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1.
Ther Adv Med Oncol ; 16: 17588359241236450, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455710

RESUMEN

Histological transformation is a phenomenon that is well described as one of the causes of tyrosine kinase inhibitor resistance in oncogene-driven non-small-cell lung cancer (NSCLC). The use of immune checkpoint inhibitors (ICIs) as a potential mechanism of acquired resistance to immunotherapy in NSCLC to small-cell lung cancer was also recently found. Here, we report the histological transformation of sarcomatoid carcinoma and metastasis in a lung adenocarcinoma patient without targetable genetic alterations who experienced long-term disease remission after nivolumab therapy. The patient subsequently developed rapid progression in the mediastinal and retroperitoneal lymph nodes, bones, and small intestine. Surgical resection of the small intestine lesion due to acute small intestine bleeding revealed the transformation of NSCLC to sarcomatoid carcinoma. The patient died 3 months after sarcomatoid carcinoma transformation and extensive disease progression, although he was rechallenged with immunotherapy. Genomic and immunohistochemical analyses revealed a comparable abundance of gene mutations and a limited number of immune cells in the tumor microenvironment, with low infiltration of CD8+ T cells, CD4+ T cells, regulatory T cells, and PD-L1+ macrophages in metastatic tumors, revealing a noninflamed immune microenvironment for ICI-resistant tumors.

2.
Oncogene ; 43(19): 1463-1475, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38514855

RESUMEN

Medulloblastoma (MB) is a prevalent malignant brain tumor among children, which can be classified into four primary molecular subgroups. Group 3 MB (G3-MB) is known to be highly aggressive and associated with a poor prognosis, necessitating the development of novel and effective therapeutic interventions. Ferroptosis, a regulated form of cell death induced by lipid peroxidation, has been identified as a natural tumor suppression mechanism in various cancers. Nevertheless, the potential role of ferroptosis in the treatment of G3-MB remains unexplored. In this study, we demonstrate that RNF126 acts as an anti-ferroptotic gene by interacting with ferroptosis suppressor protein 1 (FSP1, also known as AIFM2) and ubiquitinating FSP1 at the 4KR-2 sites. Additionally, the deletion of RNF126 reduces the subcellular localization of FSP1 in the plasma membrane, resulting in an increase in the CoQ/CoQH2 ratio in G3-MB. The RNF126-FSP1-CoQ10 pathway plays a pivotal role in suppressing phospholipid peroxidation and ferroptosis both in vivo and in vitro. Clinically, RNF126 exhibited elevated expression in G3-MB and its overexpression was significantly associated with reduced patient survival. Our findings indicate that RNF126 regulates G3-MB sensitivity to ferroptosis by ubiquitinating FSP1, which provides new evidence for the potential G3-MB therapy.


Asunto(s)
Ferroptosis , Proteínas Mitocondriales , Ubiquitina-Proteína Ligasas , Ubiquitinación , Ferroptosis/genética , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Animales , Ratones , Línea Celular Tumoral , Neoplasias Cerebelosas/metabolismo , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Regulación Neoplásica de la Expresión Génica
3.
Angew Chem Int Ed Engl ; 63(13): e202319728, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38285535

RESUMEN

Organic molecules bearing chiral sulfur stereocenters exert a great impact on asymmetric catalysis and synthesis, chiral drugs, and chiral materials. Compared with acyclic ones, the catalytic asymmetric synthesis of thio-heterocycles has largely lagged behind due to the lack of efficient synthetic strategies. Here we establish the first modular platform to access chiral thio-oxazolidinones via Pd-catalyzed asymmetric [3+2] annulations of vinylethylene carbonates with sulfinylanilines. This protocol is featured by readily available starting materials, and high enantio- and diastereoselectivity. In particular, an unusual effect of a non-chiral supporting ligand on the diastereoselectivity was observed. Possible reaction mechanisms and stereocontrol models were proposed.

