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1.
J Basic Microbiol ; 64(1): 106-118, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37840353

RESUMO

Phlebia genus is a relevant group of fungi with a crucial role in numerous ecosystems. In tropical and subtropical areas this genus allows the efficient degradation of lignin and carbon recovery; however, the majority of these fungal species remain undiscovered. The main purpose of this work was to determine the enzymatic activity of extracellular proteins of a novel Phlebia floridensis strain isolated in Yucatan Peninsula, Mexico. The results that are reported here demonstrate that the soluble protein extract of P. floridensis can degrade a broad spectrum of recalcitrant compounds. This induced protein extract is able to modify not only phenolic and nonphenolic compounds, but also anthroquinone dyes, even without the addition of exogenous hydrogen peroxide. Using liquid chromatography-mass spectrometry (LC-MS), we were able to identify a novel chloroperoxidase in enzymatic extract. As far as we know, this is the first report about the presence of this type of enzyme in the Phlebia genus.


Assuntos
Basidiomycota , Lacase , Polyporales , Lacase/metabolismo , Peróxido de Hidrogênio/metabolismo , Ecossistema , Lignina/metabolismo , Hidrogênio/metabolismo
3.
Cancers (Basel) ; 15(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37444476

RESUMO

Prostate cancer is the third cause of cancer-related deaths in men. Its early and reliable diagnosis is still a public health issue, generating many useless prostate biopsies. Prostate cancer cells detected in urine could be the target of a powerful test but they are considered too rare. By using an approach targeting rare cells, we have analyzed urine from 45 patients with prostate cancer and 43 healthy subjects under 50 y.o. We observed a relevant number of giant cells in patients with cancer. Giant cells, named Polyploid Giant Cancer Cells (PGCC), are thought to be involved in tumorigenesis and treatment resistance. We thus performed immune-morphological studies with cancer-related markers such as α-methylacyl-CoA racemase (AMACR), prostate-specific membrane antigen (PSMA), and telomerase reverse transcriptase (TERT) to understand if the giant cells we found are PGCC or other urinary cells. We found PGCC in the urine of 22 patients, including those with early-stage prostate cancer, and one healthy subject. Although these results are preliminary, they provide, for the first time, clinical evidence that prostate cancers release PGCC into the urine. They are expected to stimulate further studies aimed at understanding the role of urinary PGCC and their possible use as a diagnostic tool and therapeutic target.

4.
Med Oncol ; 40(7): 204, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316755

RESUMO

Myelodysplastic syndromes (MDS) are incurable diseases characterized by dysplastic hematopoietic cells, cytopenias in the blood and an inherent tendency for transformation to secondary acute myeloid leukemia (AML). Since most therapies fail to prevent rapid clonal evolution and disease resistance, new and non-invasive predictive markers are needed to monitor patients and adapt the therapeutic strategy. By using ISET, a very sensitive approach to isolate cells larger than mature leukocytes from peripheral blood samples, we looked for cellular markers in 99 patients (158 samples) with MDS and 66 healthy individuals (76 samples) used as controls. We found a total of 680 Giant Cells, defined as cells having a size of 40 microns or larger in 46 MDS patients (80 samples) and 28 Giant Cells in 11 healthy individuals (11 samples). In order to understand if we had enriched from peripheral blood atypical cells of the megakaryocyte line, we studied the Giant Cells using immunolabeling with megakaryocytes and tumor-specific markers. We report that the Giant Cells we found in the peripheral blood of MDS patients primarily express tumor markers. Our results show that Polyploid Giant Cancer Cells (PGCC), similar to those described in solid tumors, are found in the peripheral blood of patients with MDS and suggest the working hypothesis that they could play a role in hematological malignancies.


