complete removal of the cysts on post-operative MRI. At 2-year follow-up, all patients underwent dynamic X-rays and responded to a questionnaire for evaluation of outcome. None of them showed signs of relapse. The gold standard for treatment is surgery, even though other conservative treatment regimens have been proposed. Correct surgical strategy relies on pre-operative assessment of biomechanical stability for deciding whether patients need instrumented fusion during cyst removal. Patients with no instability signs are suitable for hemilaminectomy with partial arthrectomy, preserving 2/3 of the medial portion of the articular facet, because this represents a valid option of treatment with a low risk of complications and a low rate of relapse.


Assuntos
Vértebras Lombares/cirurgia , Doenças da Coluna Vertebral/cirurgia , Cisto Sinovial/complicações , Cisto Sinovial/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Laminectomia , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Doenças da Coluna Vertebral/diagnóstico , Cisto Sinovial/diagnóstico , Resultado do Tratamento
19.
Bioprocess Biosyst Eng ; 35(5): 667-81, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22042557

RESUMO

This work focuses on chloroform (CF) cometabolism by a butane-grown aerobic pure culture (Rhodococcus aetherovorans BCP1) in continuous-flow biofilm reactors. The goals were to obtain preliminary information on the feasibility of CF biodegradation by BCP1 in biofilm reactors and to evaluate the applicability of the pulsed injection of growth substrate and oxygen to biofilm reactors. The attached-cell tests were initially conducted in a 0.165-L bioreactor and, then, scaled-up to a 1.772-L bioreactor. Glass cylinders were utilized as biofilm carriers. The continuous supply of growth substrate (butane), which led to the attainment of the highest CF degradation rate (8.4 mg(CF) day(-1) m (biofilm surface)(-2)), was compared with four schedules of butane and oxygen pulsed feeding. The pulsed injection technique allowed the attainment of a ratio of CF mass degraded per unit mass of butane supplied equal to 0.16 mg(CF) mg (butane)(-1), a value 4.4 times higher than that obtained with the continuous substrate supply. A procedure based on the utilization of integral mass balances and of average concentrations along the bioreactors resulted in a satisfactory match between the predicted and the experimental CF degradation performances, and can therefore be utilized to provide a guideline for optimizing the substrate pulsed injection schedule.


Assuntos
Reatores Biológicos , Butanos/metabolismo , Clorofórmio/metabolismo , Rhodococcus/crescimento & desenvolvimento , Aerobiose/fisiologia
20.
Neurocase ; 18(4): 271-85, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21936740

RESUMO

We investigated the neural systems that support number processing in a patient (JL) who had damage to the left ventral occipito-temporal cortex (LvOT). JL had severely impaired written word recognition but he was remarkably accurate in number tasks, albeit slower than normal. This suggests LvOT activation is necessary for efficient but not for accurate number decisions. Here we investigated how JL made accurate number decisions using fMRI; we compared JL's brain activation to that in healthy controls and in two patients with frontal lobe damage who, like JL, made slow but accurate responses in number tasks. For semantic relative to perceptual decisions on numbers, JL did not activate the left occipito-temporal area that was involved in all other subjects. However, JL had significantly increased activation in a left posterior middle temporal region. In addition, during semantic and perceptual decisions on numbers, JL showed increased activation in: (1) the right occipito-temporal cortex, (2) right caudate, and (3) bilateral frontal regions. These effects were unique to JL and cannot be explained in terms of abnormally long response times because they were not observed in the other patients who made slow but accurate number decisions. Together these results show that although the LvOT usually contributes to efficient number processing, activation in this region is not essential for accurate performance because (i) perceptual processing of numbers can be supported by right occipital, right caudate, and bilateral frontal activation and (ii) semantic processing of numbers can be supported by increased left posterior middle temporal activation associated with hand actions.


Assuntos
Infarto Cerebral/patologia , Infarto Cerebral/psicologia , Cognição , Lobo Occipital/patologia , Desempenho Psicomotor , Lobo Temporal/patologia , Adulto , Idoso , Interpretação Estatística de Dados , Função Executiva , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estimulação Luminosa , Tempo de Reação/fisiologia , Adulto Jovem
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