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1.
BMJ Support Palliat Care ; 14(3): 299-302, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-38123978

RESUMO

OBJECTIVES: The perception of oncologists could impact the attractiveness of the specialty and dialogue between oncologists and other physicians. The aim of the study was to describe and understand the stereotypes and social representation (SR) associated with oncologists among medical students, residents and physicians in France. METHODS: This nationwide web-based survey conducted in 2021 was based on hierarchical evocation methods. Qualitative analyses were based on the Reinert method with factorial analyses. Each respondent's SR was graded from 1 to 5 (from 1: very positive SR to 5: very negative SR). RESULTS: Oncologists suffer from a rather negative SR. The negative representation was mostly related to difficulties in practising and the proximity with death and end of life. Oncologists were also associated with more positive notions like interdisciplinarity or intellectual complexity. Attendance to an oncology course was associated with a better SR of oncology (p=0.036), whereas having someone in the family practising oncology had a negative impact (p=0.028). CONCLUSIONS: SR of oncologists is rather contrasted. It was positively influenced by attendance to an oncology course, which could be an option to correct stereotypes and update on this rapidly evolving specialty.


Assuntos
Atitude do Pessoal de Saúde , Oncologistas , Estereotipagem , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Estudos Transversais , Masculino , Feminino , França , Oncologistas/psicologia , Adulto , Médicos/psicologia , Internato e Residência , Oncologia/educação , Pessoa de Meia-Idade , Inquéritos e Questionários
2.
Per Med ; 20(6): 467-475, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37937420

RESUMO

Background: Noninvasive prenatal tests for monogenic diseases (NIPT-SGG) have recently been reported as helpful in early-stage antenatal screening. Our study describes the clinical and genetic features of cases identified by NIPT-SGG. Materials & methods: In a cohort pregnancy with abnormal sonograms, affected cases were confirmed by invasive diagnostic tests concurrently, with NIPT-SGG targeting 25 common dominant single-gene diseases. Results: A total of 13 single-gene fetuses were confirmed, including Noonan and Costello syndromes, thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta and Apert syndrome. Two novel variants seen were tuberous sclerosis complex (TSC2 c.4154G>A) and Alagille syndrome (JAG1 c.3452del). Conclusion: NIPT-SGG and standard tests agree on the results for 13 fetuses with monogenic disorders. This panel method of screening can benefit high-risk Vietnamese pregnancies, but further research is encouraged to expand on the causative gene panel.


Assuntos
Diagnóstico Pré-Natal , Displasia Tanatofórica , Gravidez , Feminino , Humanos , Vietnã , Displasia Tanatofórica/diagnóstico , Displasia Tanatofórica/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos
3.
Placenta ; 140: 84-89, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37549441

RESUMO

INTRODUCTION: This study aimed to determine the predictive value of cancer antigen-125 (CA-125) in combination with serum beta-human chorionic gonadotropin (ß-hCG) and progesterone in the early detection of ectopic pregnancy (EP). METHODS: Between May 2019 and May 2020, the cross-sectional study recruited 42 cases of EP and 42 cases of IUP at the same gestational age who visited the Department of Obstetrics and Gynecology, Hospital of Hue University of Medicine and Pharmacy. EP was diagnosed based on surgical (laparoscopy) and postoperative pathology examination. RESULTS: There were significant differences of mean level of ß-hCG (2570 mUI/mL vs. 18357.7 mUI/mL), progesterone (10.79 ± 8.16 ng/ml vs. 27.42 ± 4.17 ng/ml) and CA-125 (26.90 ± 10.26 U/mL vs. 70.61 ± 20.89 U/mL) between the EP and the IUP groups (p < 0.001). In the prediction of early diagnosis of EP, the cut-off value of CA-125 at 30.94 U/mL has a sensitivity of 89.3% and a specificity of 87,9%; the cut-off value of ß hCG at 2750mIU/ml has the sensitivity of 75%, specificity of 78,8%; the cut-off value of progesterone at 10.24 ng/mL has the sensitivity of 85.7%, specificity of 81.8%. A combination of CA-125, ß hCG, and progesterone had a sensitivity of 92.8% and a specificity of 90.9% in early diagnosis of EP. DISCUSSION: Serum CA-125 levels can be used independently or in combination with other markers in the early diagnosis of EP.


