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1.
Braz. j. biol ; 84: e253616, 2024. tab, graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1355880

RESUMO

Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.


Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.


Assuntos
Animais , Ratos , Óleos Voláteis/farmacologia , Colágeno/metabolismo , Alpinia/química , Caveolina 1/metabolismo , Músculos/efeitos dos fármacos , Fibrose , Óleos Vegetais/farmacologia , Brasil , Ratos Wistar , Modelos Animais de Doenças , Músculos/patologia
2.
Ann Lab Med ; 43(1): 73-81, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36045059

RESUMO

Background: BRCA testing is necessary for establishing a management strategy for ovarian cancer. Several BRCA testing strategies, including germline and somatic testing, are implemented in clinical practice in Korea. We aimed to comparatively evaluate their cost-effectiveness from patients' perspective. Methods: We developed a decision model comprising five BRCA testing strategies implemented in Korea: (1) germline testing first, followed by somatic tumor testing for patients without a germline variant; (2) somatic testing first, followed by germline testing for patients with a variant detected by somatic testing; (3) both germline and somatic testing; (4) germline testing alone; and (5) somatic testing alone, with no testing as the comparator. One-way sensitivity analysis was conducted to test the uncertainty of key parameters. Results: Assuming a willingness-to-pay of $20,000 per progression-free life-year gain (PF-LYG), all five strategies were considered cost-effective. Strategy 4 was the most cost-effective option, with an incremental cost-effectiveness ratio (ICER) of $2,547.7 per PF-LYG, followed by strategy 1, with an ICER of $3,978.4 per PF-LYG. Even when the parameter values were varied within the possible range, the ICERs of all strategies did not exceed the willingness-to-pay threshold. Conclusions: Considering the importance of knowing a patient's BRCA gene status, germline testing first, followed by somatic testing, may be a reasonable option.


Assuntos
Neoplasias Ovarianas , Análise Custo-Benefício , Feminino , Células Germinativas/patologia , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , República da Coreia
3.
Ann Lab Med ; 43(1): 82-85, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36045060

RESUMO

Cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) is useful for predicting and monitoring non-small cell lung cancer prognosis. We established reference intervals (RIs) of CYFRA 21-1 in Korean adults, including those older than 60 years. Data of 4,098 apparently healthy subjects (age range, 20-87 years) were analyzed after excluding those with a history of malignancy, high tumor marker concentrations (except CYFRA 21-1), and/or abnormal findings on a chest computed tomography scan through medical chart review. After removing two outliers, RIs of CYFRA 21-1 were determined using data of 4,096 subjects based on the non-parametric method (2.5th and 97.5th percentiles) according to CLSI guidelines EP28-A3c. The subjects were divided into two and four groups according to sex and age (20-40, 41-50, 51-60, and >60 years), respectively, and the median CYFRA 21-1 concentration was compared between the groups. The RI of CYFRA 21-1 was 0.66-3.84 ng/mL, applicable to both men and women. Regardless of sex, the CYFRA 21-1 concentration increased with age, suggesting that age-dependent RIs of CYFRA 21-1 should be applied. Rather than using a single RI provided by the manufacturer, the RI of CYFRA 21-1 should be continually verified and established in each clinical laboratory.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Queratina-19 , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , República da Coreia , Adulto Jovem
4.
Diagn Cytopathol ; 50(3): E100-E106, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34870907

RESUMO

Glomus tumors make up 1% of stromal tumors of the stomach. Radiologic diagnosis of glomus tumors can be challenging as they share imaging characteristics with other neuroendocrine tumors and gastrointestinal stromal tumors. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been reported as a useful method for the evaluation of gastrointestinal lesions. We report two cases of gastric glomus tumors in which EUS-FNA diagnosis was challenging. Cytologically, neoplastic cells were round to oval, uniform, bland appearing epithelioid cells with delicate chromatin and inconspicuous to vague nucleoli. Both samples lacked worrisome features such as high nuclear grade, high mitotic rate, and necrosis. Neoplastic cells were negative for Cam5.2 and AE1/AE3 with focal expression of synaptophysin in one of the cases. A definitive diagnosis was not made based on FNA. Familiarity with glomus tumors in the GI system and procurement of adequate material for cell block allowing the use of immunohistochemistry may allow an accurate preoperative diagnosis.