Assuntos
Neoplasias Hematológicas , Síndromes Mielodisplásicas , Células Neoplásicas Circulantes , Humanos , Células Gigantes , Biomarcadores Tumorais
6.
Sex Med ; 10(5): 100558, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36027695

RESUMO

BACKGROUND: As female genital cosmetic surgeries have significantly increased, appropriate tools to evaluate self-esteem about women's own genitalia are necessary. AIM: to translate, culturally adapt to Spanish women and to evaluate the psychometric properties of the Female Genital Self-Image Scale (FGSIS). METHODS: FGSIS was forward and backward translated, culturally adapted into Spanish and its content evaluated through Delphi consensus. One item from the original scale was discarded after expert panel evaluation, developing the final Spanish scale (FGSIS-S) consisting of 6 items. Its psychometric properties were evaluated among 202 women attending gynecological consults through an online survey. The survey included socio-demographic data and FGSIS-S. MAIN OUTCOME MEASURE: Socio-demographic items, psychometric characteristics of the FGSIS-S (construct evaluation, internal consistency and test-retest reliability) were assessed. RESULTS: FGSIS-S proved to relate appropriately with the proposed construct (sum-content validity index 0.9, and significant inverse correlation with women concerned about their genital appearance or considering cosmetic surgery) with a 1-factor solution on exploratory factor analysis. The test proved good internal consistency (McDonald's omega 0.86) and test-retest reliability (intraclass correlation 0.86, P < .001). In 41.1% of cases, women referred concern about their genital's self-image and in 12.4% had considered undergoing cosmetic surgery. CLINICAL TRANSLATION: The validated version of FGSIS-S can help both professionals and patients, and its implementation can be easily made in gynecological consults. STRENGTHS AND LIMITATIONS: The main limitation is a self-selection bias in women attending gynecological consults, who may be more worried about their gynecological/sexual health. The sample is also a relatively homogeneous Caucasian population, with medium-high educational level, coming from gynecological consults. Strengths include the large sample size and the demographic survey that permitted evaluating the performance of FGSIS-S in the context of concern about genitals or consideration of cosmetic surgery. CONCLUSION: FGSIS-S is an adequate scale to measure women's genital image self-perception in Spanish-speaking population of Spain. Bartolomé A, Villalaín C, Bermejo R, et al. Spanish Translation, Transcultural Adaptation, Validation and Clinical Applicability of Female Genital-Self Image Scale (FGSIS). Sex Med 2022;10:100558.

7.
Molecules ; 27(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35566175

RESUMO

The development of novel cancer therapeutic strategies has garnered increasing interest in cancer research. Among the therapeutic choices, chemosensitizers have shown exciting prospects. Peptides are an attractive alternative among the molecules that may be used as chemosensitizers. We rationally designed a new-to-nature peptide, nurP28, derived from the 22-kDa α-zein protein sequence (entry Q00919_MAIZE). The resultant sequence of the nurP28 peptide after the addition of arginine residues was LALLALLRLRRRATTAFIIP, and we added acetyl and amide groups at the N- and C-terminus, respectively, for capping. We evaluated the cytotoxicity of the nurP28 peptide alone and in combination with docetaxel in fibroblast monolayers and breast cancer monolayers and spheroids. Our results indicated that nurP28 is not cytotoxic to human fibroblasts or cancer cells. Nevertheless, when combined with 1 µM docetaxel, 3 ng/mL nurP28 induced equivalent (in MCF7 monolayers) and higher (in MCF7 spheroids) cytotoxic effects than 10-fold higher doses of docetaxel alone. These findings suggest that nurP28 may act as a chemosensitizer in breast cancer treatment. This study describes the enhancing "anti-cancer" effects of nurP28 in breast cancer 2D and 3D cultures treated with docetaxel. Further studies should explore the mechanisms underlying these effects and assess the clinical potential of our findings using animal models.


Assuntos
Antineoplásicos , Neoplasias da Mama , Zeína , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Docetaxel/farmacologia , Feminino , Humanos , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Esferoides Celulares
8.
Life (Basel) ; 12(2)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35207452

RESUMO

There is an unmet need for reliable biomarkers to predict prostate cancer recurrence after prostatectomy in order to better guide the choice of surgical treatment. We have evaluated the predictive value of the preoperative detection of Circulating Tumor Cells (CTC) for prostate cancer recurrence after surgery. A cohort of 108 patients with non-metastatic prostate adenocarcinoma undergoing radical prostatectomy was tested for the presence of CTC before prostatectomy using ISET®. Disease recurrence was assessed by the increase in serum PSA level after prostatectomy. The following factors were assessed for statistical association with prostate cancer recurrence: the presence of CTC, serum PSA, Gleason score, and pT stage using univariate and multivariate analyses, with a mean follow-up of 34.9 months. Prostate cancer recurrence was significantly associated with the presence of at least 1 CTC at the preoperative time point (p < 0.001; Predictive value = 0.83). Conversely, the absence of prostate cancer recurrence was significantly associated with the lack of CTC detection at diagnosis (Predictive value = 1). Our multivariate analysis shows that only CTC presence is an independent risk factor associated with prostate cancer recurrence after prostatectomy (p < 0.001). Our results suggest that CTC detection by ISET® before surgery is an interesting candidate predictive marker for cancer recurrence in patients with non-metastatic PCa.