Assuntos
Antígeno Ca-125 , Gravidez Ectópica , Progesterona , Feminino , Humanos , Gravidez , Estudos de Casos e Controles , Gonadotropina Coriônica , Gonadotropina Coriônica Humana Subunidade beta , Estudos Transversais , Detecção Precoce de Câncer , Gravidez Ectópica/diagnóstico , Vietnã , Antígeno Ca-125/sangue
4.
Pediatr Surg Int ; 39(1): 131, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36800080

RESUMO

PURPOSE: This study investigated anorectal manometry (AM) findings and bowel function of patients operated on for Hirschsprung's disease (HD). METHODS: A cross-sectional study was conducted at Children's Hospital 2. Patients operated on for HD from January 2015 to January 2020 were reviewed. Their clinical characteristics, bowel function, and manometric findings were investigated and compared with the references. RESULTS: Ninety-five patients and 95 references were enrolled. Mean ages were 6.6 ± 2.2 years and 7.2 ± 2.9 years,; fecal incontinence rates were 25.3% and 2.1%, and constipation rates were 12.6% and 4.2 for the patients versus the references, respectively. Anal resting pressures were significantly decreased in the patients compared to the references (53.2 ± 16.1 mmHg versus 62.2 ± 14.0 mmHg; p < 0.05). Among the patients, the anal resting pressure was significantly decreased in the incontinents than in the continents (46.0 ± 10.6 mmHg versus 55.6 ± 16.9 mmHg, p < 0.05). During the sensation test, the value of maximum tolerated volume was significantly decreased in the incontinents than in the continents (135.9 ± 47.9 mL versus 166.6 ± 58.3 mL, p < 0.05). CONCLUSION: AM is an objective method providing beneficial information that could guide a more adapted management in HD patients with defecation disorders.


Assuntos
Incontinência Fecal , Doença de Hirschsprung , Criança , Humanos , Pré-Escolar , Reto/cirurgia , Doença de Hirschsprung/cirurgia , Estudos Transversais , Canal Anal/cirurgia , Constipação Intestinal/etiologia , Manometria , Incontinência Fecal/etiologia
5.
Front Immunol ; 13: 902135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958592

RESUMO

Peptide-loaded Major Histocompatibility Complex (pMHC) class I molecules can be expressed in a single chain trimeric (SCT) format, composed of a specific peptide fused to the light chain beta-2 microglobulin (ß2m) and MHC class I heavy chain (HC) by flexible linker peptides. pMHC SCTs have been used as effective molecular tools to investigate cellular immunity and represent a promising vaccine platform technology, due to their intracellular folding and assembly which is apparently independent of host cell folding pathways and chaperones. However, certain MHC class I HC molecules, such as the Human Leukocyte Antigen B27 (HLA-B27) allele, present a challenge due to their tendency to form HC aggregates. We constructed a series of single chain trimeric molecules to determine the behaviour of the HLA-B27 HC in a scenario that usually allows for efficient MHC class I molecule folding. When stably expressed, a pMHC SCT incorporating HLA-B27 HC formed chaperone-bound homodimers within the endoplasmic reticulum (ER). A series of HLA-B27 SCT substitution mutations revealed that the F pocket and antigen binding groove regions of the HLA-B27 HC defined the folding and dimerisation of the single chain complex, independently of the peptide sequence. Furthermore, pMHC SCTs can demonstrate variability in their association with the intracellular antigen processing machinery.