Assuntos
Tumores do Estroma Gastrointestinal , Tumor Glômico , Neoplasias Gástricas , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Tumores do Estroma Gastrointestinal/patologia , Tumor Glômico/diagnóstico , Tumor Glômico/patologia , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia
5.
Cytopathology ; 33(2): 249-252, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34599627

RESUMO

Androgen insensitivity syndrome (AIS) is described as a patient's clinical (phenotypical) presentation as a female with male karyotyping. Classically, patients are normal looking females with complaints of primary amenorrhea. The gonads may be found as extra-genital swellings; rarely, the testes may undergo malignant transformation. Thus, gonadectomy is indicated in these patients on attaining puberty. A rare and interesting case of clinically unsuspected AIS in a young female who presented with primary amenorrhea and inguinal swelling is reported. The initial diagnosis was suggested on fine needle aspiration cytology (FNAC) from the inguinal swelling that showed the presence of Sertoli cells. Further family history revealed two similar siblings; karyotyping and histopathology confirmed the diagnosis of AIS in the patient. This case highlights the importance of FNAC in early diagnosis and a multidisciplinary approach to confirm the diagnosis and help in appropriate management.


Assuntos
Síndrome de Resistência a Andrógenos , Síndrome de Resistência a Andrógenos/diagnóstico , Síndrome de Resistência a Andrógenos/patologia , Feminino , Humanos , Cariotipagem , Masculino , Irmãos , Testículo/patologia
6.
Anticancer Res ; 42(4): 1905-1910, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35347009

RESUMO

AIM: The present study evaluated the efficacy and safety of ramucirumab (RAM) in clinical practice as post-treatment, following atezolizumab plus bevacizumab (Atz/Bev) for advanced hepatocellular carcinoma (HCC) with alpha-fetoprotein (AFP) levels of ≥400 ng/ml. PATIENTS AND METHODS: Of the 77 patients treated with Atz/Bev at our institution, 13 patients for whom RAM was introduced as post-treatment following Atz/Bev were enrolled in this retrospective study. There were 9 patients (69.2%) with Child-Pugh A and 11 patients (84.6%) for whom RAM was initiated as 3rd- or later-line therapy. The median AFP level was 2259 ng/ml. RESULTS: The objective response rate by Response Evaluation Criteria in Solid Tumours at 6 weeks was 15.4%, and the disease control rate was 69.2%. The median time to progression was 3.0 months; AFP level decreased at 2 weeks in 11 patients (84.6%) and at 6 weeks in seven patients (53.8%). The most common adverse events (AEs) within 6 weeks were ascites, peripheral oedema, and proteinuria, while grade 3 AEs occurred in six patients (46.2%). Albumin-bilirubin scores at both 4 and 6 weeks were significantly worse than those at baseline. CONCLUSION: In HCC patients with AFP levels of ≥400 ng/mL, RAM after Atz/Bev is expected to be an effective treatment option. Careful attention should be paid to the development of AEs and deterioration of liver function, especially when RAM is used as 3rd- or later-line therapy. Additional studies are needed to confirm the efficacy and safety of RAM as 2nd-line treatment after Atz/Bev in Child-Pugh A patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Estudos Retrospectivos
7.
Eur J Neurol ; 29(2): 573-582, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34564924

RESUMO

BACKGROUND: We characterized and quantified peripheral nerve damage in alcohol-dependent patients (ADP) by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. METHODS: Thirty-one adult patients with a history of excessive alcohol consumption and age-/sex-matched healthy controls were prospectively examined. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into ADP with alcohol-related polyneuropathy (ALN) and without ALN (Non-ALN). 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was performed using dual-echo 2-dimensional relaxometry sequences with spectral fat saturation. Detailed quantification of nerve injury by morphometric (cross-sectional area [CSA]) and microstructural MRN markers (proton spin density [ρ], apparent T2-relaxation-time [T2app ]) was conducted in all study participants. RESULTS: MRN detected nerve damage in ADP with and without ALN. A proximal-to-distal gradient was identified for nerve T2-weighted (T2w)-signal and T2app in ADP, indicating a proximal predominance of nerve lesions. While all MRN markers differentiated significantly between ADP and controls, microstructural markers were able to additionally differentiate between subgroups: tibial nerve ρ at thigh level was increased in ALN (p < 0.0001) and in Non-ALN (p = 0.0052) versus controls, and T2app was higher in ALN versus controls (p < 0.0001) and also in ALN versus Non-ALN (p = 0.0214). T2w-signal and CSA were only higher in ALN versus controls. CONCLUSIONS: MRN detects and quantifies peripheral nerve damage in ADP in vivo even in the absence of clinically overt ALN. Microstructural markers (T2app , ρ) are most suitable for differentiating between ADP with and without manifest ALN, and may help to elucidate the underlying pathomechanism in ALN.


