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Glioma is the most common primary tumor of the central nervous system (CNS). Glioblastoma (GBM) is incurable with current treatment strategies. Additionally, the treatment of recurrent GBM (rGBM) is often referred to as terminal treatment, necessitating hospice-level care and management. The presence of the blood-brain barrier (BBB) gives GBM a more challenging or "cold" tumor microenvironment (TME) than that of other cancers and gloma stem cells (GSCs) play an important role in the TME remodeling, occurrence, development and recurrence of giloma. In this review, our primary focus will be on discussing the following topics: niche-associated GSCs and macrophages, new theories regarding GSC and TME involving pyroptosis and ferroptosis in GBM, metabolic adaptations of GSCs, the influence of the cold environment in GBM on immunotherapy, potential strategies to transform the cold GBM TME into a hot one, and the advancement of GBM immunotherapy and GBM models.
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Glioma is the most prevalent primary malignant tumor of the central nervous system. While traditional treatment modalities such as surgical resection, radiotherapy, and chemotherapy have made significant advancements in glioma treatment, the prognosis for glioma patients remains often unsatisfactory. Ferroptosis, a novel form of programmed cell death, plays a crucial role in glioma and is considered to be the most functionally rich programmed cell death process. Histone deacetylases have emerged as a key focus in regulating ferroptosis in glioma. By inhibiting the activity of histone deacetylases, histone deacetylase inhibitors elevate acetylation levels of both histones and non-histone proteins, thereby influencing various cellular processes. Numerous studies have demonstrated that histone deacetylases are implicated in the development of glioma and hold promise for its treatment. This article provides an overview of research progress on the mechanism by which histone deacetylases contribute to ferroptosis in glioma.
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Objective: To determine the efficacy of mechanical thrombectomy combined with prolonged mild hypothermia compared with conventional treatment in managing acute middle cerebral artery occlusion, and to explore whether extending the duration of hypothermia can improve neurological function. Method: From 2018 to June 2023, a retrospective analysis was conducted on 45 patients with acute middle cerebral artery occlusion treated at the NICU of Suzhou Kowloon Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. After thrombectomy, patients were admitted to the neurological intensive care unit (NICU) for targeted temperature management. Patients were divided into two groups: the mild hypothermia group (34.5-35.9°C) receiving 5-7 days of treatment, and the normothermia group (control group) whose body temperature was kept between 36 and 37.5°C using pharmacological and physical cooling methods. Baseline characteristics and temperature changes were compared between the two groups of patients. The primary outcome was the modified Rankin Scale (mRS) score at 3 month after surgery, and the secondary outcomes were related complications and mortality rate. Prognostic risk factors were investigated using both univariate and multivariate logistic regression analyses. Results: Among 45 patients, 21 underwent prolonged mild hypothermia, and 24 received normothermia, with no significant differences in baseline characteristics between the two groups. The duration of mild hypothermia ranged from 5 to 7 days. The incidence of chills (33.3% vs. 8.3%, p = 0.031) and constipation (57.1% vs. 20.8%, p = 0.028) was significantly higher in the mild hypothermia group compared with the control group. There was no significant difference in mortality rates between the mild hypothermia and the control group (4.76% vs. 8.33%, p = 1.000, OR = 1.75, 95% CI, 0.171-17.949). At 3 month, there was no significant difference in the modified mRS (0-3) score between the mild hypothermia and control groups (52.4% vs. 25%, p = 0.114, OR = 0.477, 95% CI, 0.214-1.066). Infarct core volume was an independent risk factor for adverse neurological outcomes. Conclusion: Prolonged mild hypothermia following mechanical thrombectomy had no severe complications and shows a trend to improve the prognosis of neurological function. The Infarct core volume on CTP was an independent risk factor for predicting neurological function.