Assuntos
Antígeno HLA-B27 , Antígenos de Histocompatibilidade Classe I , Apresentação de Antígeno , Genes MHC Classe I , Antígeno HLA-B27/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Chaperonas Moleculares/genética , Peptídeos/genética
6.
Biotechnol Rep (Amst) ; 34: e00714, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35686001

RESUMO

The American Cancer Society estimated around 61,090 new cases of leukemia were diagnosed, and around 23,660 people died from this disease in the United States alone in 2021. Due to its burden on society, there is an unmet need to explore innovative approaches to overcome leukemia. Among different strategies that have been explored, nanotechnology appears to be a promising and effective approach for therapeutics. Specifically, biogenic silver and gold nanoparticles (NPs) have attracted significant attention for their antineoplastic activity toward leukemia cancer cells due to their unique physicochemical properties. Indeed, these nanostructures have emerged as useful approaches in anti-leukemic applications, either as carriers to enhance drug bioavailability and its targeted delivery to a specific organ or as a novel therapeutic agent. This review explores recent advances in green synthesized nanomaterials and their potential use against leukemia, especially focusing on silver (Ag) and gold (Au) nanostructures. In detail, we have reviewed various eco-friendly methods of bio-synthesized NPs, their analytical properties, and toxicity effects against leukemic models. This overview confirms the satisfactory potency of biogenic NPs toward leukemic cells and desirable safety profiles against human native cells, which opens a promising door toward commercializing these types of nontherapeutic agents if challenges involve clinical validations, reproducibility, and scalability could be resolved.

7.
J Mol Diagn ; 24(6): 586-599, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35570134

RESUMO

With the advent of next-generation sequencing (NGS), monogenic forms of common variable immunodeficiency (CVID) have been increasingly described. Our study aimed to identify disease-causing variants in a Western Australian CVID cohort using a novel targeted NGS panel. Targeted amplicon NGS was performed on 22 unrelated subjects who met the formal European Society for Immunodeficiencies-Pan-American Group for Immunodeficiency diagnostic criteria for CVID and had at least one of the following additional criteria: disease onset at age <18 years, autoimmunity, low memory B lymphocytes, family history, and/or history of lymphoproliferation. Candidate variants were assessed by in silico predictions of deleteriousness, comparison to the literature, and classified according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology criteria. All detected genetic variants were verified independently by an external laboratory, and additional functional studies were performed if required. Pathogenic or likely pathogenic variants were detected in 6 of 22 (27%) patients. Monoallelic variants of uncertain significance were also identified in a further 4 of 22 patients (18%). Pathogenic variants, likely pathogenic variants, or variants of uncertain significance were found in TNFRSF13B, TNFRSF13C, ICOS, AICDA, IL21R, NFKB2, and CD40LG, including novel variants and variants with unexpected inheritance pattern. Targeted amplicon NGS is an effective tool to identify monogenic disease-causing variants in CVID, and is comparable or superior to other NGS methods. Moreover, targeted amplicon NGS identified patients who may benefit from targeted therapeutic strategies and had important implications for family members.


Assuntos
Imunodeficiência de Variável Comum , Adolescente , Austrália , Estudos de Coortes , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
8.
Clin Infect Dis ; 74(1): 136-139, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33252644

RESUMO

We present a case of complete deficiency of the interferon alpha/beta receptor alpha chain (IFNAR1) in a child with fatal systemic hyperinflammation, apparently provoked by live-attenuated viral vaccination. Such pathologic hyperinflammation, fulfilling criteria for hemophagocytic lymphohistiocytosis, is an emerging phenotype accompanying inborn errors of type I interferon immunity.


Assuntos
Linfo-Histiocitose Hemofagocítica , Homozigoto , Humanos , Interferon-alfa/uso terapêutico , Linfo-Histiocitose Hemofagocítica/genética , Receptor de Interferon alfa e beta/genética
9.
J Funct Biomater ; 14(1)2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36662072