Assuntos
Neuropatia Alcoólica , Doenças do Sistema Nervoso Periférico , Adulto , Neuropatia Alcoólica/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Doenças do Sistema Nervoso Periférico/patologia , Nervo Tibial
8.
Mol Cell Endocrinol ; 544: 111541, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973370

RESUMO

Glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) accounts for a big portion of non-traumatic ONFH; nevertheless, the pathogenesis has not yet been fully understood. GC-induced endothelial dysfunction might be a major contributor to ONFH progression. The Gene Expression Omnibus (GEO) dataset was analyzed to identify deregulated miRNAs in ONFH; among deregulated miRNAs, the physiological functions of miR-122-5p on ONFH and endothelial dysfunction remain unclear. In the present study, miR-122-5p showed to be under-expressed within GC-induced ONFH femoral head tissues and GC-stimulated bone microvascular endothelial cells (BMECs). In human umbilical vein endothelial cells (HUVECs) and BMECs, GC stimulation significantly repressed cell viability, promoted cell apoptosis and increased the mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and IFN-γ. After overexpressing miR-122-5p, GC-induced endothelial injuries were attenuated, as manifested by rescued cell viability, cell migration, and tube formation capacity. Regarding the BMP signaling, GC decreased the protein levels of BMP-2/6/7 and SMAD-1/5/8, whereas miR-122-5p overexpression significantly attenuated the inhibitory effects of GC on these proteins. Online tool and experimental analyses revealed the direct binding between miR-122-5p and GREM2, a specific antagonist of BMP-2. In contrast to miR-122-5p overexpression, GREM2 overexpression aggravated GC-induced endothelial injury; GREM2 silencing partially eliminated the effects of miR-122-5p inhibition on GC-stimulated HUVECs and BMECs. Finally, GREM2 silencing reversed the suppressive effects of GC on BMP-2/6/7 and SMAD-1/5/8, and attenuated the effects of miR-122-5p inhibition on these proteins upon GC stimulation. Conclusively, the present study demonstrates a miR-122-5p/GREM2 axis modulating the GC-induced endothelial damage via the BMP/SMAD signaling. Considering the critical role of endothelial function in ONFH pathogenesis, the in vivo role and clinical application of the miR-122-5p/GREM2 axis is worthy of further investigation.


Assuntos
Glucocorticoides , MicroRNAs , Apoptose , Citocinas/metabolismo , Cabeça do Fêmur/metabolismo , Cabeça do Fêmur/patologia , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais
9.
Abdom Radiol (NY) ; 47(3): 923-947, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35076742

RESUMO

Splenosis is an acquired form of ectopic splenic tissue that typically arises after trauma or splenectomy. It is often an incidental image finding in an otherwise asymptomatic patient, but the spectrum of symptoms varies based on the site of implantation. Radiologists should be familiar with the imaging features of splenosis to avoid mistaking it for malignancy. Splenosis has identical imaging features to that of the native spleen on US, CT, MRI, and nuclear medicine examinations. Therefore, when the radiologic findings support the diagnosis of splenosis, the patient can be spared invasive procedures for tissue sampling.


Assuntos
Esplenose , Abdome/patologia , Humanos , Imageamento por Ressonância Magnética , Esplenectomia , Esplenose/diagnóstico por imagem
10.
Acta Histochem ; 124(2): 151856, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35077998