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Distant metastasis is common in ocular uveal melanoma (uveal melanoma, UM) [1], with possible identification of relevant protein markers in peripheral blood [2], [3]. Proteomics analyses serve as a basis for the screening of new target proteins. However, it is difficult to determine whether the relevant proteins in peripheral blood are the same kinesins as those in primary lesions and metastases. Specially in this study, human UM cells (92.1) [4] were inoculated into the back of the eyeball and the brain of inbred line nude mice transplanted with enhanced green fluorescent protein (EGFP) [5], respectively, to simulate the growth of UM in situ and in brain metastases. A database was established as follows: Firstly, the xenograft was taken for monoclonal re-culture and amplification. Then, the cells after amplification (92.1-A in the back of the eyeball and 92.1-B in the brain) and their parent cells (92.1) were subjected to Tandem Mass Tag (TMT)-labeling proteomic analysis and liquid chromatography-mass spectrometry (LC-MS). Covering differential proteomes of three cell lines in a pairwise model, the data could be used to further screen the kinesins that play a vital role in regulating the growth of UM.
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BACKGROUND: Although uveal melanoma (UM) at the early stage is controllable to some extent, it inevitably ultimately leads to death due to its metastasis. At present, the difficulty is that there is no way to effectively tackle the metastasis. It is hypothesized that these will be treated by target molecules, but the recognized target molecule has not yet been found. In this study, the target molecule was explored through proteomics. METHODS: Transgenic enhanced green fluorescent protein (EGFP) inbred nude mice, which spontaneously display a tumor microenvironment (TME), were used as model animal carriers. The UM cell line 92.1 was inoculated into the brain ventricle stimulating metastatic growth of UM, and a graft re-cultured Next, the UM cell line 92.1-A was obtained through monoclonal amplification, and a differential proteomics database, between 92.1 and ectopic 92.1-A, was established. Finally, bioinformatics methodologies were adopted to optimize key regulatory proteins, and in vivo and in vitro functional verification and targeted drug screening were performed. RESULTS: Cells and tissues displaying green fluorescence in animal models were determined as TME characteristics provided by hosts. The data of various biological phenotypes detected proved that 92.1-A were more malignant than 92.1. Besides this malignancy, the key protein p62 (SQSTM1), selected from 5267 quantifiable differential proteomics databases, was a multifunctional autophagy linker protein, and its expression could be suppressed by chloroquine and dacarbazine. Inhibition of p62 could reduce the malignancy degree of 92.1-A. CONCLUSIONS: As the carriers of human UM orthotopic and ectopic xenotransplantation, transgenic EGFP inbred nude mice clearly display the characteristics of TME. In addition, the p62 protein optimized by the proteomics is the key protein that increases the malignancy of 92.1 cells, which therefore provides a basis for further exploration of target molecule therapy for refractory metastatic UM.
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Dacarbazina , Neoplasias de la Úvea , Animales , Línea Celular Tumoral , Cloroquina/uso terapéutico , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Humanos , Melanoma , Ratones , Ratones Desnudos , Proteómica , Microambiente Tumoral , Neoplasias de la Úvea/tratamiento farmacológico , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patologíaRESUMEN
Pollution by heavy metals in river water is becoming a major subject of global drinking water concern, and the Xiangjiang River is one of the most heavily polluted rivers in China. Water samples were collected from 17 sites spanning the entire Xiangjiang watershed from 2005 to 2016 to investigate spatial-temporal distributions and potential human health risks related to 8 metal pollutants (As, Cd, Hg, Cr, Cu, Pb, Zn, and Se). The results of spatial-temporal distribution analyses proved that most metals were below the guideline limits the majority of the time. However, the hazard index and carcinogenic risk analyses indicated that As and Cr were associated with a potential risk of cancer, although noncarcinogenic heavy metals in general and carcinogenic risk declined year by year. A nonparametric seasonal Mann-Kendall's test revealed that there were notable decreasing trends in As, Cd, Zn, Cu, Cr, and Pb for most sites, whereas Se and Hg significantly increased in some areas over the targeted 12 yr. The results of principal component analysis agreed with those of dual hierarchical cluster analysis in the identification of pollution sources, the results of which are as follows: 1) As, Cd, Pb, Hg, and Zn were mainly derived from anthropogenic activities and the smelting industry; 2) Cr and Cu mainly originated from agricultural or industrial activities; and 3) Se was predominantly from natural erosion. The present study will be conducive to optimizing the distribution of water monitoring stations and drafting remediation strategies pertaining to the protection of public health in metal-polluted areas. Environ Toxicol Chem 2019;38:1645-1657. © 2019 SETAC.