4.
J Am Chem Soc ; 146(4): 2779-2788, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38238317

RESUMEN

Catalytic enantioselective α-chlorination of ketones is a highly desirable process. Different from the conventional approaches that employ corrosive electrophilic chlorination reagents, the process disclosed here employs nucleophilic chloride, aqueous NaCl solution, and even seawater, as green inexpensive chlorine sources. This mechanistically distinct and electronically opposite approach provides facile access to diverse highly enantioenriched acyclic α-chloro ketones that are less straightforward by conventional approaches. With a chiral thiourea catalyst, a range of racemic α-keto sulfonium salts underwent enantioconvergent carbon-chlorine bond formation with high efficiency and excellent enantioselectivity under mild conditions. The sulfonium motif plays a crucial triple role by permitting smooth dynamic kinetic resolution to take place via a chiral anion binding mechanism in a well-designed phase-transfer system. This protocol represents a new general platform for the asymmetric nucleophilic α-functionalization of carbonyl compounds.

5.
J Neurosurg Pediatr ; 33(3): 285-294, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38064705

RESUMEN

OBJECTIVE: The occurrence and predictors of symptomatic subdural hygroma (SSH) subsequent to the fenestration of pediatric intracranial arachnoid cysts (IACs) are unclear. In this study, the authors aimed to investigate the likelihood of an SSH following IAC fenestration and the impact on operative efficacy with the ultimate goal of constructing a nomogram. METHODS: The medical records of 1782 consecutive patients who underwent surgical treatment at the Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were reviewed. Among these patients, a training cohort (n = 1214) underwent surgery during an earlier period and was used for the development of a nomogram. The remaining patients formed the validation cohort (n = 568) and were used to confirm the performance of the developed model. The development of the nomogram involved the use of potential predictors, while internal validation was conducted using a bootstrap-resampling approach. RESULTS: SSH was detected in 13.2% (160 of 1214) of patients in the training cohort and in 11.1% (63 of 568) of patients in the validation cohort. Through multivariate analysis, several factors including Galassi type, IAC distance to the basal cisterns, temporal bulge, midline shift, IAC shape in the coronal view, area of the stoma, and artery location near the stoma were identified as independent predictors of SSH. These 7 predictors were used to construct a nomogram, which exhibited a concordance statistic (C-statistic) of 0.826 and demonstrated good calibration. Following internal validation, the nomogram maintained good calibration and discrimination with a C-statistic of 0.799 (95% CI 0.665-0.841). Patients who had nomogram scores < 30 or ≥ 30 were considered to be at low and high risk of SSH occurrence, respectively. CONCLUSIONS: The predictive model and derived nomogram achieved satisfactory preoperative prediction of SSH. Using this nomogram, the risk for an individual patient can be estimated, and the appropriate surgery can be performed in high-risk patients.


Asunto(s)
Quistes Aracnoideos , Efusión Subdural , Humanos , Niño , Quistes Aracnoideos/diagnóstico por imagen , Quistes Aracnoideos/cirugía , Nomogramas , China , Hospitales
6.
Front Immunol ; 14: 1238684, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38094301

RESUMEN

Background: The significant progress of immune therapy in non-central nervous system tumors has sparked interest in employing the same strategy for adult brain tumors. However, the advancement of immunotherapy in pediatric central nervous system (CNS) tumors is not yet on par. Currently, there is a lack of comprehensive comparative studies investigating the immune ecosystem in pediatric and adult CNS tumors at a high-resolution single-cell level. Methods: In this study, we comprehensively analyzed over 0.3 million cells from 171 samples, encompassing adult gliomas (IDH wild type and IDH mutation) as well as four major types of pediatric brain tumors (medulloblastoma (MB), ependymoma (EPN), H3K27M-mutation (DIPG), and pediatric IDH-mutation glioma (P-IDH-M)). Our approach involved integrating publicly available and newly generated single-cell datasets. We compared the immune landscapes in different brain tumors, as well as the detailed functional phenotypes of T-cell and myeloid subpopulations. Through single-cell analysis, we identified gene sets associated with major cell types in the tumor microenvironment (gene features from single-cell data, scFes) and compared them with existing gene sets such as GSEA and xCell. The CBTTC and external GEO cohort was used to analyze and validate the immune-stromal-tumor patterns in pediatric brain tumors which might potentially respond to the immunotherapy. Results: From the perspective of single-cell analysis, it was observed that major pediatric brain tumors (MB, EPN, P-IDH-M, DIPG) exhibited lower immune contents compared with adult gliomas. Additionally, these pediatric brain tumors displayed diverse immunophenotypes, particularly in regard to myeloid cells. Notably, the presence of HLA-enriched myeloid cells in MB was found to be independently associated with prognosis. Moreover, the scFes, when compared with commonly used gene features, demonstrated superior performance in independent single-cell datasets across various tumor types. Furthermore, our study revealed the existence of heterogeneous immune ecosystems at the bulk-RNA sequencing level among different brain tumor types. In addition, we identified several immune-stromal-tumor patterns that could potentially exhibit significant responses to conventional immune checkpoint inhibitors. Conclusion: The single-cell technique provides a rational path to deeply understand the unique immune ecosystem of pediatric brain tumors. In spite of the traditional attitudes of "cold" tumor towards pediatric brain tumor, the immune-stroma-tumor patterns identified in this study suggest the feasibility of immune checkpoint inhibitors and pave the way for the upcoming tide of immunotherapy in pediatric brain tumors.


