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1.
Chem Rev ; 123(23): 12795-13208, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37967475

RESUMO

Transition metal borides, carbides, pnictides, and chalcogenides (X-ides) have emerged as a class of materials for the oxygen evolution reaction (OER). Because of their high earth abundance, electrical conductivity, and OER performance, these electrocatalysts have the potential to enable the practical application of green energy conversion and storage. Under OER potentials, X-ide electrocatalysts demonstrate various degrees of oxidation resistance due to their differences in chemical composition, crystal structure, and morphology. Depending on their resistance to oxidation, these catalysts will fall into one of three post-OER electrocatalyst categories: fully oxidized oxide/(oxy)hydroxide material, partially oxidized core@shell structure, and unoxidized material. In the past ten years (from 2013 to 2022), over 890 peer-reviewed research papers have focused on X-ide OER electrocatalysts. Previous review papers have provided limited conclusions and have omitted the significance of "catalytically active sites/species/phases" in X-ide OER electrocatalysts. In this review, a comprehensive summary of (i) experimental parameters (e.g., substrates, electrocatalyst loading amounts, geometric overpotentials, Tafel slopes, etc.) and (ii) electrochemical stability tests and post-analyses in X-ide OER electrocatalyst publications from 2013 to 2022 is provided. Both mono and polyanion X-ides are discussed and classified with respect to their material transformation during the OER. Special analytical techniques employed to study X-ide reconstruction are also evaluated. Additionally, future challenges and questions yet to be answered are provided in each section. This review aims to provide researchers with a toolkit to approach X-ide OER electrocatalyst research and to showcase necessary avenues for future investigation.

2.
J Environ Manage ; 344: 118476, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37413731

RESUMO

The accumulation in soil landfills of toxic and persistent lindane, widely used as an insecticide, triggers the risk of leaching with the concomitant contamination of surrounding rivers. Thus, viable remediation to eliminate in situ high concentrations of lindane in soil and water becomes an urgent demand. In this line, a simple and cost-effective composite is proposed, including the use of industrial wastes. It includes reductive and non-reductive base-catalyzed strategies to remove lindane in the media. A mixture of magnesium oxide (MgO) and activated carbon (AC) was selected for that purpose. The use of MgO provides a basic pH. In addition, the specific selected MgO forms double-layered hydroxides in water which permits the total adsorption of the main heavy metals in contaminated soils. AC provides adsorption microsites to hold the lindane and a reductive atmosphere that was increased when combined with the MgO. These properties trigger highly efficient remediation of the composite. It permits a complete elimination of lindane in the solution. In soils doped with lindane and heavy metals, it produces a rapid, complete, and stable elimination of lindane and immobilization of the metals. Finally, the composite tested in lindane-highly contaminated soils permits the "in situ" degradation of nearly 70% of the initial lindane. The proposed strategy opens a promising way to face this environmental issue with a simple, cost-effective composite to degrade lindane and fix heavy metals in contaminated soils.


Assuntos
Metais Pesados , Poluentes do Solo , Óxido de Magnésio , Hexaclorocicloexano , Carvão Vegetal/química , Poluentes do Solo/química , Metais Pesados/química , Solo/química , Resíduos Industriais , Água
3.
BMC Cancer ; 22(1): 1150, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348385

RESUMO

BACKGROUND: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives. METHODS: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain. Hospitals associated with the Spanish Ovarian Cancer Research Group (GEICO) recruited patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer treated with rucaparib 600 mg twice daily as maintenance or treatment (Pt-S/Pt-R) in the RAP. Baseline characteristics, efficacy, and safety data were collected. RESULTS: Between July 2020 and February 2021, 51 patients treated in 22 hospitals in the RAP were included in the study. Eighteen patients with a median of 3 (range, 1-6) prior treatment lines received rucaparib as maintenance; median progression-free survival (PFS) for this group was 9.1 months (95% confidence interval [CI], 4.2-11.6 months). Among 33 patients (median 5 [range, 1-9] prior treatment lines) who received rucaparib as treatment, 7 and 26 patients had Pt-S and Pt-R disease, respectively. Median PFS was 10.6 months (95% CI, 2.5 months-not reached) in the Pt-S group and 2.2 months (95% CI, 1.1-3.2 months) in the Pt-R group. Grade ≥ 3 treatment-emergent adverse events were reported in 39% of all patients, the most common being anaemia (12% and 15% in the maintenance and treatment groups, respectively). At data cut-off, 5 patients remained on treatment. CONCLUSION: Efficacy results in these heavily pre-treated patients were similar to those from previous trials. The safety profile of rucaparib in real life was predictable and manageable.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Humanos , Feminino , Espanha , Neoplasias Ovarianas/tratamento farmacológico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Antineoplásicos/uso terapêutico
4.
Aesthetic Plast Surg ; 46(Suppl 1): 94-95, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34231024

