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1.
Medicina (B.Aires) ; 82(3): 370-375, ago. 2022. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1394453

ABSTRACT

Resumen La aplicación de las diferentes técnicas moleculares para el diagnóstico de los gliomas según la clasificación de la OMS, sigue sin estar al alcance de todos en nuestro país. Nuestro objetivo fue describir el protocolo diagnóstico desarrollado en función de los recursos disponibles, conforme con la clasificación vigente (2021). También, describir el perfil epidemiológico de los gliomas diagnosticados entre 2018-2021 en el Instituto Roffo y contrastarlo con la literatura. Se evaluó la mutación en IDH1-R132H, ATRX, el estado del 1p19q, CDKN2A, EGFR y del p53. Se incluyeron 94 pacientes, 53.2% fueron masculinos, con una edad promedio de 50.9 años. El diagnóstico más frecuente fue el de GB IDH1-no mutado (63.8%). Considerando únicamente a los gliomas grado 2 y 3, el astrocitoma difuso IDH1-Mutado/ATRX-Mutado/p53-sobreexpresado, grado 2 (11.7%) fue el más frecuente. En cuanto a su localización, el 67% de los tumores se ubicaron en el telencéfalo neocortical: 24.5% del total en el lóbulo frontal. En el 95.7% de los casos se arribó a un diagnóstico integrado concluyente siguiendo el algoritmo propuesto. Las características epidemiológicas coinciden con lo publicado en la literatura. La biología molecular nos permitió diferenciar nítidamente enfermedades que suponíamos emparentadas desde un punto de vista histológico, pero que observando su historia natural, su genética y su respuesta a tratamientos instaurados eran tumores distintos, aunque todos fueran llamados "gliomas". Los estándares internacionales no conciben su diagnóstico sin la biología molecular. No es aceptable que se siga diagnosticando únicamente con estándares histológicos. El algoritmo propuesto podría ser una alternativa viable y confiable.


Abstract The utilization of the different molecular techniques for the diagnosis of gliomas according to the WHO classification is still not available to everyone in our country. Our objective was to describe the diagnostic algorithm devel oped based on available resources, in accordance with the current classification (2021). Also, to describe the epidemiological profile of gliomas diagnosed between 2018-2021 at the Roffo Institute and compare it with the international literature. IDH1-R132H and ATRX mutation, as well as 1p19q status, CDKN2A, EGFR, and p53 were evaluated. 94 patients were included, 53.2% were male, with a mean age of 50.9 years. The most frequent diagnosis was GB IDH1-wild type (63.8%). Considering only grade 2 and 3 gliomas, diffuse astrocytoma IDH1- Mutated / ATRX-Mutated / p53-overexpressed, grade 2 (11.7%) was the most frequent diagnosis. Regarding their location, 67% of the tumors were located in the neocortical telencephalon: 24.5% of the total in the frontal lobe. In 95.7% of cases, a conclusive integrated diagnosis was reached following the proposed algorithm. The epidemiological characteristics coincide with what has been published in the literature. Molecular biology allowed us to clearly differentiate pathologies that we assumed were related from a histological point of view, but which, observing their natural history, their genetics and their response to established treatments were different tumors, although they were all called "gliomas". International standards do not conceive CNS tumor diagnosis without molecular biology. It is not acceptable to continue to diagnose only with histological standards. The proposed algorithm could be a viable and reliable alternative.

2.
Acta neurol. colomb ; 38(2): 66-70, abr.-jun. 2022. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1383398

ABSTRACT

RESUMEN INTRODUCCIÓN: Las crisis epilépticas son la manifestación clínica inicial en un 30-50 % de los pacientes con tumores cerebrales. Algunos de los tumores más frecuentes, como los gliomas y los meningiomas se asocian con manifestaciones epilépticas. En el país no hay estudios que especifiquen cuáles son los tumores del encéfalo más frecuentemente relacionados con epilepsia. OBJETIVO: Determinar los tumores del encéfalo más frecuentes relacionados con epilepsia en pacientes del hospital Universitario Erasmo Meoz, en Cúcuta, Colombia entre los años 2015 y 2018. METODOLOGÍA: Estudio retrospectivo. Se recolectaron historias clínicas de pacientes mayores de 18 años que ingresaron al servicio de Neurocirugía del Hospital Universitario Erasmo Meoz, en Cúcuta, Colombia con diagnóstico de tumor del encéfalo entre el año 2015 y el 2018. RESULTADOS: Se incluyeron 220 historias, el 56 % correspondió al sexo femenino y la media de edad fue de 48 años; 98 (45 %) de los casos presentó crisis epilépticas. El tumor del encéfalo más frecuente relacionado con epilepsia fue el glioma (46 casos). El tipo de glioma que más se relacionó con crisis epilépticas fue el glioblastoma (27 casos); 82 % de los gliomas de bajo grado se manifestaron con epilepsia, y 71 % de los de alto grado (70,6 %). En los hombres el tumor más frecuente relacionado con epilepsia fue el glioblastoma y en las mujeres el meningioma. La localización tumoral más frecuente fue la región frontal (27 %). CONCLUSIONES: Los gliomas son el tipo de tumor cerebral más común relacionado con epilepsia, siendo el glioblastoma el tumor más frecuente de este grupo.