RESUMO

The production of nanoparticles for biomedical applications (namely with antimicrobial and anticancer properties) has been significantly hampered using traditional physicochemical approaches, which often produce nanostructures with poor biocompatibility properties requiring post-synthesis functionalization to implement features that such biomedical applications require. As an alternative, green nanotechnology and the synthesis of environmentally friendly nanomaterials have been gaining attention over the last few decades, using living organisms or biomolecules derived from them, as the main raw materials to produce cost-effective, environmentally friendly, and ready-to-be-used nanomaterials. In this article and building upon previous knowledge, we have designed and implemented the synthesis of selenium and tellurium nanoparticles using extracts from fresh jalapeño and habanero peppers. After characterization, in this study, the nanoparticles were tested for both their antimicrobial and anticancer features against isolates of antibiotic-resistant bacterial strains and skin cancer cell lines, respectively. The nanosystems produced nanoparticles via a fast, eco-friendly, and cost-effective method showing different antimicrobial profiles between elements. While selenium nanoparticles lacked an antimicrobial effect at the concentrations tested, those made of tellurium produced a significant antibacterial effect even at the lowest concentration tested. These effects were correlated when the nanoparticles were tested for their cytocompatibility and anticancer properties. While selenium nanoparticles were biocompatible and had a dose-dependent anticancer effect, tellurium-based nanoparticles lacked such biocompatibility while exerting a powerful anti-cancer effect. Further, this study demonstrated a suitable mechanism of action for killing bacteria and cancer cells involving reactive oxygen species (ROS) generation. In summary, this study introduces a new green nanomedicine synthesis approach to create novel selenium and tellurium nanoparticles with attractive properties for numerous biomedical applications.

10.
Biosens Bioelectron ; 197: 113732, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34741959

RESUMO

CRISPR diagnostics (CRISPR-Dx) offer a wide range of enhancements compared to traditional nanobiosensors by taking advantage of the excellent trans-cleavage activity of the CRISPR/Cas systems. However, the single-stranded DNA/RNA reporters of the current CRISPR-Dx suffer from poor stability and limited sensitivity, which make their application in complex biological environments difficult. In comparison, nanomaterials, especially metal nanoparticles, exhibits robust stability and desirable optical and electrocatalytical properties, which make them ideal as reporter molecules. Therefore, biosensing research is moving towards the use of the trans-cleavage activity of CRISPR/Cas effectors on metal nanoparticles and apply the new phenomenon to develop novel nanobiosensors to target various targets such as viral infections, genetic mutations and tumor biomarkers, by using different sensing methods, including, but not limited to fluorescence, luminescence resonance, colorimetric and electrochemical signal readout. In this review, we explore some of the most recent advances in the field of CRISPR-powered nanotechnological biosensors. Demonstrating high accuracy, sensitivity, selectivity and versatility, nanobiosensors along with CRISPR/Cas technology offer tremendous potential for next-generation diagnostics of multiple targets, especially at the point of care and without any target amplification.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Sistemas CRISPR-Cas/genética , DNA/genética , DNA de Cadeia Simples
11.
Cancers (Basel) ; 13(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34638513

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal human solid tumors, despite great efforts in improving therapeutics over the past few decades. In PDAC, the distinct characteristic of the tumor microenvironment (TME) is the main barrier for developing effective treatments. PDAC TME is characterized by a dense stroma, cancer-associated fibroblasts, and immune cells populations that crosstalk to the subpopulations of neoplastic cells that include cancer stem cells (CSCs). The heterogeneity in TME is also exhibited in the diversity and dynamics of acellular components, including the Extracellular matrix (ECM), cytokines, growth factors, and secreted ligands to signaling pathways. These contribute to drug resistance, metastasis, and relapse in PDAC. However, clinical trials targeting TME components have often reported unexpected results and still have not benefited patients. The failures in those trials and various efforts to understand the PDAC biology demonstrate the highly heterogeneous and multi-faceted TME compositions and the complexity of their interplay within TME. Hence, further functional and mechanistic insight is needed. In this review, we will present a current understanding of PDAC biology with a focus on the heterogeneity in TME and crosstalk among its components. We also discuss clinical challenges and the arising therapeutic opportunities in PDAC research.