RESUMO

This is a letter to the editor about a meta-analysis titled "The efficacy of cell-assisted lipotransfer versus conventional lipotransfer in breast augmentation: a systematic review and meta-analysis" by Li and Chen published in the year 2021. The most frequently performed aesthetic procedure is breast augmentation surgery. In breast augmentation, cell-assisted lipotransfer (CAL) has received high recognition due to its positive outcomes. There are controversies in the medical literature on the use of CAL for breast augmentation. This meta-analysis by Li and Chen has concluded that CAL using ASC was superior to other methods as it improved fat survival rate in breast augmentation. We have written this letter to the editor of the Aesthetic Plastic Surgery journal about this meta-analysis because of its impactful information provided by this study to the medical literature for breast augmentation surgery using cell-assisted lipotransfer. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


Assuntos
Mamoplastia , Estética , Humanos , Mamoplastia/métodos
6.
Clin Transl Oncol ; 26(8): 1896-1907, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38578537

RESUMO

BACKGROUND: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. METHODS: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. RESULTS: From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. CONCLUSIONS: Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT01733628.


Assuntos
Bevacizumab , Neoplasias da Mama , Neoplasias Colorretais , Hipertensão , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Hipertensão/induzido quimicamente , Estudos Prospectivos , Idoso , Masculino , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão , Metilação de DNA
7.
Gynecol Oncol Rep ; 48: 101211, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37396679

RESUMO

The poly(ADP-ribose) polymerase inhibitor (PARPi) rucaparib is approved as maintenance therapy for patients with platinum-sensitive recurrent high-grade ovarian cancer (HGOC). The efficacy and safety of rucaparib after PARPi therapy are largely unknown; therefore, we analyzed outcomes in the subgroup of PARPi-pretreated patients from Spanish hospitals participating in the Rucaparib Access Program. This post hoc subgroup analysis explored baseline characteristics, treatment exposure, safety, effectiveness, and subsequent therapy among women receiving rucaparib 600 mg twice daily after at least one prior PARPi for HGOC. Of 14 women eligible for the analysis, 11 (79%) had tumors harboring BRCA1/2 mutations. Patients had received a median of 5 (range 3-8) treatment lines before rucaparib. Twelve patients (86%) had previously received olaparib and two (14%) niraparib; 12 patients received rucaparib as treatment for platinum-resistant HGOC, one as treatment for platinum-sensitive HGOC, and one as maintenance therapy. Progression-free survival was 0.2-9.1 months. One of seven patients assessable for response by RECIST achieved stable disease. Adverse events occurred in 11 patients (79%; grade 3 in 29%), leading to treatment interruption in eight patients (57%), dose reduction in six (43%), but treatment discontinuation in only one (7%). No new safety signals were observed. This is one of the first reported series of real-world data on rucaparib after prior PARPi for HGOC. In this heavily pretreated population, rucaparib demonstrated meaningful activity in some patients and tolerability consistent with previous prospective trials. Future investigation should focus on identifying patients who may benefit from rucaparib after prior PARPi exposure.

8.
Cancers (Basel) ; 15(11)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37296992

RESUMO

Genomic Instability (GI) is a transversal phenomenon shared by several tumor types that provide both prognostic and predictive information. In the context of high-grade serous ovarian cancer (HGSOC), response to DNA-damaging agents such as platinum-based and poly(ADP-ribose) polymerase inhibitors (PARPi) has been closely linked to deficiencies in the DNA repair machinery by homologous recombination repair (HRR) and GI. In this study, we have developed the Scarface score, an integrative algorithm based on genomic and transcriptomic data obtained from the NGS analysis of a prospective GEICO cohort of 190 formalin-fixed paraffin-embedded (FFPE) tumor samples from patients diagnosed with HGSOC with a median follow up of 31.03 months (5.87-159.27 months). In the first step, three single-source models, including the SNP-based model (accuracy = 0.8077), analyzing 8 SNPs distributed along the genome; the GI-based model (accuracy = 0.9038) interrogating 28 parameters of GI; and the HTG-based model (accuracy = 0.8077), evaluating the expression of 7 genes related with tumor biology; were proved to predict response. Then, an ensemble model called the Scarface score was found to predict response to DNA-damaging agents with an accuracy of 0.9615 and a kappa index of 0.9128 (p < 0.0001). The Scarface Score approaches the routine establishment of GI in the clinical setting, enabling its incorporation as a predictive and prognostic tool in the management of HGSOC.