ABSTRACT INTRODUCTION: Seizures are the initial clinical symptom in 30 to 50 % of patients with brain tumors. With a high percentage, gliomas and meningiomas have been reported as tumors associated with epilepsy, these also being frequent tumors in Colombia. Currently in the country there are no studies that specify which are the most frequent brain tumors related to epilepsy, an investigation being necessary to clarify these data. OBJECTIVE: To determine the most frequent brain tumors associated with epilepsy in patients at the Erasmo Meoz University Hospital in Cúcuta. METHODS: Medical records were collected from all patients over 18 years of age who were admitted to the Neurosurgery service of the Erasmo Meoz University Hospital in Cúcuta with a diagnosis of brain tumor between 2015 and 2018. RESULTS: 220 patients were included, 56% were female. The mean age was 48 years; 98 cases (45%) presented with epilepsy. The most frequent brain tumor related to epilepsy were gliomas (46 cases). The glioma with the highest frequency of seizures was glioblastoma (27 cases). Low-grade gliomas had a higher percentage of epilepsy (82%) than high-grade gliomas (71%). In men, the most frequent tumor related to epilepsy was glioblastoma and in women, meningioma. The most frequent location was the frontal region (27%). CONCLUSIONS: Gliomas are the most common type of brain tumor associated with epilepsy, with the most common tumor in this group being glioblastoma.

3.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1388413

ABSTRACT

Resumen Los tumores cerebrales se caracterizan por su gran morbilidad y mortalidad. La gran mayoría corresponde a tumores secundarios (metástasis). Dentro de los tumores primarios del sistema nervioso central, los gliomas corresponden al 30% de éstos. En EEUU, entre el 2007-2011, se estima una incidencia aproximada de 21,4 casos por 100.000 habitantes. Los recientes avances en la comprensión molecular de la biología de estos tumores han permitido mejorar sustancialmente su clasificación, posibilitando realizar un mejor correlato con los desenlaces clínicos y el pronóstico. En esta línea, hoy en día es posible estratificar a los pacientes por riesgo y entregar tratamientos capaces de prolongar la sobrevida global entre 5-7 años, para los gliomas grado II y III. El presente consenso, elaborado por un panel multidisciplinario de expertos de diversas sociedades científicas chilenas y, por tanto, de todas las especialidades involucradas en el manejo médico-quirúrgico de las personas portadoras de gliomas cerebrales. A la luz de este nuevo conocimiento desarrollado al alero de la oncología molecular, esta propuesta ofrece un insumo de utilidad clínica real, que, articulado a una revisión actualizada en relación con el tratamiento y seguimiento de estos pacientes, permite entender la relevancia de estos biomarcadores en el manejo de precisión de la enfermedad. Cabe señalar que, este manuscrito emerge de la misma fuerza de trabajo, que elaboró el Protocolo Clínico de Gliomas del Adulto 2019, publicado por el Ministerio de Salud, y que ha diferencia de esta, que ofrece los detalles clínicos-operativos, como flujogramas y dosis, nuestra revisión intenta relevar los avances imagenológicos y moleculares y como estos impactan en el manejo actual de la enfermedad.


Brain tumors are characterized by high morbidity and mortality. The vast majority correspond to secondary tumors (metastasis). On the other hand, within the primary tumors of the central nervous system, gliomas correspond to 30% of these. In the US, between 2007-2011, an approximate incidence of 21.4 cases per 100,000 inhabitants was estimated. Recent advances in the molecular understanding of the biology of these tumors have made it possible to substantially improve their classification, allowing a better correlation with clinical outcomes and prognosis. Along these lines, today, it is possible to stratify patients by risk and deliver treatments capable of prolonging global survival between 5-7 years, for grade II and III gliomas. The present consensus, prepared by a multidisciplinary panel of experts from various Chilean scientific societies and, therefore, from all the specialties involved in the medical and surgical therapy. Enlightened from the molecular oncology, this proposal offers an input of clinical utility, which, together with an updated review in relation to the treatment and follow-up of these patients, allows us to understand the relevance of these biomarkers in precision disease management. It should be noted that this manuscript emerges from the same work force, which prepared the Clinical Protocol for Adult Gliomas 2019, published by the Ministry of Health, and that differs from it, which offers clinical-operative details, such as flowcharts and dose, our review attempts to reveal imaging and molecular advances and how they impact the current management of the disease.