RESUMO

Neuroblastoma is a metastatic brain tumor particularly common in children. The cure rate is below 50% for patients of high-risk condition. Novel therapeutic agents and approaches are needed to improve the cure rate. Tumor necrosis factor-related and apoptosis-inducing ligand (TRAIL) is a promising proapoptotic factor that rapidly induces apoptosis preferentially in transformed and cancerous cells. Unfortunately, the common TRAIL resistance in cancers has hampered the clinical application of the ligand. Previously we prepared a novel TRAIL-armed ER derived nanosomal agent (ERN-T) that overcomes TRAIL resistance in some cancer lines when combined with a synthetic antagonist of inhibitors of apoptosis proteins (IAPs), AZD5582. However, how AZD5582 sensitizes cancer cells to ERN-T remains not well understood. In this study we continued to test the therapeutic efficacy of the combinatory therapy of ERN-T and AZD5582 on neuroblastoma, aiming to reveal the molecular mechanism underlying the synergism between AZD5582 and ERN-T. The obtained data revealed that ERN-Ts overcame TRAIL resistance and showed significant cytotoxicity on the resistant neuroblastoma line SH-SH5Y when combined with AZD5582 whilst sparing normal cells. The combination of low doses of ERN-Ts and AZD5582 induced intensive apoptosis in SH-SY5Y but not in normal skin fibroblasts (NSFs). Importantly we discovered that TRAIL sensitization in SH-SY5Y was associated with the concomitant downregulation of antiapoptotic factors cFLIP, MCL-1 and IAPs and upregulation of proapoptotic protein BAX and the death receptor 5 (DR5) by the cotreatment of ERN-T and AZD5582. In vivo study demonstrated that the combination of ERN-T and AZD5582 constituted a highly effective and safe therapy for subcutaneous SH-SY5Y xenograft neuroblastoma in nude mice. In conclusion, we identified that the concomitant regulation of both antiapoptotic and proapoptotic factors and DR5 is an essential molecular mechanism for overcoming TRAIL resistance in SH-SY5Y and the combination of ERN-T and AZD5582 potentially constitutes a novel therapeutic strategy, which is highly effective and safe for neuroblastoma.


Assuntos
Neuroblastoma , Ligante Indutor de Apoptose Relacionado a TNF , Alcinos , Animais , Apoptose , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Nus , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Oligopeptídeos , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/uso terapêutico
11.
Cell Biol Int ; 46(3): 336-343, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34941001

RESUMO

Osteosarcoma is a malignant tumor that often occurs in adolescents. There is an urgent need for new treatment options for osteosarcoma due to its poor prognosis after metastasis. Cancer stem cell (CSC) theory states that CSCs represent a small proportion of cancer cells. These CSC have self-renewal ability and are closely associated with cancer growth and metastasis as well as chemotherapy resistance. Similarly, osteosarcoma stem cells (OSCs) play an important role in the growth, metastasis, and chemotherapy resistance of osteosarcoma cells. Targeting OSCs may represent a future treatment of osteosarcoma. Furthermore, some genes have been shown to regulate the growth, metastasis, and chemotherapy resistance of osteosarcoma cells by altering the stemness of OSCs. Targeting these genes may help in the treatment of osteosarcoma. This review mainly discusses recent advances in the research of OSCs and their related genes.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Adolescente , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Células-Tronco Neoplásicas/patologia , Osteossarcoma/patologia
12.
Cytopathology ; 33(1): 14-22, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333812

RESUMO

There is growing evidence that molecular testing is feasible on all types of cytological preparation, which is fortunate as more diagnostic markers and biomarkers for targeted therapies are discovered for use in pulmonary and pleural malignancies. In this article we will discuss the pre-analytic, analytic, and post-analytic (interpretive) considerations for successful implementation of molecular tests for diagnostic and predictive markers in respiratory and pleural cytology. The vast majority of laboratories are familiar with, and have validated their molecular protocols for, formalin-fixed paraffin-embedded surgical specimens, which are not directly applicable to cytology specimens. Thus, rigorous validation must be performed for each type of fixative and cytology preparation before it is implemented in the clinical setting.


Assuntos
Neoplasias Pulmonares , Neoplasias Pleurais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Citodiagnóstico , Humanos , Neoplasias Pulmonares/patologia , Pleura/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia
13.
Oxid Med Cell Longev ; 2022: 1821780, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320978

RESUMO

Vitiligo is a common acquired depigmenting disease characterized by the loss of functional melanocytes and epidermal melanin. Vitiligo has a long treatment cycle and slow results, which is one of the most difficult challenges for skin diseases. Oxidative stress plays an important role as an initiating and driving factor in the pathogenesis of vitiligo. Antioxidant therapy has recently become a research hotspot in vitiligo treatment. A series of antioxidants has been discovered and applied to the treatment of vitiligo, which has returned satisfactory results. This article briefly reviews the relationship between oxidative stress and vitiligo. We also describe the progress of targeted antioxidant therapy in vitiligo, with the aim of providing a reference for new drug development and treatment options for this condition.