9.
ACS Appl Mater Interfaces ; 14(37): 42153-42170, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36084243

RESUMO

Alkaline water electrolysis, a promising technology for clean energy storage, is constrained by extrinsic factors in addition to intrinsic electrocatalytic activity. To begin to compare between catalytic materials for electrolysis applications, these extrinsic factors must first be understood and controlled. Here, we modify extrinsic electrode properties and study the effects of bubble release to examine how the electrode and surface design impact the performance of water electrolysis. We fabricate robust and cost-effective electrodes through a sequential three-dimensional (3D) printing and metal deposition procedure. Through a systematic assessment of the deposition procedure, we confirm the close relationship between extrinsic electrode properties (i.e., wettability, surface roughness, and electrochemically active surface area) and electrochemical performance. Modifying the electrode geometry, size, and electrolyte flow rate results in an overpotential decrease and different bubble diameters and lifetimes for the hydrogen (HER) and oxygen evolution reactions (OER). Hence, we demonstrate the essential role of the electrode architecture and forced electrolyte convection on bubble release. Additionally, we confirm the suitability of ordered, Ni-coated 3D porous structures by evaluating the HER/OER performance, bubble dissipation, and long-term stability. Finally, we utilize the 3D porous electrode as a support for studying a benchmark NiFe electrocatalyst, confirming the robustness and effectiveness of 3D-printed electrodes for testing electrocatalytic materials while extrinsic properties are precisely controlled. Overall, we demonstrate that tailoring electrode architectures and surface properties result in precise tuning of extrinsic electrode properties, providing more reproducible and comparable conditions for testing the efficiency of electrode materials for water electrolysis.

10.
J Pers Med ; 12(11)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36579549

RESUMO

Germline and tumor BRCA testing constitutes a valuable tool for clinical decision-making in the management of epithelial ovarian cancer (EOC) patients. Tissue testing is able to identify both germline (g) and somatic (s) BRCA variants, but tissue preservation methods and the widespread implementation of NGS represent pre-analytical and analytical challenges that need to be managed. This study was carried out on a multicenter prospective GEICO cohort of EOC patients with known gBRCA status in order to determine the inter-laboratory reproducibility of tissue sBRCA testing. The study consisted of two independent experimental approaches, a bilateral comparison between two reference laboratories (RLs) testing 82 formalin-paraffin-embedded (FFPE) EOC samples each, and a Ring Test Trial (RTT) with five participating clinical laboratories (CLs) evaluating the performance of tissue BRCA testing in a total of nine samples. Importantly, labs employed their own locally adopted next-generation sequencing (NGS) analytical approach. BRCA mutation frequency in the RL sub-study cohort was 23.17%: 12 (63.1%) germline and 6 (31.6%) somatic. Concordance between the two RLs with respect to BRCA status was 84.2% (gBRCA 100%). The RTT study distributed a total of nine samples (three commercial synthetic human FFPE references, three FFPE, and three OC DNA) among five CLs. The median concordance detection rate among them was 64.7% (range: 35.3-70.6%). Analytical discrepancies were mainly due to the minimum variant allele frequency thresholds, bioinformatic pipeline filters, and downstream variant interpretation, some of them with consequences of clinical relevance. Our study demonstrates a wide range of concordance in the identification and interpretation of BRCA sequencing data, highlighting the relevance of establishing standard criteria for detecting, interpreting, and reporting BRCA variants.