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Monitoreo del Ambiente/métodos , Sedimentos Geológicos/química , Ríos/química , Contaminantes Químicos del Agua/análisis , Calidad del Agua , Agricultura , China , Análisis por Conglomerados , Humanos , Mercurio/análisis , Metales Pesados/análisis , Análisis Multivariante , Medición de RiesgoRESUMEN
With the change in global climate and environment, water scarcity has been of great concern around the word and exacerbated by serious pollution in water resources. Pollutants accumulated in sediments are threatening water safety and ecological security. Different from others focusing on prevalent heavy metals (Cu, Pb, Zn, As, Cd, Cr, Hg, etc.), in this study, some unheeded metal pollutants Tl, Sb, Mo, Sr, Co, V, Ti, Ca, Mg, Be and Li were monitored in sediments of the Xiangjiang River, China. It was found that there was no remarkable vertical variation with depth, but the seasonal characteristics of Tl, Sb, Mo, Be and Li. The enrichment, pollution and potential ecological risk of Tl, Sb and Mo were revealed by the enrichment factor (EF), geoaccumulation index (Igeo), pollution load index (PLIsite and PLIzone) and potential ecological risk index (RI). It is noticed that the pollution of Tl mainly occurred in summer at midstream and downstream and Mo pollution was much higher than Sb in summer and the reverse in other seasons. Additionally, sediment quality on east side was worse than on west side in Songbai section of the Xiangjiang River. For the first time, the toxic-response factor was figured out as Mo = 18, Tl = 17, Sb = 13, Sr = 6, Co = Be = 1, V = Li = 0, and importantly, the high potential ecological risk of Tl, Sb and Mo needs to be taken seriously for the comprehensive assessment on watershed environmental quality.
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Sedimentos Geológicos/análisis , Metales/análisis , Contaminantes Químicos del Agua/análisis , China , Monitoreo del Ambiente , Medición de Riesgo , RíosRESUMEN
Two different SO4-free tooeleite were prepared for the first time through structural substitution for SO4 group by As(V) and As(III). As(III)-tooeleite and As(V)-tooeleite have similar crystalline structure to SO4-tooeleite but incorporate different anions in the interlayer space. The removal of As can reach 94% by forming SO4-free tooeleite crystals, and As leaching in TCLP tests can be much lower than that of SO4-tooeleite. Therefore, SO4-free tooeleite crystals are of great potential in As removal and immobilization. Moreover, our study indicates the different affinities of Fe(III) towards As(III), As(V) and SO4, which can explain that a) the coordination structure of As(III)-tooeleite is much closer to the ideal crystal structure but easily affected by As(V) and SO4 group; b) tooeleite mineral found in natural environments is commonly a SO4-containing mineral and associated with scorodite due to the abundance of As(V) and SO4 group.
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Arsénico/química , Hierro/química , Óxidos/química , Compuestos de Azufre/químicaRESUMEN
OBJECTIVE: The proportion of the super-aged population (at the age of 80 or above) in patients with chronic subdural hematoma (CSDH) and the incidence of CSDH of the population have been increasing. Since it is widely accepted that YL-1 needle is effective in CSDH treatment, this paper aimed to probe into the efficacy of YL-1 needle in minimally invasive surgery for super-aged (at the age of 80-90) CSDH patients. METHODS: A retrospective analysis on the clinical information of 17 super-aged CSDH patients having received the YL-1 needle puncture treatment provided by the hospital from May 2012 to December 2016 was performed. At the same time, another 19 CSDH patients (ages 60-79) who were hospitalized during the same period were randomly selected to form a control group. The same surgical treatment was provided for both groups to observe and compare the treatment efficacy. RESULTS: The patients of both groups were cured and discharged. Among the super-aged patients, there was 1 patient with postoperative hematoma recurrence, 1 patient with pneumocephalus, and 1 patient with wound infection; among the aged patients, 1 reported postoperative recurrence and 2 had pneumocephalus; The average length of stay of the super-aged group was 9.235â±â2.948 days while that of the aged group was 7.316â±â3.660 days, which showed no statistical difference. CONCLUSION: The YL-1 needle puncture treatment is safe and efficacious for both the super-aged and the aged CSDH patients.