10.
Folia Microbiol (Praha) ; 67(1): 1-13, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34401996

RESUMO

Bromelia karatas L. is a plant species from the Americas. The presence of proteases in fruits of B. karatas has been reported but scarcely studied in detail. Proteolytic enzymes from Ananas comosus have displayed antifungal and antibacterial activity. Thus, novel proteases present in B. karatas may be useful as a source of compounds against microorganisms in medicine and food production. In this work, the protein extract from the fruits of B. karatas was characterized and its antibacterial activity against Salmonella Typhimurium and Listeria monocytogenes was determined for the first time. Proteins highly similar to ananain and the fruit bromelain from A. comosus were identified as the main proteases in B. karatas fruits using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The soluble protein extract (SPE) at a concentration of 2.0 mg/mL displayed up to 80% of antibacterial activity against S. Typhimurium. Complete inhibition of L. monocytogenes was reached with up to 1.65 mg/mL of SPE. Plant protease extract containing ananain-like enzyme inhibited up to 90% against S. Typhimurium and up to 85% against L. monocytogenes using only 10 µg/mL of the partial-purified enzyme.


Assuntos
Antibacterianos , Bromelia , Cisteína Proteases , Listeria monocytogenes , Extratos Vegetais/farmacologia , Salmonella typhimurium , Antibacterianos/farmacologia , Bromelaínas , Bromelia/química , Cromatografia Líquida , Cisteína Endopeptidases , Listeria monocytogenes/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Espectrometria de Massas em Tandem
11.
Stereotact Funct Neurosurg ; 100(1): 53-60, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34818656

RESUMO

BACKGROUND: Radiosurgery has demonstrated good safety and efficacy in the treatment of multiple brain metastases (BMs). However, multi-target dose planning can be challenging and time-consuming. A recently developed real-time inverse treatment planning (IP) by convex optimization has been demonstrated to produce high-quality treatment plans with good conformity and selectivity in single-target plans. We intended to test the capacity of this IP to rapidly generate efficient plans while optimizing the preservation of normal tissue in multiple BM. METHODS: Seventy-nine patients (mean age 62.4, age range 22-85) with a total of 272 BMs were treated by Gamma Knife Radiosurgery. All subjects were treated using a forward planning (FP) technique by an expert neurosurgeon. The new Intuitive Plan was applied and able to automatically generate an alternative plan for each patient. All planning variables were collected from the IP to be compared with the corresponding measurements obtained from the FP. A paired sample t test was applied to compare the 2 plans for the following variables: brain volumes receiving 10 Gy (V10) (primary endpoint), and 12 Gy (V12), planning indices (selectivity, coverage, gradient, and Paddick Conformity Index [PCI]), beam-on time (BOT), and integral doses. Additionally, the noninferiority margin for each item was calculated, and the 2 plans were compared for noninferiority using a paired t test. RESULTS: The mean age of patients was 62.4 years old (age range 22-85), with a sex ratio of 1.02. The average number of lesions per patient was 3.4 (range 1-12). The mean prescription dose was 21.46 Gy (range 14-24 Gy). Noninferiority of the IP was concluded for V10, V12, prescription isodose volume, BOT, PCI, and selectivity. The V10 (and V12) was significantly lower with the IP (p < 0.001). These volumes were 8.69 cm3 ± 11.39 and 5.47 cm3 ± 7.03, respectively, for the FP and 7.57 cm3 ± 9.44 and 4.78 cm3 ± 5.86 for the IP. Only the coverage was significantly lower with the IP (-2.3%, p < 0.001), but both selectivity (+17%) and PCI (+15%) were significantly higher with the IP than FP (p < 0.001). CONCLUSION: This IP demonstrated its capacity to generate multi-target plans rapidly, with a dose to the brain (V10) and BOT noninferior to the one of a human expert planner. These results would benefit from confirmation in a larger prospective series.