11.
EXCLI J ; 20: 1328-1345, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650387

RESUMO

Peritoneal metastasis is associated with poor prognosis, with studies in the literature reporting the survival of peritoneal metastasis without treatment to be three to six months. Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown positive outcomes by improving the prognosis in patients with gastrointestinal malignancies. This systematic review of randomized controlled trials was done to determine the prophylactic role of hyperthermic intraperitoneal chemotherapy in preventing and controlling peritoneal metastasis gastrointestinal origin. Randomized controlled trials published between January 2019 to June 2021 were included. The databases used were MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane library. Cochrane handbook for systematic review of intervention was used to assess the risk of bias in included trials. The results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of five trials met the inclusion criteria. Two studies were on patients with gastric cancer, and the other three studies were on patients with colorectal cancer. HIPEC was given to a total of 116 gastric cancer patients and 308 colorectal cancer patients. In all the included studies on patients with gastric cancer, the peritoneal recurrence-free survival was significantly higher in the group that received HIPEC. There was no significant improvement in peritoneal-free survival in patients with colorectal cancer who received HIPEC. HIPEC appears to be effective in preventing peritoneal metastasis in patients with locally advanced gastric cancer without minimal postoperative complications. However, in patients with advanced colorectal malignancy, HIPEC does not seem to play a crucial role in preventing and controlling peritoneal metastasis.

12.
Acta Oncol ; 47(8): 1584-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18607841

RESUMO

BACKGROUND: Standard treatment of patients with T4b squamous cell head and neck cancer (T4b-SCHNC) is concomitant chemo-radiotherapy (CT-RT). Recent Phase III trials with Taxane containing induction chemotherapy (IC) suggest that IC could also play a role in this setting. The value of resecting the residual mass after IC and before RT is not yet clear in this context. METHODS: We present the results of a retrospective analysis. RESULTS: Between 1984 and 2001, 113 patients (patients) with T4b-SCHNC were treated at our institution with IC. Four patients dead during IC and 57 patients achieved a complete or a >90% partial response at primary and proceeded to definitive RT (or concomitant CT/RT). Surgical resection was reconsidered after IC and before RT in the other 52 patients. Surgery was performed in 13 of them: in 7 patients resection was R1, all of them had loco-regional progression (2 also developed systemic metastases) and median OS after surgery was 21 months, with no patient alive at 48 months. In the other 6 patients a R0 resection was performed: 3 of these patients had loco-regional relapses (1 also developed systemic metastases) and the other 3 patients remain alive and disease free 56, 62 and 72 months after surgery. Considering the 52 patients that achieved less than a 90% partial response at primary with IC, overall survival was equivalent when no Resection or an R1 resection was performed after IC (5 year OS 8 vs. 0%, lrk, p=0.74), but a statistically significant improvement in OS was observed when an R0 resection was obtained (5 years OS 50%, lrk, p=0.02). CONCLUSIONS: R0 resections after IC and before RT could indicate an improvement in OS in patients with T4b-SCHNC that obtain less than a 90% PR at primary after IC. We consider that this approach deserves further research in prospective clinical trials.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/terapia , Adulto , Idoso , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Uracila/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina
14.
J Exp Psychol Anim Learn Cogn ; 40(4): 425-30, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25546100

RESUMO

According to a recent theory (Hall & Rodriguez, 2010), the latent inhibition produced by nonreinforced exposure to a target stimulus (B) will be deepened by subsequent exposure of that stimulus in compound with another (AB). This effect of compound exposure is taken to depend on the addition of a novel A to the familiar B and is not predicted for equivalent preexposure on which AB trials precede the A trials. This prediction was tested in 2 experiments using rats. Experiment 1 used an aversive procedure with flavors as the stimuli; Experiment 2 used an appetitive procedure with visual and auditory stimuli. In both, we found that conditioning with B as the conditioned stimulus proceeded more slowly (i.e., latent inhibition was greater) in subjects given the B-AB sequence in preexposure than in subjects given the AB-B sequence.


Assuntos
Aprendizagem por Associação/fisiologia , Condicionamento Psicológico/fisiologia , Inibição Psicológica , Teoria Psicológica , Animais , Masculino , Ratos
15.
Drugs ; 74(8): 879-89, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24848752