4.
Chinese Journal of Oncology ; (12): 228-237, 2022.
Article in Chinese | WPRIM | ID: wpr-935205

ABSTRACT

Objective: To study the effects of Homeobox C10 (HOXC10) on biological characteristics such as migration, invasion and proliferation of glioma cancer cells and to explore the role of HOXC10 gene in glioma microenvironment. Methods: The expression level of HOXC10 in high grade glioma (glioblastoma) and low grade glioma and its effect on patient survival were analyzed by using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database. Hoxc10-siRNA-1, HOXC10-siRNA-2 and siRNA negative control (NC) were transfected into U251 cells according to the operation instructions of HOXC10-siRNA transfection. 100 ng/ mL recombinant protein chemokine ligand 2 (reCCL2) was added into the transfection group, and was labeled as HOXC10-siRNA-1+ reCCL2 and HOXC10-siRNA-2+ reCCL2 groups. The expressions of HOXC10 mRNA and target protein in each group was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and western blot. The proliferation ability of cells in each group was detected by cell counting kit 8 (CCK8) method. The migration ability of cells was detected by Transwell assay and Nick assay, and cell apoptosis was detected by flow cytometry. The expression of chemokines in each group was detected by multiple factors. Co-incubation assays were performed to determine the role of HOXC10 and chemokine ligand 2 (CCL2) in recruiting and polarizing tumor-associated macrophages (M2-type macrophages). Results: The median expression level of HOXC10 in high grade gliomas was 8.51, higher than 1.00 in low grade gliomas (P<0.001) in TCGA database. The median expression level of HOXC10 in high grade gliomas was 0.83, higher than 0.00 in low grade gliomas (P=0.002) in CGGA database. The 5-year survival rate of patients with high HOXC10 expression in TCGA database was 28.2%, lower than 78.7% of those with low HOXC10 expression (P<0.001), and the 5-year survival rate of patients with high HOXC10 expression in CGGA database was 20.3%, lower than 58.0% of those with low HOXC10 expression (P<0.001). The numbers of cell migration in HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (45±3) and (69±4) respectively, lower than (159±3) in NC group (P<0.05). The cell mobility of HOXC10-siRNA-1 group and HOXC10-siRNA-2 group at 48 hours were (15±2)% and (28±4)% respectively, lower than (80±5)% of NC group (P<0.05). The expressions of vimentin in HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (141 740.00±34 024.56) and (94 655.00±5 687.97), N-cadherin were (76 810.00±14.14) and (94 254.00±701.45), β-catenin were (75 786.50±789.84) and (107 296.50±9 614.53), lower than (233 768.50±34 114.37), (237 154.50±24 715.50) and (192 449.50±24 178.10) of NC group (P<0.05). The A value of HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (0.44±0.05) and (0.32±0.02) at 96 hours, lower than 0.92±0.12 of NC group (P<0.05). The apoptosis rates of HOXC10-siRNA-1 group and HOXC10 siRNA-2 group were (10.23±1.24)% and (13.81±2.16)%, higher than (4.60±0.07)% of NC group (P<0.05). The expression levels of CCL2 in U251 cells in HOXC10-siRNA-1 and HOXC10-siRNA-2 groups were (271.63±44.27) and (371.66±50.21), lower than (933.93±29.84) in NC group (P<0.05). The expression levels of CCL5 (234.81±5.95 and 232.62±5.72), CXCL10 (544.13±48.14 and 500.87±15.65) and CXCL11 (215.75±15.30 and 176.18±16.49) in HOXC10-siRNA-1 and HOXC10-siRNA-2 groups were higher than those in NC group (9.98±0.71, 470.54±18.84 and 13.55±0.73, respectively, P<0.05). The recruited numbers of CD14(+) THP1 in HOXC10-siRNA-1 and HOXC10-siRNA-2 groups were (159.33±1.15) and (170.67±1.15), respectively, lower than (360.00±7.81) in NC group (P<0.05), while addition of reCCL2 promoted the recruitment of CD14(+) THP1 cells (287.00±3.61 and 280.67±2.31 in HOXC10-siRNA-1+ reCCL2 group and HOXC10-siRNA-2+ reCCL2 group, respectively, P<0.05). The expressions level of M2-type macrophage-related gene TGF-β in HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (0.30±0.02) and (0.28±0.02), respectively, lower than (1.06±0.10) in NC group (P<0.05). The expressions level of M1-related gene NOS2 in HOXC10-siRNA-1 and HOXC10-siRNA-2 were (11 413.95±1 911.85) and (5 894.00±945.21), respectively, higher than (13.39±4.32) in NC group (P<0.05). Conclusions: The expression of HOXC10 in glioma is high and positively correlated with the poor prognosis of glioma patients. Knockdown of HOXC10 can inhibit the proliferation, migration and metastasis of human glioma U251 cells. HOXC10 may play an immunosuppressive role in glioma microenvironment by promoting the expression of CCL2 and recruiting and polarizing tumor-associated macrophages (M2 macrophages).