Asunto(s)
Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Neoplasias Cerebelosas , Glioma , Meduloblastoma , Humanos , Niño , Adulto , Ecosistema , Inhibidores de Puntos de Control Inmunológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Glioma/genética , Glioma/terapia , Análisis de Secuencia de ARN , ARN , Microambiente Tumoral/genética
7.
Thorac Cancer ; 14(30): 3051-3057, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37675621

RESUMEN

BACKGROUND: The aim of this study was to analyze the effectiveness and safety of H101 in Chinese patients with malignant pleural effusion and ascites (MPE/MA) in the real world. METHODS: This multicenter, observational, real-world study recruited patients with MPE/MA caused by malignant tumor receiving H101-containing treatment between January 2020 and June 2022. Effectiveness was evaluated by overall remission rate (ORR), and safety was evaluated based on adverse events (AEs). Subgroup analysis was performed on patients grouped according to tumor type, the volume of MPE and MA, and dosage of H101. RESULTS: A total of 643 eligible patients were enrolled, and 467 received H101 monotherapy and 176 received H101 combined with chemotherapy. The ORR of total patients was60.3% with 388 case of PR. In the H101 monotherapy group, the decrease of MPE or MA was achieved in 282 (60.4%, PR) patients, 176 (37.7%, NC) patients showed no change in volume of MPE or MA, and nine (1.9%, PD) patients showed an increase, yielding an ORR of 60.4% (282/467). The ORR for the combination therapy group was 60.2% (106/176), with 106 cases of PR, 69 cases of NC and one case of PD. Subgroup analyses based on tumor type, volume of MPE and MA, and dosage of H101 all showed high ORR, approximately 60%. The main AEs associated with H101-containing regimens were fever, nausea and vomiting. No serious AEs occurred in both groups. CONCLUSION: Encouraging clinical benefits and manageable toxicity of H101 against MPE/MA were preliminarily observed in the real-world clinical setting, indicating that the H101-containing regimen is reliable, safe, and feasible, providing a novel and effective option for the treatment of this disease.


Asunto(s)
Adenovirus Humanos , Derrame Pleural Maligno , Derrame Pleural , Humanos , Derrame Pleural Maligno/patología , Ascitis/tratamiento farmacológico , Ascitis/etiología , Terapia Combinada
8.
Nat Food ; 4(8): 721-732, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37563492

RESUMEN

Infusing human taste perception into smart sensing devices to mimic the processing ability of gustatory organs to perceive liquid substances remains challenging. Here we developed a self-powered droplet-tasting sensor system based on the dynamic morphological changes of droplets and liquid-solid contact electrification. The sensor system has achieved accuracies of liquid recognition higher than 90% in five different applications by combining triboelectric fingerprint signals and deep learning. Furthermore, an image sensor is integrated to extract the visual features of liquids, and the recognition capability of the liquid-sensing system is improved to up to 96.0%. The design of this dual-sensory fusion self-powered liquid-sensing system, along with the droplet-tasting sensor that can autonomously generate triboelectric signals, provides a promising technological approach for the development of effective and low-cost liquid sensing for liquid food safety identification and management.