RESUMO

Paclitaxel and carboplatin combination chemotherapy has remained the standard of care in the frontline therapy of advanced epithelial ovarian carcinoma during the last decade. Maintenance chemotherapy or immunotherapy has not been proven to impact on overall survival and only one clinical trial that explored the administration of monthly paclitaxel for 1 year showed a benefit in terms of progression-free survival (PFS), but at the cost of maintained alopecia and increased peripheral neuropathy. This scenario may be changing with the incorporation of targeted therapy to the frontline therapy of ovarian cancer. In particular, anti-angiogenic therapy has been identified as the most promising targeted therapy, and the addition of bevacizumab to first-line chemotherapy followed by a maintenance period of bevacizumab in monotherapy has shown to prolong PFS. This was considered the proof of concept of the value of anti-angiogenic therapy in the frontline of ovarian cancer, and the results of two additional clinical trials with anti-angiogenic tyrosine-kinase inhibitors have shown results in the same direction.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bevacizumab , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Feminino , Humanos , Terapia de Alvo Molecular , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
16.
Mol Oncol ; 8(8): 1719-28, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25103625

RESUMO

BACKGROUND: Given our preclinical data showing synergy between dovitinib and paclitaxel in preclinical models we conducted this phase I trial aiming to define the recommended phase II-dose (RP2D) on the basis of toxicity and pharmacodynamic criteria while searching for genetic variants that could sensitize patients to the regimen under study. PATIENTS AND METHODS: A 3+3 escalation schedule was adopted. Seriated FGF23 and dovitinib and paclitaxel pharmacokinetic profiles were determined along a single-agent dovitinib "priming-phase" followed by a dovitinib + paclitaxel combination phase. RECIST 1.1 criteria and NCI CTCAE V.4.0 were used. In fresh pre-treatment tumor biopsy samples, FGFR1, 2 and 3 amplifications were revealed by FISH probes; 32 missense variants were genotyped in tumors and peripheral blood mononuclear cells with Taqman genotyping assays (FGFR1-3 and RET). Constructs encoding for wild-type and variant genes associated with clinical benefit were transfected into HEK-293 cells for preclinical experiments checking constitutive activation and dovitinib sensitivity of the variants. RESULTS: twelve patients were recruited in three dose-levels. At level 1B (200 mg dovitinib 5-days-on/2-days-off plus 60 mg/m 2-week of paclitaxel) more than 50% FGF23 upregulation was observed and no dose-limiting-toxicities (DLTs) occurred. The most frequent toxicities were asthenia, neutropenia, nausea/vomiting and transaminitis. Two patients with progressive disease prior to trial inclusion achieved prolonged disease stabilization. Both had the germline variant G2071A in the RET gene, which led to constitutive activation of the protein product and Y-905 phosphorylation, both in transfectants and in patients with the alteration. This variant was sensitive to dovitinib; in addition both patients experienced progression upon medication withdrawal. CONCLUSIONS: Level 1B was the RP2D as it provided adequate pharmacodynamic exposure to dovitinib. The G2071A germline variant act as a genetic modifier that renders different tumors sensitive to dovitinib.


Assuntos
Benzimidazóis/uso terapêutico , Paclitaxel/uso terapêutico , Quinolonas/uso terapêutico , Adulto , Idoso , Benzimidazóis/farmacocinética , Linhagem Celular Tumoral , Fator de Crescimento de Fibroblastos 23 , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Paclitaxel/farmacocinética , Quinolonas/farmacocinética
17.
Expert Rev Anticancer Ther ; 13(2): 123-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23406552

RESUMO

Ovarian cancer is the leading cause of death due to gynecological tumors. Despite the progress made during the last two decades in the surgery and chemotherapy of ovarian cancer, more than 70% of patients with advanced ovarian cancer will recur and die. Improvements in this field are coming from a better knowledge of the biology and the development of new-targeted agents. Bevacizumab, is a monoclonal antibody against VEGF that has shown activity as a monotherapy in recurrent ovarian cancer. The addition of bevacizumab to the front-line therapy of ovarian cancer has produced a benefit in progression-free survival in two randomized Phase III trials. This benefit seems to be greater in patients with more advanced disease. However, several questions remain to be clarified in the future, specially the optimal patient selection based on predictive biomarkers and the duration of therapy. Nevertheless, for the first time, the addition of a biologically targeted agent has shown an improvement in progression-free survival in the front-line treatment of advanced ovarian cancer and it is a proof of concept of the potential value of antiangiogenic therapy in ovarian cancer.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/imunologia , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Bevacizumab , Carcinoma Epitelial do Ovário , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos
18.
J. oral res. (Impresa) ; 7(4): 134-140, abr. 27, 2018. ilus, tab, graf
Artigo em Inglês | LILACS | ID: biblio-1120767

