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1.
BMC Med ; 22(1): 218, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816877

RESUMO

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.


Assuntos
Estimulação Encefálica Profunda , Síndrome de Tourette , Humanos , Síndrome de Tourette/terapia , Estimulação Encefálica Profunda/métodos , Masculino , Feminino , Criança , Adulto , Adolescente , Estudos Retrospectivos , Seguimentos , Adulto Jovem , Resultado do Tratamento , Qualidade de Vida , Pessoa de Meia-Idade , Fatores Etários
2.
ACS Appl Mater Interfaces ; 16(20): 25622-25636, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38739745

RESUMO

Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.


Assuntos
Neoplasias da Mama , Hipertermia Induzida , Metotrexato , Camundongos Nus , Nanotubos , Metotrexato/química , Metotrexato/farmacologia , Animais , Nanotubos/química , Camundongos , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Camundongos Endogâmicos BALB C , Terapia Fototérmica , Ferro/química , Compostos de Selênio/química , Compostos de Selênio/farmacologia , Compostos de Selênio/efeitos da radiação , Linhagem Celular Tumoral , Raios Infravermelhos
4.
Int J Nanomedicine ; 19: 2879-2888, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525007

RESUMO

Background: Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and nanomedicines. In the present studies, we established a more realistic large tumor model to test the antitumor activity of a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) on advanced breast cancer. Methods: Both cholesterol and PEG were substituted by Rh2 to prepare the Rh2-lipo using ethanol-water system and characterized. The effects of Rh2-lipo on cell uptake, penetration of the tumor spheroid, cytotoxicity assay was investigated with 4T1 breast cancer cells and L929 fibroblast cells. The 4T1 orthotopic-bearing large tumor model was established to study the targeting effect of Rh2-lipo and inhibitory effect of paclitaxel loaded Rh2-lipo (PTX-Rh2-lipo) on advanced breast tumors. Results: Rh2-lipo exhibit many advantages that address the limitations of current liposome formulations against large tumors, such as enhanced uptake in TAFs and tumor cells, high targeting and penetration capacity, cytotoxicity against TAFs, normalization of the vessel network, and depletion of stromal collagen. In in vivo study, PTX-Rh2-lipo effectively inhibiting the growth of advanced breast tumors and outperformed most reported PTX formulations, including Lipusu® and Abraxane®. Conclusion: Rh2-lipo have improved drug delivery efficiency and antitumor efficacy in advanced breast cancer, which offers a novel promising platform for advanced tumor therapy.


Assuntos
Neoplasias da Mama , Ginsenosídeos , Lipossomos , Humanos , Feminino , Lipossomos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Linhagem Celular Tumoral
5.
J Mater Chem B ; 12(15): 3569-3593, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38494982

RESUMO

In recent years, inorganic nanoparticles (NPs) have attracted increasing attention as potential theranostic agents in the field of oncology. Photothermal therapy (PTT) is a minimally invasive technique that uses nanoparticles to produce heat from light to kill cancer cells. PTT requires two essential elements: a photothermal agent (PTA) and near-infrared (NIR) radiation. The role of PTAs is to absorb NIR, which subsequently triggers hyperthermia within cancer cells. By raising the temperature in the tumor microenvironment (TME), PTT causes damage to the cancer cells. Nanoparticles (NPs) are instrumental in PTT given that they facilitate the passive and active targeting of the PTA to the TME, making them crucial for the effectiveness of the treatment. In addition, specific targeting can be achieved through their enhanced permeation and retention effect. Thus, owing to their significant advantages, such as altering the morphology and surface characteristics of nanocarriers comprised of PTA, NPs have been exploited to facilitate tumor regression significantly. This review highlights the properties of PTAs, the mechanism of PTT, and the results obtained from the improved curative efficacy of PTT by utilizing NPs platforms.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Humanos , Fototerapia/métodos , Hipertermia Induzida/métodos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
6.
Support Care Cancer ; 32(3): 155, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38347229

RESUMO

PURPOSE: Sleep problems are a significant issue in patients with lung cancer, and resilience is a closely related factor. However, few studies have identified subgroups of resilience and their relationship with sleep quality. This study aimed to investigate whether there are different profiles of resilience in patients with lung cancer, to determine the sociodemographic characteristics of each subgroup, and to determine the relationship between resilience and sleep quality in different subgroups. METHODS: A total of 303 patients with lung cancer from four tertiary hospitals in China completed the General Sociodemographic sheet, the Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis was applied to explore the latent profiles of resilience. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between resilience profiles and sleep quality. RESULTS: The following three latent profiles were identified: the "high-resilience group" (30.2%), the "moderate-resilience group" (46.0%), and the "low-resilience group" (23.8%). Gender, place of residence, and average monthly household income significantly influenced the distribution of resilience in patients with lung cancer. CONCLUSION: The resilience patterns of patients with lung cancer varied. It is suggested that health care providers screen out various types of patients with multiple levels of resilience and pay more attention to female, rural, and poor patients. Additionally, individual differences in resilience may provide an actionable means for addressing sleep problems.