Subject(s)
Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Genes, Homeobox , Glioma/pathology , Homeodomain Proteins/metabolism , Humans , Neoplasm Invasiveness/genetics , Tumor Microenvironment
5.
Chinese Journal of Neurology ; (12): 501-506, 2022.
Article in Chinese | WPRIM | ID: wpr-933816

ABSTRACT

A case of limbic encephalitis with positive anti-leucine-rich glioma inactivated 1 protein (LGI1) antibody and anti-myelin oligodendrocyte glycoprotein (MOG) antibody was reported. The patient was a middle-aged male with a history of retinal vein occlusion. The main symptoms were temporal lobe epilepsy, facial arm dystonia, autonomic nerve dysfunction. Magnetic resonance imaging showed long T 2 signal in the right hippocampus without enhancement and normal perfusion. Electroencephalogram showed paroxysmal slow wave and sharp slow wave in interictal period. Blood anti-MOG antibody, blood and cerebrospinal fluid anti-LGI1 antibody were double positive. The main diagnosis was limbic encephalitis. After treatment with hormone and gamma globulin, the symptoms were improved and double antibodies were turned negative. Anti-LGI1/MOG double positive cases are rare, and the clinical manifestations and imaging manifestations of double positive antibody cases are not completely consistent with those with each single antibody, with different characteristics. This report can help clinicians enhance awareness.

6.
Chinese Journal of Neurology ; (12): 117-124, 2022.
Article in Chinese | WPRIM | ID: wpr-933767

ABSTRACT

Objective:To investigate the additional value of unenhanced computed tomography (CT) in the differential diagnosis of brain tumors and non-neoplastic lesions.Methods:A total of 237 cases [140 males and 97 females; (49±16) years old; including 48 cases of low-grade glioma, 134 cases of high-grade glioma, 38 cases of primary central nervous system lymphoma, 9 cases of medulloblastoma, 5 cases of germinoma, and 3 cases of central neurocytoma] of brain tumors (diffuse gliomas and non-glial tumors) diagnosed by biopsy or surgery and pathology in the Affiliated Hospital of Qingdao University from September 2016 to October 2020 were collected retrospectively. Sixty-six cases [46 males and 20 females; (42±13) years old; including 12 cases of abscesses, 5 cases of infarcts, 33 cases of demyelinating lesions, 11 cases of autoimmune encephalitis, and 5 cases of central nervous system vasculitis] of brain non-neoplastic lesions were confirmed by biopsy or clinic. All patients underwent routine magnetic resonance imaging (MRI) scan and unenhanced CT before the treatment. The images were reviewed by two neuroradiologists together blind to the final diagnosis with and without CT images respectively. The diagnostic results and reliability scores were recorded, and the accuracy of the two evaluations was compared.Results:CT hyperattenuation exhibited a higher specificity (95%) than conventional MRI scan (86%), and a lower diagnostic sensitivity (34% vs 86%). Compared to MRI alone, the combined modality of MRI and unenhanced CT significantly improved diagnostic accuracy (94% vs 86%). Additionally, the CT attenuation ratio of non-neoplastic lesions was significantly lower than that of neoplastic lesions [0.69 (0.61,0.78) and 1.14 (1.00,1.25), W=2 123, P<0.05]. The CT attenuation ratio in the non-glial origin tumor group was significantly higher than that in the diffuse glioma group [1.28 (1.18,1.41) and 1.13 (0.97,1.21), W=1 858, P<0.05]. There was no significant difference in grade Ⅲ and Ⅳ groups of diffuse glioma [1.11 (0.99,1.20) vs 1.16 (1.09,1.24), P>0.05 (Nemenyi test)]. However, both were significantly higher than that of grade Ⅱgroup of diffuse glioma [0.89 (0.76,1.07), P<0.05 (Nemenyi test)]. No significant difference was observed between astrocytic tumors and oligodendroglial tumors at the same grade. Conclusions:Hyperattenuation on unenhanced CT is highly specific for the diagnosis of brain tumors. Unenhanced CT plus MRI is more accurate for distinguishing the two entities in hypoattenuation lesion on unenhanced CT.

7.
Article in Chinese | WPRIM | ID: wpr-933479

ABSTRACT

To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.