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Hematoma Subdural Crónico/epidemiología , Hematoma Subdural Crónico/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Procedimientos Neuroquirúrgicos , Anciano , Anciano de 80 o más Años , Humanos , Tiempo de Internación , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Agujas , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Distribución Aleatoria , Estudios RetrospectivosRESUMEN
OBJECTIVE: The aim of the present study was to explore the clinical effects, including the prevention of complications, of the treatment of chronic subdural hematoma with double needle aspiration. METHODS: The clinical data of 31 patients with chronic subdural hematoma treated by double YL-1 needle double skull drilling and 31 controls treated by traditional drilling and drainage were analyzed retrospectively. RESULTS: In the YL-1 needle group, only 1 patient was with hematoma recurrence, 1 patient was with intracranial pneumocephalus, and the remaining patients who were followed up for 3 months achieved a clinical cure. In the traditional drilling and drainage group, 13 patients were with hematoma recurrence within 3 months after the operation and 7 patients were with postoperative intracranial pneumocephalus. CONCLUSIONS: The method of double YL-1 needle is better than the traditional drilling and drainage method for the treatment of chronic subdural hematoma because it reduces the postoperative recurrence rate and complications.
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Hematoma Subdural Crónico/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Agujas , Paracentesis/normas , Trepanación/instrumentación , Trepanación/normas , Anciano , Anciano de 80 o más Años , Drenaje/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neumocéfalo/etiología , Complicaciones Posoperatorias/etiología , Recurrencia , Resultado del TratamientoRESUMEN
This study aimed to investigate the effect of miR-423-5p on the sensitivity of glioma stem cells to apigenin and to explore the potential mechanism. Previous research indicated that apigenin can effectively inhibit the proliferation of many cancer cells, including glioma cells, though our data unexpectedly showed that apigenin had no effect on glioma stem cell apoptosis. As many studies have reported that malignant transformation and progression of glioma are due to glioma stem cells, an anti-glioma stem cell approach has become an important direction for glioma treatment. In this study, we found miR-423-5p to be overexpressed in glioma tissues and corresponding glioma stem cells. Downregulation of miR-423-5p repressed glioma stem cell growth but did not cause apoptosis. Based on the concept of "Pharmaco-miR," this study further demonstrated that the combination of miR-423-5p knockdown and apigenin had a notable additive effect on inhibiting proliferation and promoting apoptosis in glioma stem cells. Hoechst staining showed higher apoptosis rates and typical apoptotic morphological changes of the cell nucleus, and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocya-nine iodide) staining revealed reduced mitochondrial membrane potential. Further research demonstrated that the mechanism is associated with a shift in the Bax/Bcl-2 ratio, an increased cytochrome c level, Apaf-1 induction, and caspase-3 activation. In conclusion, this study indicates that downregulation of miR-423-5p enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway.
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Apigenina/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , MicroARNs/fisiología , Células Madre Neoplásicas/efectos de los fármacos , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/patología , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Glioma/patología , Humanos , Potencial de la Membrana Mitocondrial/fisiología , MicroARNs/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/fisiologíaRESUMEN
OBJECTIVE: This study was performed to investigate the method of cranioplasty in patients with abnormal bone window pressure after decompressive craniectomy. METHODS: We performed a retrospective analysis for 25 cases after decompressive craniectomy in patients with abnormal flap pressure of clinical data. RESULTS: Flap pressure increased in 15 cases, including 6 cases of hydrocephalus, 5 cases of contralateral subdural effusion, 2 cases of subdural effusion bone window, 2 cases of bone window cystic encephalomalacia communicating with the ventricle; Flap pressure decreased in 10 cases, including 6 cases of hydrocephalus after ventriculoperitoneal shunt, and 4 cases of low intracranial pressure. ALL of patients were treated by appropriate measures to make the operation smoothly. CONCLUSION: Our data suggest that after analysis of the factors for abnormal bone window flap pressure by decompressive craniectomy and symptomatic treatment, the difficulty of operation and operative complications can be reduced.