Assuntos
Neoplasias Encefálicas , Intervenção Coronária Percutânea , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Radiocirurgia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto Jovem
12.
IEEE Trans Med Imaging ; 40(12): 3748-3761, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34264825

RESUMO

Lung cancer is by far the leading cause of cancer death in the US. Recent studies have demonstrated the effectiveness of screening using low dose CT (LDCT) in reducing lung cancer related mortality. While lung nodules are detected with a high rate of sensitivity, this exam has a low specificity rate and it is still difficult to separate benign and malignant lesions. The ISBI 2018 Lung Nodule Malignancy Prediction Challenge, developed by a team from the Quantitative Imaging Network of the National Cancer Institute, was focused on the prediction of lung nodule malignancy from two sequential LDCT screening exams using automated (non-manual) algorithms. We curated a cohort of 100 subjects who participated in the National Lung Screening Trial and had established pathological diagnoses. Data from 30 subjects were randomly selected for training and the remaining was used for testing. Participants were evaluated based on the area under the receiver operating characteristic curve (AUC) of nodule-wise malignancy scores generated by their algorithms on the test set. The challenge had 17 participants, with 11 teams submitting reports with method description, mandated by the challenge rules. Participants used quantitative methods, resulting in a reporting test AUC ranging from 0.698 to 0.913. The top five contestants used deep learning approaches, reporting an AUC between 0.87 - 0.91. The team's predictor did not achieve significant differences from each other nor from a volume change estimate (p =.05 with Bonferroni-Holm's correction).


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Algoritmos , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Curva ROC , Nódulo Pulmonar Solitário/diagnóstico por imagem , Tomografia Computadorizada por Raios X
13.
Acta Neurochir (Wien) ; 163(4): 981-989, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398540

RESUMO

BACKGROUND: Gamma Knife radiosurgery (GKRS) inverse dose planning is currently far from competing effectively with the quality of dose planning developed by experienced experts. A new inverse planning (IP) method based on « efficient convex optimization algorithms ¼ is proposed, providing high-quality dose plans in real time. MATERIALS AND METHODS: Eighty-six patients treated by GKRS for vestibular schwannomas (VS) were recruited. The treatment plans created by the first author, who has 27 years of experience and has developed and delivered more than 15,000 dose plans, served as reference. A first set of basic constraints determined by default led the IP for an initial real-time dose plan. Additional constraints were interactively proposed by the planner to take other parameters into account. A second optimized plan was then calculated by the IP. The primary endpoint was the Paddick Conformity Index (PCI). The statistical analysis was planned on a non-inferiority trial design. Coverage, selectivity, and gradient indexes, dose at the organ(s) at risk, and 12 Gy isodose line volume were compared. RESULTS: After a single run of the IP, the PCI was shown to be non-inferior to that of the "expert." For the expert and the IP, respectively, the median coverage index was 0.99 and 0.98, the median selectivity index 0.92 and 0.90, the median gradient index 2.95 and 2.84, the median dose at the modiolus of the cochlea 2.83 Gy and 2.86 Gy, the median number of shots 14.31 and 24.13, and the median beam-on time 46.20 min and 26.77 min. In a few specific cases, advanced tools of the IP were used to generate a second run by adding new constraints either globally (for higher selectivity) or locally, in order to increase or decrease these constraints focally. CONCLUSION: These preliminary results showed that this new IP method based on « efficient convex optimization algorithms ¼, called IntuitivePlan®, provided high-quality dose plans in real time with excellent coverage, selectivity, and gradient indexes with optimized beam-on time. If the new IP evaluated here is able to compete in real time with the quality of the treatment plans of an expert with extensive radiosurgical experience, this could allow new planners/radiosurgeons with limited or no experience to immediately provide patients with high-quality GKRS for benign and malignant lesions.