RESUMO

Objective. to evaluate the clinical effect of a probiotic mouthwash in reducing generalized marginal chronic gingivitis using positive and negative control groups. methodology. four-week study conducted in San Luis Potosí, Mexico, from january to march 2017. participants were healthy, non-smokers with generalized marginal chronic gingivitis; age range 18-45 years. subjects were randomized and divided into three groups: group A: mouthwash based on 0.05 percent cetylpyridinium chloride (CPC) (positive control); group B: mouthwash based on probiotics (experimental); group C: placebo mouthwash (negative control). no oral hygiene practices or routines were modified; subjects were followed for 4 weeks. the primary outcome variable of interest was the Löe and Silness gingival index, and the secondary one, the Quigley Heinn plaque index modified by Turesky. results. of the 45 patients included, 19 (42.2 percent) were men and 26 (57.7 percent) women, mean age was 22.8±2.07. each group consisted of 15 subjects; all subjects completed the study. there was no statistically significant reduction in gingival inflammation when comparing the 3 treatment groups (p=0.540) with respect to the gingival index. A comparison was made before and after the treatment and in the 3 groups there was no reduction of the gingival inflammation. plaque reduction was not statistically significant when comparing the 3 groups (p=0.278). however, when doing intra-group comparison, it was found that the patients in group A had a reduction in plaque index (p<0.005), which was not observed in groups B (p=0.1103) and C (p=0.1508). conclusions. the use of a probiotic mouth mouthwash did not reduce gingival inflammation or the accumulation of dentobacterial plaque in a period of 4 weeks. there were no statistically significant differences between the study groups.


Assuntos
Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Clorexidina/uso terapêutico , Probióticos/uso terapêutico , Placa Dentária/prevenção & controle , Gengivite/prevenção & controle , Anti-Infecciosos Locais/uso terapêutico , Antissépticos Bucais/uso terapêutico , Índice Periodontal , Projetos Piloto , México , Antissépticos Bucais/química
19.
Acta Oncol ; 47(1): 9-19, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18097777

RESUMO

EGFR overexpression usually correlates with a more advanced disease stage, a poorer prognosis and a worse chemotherapy response. EGFR expression increase has been observed in many tumours. For all the aforementioned reasons, EGFR inhibition can be considered an attractive approach in cancer treatment. One strategy has been receptor inhibition of extracellular domain using monoclonal antibodies. Cetuximab is the most developed one and there is plenty information on the literature about its current status. In this review we focus on other EGFR monoclonal antibodies under clinical development. The more developed one is Panitumumab. Its clinical development is taking place very quickly and it has mainly been studied in colorectal cancer showing promising results. There are also other interesting drugs such as Matuzumab, Nimotuzumab and Zalutumumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Anticorpos Monoclonais Humanizados , Cetuximab , Receptores ErbB/biossíntese , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Humanos , Panitumumabe , Neoplasias Gástricas/tratamento farmacológico
20.
Bol. Col. Mex. Urol ; 9(1): 13-7, ene-abr. 1992. tab
Artigo em Espanhol | LILACS | ID: lil-117957

RESUMO

Se estudiaron en forma prospectiva 75 pacientes del sexo femenino con incontinencia urinaria identificada desde el punto de vista clínico. Se les realizó perfil de presión uretral estático sin micción y se encontró incontinencia de urgencia en 26, de esfuerzo en 25 y de tipo mixto en 24. No hubo diferencias en la previsión vesicalbasal. La longitud funcional de la uretra sí se afecta en el tipo de urgencia, y da como resultado diferencias con respecto a la de esfuerzo y mixta. Tanto la presión máxima de cierre como la uretral máxima disminuyen conforme progresa la edad de la mujer, sin guardar relación con el tipo de incontinencia. La presión máxima de cierre y uretral máxima en la incontinencia de urgencia produce diferencias a una p en relación con las de esfuerzo y mixta. La utilidad clínica del perfil de presión uretral es un aspecto controvertido. Los datos que se informan en este artículo indican que se tiene que revalorar su posición, pues podrían ser de gran ayuda para la valoración integral de la incontinencia urinaria de urgencia.


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Doenças Uretrais/fisiopatologia , Bexiga Urinária/fisiopatologia , Incontinência Urinária por Estresse/diagnóstico , Incontinência Urinária/diagnóstico , Sistema Urinário/fisiopatologia , Urodinâmica , Incontinência Urinária/classificação , Incontinência Urinária/fisiopatologia
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