8.
Article in Chinese | WPRIM | ID: wpr-933337

ABSTRACT

Objective:To evaluate the effect of propofol on the sensitivity of glioma cells to temozolomide and the role of long noncoding RNAs (lncRNAs)-growth arrest-specific transcript 5 (GAS5) in it.Methods:Human glioma cell line U251 were cultured in vitro and seeded in 6-, 24- or 96-well plates at a density of 1×10 5 cells/ml, and were divided into 5 groups ( n=30 each) using a random number table method: control group (group C), temozolomide group (group T), propofol + temozolomide group (group PT), negative-siRNA + propofol + temozolomide group (group NPT) and GAS5-siRNA + propofol + temozolomide group (group GPT). The U251 cells in group C were cultured in the common culture medium.In group T, temozolomide 400 μmol/L was added to the culture medium.In group PT, the cells were cultured with propofol 8 μg/ml first and then with temozolomide 400 μmol/L.In group NPT and group GPT, U251 cells were transfected with negative-siRNA and GAS5-siRNA, respectively, and then cultured in the same way as previously described in group PT.The expression of lncRNA-GAS5 in U251 cells was detected by quantitative real-time polymerase chain reaction, the cell survival rate was measured by CCK-8 assay, the apoptosis rate was determined by flow cytometry, cell invasion was determined by Transwell invasion assay, and the expression of c-Myc, glutathione S-transferase mu 3 (GSTM3) and P21 was detected by Western blot. Results:Compared with group C, the cell survival rate was significantly decreased, the apoptosis rate was increased, the number of invasive cells was decreased, the expression of c-Myc and GSTM3 was down-regulated, and the expression of P21 and lncRNA-GAS5 was up-regulated in the other four groups ( P<0.05). Compared with group T, the cell survival rate was significantly decreased, the apoptosis rate was increased, the number of invasive cells was decreased, the expression of c-Myc and GSTM3 was down-regulated, and the expression of P21 and lncRNA-GAS5 was up-regulated in group PT and group NPT ( P<0.05). Compared with group PT, the cell survival rate was significantly increased, the apoptosis rate was decreased, the number of invasive cells was increased, the expression of c-Myc and GSTM3 was up-regulated, and the expression of P21 and lncRNA-GAS5 was down-regulated in group GPT ( P<0.05), and no significant change was found in the parameters mentioned above in group NPT ( P>0.05). Conclusions:Propofol can enhance the sensitivity of glioma cells to temozolomide, and the expression of lncRNA-GAS5 is involved in the process.

9.
Article in Chinese | WPRIM | ID: wpr-932708

ABSTRACT

Glioma is the most common central nervous system tumor, mainly derived from the interstitial cells of the nervous system, showing diffuse and infiltrative growth, with the characteristics of high morbidity, high postoperative recurrence, high mortality and low cure rate. Currently, radical resection followed by radiotherapy and chemotherapy is the first choice of treatment. Accurate delineation of GTV-T is of significance for precision radiotherapy after surgery. In addition, CT/MR fusion imaging has been commonly used in the delineation of tumor targets in glioma. In recent years, PET/MR has been more and more widely applied in tumors. In this article, the application and differences between PET/MR and CT/MR for target delineation in glioma were reviewed.

10.
Article in Chinese | WPRIM | ID: wpr-932698

ABSTRACT

Objective:To compare the efficacy and side effects between simultaneous and sequential integrated boost intensity-modulated radiotherapy after operation for high-grade glioma.Methods:We retrospectively analyzed 142 patients with high-grade glioma who underwent postoperative radiotherapy from January 2010 to December 2017. All patients were divided into the simultaneous and sequential integrated boost intensity-modulated radiotherapy groups. Concurrent temozolomide chemotherapy was delivered during radiotherapy in two groups. The follow-up outcomes were statistically compared between two groups.Results:For the whole group, the median overall survival (OS) was 24 months, the median progression-free survival (PFS) was 17 months, and the median disease-free survival (DFS) was 25 months. In the simultaneous and sequential integrated boost intensity-modulated radiotherapy groups, the median OS were 27.2 and 21.0 months ( P=0.950), the median PFS were 21.2 and 15.0 months ( P=0.21), and the median DFS were 28.0 and 18.0 months ( P=0.171), and the disease control rates were 92.86% and 85.17%( P=0.541), respectively. There was no statistical difference in OS, PFS, DFS, short-term efficacy and side effects between two groups. However, the conformity index in the simultaneous integrated boost intensity-modulated radiotherapy group was better than that in the sequential integrated boost intensity-modulated radiotherapy group ( P=0.032). Conclusions:Postoperative simultaneous and sequential integrated boost intensity-modulated radiotherapy yield no statistical differences in the survival, short-term efficacy and side effects in the treatment of high-grade glioma. However, the conformity index in the simultaneous integrated boost intensity-modulated radiotherapy group is significantly better, which can be recommended for postoperative radiotherapy of high-grade glioma.

11.
Article in Chinese | WPRIM | ID: wpr-932654

ABSTRACT

Glioma is the most common primary malignant brain tumor. Surgery combined with postoperative radiotherapy is the standard treatment, but the outcome is unsatisfactory. Currently, proton and carbon ion, the most advanced radiotherapy technology, offer substantial clinical advantages over the conventional photon therapy in multiple tumors. However, the effect of proton and carbon ion radiotherapy in glioma has not been clarified clearly. This article will elaborate on the basic research and clinical outcomes of proton and carbon ion radiotherapy for glioma.