Asunto(s)
Percepción del Gusto , Gusto , Humanos , Inocuidad de los Alimentos , Reconocimiento en Psicología , Órganos de los Sentidos
9.
Cell Rep ; 42(8): 112910, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37531255

RESUMEN

Amino acid (aa) metabolism is closely correlated with the pathogenesis of psoriasis; however, details on aa transportation during this process are barely known. Here, we find that SLC38A5, a sodium-dependent neutral aa transporter that counter-transports protons, is markedly upregulated in the psoriatic skin of both human patients and mouse models. SLC38A5 deficiency significantly ameliorates the pathogenesis of psoriasis, indicating a pathogenic role of SLC38A5. Surprisingly, SLC38A5 is almost exclusively expressed in dendritic cells (DCs) when analyzing the psoriatic lesion and mainly locates on the lysosome. Mechanistically, SLC38A5 potentiates lysosomal acidification, which dictates the cleavage and activation of TLR7 with ensuing production of pro-inflammatory cytokines such as interleukin-23 (IL-23) and IL-1ß from DCs and eventually aggravates psoriatic inflammation. In summary, this work uncovers an auxiliary mechanism in driving lysosomal acidification, provides inspiring insights for DC biology and psoriasis etiology, and reveals SLC38A5 as a promising therapeutic target for treating psoriasis.


Asunto(s)
Sistemas de Transporte de Aminoácidos Neutros , Psoriasis , Animales , Ratones , Humanos , Células Dendríticas/metabolismo , Piel/patología , Psoriasis/patología , Inflamación/patología , Modelos Animales de Enfermedad , Lisosomas/patología , Concentración de Iones de Hidrógeno
10.
Ther Adv Med Oncol ; 15: 17588359231187205, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37484525

RESUMEN

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1, programmed cell death ligand 1, and cytotoxic T lymphocyte-associated antigen-4 have shown significantly durable clinical benefits and tolerable toxicities and have improved the survival of patients with various types of cancer. Since 2018, the National Medical Products Administration of China has approved 17 ICIs as the standard treatment for certain advanced or metastatic solid tumors. As ICIs represent a broad-spectrum antitumor strategy, the populations eligible for cancer immunotherapy are rapidly expanding. However, the clinical applications of ICIs in cancer patient populations with special issues, a term that refers to complex subgroups of patients with comorbidities, special clinical conditions, or concomitant medications who are routinely excluded from prospective clinical trials of ICIs or are underrepresented in these trials, represent a great real-world challenge. Although the Chinese Society of Clinical Oncology (CSCO) has provided recommendations for screening before the use of ICIs in special populations, the recommendations for full-course management remain insufficient. The CSCO Expert Committee on Immunotherapy organized leading medical oncology and multidisciplinary experts to develop a consensus that will serve as an important reference for clinicians to guide the proper application of ICIs in special patient populations. This article is a translation of a study first published in Chinese in The Chinese Clinical Oncology (ISSN 1009-0460, CN 32-1577/R) in May 2022 (27(5):442-454). The publisher of the original paper has provided written confirmation of permission to publish this translation in Therapeutic Advances in Medical Oncology.