Assuntos
Vitiligo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Epiderme , Humanos , Melanócitos/patologia , Estresse Oxidativo , Vitiligo/tratamento farmacológico , Vitiligo/patologia
14.
J Chem Neuroanat ; 119: 102043, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34808256

RESUMO

The purpose of this study was to highlight the possible effects on the hippocampus of the electromagnetic field (EMF) emitted by mobile phones, and to investigate whether these potential effects can be reduced using various antioxidant substances. Twenty-seven female Wistar albino rats were divided into nine equal groups, each containing three pregnant rats aged 8-10 weeks and weighing 200-250 gr. The EMF groups were exposed to 900 Megahertz (MHz) EMF for 1 h (hr) a day for 21 days. No EMF exposure was applied to the Cont and also the groups given only Garcinia kola (GK), Momordica charantia (MC), and thymoquinone (TQ). The Sham group was kept in the polycarbonate EMF exposure system, but was not exposed to EMF. Four weeks after birth, rat pups were subjected to behavioural tests. Brain tissue samples were evaluated using histological, stereological, functional, and immunohistochemical methods. The numbers of pyramidal neurons in the rat cornu ammonis (CA) were determined using the optical fractionator method. Superoxide dismutase (SOD) and catalase (CAT) enzyme activities in the blood samples were also evaluated. The analysis data indicated that total pyramidal neuron numbers were decreased significantly in the CA of the EMF (1 hr) group (p < 0.01). Our results also showed that the protective effect of MC was more potent than that of the other antioxidant substances (p < 0.01). A 900 MHz EMF can cause deleterious changes in the brain. It can also be suggested that GK, MC and TQ are capable of reducing these adverse effects.


Assuntos
Telefone Celular , Campos Eletromagnéticos , Animais , Campos Eletromagnéticos/efeitos adversos , Feminino , Hipocampo/patologia , Gravidez , Células Piramidais , Ratos , Ratos Wistar
15.
Eur J Neurol ; 29(3): 905-909, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34808013

RESUMO

BACKGROUND AND PURPOSE: A sensitive and frequent clinical sign of a vestibular tone imbalance is the tilt of the perceived subjective visual vertical (SVV). There are no data yet focusing on lesion location at the cortical level as a factor for predicting compensation from the tilt of the SVV. METHODS: With modern voxelwise lesion behavior mapping analysis, the present study determines whether lesion location in 23 right-hemispheric cortical stroke patients with an otolith dysfunction could predict the compensation of a vestibular tone imbalance in the chronic stage. RESULTS: Our statistical anatomical lesion analysis revealed that lesions of the posterior insular cortex are involved in vestibular otolith compensation. CONCLUSION: The insular cortex appears to be a critical anatomical region for predicting a tilt of the SVV as a chronic disorder in stroke patients.


Assuntos
Membrana dos Otólitos , Acidente Vascular Cerebral , Córtex Cerebral/patologia , Humanos , Membrana dos Otólitos/patologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia
16.
Nanotechnology ; 33(23)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35193121

RESUMO

We combined phosphoinositol-3-kinin inhibitor IPI-549 and photodynamic Chlorin e6 (Ce6) on carboxymethyl chitosan to develop a novel drug delivery nanoparticle (NP) system (Ce6/CMCS-DSP-IPI549) and evaluate its glutathione (GSH) sensitivity and targeting ability for breast cancer treatment. The NPs were spherical with a uniform size of 218.8 nm, a stable structure over 7 days. The maximum encapsulation efficiency was 64.42%, and NPs drug loading was 8.05%. The NPs released drugs within tumor cells due to their high GSH concentration, while they maintained structural integrity in normal cells, which have low GSH concentration. The cumulative release rates of IPI-549 and Ce6 at 108 h were 70.67% and 40.35% (at GSH 10 mM) and 8.11% and 2.71% (at GSH 2µM), respectively. The NPs showed a strong inhibitory effect on 4T1 cells yet did not affect human umbilical vein endothelial cells (HUVECs). After irradiation by a 660 nm infrared laser for 72 h, the survival rate of 4T1 cells was 15.51%. Cellular uptake studies indicated that the NPs could accurately release drugs into tumor cells. In addition, the NPs had a good photodynamic effect and promoted the release of reactive oxygen species to damage tumor cells. Overall, the combination therapy of IPI-549 and Ce6 is safe and effective, and may provide a new avenue for the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Clorofilídeos , Nanopartículas , Fotoquimioterapia , Porfirinas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Clorofilídeos/uso terapêutico , Células Endoteliais/patologia , Feminino , Glutationa , Humanos , Isoquinolinas , Nanopartículas/química , Fármacos Fotossensibilizantes , Porfirinas/química , Pirazóis , Pirimidinas
17.
Mol Pharm ; 19(2): 720-727, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-34936367