Assuntos
Neoplasias Pulmonares , Testes Psicológicos , Resiliência Psicológica , Transtornos do Sono-Vigília , Humanos , Feminino , Qualidade do Sono , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia
7.
Biomater Adv ; 158: 213778, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38325029

RESUMO

Combining chemodynamic therapy (CDT) with photothermal therapy (PTT) has developed as a promising approach for cancer treatment, as it enhances therapeutic efficiency through redox reactions and external laser induction. In this study, we designed metal organic framework (MOF) -derived Cu5Zn8/HPCNC through a carbonization process and decorated them with gold nanoparticles (Au@Cu5Zn8/HPCNC). The resulting nanoparticles were employed as a photothermal agent and Fenton catalyst. The Fenton reaction facilitated the conversation of Cu2+ to Cu+ through reaction with local H2O2, generating reactive hydroxyl radicals (·OH) with potent cytotoxic effects. To enhance the Fenton-like reaction and achieve combined therapy, laser irradiation of the Au@Cu5Zn8/HPCNC induced efficient photothermal therapy by generating localized heat. With a significantly increased absorption of Au@Cu5Zn8/HPCNC at 808 nm, the photothermal efficiency was determined to be 57.45 %. Additionally, Au@Cu5Zn8/HPCNC demonstrated potential as a contrast agent for magnetic resonance imaging (MRI) of cancers. Furthermore, the synergistic combination of PTT and CDT significantly inhibited tumor growth. This integrated approach of PTT and CDT holds great promise for cancer therapy, offering enhanced CDT and modulation of the tumor microenvironment (TME), and opening new avenues in the fight against cancer.


Assuntos
Nanopartículas Metálicas , Estruturas Metalorgânicas , Ouro , Nanopartículas Metálicas/uso terapêutico , Terapia Fototérmica , Porosidade , Microambiente Tumoral , Carbono , Imageamento por Ressonância Magnética , Zinco
8.
Biomater Adv ; 157: 213724, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38134729

RESUMO

Traditional cancer treatments are ineffective and cause severe adverse effects. Thus, the development of chemodynamic therapy (CDT) has the potential for in situ catalysis of endogenous molecules into highly toxic species, which would then effectively destroy cancer cells. However, the shortage of high-performance nanomaterials hinders the broad clinical application of this approach. In present study, an effective therapeutic platform was developed using a simple hydrothermal method for the in-situ activation of the Fenton reaction within the tumor microenvironment (TME) to generate substantial quantities of •OH and ultimately destroy cancer cells, which could be further synergistically increased by photothermal therapy (PHT) and magnetic hyperthermia (MHT) aided by FeMoO4 nanorods (NRs). The produced FeMoO4 NRs were used as MHT/PHT and Fenton catalysts. The photothermal conversion efficiency of the FeMoO4 NRs was 31.75 %. In vitro and \ experiments demonstrated that the synergistic combination of MHT/PHT/CDT notably improved anticancer efficacy. This work reveals the significant efficacy of CDT aided by both photothermal and magnetic hyperthermia and offers a feasible strategy for the use of iron-based nanoparticles in the field of biomedical applications.


Assuntos
Hipertermia Induzida , Nanoestruturas , Fototerapia , Microambiente Tumoral , Fenômenos Magnéticos
9.
Cancer Nurs ; 47(1): 64-71, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36322694