12.
Materials (Basel) ; 14(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34300763

RESUMO

Bioceramics such as calcium silicate (Ca-Si), have gained a lot of interest in the biomedical field due to their strength, osteogenesis capability, mechanical stability, and biocompatibility. As such, these materials are excellent candidates to promote bone and tissue regeneration along with treating bone cancer. Bioceramic scaffolds, functionalized with appropriate materials, can achieve desirable photothermal effects, opening up a bifunctional approach to osteosarcoma treatments-simultaneously killing cancerous cells while expediting healthy bone tissue regeneration. At the same time, they can also be used as vehicles and cargo structures to deliver anticancer drugs and molecules in a targeted manner to tumorous tissue. However, the traditional synthesis routes for these bioceramic scaffolds limit the macro-, micro-, and nanostructures necessary for maximal benefits for photothermal therapy and drug delivery. Therefore, a different approach to formulate bioceramic scaffolds has emerged in the form of 3D printing, which offers a sustainable, highly reproducible, and scalable method for the production of valuable biomedical materials. Here, calcium silicate (Ca-Si) is reviewed as a novel 3D printing base material, functionalized with highly photothermal materials for osteosarcoma therapy and drug delivery platforms. Consequently, this review aims to detail advances made towards functionalizing 3D-printed Ca-Si and similar bioceramic scaffold structures as well as their resulting applications for various aspects of tumor therapy, with a focus on the external surface and internal dispersion functionalization of the scaffolds.

14.
HLA ; 96(3): 299-311, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32536006

RESUMO

DPB1 and DPA1 genes share the same promoter region. Single-nucleotide polymorphisms (SNPs) within the regulatory regions of DP have been reported. This study hypothesizes that by including the SNPs in the promoter region of DP, extended haplotypes are defined, and promoter polymorphism is more extensive than what is currently reported. To identify the SNPs in the region of interest, the DP region spanning 21.5 kb was amplified in three separate long-ranged polymerase chain reactions. A DNA panel consisting of 100 samples was selected to represent a broad range of DPB1 alleles. The panel was amplified and sequenced using a dual sequencing strategy. Binary alignment map (BAM) alignments were generated and the mapped sequence alignments were analyzed using Integrative Genomics Viewer. A total of 76 SNPs were identified, and SNPs were clustered into 12 SNP-linked haplotypes. Multiple sequence alignments of promoter sequences indicated four distinct lineages within the connective region (CR) between two genes. The relationship between DPA1, CR, DPB1, and amino acid motifs was found to be correlated with HV1 and HV6. Of the 12 promoter haplotypes, DPB1 alleles observed with ProDP-4 were in complete linkage with HV1/2/5/6, the rs9277534G SNP, and the highly immunogenic T-cell epitope group. Multiple extended haplotypes of different intronic subtypes of the same DPB1 alleles were also identified. This new view of the full DP haplotype shows the relation of polymorphism, genes, and alleles, and provides a basis for future functionality related nomenclature. The novel clustering of the DP-extended haplotype warrants future investigations of DP haplotype matching in the outcome of haematopoietic stem cell transplantation (HSCT).


Assuntos
Cadeias alfa de HLA-DP , Alelos , Análise por Conglomerados , Cadeias alfa de HLA-DP/genética , Cadeias beta de HLA-DP/genética , Haplótipos
15.
HLA ; 95(2): 104-116, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31617672

RESUMO

The rapid progress of HLA typing techniques has contributed to improving the outcome of haematopoietic stem cell transplantation (HSCT). However, unambiguous HLA typing remains challenging. Next generation sequencing (NGS) has been shown to resolve the HLA typing ambiguity and simplify HLA typing workflows. The aim of this study is to develop a multiplexed full-gene PCR assay for 11 HLA loci that can be used on any NGS platform to provide additional information to the traditionally sequenced regions. The entire gene of HLA-A, HLA-B, HLA-C, DRB1, DRB3/4/5, DQB1, DQA1, DPB1, and DPA1 were amplified in four multiplexed reactions. A DNA reference panel of 47 samples representing the most common allele groups was selected to evaluate this novel assay using the Ion Torrent sequencing platform. The specificity and sensitivity of this assay was confirmed on additional 158 samples from a local Caucasian control cohort. Full gene sequences from start to stop codons including some UTR regions were obtained for all 11 HLA loci with complete gene coverage and sufficient read-depth for 3619 alleles. The whole amplicon was analysed for HLA class I genes, while only exons were analysed for class II genes. All alleles were amplified as expected with 100% concordance at full gene resolution for HLA class I and exon resolution for HLA class II loci when compared with previously used NGS or Sanger sequencing methods. In summary, the novel multiplexed PCR approach for full-gene HLA typing enabled for a large amount of genetic information to be generated in a simple and fast workflow.