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Craniectomía Descompresiva/efectos adversos , Hipertensión Intracraneal/diagnóstico por imagen , Hipertensión Intracraneal/cirugía , Cuidados Intraoperatorios/métodos , Colgajos Quirúrgicos/efectos adversos , Adulto , Anciano , Femenino , Humanos , Hipertensión Intracraneal/etiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Recently, microRNAs (miRNAs), a kind of small and non-coding RNA, can target the downstream molecules. Increasing evidence demonstrates that miRNAs meditate the onset and progression of a variety of tumors. In the present study, we carried out gene transfection, western blot, and reverse transcription PCR (RT-PCR) to explore the role of miR-22 in glioblastoma tissues and cell lines. Here, we verified that the expression of miR-22 was downregulated in glioblastoma tissues and cells rather than matched non-tumor tissues and normal human astrocyte (NHA) cells (p < 0.001). By contrast, SIRT1 messenger RNA (mRNA) and protein were upregulated in glioblastoma tissues and cells (p < 0.001). In vitro miR-22 mimics interfered with cell proliferation, migration, and invasion of U87 and U251 cells. Mechanically, the 3'-untranslated regions (3'-UTRs) of SIRT1 were a direct target of miR-22, leading to the decreased expression of SIRT1 protein in U87 and U251 cells. Meanwhile, miR-22 mimics also inhibited the expression of epidermal growth factor receptor (EGFR) and matrix metallopeptidase 9 (MMP9). In conclusion, miR-22 inhibited cell proliferation, migration, and invasion via targeting the 3'-UTR of SIRT1 in the progression of glioblastoma and miR-22-SIRT1 pathway can be recommended as a potential target for treatment of glioblastoma.
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Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , MicroARNs/genética , Interferencia de ARN , Sirtuina 1/genética , Regiones no Traducidas 3' , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Perfilación de la Expresión Génica , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , MicroARNs/química , ARN Mensajero/química , ARN Mensajero/genética , Sirtuina 1/química , TranscriptomaRESUMEN
OBJECTIVES: The objectives of this work are to report the outcomes of our finding during microvascular decompression (MVD) for patients with recurrent trigeminal neuralgia (TN) and to introduce the sling retraction technique. METHODS: The authors performed a retrospective review of redo MVD for consecutive cases with recurrent TN after previous operation. Sling retraction techniques were used during the reoperation. RESULTS: Fifteen patients underwent redo MVD. During the second operation, arachnoid adhesion of the Teflon felt was confirmed at the trigeminal nerve in 10 cases, and neurovascular conflict was found in 4 cases. Symptoms were completely relieved in 14 patients (93.3%) and partially relieved in 1 patient (6.7%). The mean follow-up period was 38 months (range, 21-60 months), and no patient experienced recurrence. CONCLUSIONS: Arachnoid adhesion of the Teflon felt and vascular compression to the nerve were main causes of recurrence. The sling retraction technique is still an effective and useful treatment for recurrent TN after MVD.
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Cirugía para Descompresión Microvascular/métodos , Complicaciones Posoperatorias/cirugía , Neuralgia del Trigémino/cirugía , Adulto , Anciano , Anciano de 80 o más Años , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios RetrospectivosRESUMEN
OBJECTIVE: The aim of this study was to review the efficacy and safety of microvascular decompression (MVD) for idiopathic trigeminal neuralgia (ITN) in elderly patients older than 65 years. METHODS: From June 2006 to June 2011, a total of 59 elderly patients with ITN underwent MVD. We performed a retrospective study of the medical records and compared the outcome data with those from 164 patients younger than 64 years during the same period. RESULTS: The mean age of the elderly and younger patient groups was 72 and 55 years. The pain was completely relieved in 93.2% and partially relieved in another 5.1% of the elderly patient group after surgery. The mean follow-up period was 42 months (range, 16-75 mo). A total of 8.9% of the patients in the elderly patient group experienced recurrence. Headaches, nausea, and vomiting were more frequent complications. There were no mortalities and severe morbidities after surgery. Between the elderly and younger patient groups, no statistically significant differences existed in the outcomes. CONCLUSIONS: Microvascular decompression is a safe and effective procedure for elderly patients with ITN. It is recommended that any patients with ITN should have the opportunity to choose MVD, unless their condition cannot tolerate general anesthesia.