Assuntos
Neuroma Acústico/radioterapia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Humanos , Masculino , Dosagem Radioterapêutica
14.
Molecules ; 25(22)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33227894

RESUMO

In this study, we characterized three novel peptides derived from the 19 kDa α-zein, and determined their bioactive profile in vitro and developed a structural model in silico. The peptides, 19ZP1, 19ZP2 and 19ZP3, formed α-helical structures and had positive and negative electrostatic potential surfaces (range of -1 to +1). According to the in silico algorithms, the peptides displayed low probabilities for cytotoxicity (≤0.05%), cell penetration (10-33%) and antioxidant activities (9-12.5%). Instead, they displayed a 40% probability for angiotensin-converting enzyme (ACE) inhibitory activity. For in vitro characterization, peptides were synthesized by solid phase synthesis and tested accordingly. We assumed α-helical structures for 19ZP1 and 19ZP2 under hydrophobic conditions. The peptides displayed antioxidant activity and ACE-inhibitory activity, with 19ZP1 being the most active. Our results highlight that the 19 kDa α-zein sequences could be explored as a source of bioactive peptides, and indicate that in silico approaches are useful to predict peptide bioactivities, but more structural analysis is necessary to obtain more accurate data.


Assuntos
Simulação por Computador , Peptídeos/análise , Peptídeos/farmacologia , Zea mays/química , Zeína/química , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antioxidantes/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Peptídeos/síntese química , Peptídeos/química , Solventes/química
15.
Nat Chem Biol ; 16(6): 667-675, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32393901

RESUMO

N-acylethanolamines (NAEs), which include the endocannabinoid anandamide, represent an important family of signaling lipids in the brain. The lack of chemical probes that modulate NAE biosynthesis in living systems hamper the understanding of the biological role of these lipids. Using a high-throughput screen, chemical proteomics and targeted lipidomics, we report here the discovery and characterization of LEI-401 as a CNS-active N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor. LEI-401 reduced NAE levels in neuroblastoma cells and in the brain of freely moving mice, but not in NAPE-PLD KO cells and mice, respectively. LEI-401 activated the hypothalamus-pituitary-adrenal axis and impaired fear extinction, thereby emulating the effect of a cannabinoid CB1 receptor antagonist, which could be reversed by a fatty acid amide hydrolase inhibitor. Our findings highlight the distinctive role of NAPE-PLD in NAE biosynthesis in the brain and suggest the presence of an endogenous NAE tone controlling emotional behavior.


Assuntos
Comportamento Animal/efeitos dos fármacos , Inibidores Enzimáticos/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Fosfatidiletanolaminas/metabolismo , Fosfolipase D/antagonistas & inibidores , Amidoidrolases/metabolismo , Animais , Proteínas Sanguíneas/metabolismo , Encéfalo/metabolismo , Antagonistas de Receptores de Canabinoides/metabolismo , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacocinética , Medo/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Receptores de Canabinoides/metabolismo , Transdução de Sinais
16.
Eur J Cardiothorac Surg ; 57(2): 252-262, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31711150

RESUMO

In non-rheumatic atrial fibrillation (AF), left atrial appendage (LAA) is thought to be the source of embolism in 90% of the strokes. Thus, as recent clinical trials have shown the non-inferiority of percutaneous LAA closure (LAAc) in comparison to medical treatment, and despite a IIb recommendation in the latest guidelines for concomitant surgical LAAc, we sought to investigate the beneficial effect of LAAc in the surgical population. A meta-analysis model was performed comparing studies including any cardiac surgery with or without concomitant surgical LAAc reporting stoke/embolic events and/or mortality, from inception to January 2019. Twenty-two studies (280 585 patients) were included in the model. Stroke/embolic events both in the perioperative period [relative risk (RR) 0.66, 95% confidence interval (CI) 0.53-0.82; P = 0.0001] and during follow-up of >2 years (RR 0.67, 95% CI 0.51-0.89; P < 0.005) were significantly reduced in patients who underwent surgical LAAc (RR 0.71, 95% CI 0.58-0.87; P = 0.001). Regarding the rate of preoperative AF, LAAc showed protective effect against stroke/embolic events in studies with >70% preoperative AF (RR 0.64, 95% CI 0.53-0.77; P < 0.00001) but no benefit in the studies with <30% of preoperative AF (RR 0.77, 95% CI 0.46-1.28; P = 0.31). Postoperative mortality was also significantly lower in surgical patients with LAAc at the mid- and long-term follow-up. (RR 0.72, 95% CI 0.67-0.78; P < 0.00001; I2 = 0%). Based on these findings, concomitant surgical LAAc is associated with lower rates of embolic events and stroke in the postoperative period in patients with preoperative AF and also improves postoperative mortality in the mid- and long-term follow-up.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Embolia , Acidente Vascular Cerebral , Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Humanos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
17.
J Clin Med ; 8(12)2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31835708