11.
Front Cardiovasc Med ; 10: 1093383, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37089888

RESUMEN

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy in the past decade and amplify T-cell-mediated immune responses by disrupting immunoinhibitory signals. The augmented T-cell immune response has led to a range of immune-related adverse effects (irAEs). Immune-related cardiotoxicity has been reported in case series but has been underappreciated due to difficulties in diagnosis. This article describes epidemiological, clinical presentation, subtype, and treatment data and a new systematic framework for the clinical management of cardiotoxicity. Methods: Data were extracted for cancer patients who received ICIs in a single center between January 1, 2020, and February 28, 2022. ICI-associated cardiotoxicity was clinically diagnosed based on clinical presentations, biochemical biomarkers, and imaging features. Results: We identified a total of 12 (2.46%) cases of ICI-related cardiotoxicity from 487 patients who received PD-1 or PD-L1 inhibitors. All patients were diagnosed with advanced or metastatic solid tumors. The severity of ICI-related cardiotoxicity ranged from subclinical cardiac abnormalities (subclinical type) with only asymptomatic troponin-I (TnI) elevations (25.0%) to symptomatic cardiac abnormalities (clinical type) (75.0%). Patients with symptomatic cardiac abnormalities had several manifestations, including tachyarrhythmia (16.7%), bradyarrhythmia (41.7%), or cardiac failure (8.3%). The median immunotherapy exposure time was 1.5 doses (range: 1 to 5), and the median time from the initial immunotherapy to the onset of ICI-related cardiotoxicity was 33.5 days (IQR: 20.3 to 46.8). Most patients, including those with subclinical cardiac abnormalities, were administered systemic corticosteroids (58.3%). One (8.3%) patient was put on mechanical ventilation, one (8.3%) received plasma exchange therapy, one (8.3%) was implanted with a pacemaker, and one (8.3%) was admitted to the ICU. Three patients with symptomatic cardiac abnormalities (25.0%) died, and other patients presented with significant clinical improvement with good outcomes. Conclusion: ICI-related cardiotoxicity is uncommon but critical with a high mortality rate and poor prognosis, especially for a small group of patients with symptomatic cardiac abnormalities. More attention should be given to cardiotoxicity associated with ICIs, and these patients should be given baseline examinations and biochemical analyses before and after the initiation of immunotherapy, intensive cardiac assessments, an accurate and rapid diagnosis, and timely multidisciplinary management with immunosuppressive agents and other necessary clinical interventions.

12.
Front Immunol ; 14: 1081790, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37114049

RESUMEN

Background: Previous studies indicate that exogenous use of glucocorticoid (GC) affects immune checkpoint inhibitor (ICI) efficacy. However, there is a paucity of clinical data evaluating the direct impact of endogenous GC on the efficacy for cancer patients with immune checkpoint blockade. Methods: We first compared the endogenous circulating GC levels in healthy individuals and patients with cancer. We next retrospectively reviewed patients with advanced cancer with PD-1/PD-L1 inhibitor alone or combination therapy in a single center. The effects of baseline circulating GC levels on objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analyzed. The association of the endogenous GC levels with circulating lymphocytes, cytokines levels, and neutrophil to lymphocyte ratio, and tumor infiltrating immune cells, were systematically analyzed. Results: The endogenous GC levels in advanced cancer patients were higher than those in early-stage cancer patients as well as healthy people. In the advanced cancer cohort with immune checkpoint blockade (n=130), patients with high baseline endogenous GC levels (n=80) had a significantly reduced ORR (10.0% vs 40.0%; p<0.0001) and DCB (35.0% vs 73.5%, p=0.001) compared to those with low endogenous GC levels (n=50). The increased GC levels was significantly associated with reduced PFS (HR 2.023; p=0.0008) and OS (HR 2.809; p=0.0005). Moreover, statistically significant differences regarding PFS, and OS were also detected after propensity score matching. In a multivariable model, the endogenous GC was identified as an independent indicator for predicting PFS (HR 1.779; p=0.012) and OS (HR 2.468; p=0.013). High endogenous GC levels were significantly associated with reduced lymphocytes (p=0.019), increased neutrophil to lymphocyte ratio (p=0.0009), and increased interleukin-6 levels (p=0.025). Patients with high levels of endogenous GC had low numbers of tumor infiltrating CD3+ (p=0.001), CD8+ T (p=0.059), and CD4+ T (p=0.002) cells, and the numbers of circulating PD-1+ NK cells (p=0.012), and the ratio of CD8+PD-1+ to CD4+PD-1+ (p=0.031) were higher in patients with high levels of endogenous GC compared to low levels of endogenous GC. Conclusion: Baseline endogenous GC increase executes a comprehensive negative effect on immunosurveillance and response to immunotherapy in real-world cancer patients accompanied with cancer progression.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Glucocorticoides/uso terapéutico , Receptor de Muerte Celular Programada 1 , Estudios Retrospectivos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/patología
13.
Front Pediatr ; 11: 1075087, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36937976