RESUMO

BACKGROUND: Although the number of studies focusing on life satisfaction in women with cervical cancer is increasing, there are limited studies on the pathway between social support and life satisfaction in this population. OBJECTIVE: This study explored the pathway between social support and life satisfaction in women with cervical cancer by examining the serial mediating effects of self-care self-efficacy, coping strategies, and depressive symptoms. METHODS: In this cross-sectional study, a total of 292 women with cervical cancer completed a questionnaire for assessing social support, self-efficacy, coping strategies, depressive symptoms, and life satisfaction. Structural equation modeling was used to test the direct and/or indirect effects of the variables on life satisfaction. RESULTS: Structural equation modeling analysis indicated that self-efficacy, coping strategies, and depressive symptoms mediates the effect of social support on life satisfaction. Direct paths from social support to life satisfaction, social support to self-efficacy, self-efficacy to coping strategies, coping strategies to depressive symptoms, and depressive symptoms to life satisfaction were significant ( P < .05). Moreover, indirect paths from social support to life satisfaction, self-efficacy to life satisfaction, and coping strategies to life satisfaction were also significant ( P < .05). CONCLUSIONS: Self-care self-efficacy, coping strategies, and depressive symptoms are potential pathways through which social support may affect life satisfaction in women with cervical cancer. IMPLICATION: Healthcare providers, family, and friends should offer more social support to the patients and make efforts to strengthen their self-care self-efficacy, facilitate active coping, and alleviate depressive symptoms to improve women's life satisfaction.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Estudos Transversais , Apoio Social , Adaptação Psicológica , Satisfação Pessoal , Depressão
10.
Cancer Med ; 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38124509

RESUMO

PURPOSE: SMARCA4-deficient thoracic tumors, characterized by distinct clinicopathological, morphological, immunohistochemical, and genetic features, differ significantly from conventional non-small-cell lung carcinomas (NSCLCs). This group encompasses both SMARCA4-deficient NSCLCs (SMARCA4-NSCLCs) and SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs). The efficacy of PD-1 inhibitors in treating SMARCA4-deficient thoracic tumors remains uncertain. METHODS: Medical records of 36 patients diagnosed with stage IIIB, IIIC, or IV SMARCA4-deficient thoracic tumors were analyzed. We assessed the clinical, pathological, and genetic features of these patients through immunohistochemistry (IHC) and a 68-gene panel next-generation sequencing (NGS). We compared the differences between SMARCA4-NSCLCs and SMARCA4-UTs, and evaluated the impact of chemotherapy and immunotherapy on patient outcomes. RESULTS: The majority of patients with SMARCA4-deficient thoracic tumors were heavy-smoking males, averaging 64.6 years in age. IHC predominantly showed weak or negative staining for markers such as TTF-1, CK5/6, p40, synaptophysin, chromogranin A, and CD56, which are often associated with adenocarcinoma, squamous cell carcinoma, and neuroendocrine tumors. The most common genetic mutations identified via NGS included TP53, CDKN2A, KRAS, STK11, NF1, and PTEN. No significant overall survival (OS) difference was observed between SMARCA4-NSCLCs and SMARCA4-UTs (p = 0.366). The median OS for patients treated with chemotherapy (n = 9) was 447 days, while the median OS for patients undergoing PD-1-inhibitor-based therapy (n = 16) was not reached (p = 0.105). CONCLUSION: SMARCA4-deficient thoracic tumors exhibit distinct characteristics from conventional NSCLCs, and PD-1 inhibitors show promise in treating advanced SMARCA4-deficient thoracic tumors.

11.
Med Mycol ; 61(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38031335

RESUMO

Although non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is a severe disease, there are still some non-HIV CM patients with a low risk of therapeutic failure. Recognizing clinical characteristics of low-risk non-HIV-associated CM may enable clinicians to treat non-HIV-associated CM more reasonably. According to the definition of low-risk non-HIV-associated CM in the 2010 Infectious Diseases Society of America guideline, a total of 220 non-HIV CM patients were divided into two groups (Group 1: 35 low-risk patients and Group 2: 185 non-low-risk patients). Clinical characteristics, treatment, and outcome were compared between the two groups. Compared with non-low-risk patients, low-risk patients had a lower rate of headache (82.9% vs. 95.7%, P = .012), cerebrospinal fluid (CSF) opening pressure (OP) at baseline (CSF OP < 250-mm H2O, 60.0% vs. 32.4%, P = .001), and baseline CSF cryptococcal count (median, 0 vs. 2376, P < .001), higher baseline CSF white blood cell (median, 130 vs. 90, P = .029) and CSF protein (median, 0.87 vs. 0.73, P = .011). Multivariate analysis showed that baseline CSF OP <250-mm H2O (OR: 2.545, 95% CI 1.168, 5.545, P = .019) was independently associated with low-risk for non-HIV-associated CM. The lengths of AMB-d-based induction therapy of low-risk patients (median, 20 days) were shorter (P < .001) than that of non-low-risk patients (median, 38 days). The successful outcome rate of low-risk patients was higher than non-low-risk patients (97.1% vs. 54.6%, P < .001). We demonstrated that non-HIV-associated CM patients with baseline CSF OP < 250-mm H2O were prone to the low-risk status.