RESUMO

The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC cells in patients failing to achieve pathological complete response (pCR) after pre-operative therapy. We performed a prospective analysis involving the intention-to-treat population of the (Metformin and Trastuzumab in Neoadjuvancy) METTEN study, a randomized multicenter phase II trial of women with primary, non-metastatic (human epidermal growth factor receptor 2) HER2-positive BC evaluating the efficacy, tolerability, and safety of oral metformin (850 mg twice-daily) for 24 weeks combined with anthracycline/taxane-based chemotherapy and trastuzumab (arm A) or equivalent regimen without metformin (arm B), before surgery. We centrally evaluated the proliferation marker Ki67 on sequential core biopsies using visual assessment (VA) and an (Food and Drug Administration) FDA-cleared automated digital image analysis (ADIA) algorithm. ADIA-based pre-operative values of high Ki67 (≥20%), but not those from VA, significantly predicted the occurrence of pCR in both arms irrespective of the hormone receptor status (p = 0.024 and 0.120, respectively). Changes in Ki67 in residual tumors of non-pCR patients were significantly higher in the metformin-containing arm (p = 0.025), with half of all patients exhibiting high Ki67 at baseline moving into the low-Ki67 (<20%) category after neoadjuvant treatment. By contrast, no statistically significant changes in Ki67 occurred in residual tumors of the control treatment arm (p = 0.293). There is an urgent need for innovative therapeutic strategies aiming to provide the protective effects of decreasing Ki67 after neoadjuvant treatment even if pCR is not achieved. Metformin would be evaluated as a safe candidate to decrease the aggressiveness of residual disease after neoadjuvant (pre-operative) systemic therapy of BC patients.

18.
Plant J ; 99(5): 950-964, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31034710

RESUMO

Reactive oxidative species (ROS) and S-glutathionylation modulate the activity of plant cytosolic triosephosphate isomerases (cTPI). Arabidopsis thaliana cTPI (AtcTPI) is subject of redox regulation at two reactive cysteines that function as thiol switches. Here we investigate the role of these residues, AtcTPI-Cys13 and At-Cys218, by substituting them with aspartic acid that mimics the irreversible oxidation of cysteine to sulfinic acid and with amino acids that mimic thiol conjugation. Crystallographic studies show that mimicking AtcTPI-Cys13 oxidation promotes the formation of inactive monomers by reposition residue Phe75 of the neighboring subunit, into a conformation that destabilizes the dimer interface. Mutations in residue AtcTPI-Cys218 to Asp, Lys, or Tyr generate TPI variants with a decreased enzymatic activity by creating structural modifications in two loops (loop 7 and loop 6) whose integrity is necessary to assemble the active site. In contrast with mutations in residue AtcTPI-Cys13, mutations in AtcTPI-Cys218 do not alter the dimeric nature of AtcTPI. Therefore, modifications of residues AtcTPI-Cys13 and AtcTPI-Cys218 modulate AtcTPI activity by inducing the formation of inactive monomers and by altering the active site of the dimeric enzyme, respectively. The identity of residue AtcTPI-Cys218 is conserved in the majority of plant cytosolic TPIs, this conservation and its solvent-exposed localization make it the most probable target for TPI regulation upon oxidative damage by reactive oxygen species. Our data reveal the structural mechanisms by which S-glutathionylation protects AtcTPI from irreversible chemical modifications and re-routes carbon metabolism to the pentose phosphate pathway to decrease oxidative stress.