RESUMO

Radiolabeled prostate-specific membrane antigen (PSMA) ligands have been rapidly adopted as part of patient care for prostate cancer. In this study, a new series of 18F-labeled PSMA-targeting agents was developed based on the high-affinity Glu-ureido-Lys scaffold and 18F-vinyl sulfones (VSs), the tumor uptake and tumor/major organ contrast of which could be tuned by pharmacokinetic linkers within the molecules. In particular, 18F-PEG3-VS-PSMAi showed the highest tumor uptake (12.1 ± 2.2%ID/g at 0.5 h p.i.) and 18F-PEG2-VS-PSMAi showed the highest tumor-to-liver ratio (T/L = 3.7 ± 1.0, 4.8 ± 1.2, and 6.3 ± 1.1 at 0.5, 1.5, and 3 h p.i. respectively). Significantly, compared with the FDA-approved 68Ga-PSMA-11, the newly developed 18F-PEG3-VS-PSMAi has an almost double tumor uptake (P < 0.0001) when tested in the same animal model. In conclusion, 18F-VS-labeled PSMA ligands are promising PET agents with prominent tumor uptake and high contrast. The lead agents 18F-PEG2-VS-PSMAi and 18F-PEG3-VS-PSMAi warrant further evaluation in prostate cancer patients.


Assuntos
Próstata , Neoplasias da Próstata , Animais , Antígenos de Superfície , Linhagem Celular Tumoral , Radioisótopos de Flúor/farmacocinética , Isótopos de Gálio , Radioisótopos de Gálio , Glutamato Carboxipeptidase II , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Compostos Radiofarmacêuticos/farmacocinética , Sulfonas
18.
Diagn Cytopathol ; 50(3): 123-132, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34981669

RESUMO

BACKGROUND: Bile cytology is useful in diagnosing biliary tract lesions, albeit often challenging due to equivocal findings. To achieve better diagnoses for clinical decisions, we conducted cytomorphological and immunocytochemical studies of bile cytology cases. MATERIALS AND METHODS: We re-evaluated 40 bile cytology cases with initial equivocal diagnoses, taken from the cytology records of Jichi Medical University Hospital, including 1778 bile cytology specimens. First, we assessed the cases by the diagnostic bile cytology criteria of the Japanese Society of Clinical Cytology. Second, we searched for useful immunocytochemical markers by extensive immunohistochemical analyses using tissue microarray for 10 antibodies: S100P, IMP3, GLUT1, p53, S100A4, Mapsin, MUC17, CD10, MDM2, and SMAD4. Microarrays were from 257 extrahepatic bile duct carcinoma cases. To elucidate the utility of immunocytochemistry, we applied selected markers to immunocytochemical evaluation of the equivocal cases after cell transfer. RESULTS: The criteria indicated a sensitivity 60%, specificity 87%, and accuracy 70%. Irregularly overlapping (88%), arranged (96%), and shaped (76%) nuclei were more common in malignant cases, while enlarged nuclei were more frequent in benign cases (67% vs. 28%). We applied S100P and IMP3, which showed higher accuracy (88% and 77%) in tissue microarray, to immunocytochemistry. The sensitivity of S100P and IMP3 were 69% and 70%, respectively. The specificity of S100P and IMP3 were 50% and 100%, respectively. CONCLUSION: The criteria showed a certain effectiveness even in challenging cases, and some pitfalls associated with reactive changes of benign cells. Although comprehensive diagnosis including cytomorphology seems preferable, S100P and IMP3 are promising immunocytochemical markers.