12.
Chinese Journal of Radiology ; (12): 524-529, 2022.
Article in Chinese | WPRIM | ID: wpr-932534

ABSTRACT

Objective:To evaluate the value of synthetic MRI combined with three dimensional-arterial spin labeling (3D-ASL) imaging in the grading of diffuse glioma and its correlation with tumor cell proliferative activity (Ki-67).Methods:This study was prospective. The clinical and imaging manifestations of 66 patients with diffuse glioma who underwent synthetic MRI combined with 3D-ASL imaging from August 2020 to June 2021 in General Hospital of Ningxia Medical University were analyzed. Among 66 patients, there were 36 males and 30 females, aged 4-76 years, and divided into low grade glioma (LGG) group ( n=25) (WHO Ⅱ) and high grade glioma (HGG) group ( n=41) (WHO Ⅲ and vⅣ). T 1, T 2, proton density (PD) and cerebral blood flow (CBF) of tumor parenchyma were measured by GE ADW4.7 postprocessing software. The Ki-67 label index (Ki-67 LI) in postoperative pathological sections was detected by immunohistochemistry. Independent sample t test or Mann-Whitney U test was used to compare the differences of quantitative parameters between HGG group and LGG group. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of T 1, PD, CBF and the combination. Spearman test was used to analyze the correlation between the parameters and Ki-67 label index (LI). Results:T 1[(1 573±173)ms], PD[(86.2±2.4)pu] and CBF[(129±48)ml·100 g -1·min -1] in HGG group were significantly higher than those in LGG group [(1 376±134)ms, (83.0±2.5)pu and (77±49)ml·100g -1·min -1 respectively], and difference had statistical significance ( t=-4.86, -5.08, -4.24, P<0.01). ROC confirmed that the area under curve (AUC) of T 1, PD and CBF in differentiating HGG from LGG were 0.847, 0.843 and 0.777, respectively. In multi-parameter analysis, the combination of three parameters had the best diagnostic efficiency (AUC=0.973) and the sensitivity and specificity were 87.8% and 100%, respectively. In LGG and HGG groups, there was no correlation between T 1, T 2, PD, CBF and Ki-67 LI. In the overall cohort, T 1, PD and CBF had slight positive correlation with Ki-67 LI ( r=0.394, 0.411 and 0.406, respectively, all P<0.01). There was no correlation between T 2 and Ki-67 LI ( r=-0.100, P=0.423). Conclusion:Synthetic MRI and 3D-ASL can noninvasively evaluate the pathological grade of glioma and predict the expression of Ki-67, among which T 1 and PD are novel imaging marks.

13.
Chinese Journal of Radiology ; (12): 163-167, 2022.
Article in Chinese | WPRIM | ID: wpr-932494

ABSTRACT

Objective:To evaluate the clinical application value of MR amide proton transfer weighted imaging (APTWI) in predicting the pathological grade of brainstem glioma (BSG).Methods:The data of 41 BSG patients in Beijing Tiantan Hospital, Capital Medical University from August 2019 to June 2020 who underwent both MRI and APTWI 2 weeks before surgery and had pathological grading results were retrospectively analyzed. According to the pathological results, 41 patients were classified into high-grade BSG (20 patients) and low-grade BSG (21 patients). Combined with conventional MR images, the signal intensity (%) of amide proton transfer (APT) in the parenchymal area of the tumor was obtained on APTWI images. χ 2 test or independent sample t-test was used to analyze the differences in gender distribution, age and APT signal intensity between patients with high and low grade BSG. Receiver operating characteristic (ROC) curve was drawn to predict the efficacy of APT signal intensity in the differential diagnosis of high and low grade BSG, and Youden index was calculated to obtain the optimal diagnostic threshold; the predictive ability of APT signal intensity was analyzed in combination with Hosmer-Lemeshow goodness of fit test. Results:There was no significant difference in age [(23±18) years, (20±17) years, t=0.97, P=0.340] and gender distribution (9/11, 9/12 for males/females, χ 2=0.02, P=0.890) between high-grade and low-grade BSG patients. The APT signal intensity of high-grade BSG [(3.9±0.9)%] was significantly higher than that of low-grade BSG [(2.8±0.9)%], and the difference had statistical significance ( t=4.16, P<0.001). The area under the ROC curve of APT signal intensity to distinguish high-grade and low grade BSG was 0.836, and with 2.85% as the optimal diagnostic threshold of APT signal intensity, its sensitivity for the diagnosis of high-grade BSG was 90.0% and specificity was 71.4%. The Hosmer-Lemeshow test showed that APTWI had a good predictive ability for BSG grade (χ 2=13.33, P=0.101). Conclusion:APTWI can be applied in distinguishing high grade BSG from low grade BSG, and has clinical value in predicting glioma grading.

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Journal of Chinese Physician ; (12): 745-748, 2022.
Article in Chinese | WPRIM | ID: wpr-932132

ABSTRACT

Objective:To investigate the curative efficacy of X-ray stereotactic radiotherapy combined with temozolomide in the treatment of recurrent glioma.Methods:48 patients with recurrent glioma treated in Mianyang Central Hospital from January 2018 to January 2019 were retrospectively selected, including 24 patients treated with stereotactic radiotherapy as the control group and 24 patients treated with temozolomide combined with stereotactic radiotherapy as the observation group. The treatment effect, inflammatory factor level, incidence of adverse events and survival rate were compared between the two groups.Results:The complete remission rate and total effective rate in the observation group were significantly higher than those in the control group (66.7% vs 37.5%, 87.5% vs 62.5%) (all P<0.05). There were no significant differences in serum levels of hepatocyte growth factor (HGF), tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17) between the two groups before treatment (all P>0.05). After treatment, the serum levels of HGF, TNF-α and IL-17 in observation group was significantly lower than those in control group (all P<0.05). The incidence of adverse events in the observation group was significantly lower than that in the control group ( P<0.05). During follow-up of 6, 12 and 18 months, the survival rate of patients in the observation group was significantly higher than that in the control group, with statistically significant difference (all P<0.05). Conclusions:The combination of X-ray stereotactic radiotherapy with temozolomide in the treatment of recurrent glioma shows better clinical outcome and extended survival rate. To conclude, this combined treatment is recommended in further clinical promotion.