This was a retrospective cohort study to find the features of low-risk non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM). We found that non-HIV-associated CM patients with baseline cerebrospinal fluid opening pressure <250-mm H2O were prone to low-risk status.


Assuntos
Cryptococcus , Infecções por HIV , Meningite Criptocócica , Humanos , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/líquido cefalorraquidiano , Meningite Criptocócica/veterinária , Estudos Retrospectivos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/veterinária , Resultado do Tratamento
12.
Eur J Clin Microbiol Infect Dis ; 42(10): 1183-1194, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37606868

RESUMO

PURPOSE: To predict prognosis in HIV-negative cryptococcal meningitis (CM) patients by developing and validating a machine learning (ML) model. METHODS: This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10 weeks after the initiation of antifungal therapy. RESULTS: The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid (CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2 weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence (AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. CONCLUSION: A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.


Assuntos
Cryptococcus , Infecções por HIV , Meningite Criptocócica , Humanos , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , Inteligência Artificial , Prognóstico , Aprendizado de Máquina , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico
13.
Nat Med ; 29(6): 1520-1529, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37322120

RESUMO

Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.


Assuntos
Colangite Esclerosante , Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Humanos , Colangite Esclerosante/complicações , Colangite Esclerosante/patologia , Inflamação/complicações , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Neoplasias Colorretais/patologia
14.
Med Mycol ; 61(4)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37055372

RESUMO

Oxidative imbalances have been observed in various neurological diseases. Despite the microbiological control in cryptococcal meningitis (CM), a proportion of previously healthy patients experience a clinical deterioration known as post-infectious inflammatory response syndrome (PIIRS). However, the antioxidant status in PIIRS remains unclear. In this study, we found that the serum antioxidant status of HIV-negative immunocompetent CM patients during PIIRS episodes was lower than that of healthy controls. There was a relationship between baseline serum indirect bilirubin levels and the development of PIIRS, and serum uric acid levels may indicate the severity of the disease during PIIRS episodes. Oxidative stress may play a role in the development of PIIRS.


This retrospective study on the serum antioxidant status in HIV-negative immunocompetent CM patients suggested that during PIIRS episodes, the serum antioxidant status in CM patients may be lower. CM patients with high baseline serum Ibil levels were more likely to develop PIIRS.


Assuntos
Infecções por HIV , Meningite Criptocócica , Animais , Antioxidantes , Bilirrubina , Meningite Criptocócica/veterinária , Ácido Úrico , Infecções por HIV/veterinária , Albuminas
15.
J Mycol Med ; 33(2): 101357, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36716508

RESUMO

Cryptococcus gattii (C. gattii) has been considered a leading cause of meningitis in immunocompetent hosts in tropical and subtropical regions. Visual loss is common but hearing impairment is relatively infrequent in C. gattii meningitis. Notably, there have been limited studies on the etiology, and especially therapy of auditory and ocular complications associated with C. gattii meningitis. Here we report a case of reversible deafness and blindness treated with a ventriculoperitoneal shunt (VPS) surgery in C. gattii meningitis. This case indicated that elevated intracranial pressure (ICP) may play a role in the concurrent hearing and vision impairments associated with C. gattii meningitis and the early VPS surgery after the initiation of the antifungal therapy may effectively improve both hearing and vision in this condition.


Assuntos
Criptococose , Cryptococcus gattii , Surdez , Meningite Criptocócica , Meningite , Humanos , Derivação Ventriculoperitoneal/efeitos adversos , Meningite Criptocócica/complicações , Meningite Criptocócica/microbiologia , Meningite/complicações , Meningite/microbiologia , Cegueira/etiologia , Surdez/complicações , Surdez/cirurgia , Criptococose/microbiologia
16.
J Adv Res ; 49: 159-173, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36167294