RESUMEN

Objectives: To investigate the potential factors affecting the clinical prognosis of intracranial sylvian arachnoid cysts(IAC) in children. Methods: All patients with IAC admitted to our department from January, 1, 2015 to December, 31, 2016, were retrospectively reviewed. Patients were grouped based on surgical treatment (surgery cohort vs non-surgery cohort). The clinical and image outcome of the patients were followed routinely. The clinical characteristics and the prognosis of the patients were compared in different cohorts. Binary logistic regression analysis was applied to analyze the potential factors which may post an influence on the prognosis of the patients. Results: Of 500 patients admitted to our department for IAC, 424 patients had good prognosis and 76 had poor prognosis, with no deaths occurred during the follow-ups. 68 patients had IAC related complications and 91 patients developed new symptoms during the follow-ups. There were significant differences (P < 0.05) between the 2 cohorts in below aspects: age, gender, Galassi subtype, whether the mother was a unipara, the maximum diameter of the cysts at the first visit and the last follow-up, headache, head circumference, temporal bulge, new symptoms, cysts rupture and hemorrhage, subdural effusion, and IAC disappearance. The mean changes in the maximum diameter of the IAC for the patients were marginally higher for the surgery cohort than for the non-surgery cohort (P < 0.01). Binary logistic regression analysis suggested that the number of symptom, no new symptoms during follow-up, surgical treatment, age, maximum diameter of cysts at first diagnosis were independent risk factors affecting the prognosis of patients (P < 0.05). Conclusions: Patients older than 22.5 months, with the maximum diameter of IAC greater than 5.75 cm, who have multiple symptoms, born prematurely, develope new symptoms during the follow-ups and obvious symptoms after trauma need to conduct necessary surgical treatment in time. Patients with complications such as cysts rupture with hemorrhage and subdural effusion will acquire good prognosis after timely surgical treatment. IAC complete disappearance warrants no such important attention for the good prognosis.

14.
Angew Chem Int Ed Engl ; 62(21): e202301592, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-36932035

RESUMEN

Metal-polarized aza-ortho-quinone methides (aza-o-QMs) are a unique and efficient handle for azaheterocycle synthesis. Despite great achievements, the potential of these reactive intermediates has not yet been fully exploited, especially the new reaction modes. Herein, we disclosed an unprecedented dearomatization process of metal-polarized aza-o-QMs, affording transient dearomatized spiroaziridine intermediates. Based on this serendipity, we accomplished three sequential dearomatization-rearomatization reactions of benzimidazolines with aza-sulfur ylides, enabling the divergent synthesis of bis-nitrogen heterocycles with high efficiency and flexibility. Moreover, experimental and theoretical studies were performed to explain the proposed mechanisms and observed selectivity. Further cellular evaluation of the dibenzodiazepine products identified a hit compound for new antitumor drugs.

16.
Childs Nerv Syst ; 39(1): 151-158, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36316483

RESUMEN

PURPOSE: Lateral ventricle meningiomas (LVM) in children are very rare. The current research is mostly limited to adults, and there are very few related studies on children. The purpose of this study was to analyze the clinicopathological and imaging features of lateral ventricle meningiomas in children. METHODS: A retrospective analysis of five children with pathologically confirmed lateral ventricle meningioma was performed, and we collected clinical data, including clinicopathological data, treatment prognosis data, and imaging features (including tumor location, signal intensity, enhancement degree, intratumoral cyst, calcification, peritumoral edema, and associated hydrocephalus). RESULTS: Among the 5 patients with LVM, 4 were male and 1 was female with an average age of 7.6 years (range 2 to 12 years). All CT scans showed slight hyperintensity or isodensity, and only 1 patient had calcification. Two patients demonstrated cyst changes. Four patients had varying degrees of peritumoral edema. The average tumor volume was 164.1 cm3 (1.4-314.9 cm3). All 5 patients with LVM were iso- or hypointense on T1WI. The T2WI signals had no obvious features. Four patients had a high signal on DWI (80%). The contrast-enhanced signals were mostly homogeneously strong (80%). MRI showed hydrocephalus in 3 patients. All patients underwent gross total resection, and they were followed up regularly after the operation. The average follow-up time was 47.4 months. No recurrence was found in any of the children. All patients were pathologically confirmed to have meningiomas, and WHO grades were all grade I. CONCLUSION: Lateral ventricle meningiomas in children are very rare, and the imaging manifestations of the tumor have certain characteristics, but the clinical diagnosis is still difficult, and the diagnosis still requires pathological analysis.