15.
Article in Chinese | WPRIM | ID: wpr-931146

ABSTRACT

Objective:To study the expression and clinical significance of collagen type Ⅰ alpha 2 chain (COL1A2) in glioma , and its effect on the migration and invasion of glioma cell lines.Methods:Through in-depth mining of the data related to COL1A2 in the Oncomine database, meta-analysis of its expression in different types of tumors, different grades and different molecular types of glioma, and then through the Chinese glioma genome map project (Chinese Glioma Genome Atlas, CGGA) database to explore the relationship between its expression level and the prognosis of glioma patients. The COL1A2 gene was functionally annotated by gene ontology (GO) and Pathway analysis. The annotation content includes cell components, biological processes, molecular functions and related signal pathways.Results:A total of 426 research results on COL1A2 in different types of tumors were collected in the Oncomine database, 114 of which were statistically different, 103 studies with increased COL1A2 expression, and 11 studies with decreased expression; the analysis shows there were 22 studies on high expression of COL1A2 in tumors, and no studies on low expression. Analysis of different grades of glioma and different molecular types of glioma Compared with the control group, COL1A2 was highly expressed in various types of glioma. Through the analysis of the gene chip data of the CGGA database, it was found that in glioblastoma, low expression levels of COL1A2 were significantly associated with an improved prognosis in patients with glioma ( P<0.05). Next, through GO and Pathway annotations, it was found that COL1A2 was involved in the biological processes of NAD metabolic salvage pathway, cell and cell signal transduction, circadian rhythm regulation and so on. Finally, through the construction of overexpression and knockdown cell lines in glioblastoma cell lines U87 and T98, scratch experiments and transwell cell function experiments confirmed that COL1A2 can significantly promote the migration and invasion of glioblastoma cell lines. Conclusions:Low expression levels of COL1A2 were significantly associated with improved prognosis in patients with glioma. Knockdown and overexpression of COL1A2 on glioblastoma cell lines U87 and T98 manifested that COL1A2 can promote glioblastoma cell lines migration and invasion ability. Based on the above results, COL1A2 may be used as an indicator for judging the prognosis of glioblastoma and as a potential biological target for therapy.

16.
Article in Chinese | WPRIM | ID: wpr-930044

ABSTRACT

Objective:To investigate the related factors of early postoperative recurrence of glioma patients and to establish a prediction model for early recurrence.Methods:A total of 94 patients with pathologically diagnosed glioma treated at Affiliated Hospital of Xuzhou Medical University from August 2014 to July 2016 were retrospectively analyzed. Kaplan-Meier method was used for survival analysis and log-rank test was carried out. Cox proportional risk regression model was used to analyze the clinical factors influencing early postoperative recurrence of glioma patients, and the prediction model of early recurrence was established.Results:The recurrence rates were 26.6% (25/94) and 39.4% (37/94) at 12 months and 24 months after operation, respectively. Univariate analysis showed that age ( χ2=9.59, P=0.008), degree of tumor resection ( χ2=14.26, P<0.001), Karnofsky performance status (KPS) score ( χ2=19.41, P<0.001), radiochemotherapy ( χ2=5.10, P=0.024) and pathological grade ( χ2=5.83, P=0.016) were significantly associated with early postoperative recurrence in glioma patients. Multivariate Cox proportional hazards regression model analysis showed that pathological grade ( OR=2.64, 95% CI: 1.75-3.97, P<0.001), degree of resection ( OR=0.34, 95% CI: 0.19-0.62, P<0.001) and radiochemotherapy ( OR=2.58, 95% CI: 1.34-4.99, P=0.005) were independent factors influencing early postoperative recurrence in glioma patients. The risk function model expression of early recurrence in glioma patients was h(t)=h 0exp(0.970X 1-1.081X 2+ 0.949X 3). X 1, X 2 and X 3 represented pathological grade, resection degree and radiochemotherapy respectively. Conclusion:High grade pathology and the absence of radiochemotherapy are independent predictors of early recurrence in glioma patients, and complete tumor resection can reduce the risk of early recurrence and improve the prognosis. The model of early recurrence prediction can provide some reference for clinical diagnosis and treatment.