Assuntos
Antígenos HLA , Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Amplificação de Genes , Genótipo , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA
16.
Biopreserv Biobank ; 18(1): 18-24, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31841643

RESUMO

Background: Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells and is useful for the treatment of blood diseases. The cost of UCB storage is high; thus, it is necessary to evaluate the quality of UCB before collection and cryopreservation. Aim: This study aimed to determine the maternal and neonatal factors that influence UCB before selection for cryopreservation. Materials and Methods: The analysis included 403 processed UCB units. The effects of maternal characteristics including maternal age and delivery method and neonatal factors such as birth weight, gestation duration, and sex on UCB quality were determined based on the collected blood volume, total nucleated cell (TNC) count, and CD34+ cell count. Results: The neonatal birth weight influenced the collected blood volume, TNC count, and CD34+ cell count. Neonates with higher birth weights produced better quality UCB units because of increased collected blood volumes, TNC counts, and CD34+ cell counts. However, an increase in the gestational age from 35 to 41 weeks led to decreases in the collected blood volume and CD34+ cell count. Conclusion: These data may be useful for determining the optimal cord blood units for collection and cryopreservation and for advising pregnant women using private banking services.


Assuntos
Antígenos CD34/metabolismo , Bancos de Sangue , Criopreservação/métodos , Sangue Fetal/citologia , Adulto , Peso ao Nascer , Coleta de Amostras Sanguíneas , Contagem de Células , Sobrevivência Celular , Feminino , Sangue Fetal/imunologia , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Idade Materna , Gravidez
17.
Int J Mol Sci ; 20(13)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261712

RESUMO

(1) Background: Immune cell therapy recently attracted enormous attention among scientists as a cancer treatment, but, so far, it has been poorly studied and applied in Vietnam. The aim of this study was to assess the safety of autologous immune cell therapy for treating lung, liver, and colon cancers-three prevalent cancers in Vietnam. (2) Method: This was an open-label, single-group clinical trial that included 10 patients with confirmed diagnosis of colon, liver, or lung cancer, conducted between March 2016 and December 2017. (3) Results: After 20-21 days of culture, the average number of cytotoxic T lymphocytes (CTLs) increased 488.5-fold and the average cell viability was 96.3%. The average number of natural killer cells (NKs) increased 542.5-fold, with an average viability of 95%. Most patients exhibited improved quality of life, with the majority of patients presenting a score of 1 to 2 in the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG/PS) scale, a decrease in symptoms on fatigue scales, and an increase in the mean survival time to 18.7 months at the end of the study. (4) Conclusion: This method of immune cell expansion met the requirements for clinical applications in cancer treatment and demonstrated the safety of this therapy for the cancer patients in Vietnam.


Assuntos
Neoplasias do Colo/terapia , Imunoterapia/métodos , Células Matadoras Naturais/transplante , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Linfócitos T Citotóxicos/transplante , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue Autóloga/métodos , Células Cultivadas , Feminino , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Citotóxicos/imunologia
18.
J Am Soc Mass Spectrom ; 30(10): 2068-2081, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31332742

RESUMO

Zinc fingers are proteins that are characterized by the coordination of zinc ions by an amino acid sequence that commonly contains two histidines and two cysteines (2His-2Cys motif). Investigations of oligopeptides that contain the 2His-2Cys motif, e.g., acetyl-His1-Cys2-Gly3-Pro4-Tyr5-His6-Cys7, have discovered they exhibit pH-dependent Zn(II) chelation and have redox activities with Cu(I/II), forming a variety of metal complexes. To further understand how these 2His-2Cys oligopeptides bind these metal ions, we have undertaken a series of ion mobility-mass spectrometry and B3LYP/LanL2DZ computational studies of structurally related heptapeptides. Starting with the sequence above, we have modified the potential His, Cys, or C-terminus binding sites and report how these changes in primary structure affect the oligopeptides positive and negative charge states, conformational structure, collision-induced breakdown energies, and how effectively Zn(II) binds to these sequences. The results show evidence that the weak acid-base properties of Cys-His are intrinsically linked and can result in an intramolecular salt-bridged network that affects the oligopeptide properties.