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Cirugía para Descompresión Microvascular/métodos , Neuralgia del Trigémino/cirugía , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Arterias/cirugía , Cerebelo/irrigación sanguínea , Femenino , Estudios de Seguimiento , Cefalea/etiología , Humanos , Masculino , Persona de Mediana Edad , Síndromes de Compresión Nerviosa/cirugía , Complicaciones Posoperatorias , Náusea y Vómito Posoperatorios/etiología , Recurrencia , Estudios Retrospectivos , Seguridad , Resultado del Tratamiento , Enfermedades del Nervio Trigémino/cirugíaRESUMEN
Temozolomide (TMZ) is a promising chemotherapeutic agent for treating glioblastomas. However, resistance develops quickly with a high frequency. Glioblastoma stem cells (GSCs) causing resistance to drug therapy were considered to be one of key factors. The mechanisms underlying GSCs resistance to TMZ are not fully understood. MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug resistance. Previous study showed that miR-125b was necessary for GSCs fission and for making stem cells insensitive to chemotherapy. Thus, exploring the functions and mechanisms of miR-125b action on TMZ-treated GSCs would be valuable. In this study, we found that miR-125b was up-regulated in TMZ-resistant cells, inhibition of which caused a marked increase of TMZ-induced cytotoxicity and apoptosis and a subsequent decrease in the resistance to TMZ in GSCs. Moreover, we demonstrated that the pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) was a direct target of miR-125b. Down-regulation of Bak1 inhibited TMZ-induced apoptosis and led to an increased resistance to TMZ. Restoring Bak1 expression recovered TMZ sensitivity on GSCs. Taken together; our data strongly support an important role for miR-125b on conferring TMZ resistance through targeting Bak1 expression.
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Dacarbazina/análogos & derivados , Glioblastoma/tratamiento farmacológico , MicroARNs/genética , Proteína Destructora del Antagonista Homólogo bcl-2/genética , Apoptosis/efectos de los fármacos , Transformación Celular Neoplásica , Dacarbazina/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/genética , Glioblastoma/patología , Humanos , MicroARNs/antagonistas & inhibidores , Células Madre Neoplásicas/efectos de los fármacos , Temozolomida , Proteína Destructora del Antagonista Homólogo bcl-2/biosíntesisRESUMEN
Meningiomas, one of the most common benign brain tumors in humans, arise from arachnoid cells in the brain meninges. Our investigations have revealed that miR-335 is a typical microRNA overexpressed in meningiomas in humans. Characterization of the effects of miR-335 overexpression in meningiomas demonstrated that elevated levels of miR-335 increased cell growth and inhibited cell cycle arrest in the G0/G1 phase in vitro; in addition, reduction of the miR-335 levels had the opposite effect on tumor growth and progression. Further, previous studies have shown that the mechanism of effect of miR-335 on the proliferation of meningioma cells is associated with alterations in the expression of human retinoblastoma 1 (Rb1). Our results indicate that miR-335 plays an essential role in the proliferation of meningioma cells by directly targeting the Rb1 signaling pathway. Thus, our results highlight a novel molecular interaction between miR-335 and Rb1, and miR-335 may represent a potential novel therapeutic agent to target the proliferation of meningioma cells.