Asunto(s)
Coristoma , Quistes , Hidrocefalia , Neoplasias Meníngeas , Meningioma , Adulto , Humanos , Masculino , Niño , Femenino , Preescolar , Meningioma/cirugía , Neoplasias Meníngeas/cirugía , Estudios Retrospectivos , Ventrículos Laterales/patología , Imagen por Resonancia Magnética/métodos , Edema
17.
Biomater Adv ; 144: 213229, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36502749

RESUMEN

New strategies that enhance both the targetability of chemotherapy drugs and the synergistic effects of chemotherapy and immunotherapy are urgently needed for efficacious solid tumor therapy. In this study, a novel biomimetic nanoparticle system possessing the properties of tumor targeting and immune synergy was designed to meet these requirements. Mesoporous silica nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX) were coated with cell membranes modified by glycosylphosphatidylinositol (GPI)-anchored anti-HER2 single chain variable fragment (scFv) and the GPI-anchored co-stimulatory molecule CD80 (to promote solid tumor-targeted chemotherapy and cooperated immunotherapy, respectively). The impact of the nanotherapeutic system on both tumor-targeted chemotherapy and cellular immune response was investigated through in vitro and in vivo experiments. The results show that the novel biomimetic therapeutic system effectively promoted antitumor efficiency in vitro and in vivo. In addition, this therapeutic system further enhanced antitumor capacity by increasing CD8+ T cell activation and cytokine production and reducing myeloid-derived suppressor cell (MDSC) levels in tumors.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Dióxido de Silicio , Biomimética , Porosidad , Inmunoterapia
18.
Childs Nerv Syst ; 39(3): 767-773, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36065031

RESUMEN

OBJECTIVE: The aim of this study is to investigate the clinical characteristics and prognostic effects of different subtypes of suprasellar arachnoid cysts (SAC) in children. METHODS: Fifty patients with primary SAC who had undergone endoscopic treatment in our department between January 2010 and December 2020 were studied retrospectively. All patients underwent endoscopic treatment after diagnosis, including ventriculocystostomy (VC) in 23 cases and ventriculocystocisternostomy (VCC) in 27 cases. All patients were followed up regularly after the operation, including head computed tomography (CT)/magnetic resonance imaging (MRI), and Evans index (EI) and frontal and occipital horn ratio (FOHR) index were measured to assess changes in cyst volume and hydrocephalus. The prognosis was evaluated comprehensively on the data of the improvement of clinical symptoms, child growth and development correlation score, and reduction of cyst volume 12 months after surgery. According to the new classification of SAC, 50 cases of children were classified into three groups in which we compared the clinical characteristics of different subtypes of the three groups. Logistic regression was used to analyze the influencing factors of prognosis. RESULTS: Completed success was achieved in 50 cases, including 31 cases with cyst volume reduction of more than 50% and 19 cases with cyst volume reduction of less than 50%. The median follow-up time was 55.3 months (22 ~ 113 months). According to the new classification criteria of SAC, there were 21 cases of SAC-1, 16 cases of SAC-2, and 13 cases of SAC-3. There were no statistically significant differences among the three groups in gender, birth weight, prenatal diagnosis, hydrocephalus, endocrine abnormalities, relief of postoperative symptoms, cyst wall texture, and surgical methods (P > 0.05). There was a statistically significant difference among the three groups in the change of the cyst volume and the maximum cyst diameter (P < 0.05), in which SAC-1 had the largest volume reduction, SAC-2 was more likely to cause endocrine symptoms and SAC-3 was inclined to lie in between. Multivariate logistic analysis showed that SAC classification and cyst wall texture were independent risk factors for the prognosis. CONCLUSION: The clinical characteristics of different SAC subtypes are different, and SAC classification is one of the independent risk factors affecting prognosis.


Asunto(s)
Quistes Aracnoideos , Hidrocefalia , Femenino , Embarazo , Niño , Humanos , Quistes Aracnoideos/diagnóstico por imagen , Quistes Aracnoideos/cirugía , Quistes Aracnoideos/complicaciones , Estudios Retrospectivos , Endoscopía/métodos , Ventriculostomía/métodos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/etiología , Hidrocefalia/cirugía , Imagen por Resonancia Magnética/efectos adversos , Resultado del Tratamiento
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