Assuntos
Cisteína/química , Histidina/química , Oligopeptídeos , Zinco , Espectrometria de Massas , Modelos Moleculares , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Ligação Proteica , Zinco/química , Zinco/metabolismo
19.
Pract Radiat Oncol ; 9(5): 338-346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31063823

RESUMO

PURPOSE: Postmastectomy radiation therapy (PMRT) delivered to an immediate reconstruction increases the risk of surgical complications. Although acellular dermal matrix (ADM) has been used with immediate tissue expander (TE) reconstruction to improve cosmetic outcomes and minimize capsular contracture, there is a paucity of data on this approach in the setting of PMRT. METHODS AND MATERIALS: Thirty-two patients with stage I to III breast cancer were treated with mastectomy, immediate TE-ADM reconstruction, and PMRT between 2009 and 2012 in a prospective single-arm study. The primary objective was the "success" rate, determined by the number of patients at 2 years after PMRT having an intact final reconstruction, no major complications, and a cosmetic outcome rated by a physician as excellent or good. RESULTS: The median follow-up was 24 months. Final reconstruction status was known in 31 of 32 patients (96.9%; 1 patient left the country) and completed in 29 of 31 patients (93.5%; implant, n = 26; flap, n = 1; both, n = 2; none, n = 2). At 2 years, 6 patients were unevaluable (metastatic disease, n = 3; withdrawn consent, n = 1; left the country, n = 2). Of 26 evaluable patients, the success rate was 65.4% (17 of 26). Lack of success was the result of "fair" cosmesis (n = 2), infection (n = 2), severe capsular contracture (n = 1), major revision (n = 2), and no final reconstruction (n = 2). Most patients had good-to-excellent 2-year overall cosmesis based on patient perception (15; 62.5%) and physician evaluation (19; 79.2%). CONCLUSIONS: To the best of our knowledge, this is the first dedicated prospective trial evaluating long-term cosmetic and complication outcomes in patients treated with immediate TE-ADM reconstruction followed by PMRT. Most patients (65.4%) met the success criteria in this prospective single-arm series. The great majority (93.5%) achieved final reconstruction; most had good-to-excellent overall cosmetic outcomes (79.2%). The results with longer follow-up will be of interest, and further investigation of strategies to optimize reconstruction with PMRT are warranted.


Assuntos
Derme Acelular/metabolismo , Mastectomia/métodos , Radioterapia Adjuvante/efeitos adversos , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Radioterapia Adjuvante/métodos , Dispositivos para Expansão de Tecidos , Adulto Jovem
20.
Front Pediatr ; 7: 543, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32039110

RESUMO

Aim: The aim of this study was to present primary outcomes of autologous bone marrow mononuclear cell (BMMNC) transplantation to improve neurological sequelae in four children with intracranial hemorrhage (ICH) incidence during the neonatal period. Methods: GMFM88 and modified Ashworth score were used to assess motor function and muscle spasticity before BMMNC transplantation and after transplantation. Brain MRI was performed to evaluate brain morphology before and after BMMNC transplantation. Bone marrow were harvested from anterior iliac crest puncture and BMMNCs were isolated using Ficoll gradient centrifugation. The microbiological testing, cell counting, and hematopoietic stem cell (hHSC CD34+ cell) analysis were performed, following which BMMNCs were infused intrathecally. Results: Improvement in motor function was observed in all patients after transplantation. In addition, muscle spasticity was reduced in all four patients. Conclusion: Autologous BMMNC transplantation may improve motor function and reduce muscle spasticity in children with ICH incidence during the neonatal period.

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