Assuntos
Neoplasias dos Ductos Biliares , Bile , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/análise , Humanos , Imuno-Histoquímica , Proteínas de Ligação a RNA/análise
19.
J Bras Nefrol ; 44(1): 9-18, 2022.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34289007

RESUMO

INTRODUCTION: Aminoglycoside-induced acute kidney injury (AKI) is a pathology closely linked to oxidative and inflammatory reactions. Taking into account the previous reported antioxidant and anti-inflammatory effects of D-005, a lipid extract obtained from Cuban palm Acrocomia crispa (Arecaceae) fruits, this work aimed to evaluate the effects of D-005 on kanamycin-induced AKI. METHODS: Male Wistar rats were divided into 7 groups: negative control (vehicle, Tween 65/H2O) and six groups treated with kanamycin to induce AKI: positive control (vehicle), D-005 (25, 100, 200, and 400 mg/kg) and grape seed extract (GSE, 200 mg/kg). D-005, vehicle, and GSE oral treatments were administered once daily for seven days, 1 h before kanamycin (500 mg/kg, i.p.). Serum uric acid and urea concentrations, renal histopathology, and oxidative markers (malondialdehyde (MDA), sulfhydryl (SH) groups, and catalase (CAT) activity) were assessed. RESULTS: D-005 significantly reduced uric acid and urea levels, starting from D-005 100 mg/kg. Histopathologically, D-005, at all the tested doses, protected renal parenchyma structures (glomeruli, proximal tubules, and interstitium). These findings were accompanied by a significant reduction of MDA and SH group concentrations as well as restoration of CAT activity. The highest percentages of inhibition were obtained with the dose of 400 mg/kg. GSE, the reference substance, also prevented kanamycin-induced biochemical and histopathological changes, as well as reduced MDA and SH groups and restored CAT activity. CONCLUSION: The administration of repeated oral doses of D-005 significantly protected against kanamycin-induced AKI, which could be associated with the antioxidant and anti-inflammatory effects of this extract.


Assuntos
Injúria Renal Aguda , Arecaceae , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Frutas , Humanos , Rim/patologia , Lipídeos/farmacologia , Masculino , Malondialdeído , Estresse Oxidativo , Ratos , Ratos Wistar , Ácido Úrico
20.
BMC Pulm Med ; 22(1): 117, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361163

RESUMO

BACKGROUND: To investigate the value of endobronchial ultrasound (EBUS) and virtual bronchoscopic navigation (VBN) combined with rapid on-site evaluation (ROSE) in diagnosing peripheral pulmonary lesions (PPLs). METHODS: Between January 1st 2019 to September 1st 2021, EBUS and VBN examination were performed in expected consecutive patients with PPLs who were admitted to Zhangzhou Affiliated Hospital of Fujian Medical University (Fujian, China). Finally, based on the calculation of expected diagnostic yield of R-EBUS biopsy and drop out, 198 eligible patients were randomly divided into ROSE group (100 cases) and non-ROSE group (98 cases). The diagnostic yield of brushing and biopsy, the complications, the procedure time, the diagnosis time and expense during diagnosis were analyzed. RESULTS: In the ROSE group, the positive rate of EBUS brushing and biopsy were 68%, 84%, respectively. The average procedure time and diagnosis time were 18.6 ± 6.8 min, 3.84 ± 4.28 days, respectively, and the average expense was 643.44 ± 706.56 US.$ (4093.15 ± 4494.67 yuan ¥). In the controls, the positive rate of brushing and biopsy were 44%, 74%, respectively. The average procedure time and diagnosis time were 15.4 ± 5.7 min, 6.46 ± 3.66 days, respectively. And the average expense during diagnosis was 1009.27 ± 713.89 US.$ (6420.28 ± 4541.33 yuan ¥). There was significant difference in the positive rate of EBUS brushing and biopsy, diagnosis time and expense during diagnosis between both groups. And no significant difference was observed in the complications and the procedure time. Additionally, the impact of ROSE on diagnostic yield in right upper lobe and the size of lesion ≤ 2 cm in diameter was significant. CONCLUSION: In combination with ROSE, EBUS could significantly improve the positive rate of diagnosing PPLs, shorten diagnosis time and reduce expense during diagnosis. ROSE will be of great importance in the diagnosis of PPLs and medical resource.


Assuntos
Neoplasias Pulmonares , Broncoscopia/métodos , Endossonografia/métodos , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia
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