RESUMO

INTRODUCTION: Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various targeted drug-delivery systems, including nanoparticles and liposomes, are effective for MDR cancer treatment, their efficacy is restricted by immunosuppressive tumor microenvironment (TME). METHODS: Ginsenosides Rg3 was used to formulate unique Rg3-based liposomes loaded with PTX to establish Rg3-PTX-LPs, which were prepared by the thin-film hydration method. The stability of the Rg3-PTX-LPs was evaluated by particle size analysis through dynamic light scattering. The active targeting effect of Rg3-based liposomes was examined in an MCF-7/T xenograft model by an in a vivo imaging system. To evaluate the antitumor activity and mechanism of Rg3-PTX-LP, MTT, apoptosis assays, TAM regulation, and TME remodeling were performed in MCF-7/T cells in vitro and in vivo. RESULTS: Rg3-PTX-LPs could specifically distribute to MCF7/T cancer cells and TME simultaneously, mainly through the recognition of GLUT-1. The drug resistance reversing capability and in vivo antitumor effect of Rg3-PTX-LPs were significantly improved compared with conventional cholesterol liposomes. The TME remodeling mechanisms of Rg3-PTX-LPs included inhibiting IL-6/STAT3/p-STAT3 pathway activation to repolarize protumor M2 macrophages to antitumor M1 phenotype, suppressing myeloid-derived suppressor cells (MDSCs), decreasing tumor-associated fibroblasts (TAFs) and collagen fibers in TME, and promoting apoptosis of tumor cells. Hence, through the dual effects of targeting tumor cells and TME remodeling, Rg3-PTX-LPs achieved a high tumor inhibition rate of 90.3%. CONCLUSION: Our multifunctional Rg3-based liposome developed in the present study offered a promising strategy for rescuing the drug resistance tumor treatment.


Assuntos
Ginsenosídeos , Neoplasias , Humanos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Lipossomos , Ginsenosídeos/farmacologia , Microambiente Tumoral , Lipopolissacarídeos , Neoplasias/tratamento farmacológico
17.
J Nanobiotechnology ; 20(1): 414, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109762

RESUMO

The chemotherapy effect of docetaxel (DTX) against triple-negative breast cancer (TNBC) remains mediocre and limited when encapsulated in conventional cholesterol liposomes, mainly ascribed to poor penetration and immunosuppressive tumor microenvironment (TME) caused by tumor stroma cells, especially cancer-associated fibroblasts (CAFs). Many studies have attempted to address these problems but trapped into the common dilemma of excessively complicated formulation strategies at the expense of druggability as well as clinical translational feasibility. To better address the discrepancy, ginsenoside Rg3 was utilized to substitute cholesterol to develop a multifunctional DTX-loaded Rg3 liposome (Rg3-Lp/DTX). The obtained Rg3-Lp/DTX was proved to be preferentially uptake by 4T1 cells and accumulate more at tumor site via the interaction between the glycosyl moiety of Rg3 exposed on liposome surface and glucose transporter1 (Glut1) overexpressed on tumor cells. After reaching tumor site, Rg3 was shown to reverse the activated CAFs to the resting stage and attenuate the dense stroma barrier by suppressing secretion of TGF-ß from tumor cells and regulating TGF-ß/Smad signaling. Therefore, reduced levels of CAFs and collagens were found in TME after incorporation of Rg3, inducing enhanced penetration of Rg3-Lp/DTX in the tumor and reversed immune system which can detect and neutralize tumor cells. Compared with wooden cholesterol liposomes, the smart and versatile Rg3-Lp/DTX could significantly improve the anti-tumor effect of DTX, providing a promising approach for TNBC therapy with excellent therapeutic efficacy and simple preparation process.


Assuntos
Neoplasias de Mama Triplo Negativas , Docetaxel , Ginsenosídeos , Glucose , Transportador de Glucose Tipo 1 , Humanos , Lipossomos , Fator de Crescimento Transformador beta , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microambiente Tumoral
18.
World J Clin Cases ; 10(21): 7438-7444, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-36158020

RESUMO

BACKGROUND: Deep Sylvian meningiomas are rare and difficult to diagnose when small tumours lead to various symptoms. The difficulty associated with surgery is underestimated. Our case involved a mass (11 mm × 12 mm × 12 mm in size) in the right Sylvian fissure. It is the smallest deep Sylvian meningioma known and might be more easily misdiagnosed than previous examples. CASE SUMMARY: A well-enhanced mass in the right Sylvian fissure of a 26-year-old male with a three-month history of seizure was identified via magnetic resonance imaging. The patient underwent operations twice for seizure control. During the first operation, the tumour was surrounded by the second segment of the middle cerebral artery and its numerous perforators. Partial resection had to be selected due to mild arterial damage. After the first operation, the patient presented with simple partial seizure. During reoperation, we isolated the anatomical structure near the tumour and the tumour over and removed it from its dorsal side by piecemeal resection. CONCLUSION: This case reported the smallest deep Sylvian meningioma according to a literature review. Preoperative diagnosis is a crucial step due to deep Sylvian meningioma firmly adhering to the middle cerebral artery and its perforators. Adequate preparation is crucial to ensure the success of surgery.