17.
International Journal of Surgery ; (12): 57-62,F4, 2022.
Article in Chinese | WPRIM | ID: wpr-929969

ABSTRACT

Glioma has a high malignant degree, high recurrence rate and poor prognosis. We analyzed signal pathway of the Hippo/YAP, PI3K/AKT/mTOR, miRNA, WNT/β-catenin, Notch, Hedgehog, TGF-β and the mechanism of key enzymes in glioma. It is concluded that YAP1 inhibitor may become an effective target for the treatment of glioma in the future.Inhibiting PI3K/AKT/mTOR, Shh, Wnt/β-Catenin and HIF-1α can reduce the migration ability and drug resistance of tumor cells to improve the prognosis of glioma. The analysis shows that Notch1 and Sox2 have a positive feedback regulation mechanism, and Notch4 predicts the malignant degree of glioma. In this way, notch can not only be treated for glioma stem cells in clinic, but also be used as an evaluation index to evaluate the prognosis, and provide an exploratory attempt for the direction of glioma treatment. MiRNA plays an important role in diagnosis, and in the treatment of glioma, it can play a further role with the delivery of nanoparticles and TMZ. It is believed that these studies will help us to have a deeper understanding of glioma, so that we will find new and better treatment schemes to gradually conquer the problem of glioma.

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Acta Pharmaceutica Sinica B ; (6): 1100-1125, 2022.
Article in English | WPRIM | ID: wpr-929369

ABSTRACT

Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

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Article in Chinese | WPRIM | ID: wpr-941019

ABSTRACT

OBJECTIVE@#To explore the effect of atorvastatin (AVT) on biological behaviors and the miR-146a/PI3K/Akt signaling pathway in human glioma cells.@*METHODS@#Human glioma U251 cells were treated with 8.0 μmol/L AVT or transfected with a miR-146a inhibitor or a negative control fragment (miR-146a NC) prior to AVT treatment. RT-PCR was used to detect miR-146a expression in the cells, and the changes in cell proliferation rate, apoptosis, cell invasion and migration were detected using MTT assay, flow cytometry, and Transwell assay. Western blotting was performed to detect the changes in cellular expressions of proteins in the PI3K/Akt signaling pathway.@*RESULTS@#AVT treatment for 48 h resulted in significantly increased miR-146a expression and cell apoptosis (P < 0.01) and obviously lowered the cell proliferation rate, invasion index, migration index, and expressions of p-PI3K and p-Akt protein in U251 cells (P < 0.01). Compared with AVT treatment alone, transfection with miR-146a inhibitor prior to AVT treatment significantly reduced miR-146a expression and cell apoptosis (P < 0.01), increased the cell proliferation rate, promoted cell invasion and migration, and enhanced the expressions of p-PI3K and p-Akt proteins in the cells (P < 0.01); these effects were not observed following transfection with miR-146a NC group (P>0.05).@*CONCLUSION@#AVT can inhibit the proliferation, invasion and migration and promote apoptosis of human glioma cells possibly by up-regulating miR-146a expression and inhibiting the PI3K/Akt signaling pathway.


Subject(s)
Apoptosis , Atorvastatin/pharmacology , Cell Line, Tumor , Cell Proliferation , Glioma/pathology , Humans , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
20.
Article in Chinese | WPRIM | ID: wpr-940592

ABSTRACT

ObjectiveTo investigate the molecular mechanism of cordycepin inhibiting proliferation and promoting apoptosis of human hepatoma cells (HCCs). MethodGlioma-associated oncogene homolog 1 (Gli1) gene was silenced by small interfering RNA (siRNA) and transfected into SMMC-7721 cells, and then cell proliferation was detected by cell counting kit-8 (CCK-8) assay and cell cloning assay. SMMC-7721 cells were treated with different concentration of cordycepin, and the cell proliferation and apoptosis were examined. The expression of Gli1 and the downstream related genes was determined by Real-time polymerase chain reaction(PCR) and Western blot. ResultThe mRNA and protein expression of Gli1 in SMMC-7721 cells was higher than that in normal liver cells (P<0.01). The proliferation rate of SMMC-7721 with silenced Gli1 decreased at 72 and 96 h (P<0.05, P<0.01), and the colony-forming capacity lowered (P<0.01) compared with those in the blank group. Compared with the control, 80 μmol·L-1 and 120 μmol·L-1 cordycepin significantly inhibited the proliferation of SMMC-7721 cells at 72 and 96 h (P<0.05, P<0.01), and promoted the apoptosis of them (P<0.01). Moreover, 80 and 120 μmol·L-1 cordycepin restrained the mRNA and protein expression of Gli1 in SMMC7721 cells (P<0.05, P<0.01). At 120 μmol·L-1, cordycepin led to the decrease in the mRNA and protein levels of B-cell lymphoma-2 (Bcl-2) and c-Myc (P<0.05, P<0.01), and the increase in the mRNA and protein expression of cysteine-aspartic acid protease-3 (Caspase-3) (P<0.05). ConclusionGli1 is highly expressed in HCCs, and cordycepin can suppress the proliferation and enhance the apoptosis of HCCs by regulating Gli1 and the downstream apoptosis-related factors.

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