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Proliferación Celular , Neoplasias Meníngeas/genética , Meningioma/genética , MicroARNs/genética , Proteína de Retinoblastoma/metabolismo , Western Blotting , Ciclo Celular , Supervivencia Celular , Humanos , Luciferasas/metabolismo , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patología , Meningioma/metabolismo , Meningioma/patología , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteína de Retinoblastoma/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To discuss the feasibility of endoscopic frontal sinus surgery in the nasal septum median path. METHOD: (1) Sixty adult cadaveric heads fixed with formalin were CT scanned,and were three dimensional reconstruction. (2) Thirty adult cadaveric heads were sawn along the sagittal line close to the side of the nasal septum, then the important anatomic marks were observed and measured. (3) Combined with CT and anatomical data, thirty adult cadaveric heads were operated in different degree, and the damage of nasal septum and fila olfactoria were detected in the same time. RESULT: (1) The roots of middle nasal concha were simulated in the endoscopic frontal sinus surgery. The operation time, operative procedures, markers foundation, endoscopic back of posterior border of frontal sinus foundation and attached to the symphysis with cribriform plate and the top of ethmoidal sinus were recorded. (2) The intersection point formed by the level of middle nasal concha and the vertical of middle nasal concha corresponded with the nasal septum was called the M point. The distance from the M point to the horizon of the nasal bone was (20.07 +/- 6.21) mm, the distance from the M point to the first fila olfactoria was (24.38 +/- 7.68) mm, the distance from the first fila olfactoria to the posterior edge of frontal sinus was (9.57 +/- 2.73) mm, the distance from the root of the middle nasal concha to posterior edge of frontal sinus was (5.38 +/- 1.23) mm, the anteroposterior diameter of frontal sinus fundus was (7.62 +/- 2.45) mm, the transverse diameter of frontal sinus fundus was (9.41 +/- 3.37) mm, the seesaw diameter of frontal sinus partition was (16.97 +/- 3.23) mm, the anteroposterior diameter of frontal sinus partition was (12.34 +/- 2.23) mm. (3) The operation time through the nasal septum path was 105 minutes which combined with CT and anatomical measurements. 0 degrees endoscopy could be used to observe the frontal part of the lateral, posterior and top wall, while nasal septum remove should be finished with 30 degree endoscopy. The bottom of frontal sinus can be exposed and removed with 0 degree endoscopy. 3 cases of cadaveric frontal sinus lateral wall can not be observed with 70 degree endoscopy. 30 cases of cadaveric frontal sinus,some of the top and the lateral wall, anterior and posterior wall could be observed with 70 degree endoscopy, nasal septum damage range was about 2.23 cm x 2.59 cm, and no fila olfactoria damage was found. CONCLUSION: Endoscopic frontal sinus surgery in the nasal septum median path is a good way to find frontal sinus.
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Endoscopía/métodos , Seno Frontal/cirugía , Tabique Nasal/cirugía , Estudios de Factibilidad , Seno Frontal/diagnóstico por imagen , Humanos , Hueso Nasal/diagnóstico por imagen , Hueso Nasal/cirugía , Tabique Nasal/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
MicroRNA (miR)-125b has been shown to play a potential role in the development of glioma stem cells. However, the relationship between miRNA and glioma stem cells is still elusive. This study was designed to elucidate this potential relationship. We established a highly invasive glioma stem cell and progenitor (GSCP) cell line SU3. SU3 cell suspensions were injected into nude mice brains in situ, and the invasiveness of graft tumors was analyzed using hematoxylin and eosin staining as well as immunohistochemistry. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of miR-125b in SU3 and other cells. In vitro, SU3 cells expressed CD133 and nestin as well as differentiation markers glial fibrillary acidic protein (GFAP) and ß-tubulin III, which were consistent with the characteristics of glioma stem cells. Scratch assays indicated that the migration ability of SU3 cells was stronger than that of U251 stem cells (U251s). In vivo, SU3 cells invaded into each part of the mouse brain from the caudate nucleus in a diffuse pattern and highly expressed invasive and proliferative cell markers matrix metalloprotease 2 (MMP2), MMP9, and Ki-67. Real-time PCR results revealed that the levels of miR-125b and MMP9 were significantly higher in SU3 and SU2, also a highly invasive GSCP cell line we established before, than in U251s. High expression of miR-125b both in newly established GSCPs, SU3, and long-term cultured GSCPs, SU2 suggests that miR-125b exhibits oncogene-like behavior. This behavior should be considered in further studies of miR-125b in cancer stem cells. Furthermore, MMP9, which plays a role in cancer stem cell invasion, may be a target gene of miR-125b.