19.
Asia Pac J Oncol Nurs ; 9(9): 100080, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36060834

RESUMO

Objective: To translate Female Self-Advocacy in Cancer Survivorship (FSACS) scale and evaluate the psychometric properties of Chinese version of FSACS scale among female cancer survivors in China. Methods: This study employed a cross-sectional design. FSACS scale was forward-backward translated and cognitive interviews were conducted for cultural adaptation. The newly translated tool was distributed to female cancer survivors to test psychometric properties, including item analysis, content validity, construct validity, criterion validity, internal consistency, and test-retest reliability. Results: A total of 436 female cancer survivors were recruited in a Chinese tertiary cancer center from May to August in 2021. Item analysis showed statistical significance (P < 0.05) for each one and no ceiling or floor effect. The item-level content validity index ranged from 0.86 to 1.00 and the scale-level content validity index was 0.98. Three factors were extracted based on parallel analysis, and confirmatory factor analysis proved a good model fit with the original 3-factor structure. Pearson's correlation coefficient showed acceptable criterion validity. The Cronbach's α of 0.880 demonstrated the scale's internal consistency reliability, and the Alpha coefficients were 0.826, 0.763, and 0.859 for its three dimensions, respectively. The interclass correlation coefficients for test-retest reliability was 0.904 (0.870-0.891, P < 0.01) which confirmed the external reliability of the scale. Conclusions: The Chinese version of FSACS scale proved to be a valid and reliable instrument that can be applied among Chinese female cancer survivors. Further research could be conducted in larger populations or people in different cancer stages.

20.
BMC Neurol ; 22(1): 274, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35869441

RESUMO

BACKGROUND: Our previous study explored Amphotericin B (AMB) plus 5-flucytosine (5-FC) combined with fluconazole (FLU) therapy in the induction period, which seemed to be better than the previous AMB + 5-FC antifungal therapy in non-HIV and non-transplant-associated CM. However, based on our clinical finding, the outcomes of some CM patients who received AMB plus 5-FC combined with FLU antifungal therapy were still poor. Therefore, we need to explore new antifungal methods in non-HIV and non-transplant-associated CM during the induction period. METHODS: Clinical data from 148 patients admitted to the Third Affiliated Hospital of Sun Yat Sen University from January 2011 to December 2020 were collected. These patients were stratified based on antifungal treatment methods in the induction period (group I with AMB + 5-FC + VOR, group II with AMB + 5-FC + FLU, group III with AMB + 5-FC). RESULTS: The first hospitalization time of Group I (median: 25 days, IQR: 20-34.5) was significantly shorter than that of Group II (median: 43 days, IQR: 29-62) (p < 0.001) and Group III (median: 50.5 days, IQR: 43-77.5) (p < 0.001). After 2 weeks of follow-up, Group I (26/49) had more patients reaching CSF clearance (p = 0.004) than Group II (18/71) and Group III (7/28). In multivariable analysis, Group II (OR: 3.35, 95%CI 1.43-7.82, p = 0.005) and Group III (OR: 3.8, 95%CI 1.23-11.81, p = 0.021) were associated with higher risk about CSF clearance failure at 2 weeks follow-up than Group I. After 10 weeks of follow-up, the incidence of hypokalemia in Group I was significantly lower than that in Group II (p = 0.003) and Group III (p = 0.004), and the incidence of gastrointestinal discomfort in Group I was significantly lower than that in Group II (p = 0.004). CONCLUSION: AMB plus 5-FC combined with VOR may rapidly improve clinical manifestation, decrease CSF OP and clear the cryptococci in CSF during the early phase, substantially shorten the hospitalization time, and reduce the incidences of hypokalemia and gastrointestinal discomfort.


Assuntos
Hipopotassemia , Meningite Criptocócica , Anfotericina B/efeitos adversos , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Quimioterapia Combinada , Fluconazol/uso terapêutico , Flucitosina/uso terapêutico , Humanos , Hipopotassemia/induzido quimicamente , Hipopotassemia/tratamento farmacológico , Meningite Criptocócica/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Voriconazol
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