Assuntos
Arabidopsis/enzimologia , Citosol/enzimologia , Citosol/metabolismo , Triose-Fosfato Isomerase/química , Triose-Fosfato Isomerase/metabolismo , Sequência de Aminoácidos , Arabidopsis/metabolismo , Domínio Catalítico , Cristalografia por Raios X , Cinética , Modelos Moleculares , Mutagênese Sítio-Dirigida , Oxirredução , Conformação Proteica , Espécies Reativas de Oxigênio , Triose-Fosfato Isomerase/genética
19.
Ann Thorac Surg ; 107(5): e365-e367, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30578778

RESUMO

Transcatheter valve implantation has become an alternative to open-heart conventional surgery in high-risk patients. We describe a new surgical technique that allows the implantation of a transcatheter valvular prosthesis through an open surgical approach to prevent the appearance of paravalvular leaks in patients with large native rings.


Assuntos
Fístula Anastomótica/prevenção & controle , Implante de Prótese de Valva Cardíaca/métodos , Insuficiência da Valva Pulmonar/cirurgia , Fístula Anastomótica/diagnóstico por imagem , Próteses Valvulares Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Stents
20.
Rev. gaúch. enferm ; 40: e20180211, 2019.
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1004090

RESUMO

Resumo OBJETIVO Compreender as percepções das gestantes acerca do cuidado recebido durante o pré-natal, no âmbito da atenção primária à saúde. MÉTODO Estudo qualitativo, baseado na Grounded Theory. A coleta de dados foi realizada de agosto a dezembro de 2016, através de entrevista semiestruturada com 12 gestantes que realizaram acompanhamento pré-natal na atenção primária do município de Florianópolis/SC/Brasil. A coleta e análise dos dados foram realizadas concomitantemente. Na análise de dados utilizou-se a codificação aberta e axial. RESULTADOS Foram elaboradas três categorias, sendo elas: O cuidado antes e durante a gestação. Participação em grupos de gestantes e, Cuidado de qualidade durante a gestação. CONCLUSÃO As percepções das gestantes acerca do cuidado recebido durante o pré-natal estão relacionadas à atenção dispensada, ao acolhimento humanizado, consideração da subjetividade da gestante e amparo nos momentos difíceis que tornam este período satisfatório.


Resumen OBJETIVO Comprender las percepciones de las gestantes acerca del cuidado recibido durante el prenatal, en el ámbito de la atención primaria a la salud. MÉTODO Estudio cualitativo, basado en la Grounded Theory. La recolección de datos fue realizada de agosto a diciembre de 2016, a través de entrevista semiestructurada con 12 gestantes en la atención primaria a la salud del municipio de Florianópolis/SC/Brasil. La recolección y análisis de los datos se realizaron concomitantemente. En el análisis de datos se utilizó la codificación abierta y axial. RESULTADOS Fueron elaboradas tres categorías, siendo ellas: El cuidado antes y durante la gestación, Participación en grupos de gestantes y, Cuidado de calidad durante la gestación. CONCLUSIÓN Las percepciones de las gestantes acerca del cuidado recibido durante el prenatal están relacionadas la atención dispensada, acogida humanizada, consideración de la subjetividad de la gestante y amparo en los momentos difíciles que hacen este período satisfactorio.


Abstract OBJECTIVE To understand the perceptions of pregnant women about the care received during prenatal care, in the field of primary health care. METHOD Qualitative study, based on Grounded Theory. Data collection was performed from August to December 2016, through a semi-structured interview with 12 pregnant women who received prenatal care in the city of Florianópolis/SC/Brazil. Data collection and analysis were performed concomitantly. Data analysis was performed using open and axial coding. RESULTS Three categories were elaborated: Care before and during gestation, Participation in groups of pregnant women, and Quality care during pregnancy. CONCLUSION The perceptions of the pregnant women about the care received during the prenatal care is related to the care given, humanized reception, consideration of the pregnant woman's subjectivity and support in the difficult moments that make this period satisfactory.


Assuntos
Humanos , Feminino , Gravidez , Adolescente , Adulto , Adulto Jovem , Cuidado Pré-Natal/normas , Atenção Primária à Saúde/normas , Qualidade da Assistência à Saúde , Cuidado Pré-Natal/psicologia , Complexo Vitamínico B/administração & dosagem , Brasil , Compostos Ferrosos/administração & dosagem , Pesquisa Qualitativa , Gestantes/psicologia , Gravidez não Planejada , Ácido Fólico/administração & dosagem , Ácido Fólico/análogos & derivados
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