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This report describes a unique case of vascular Ehlers-Danlos syndrome (vEDS) characterized by multiple spontaneous direct carotid-cavernous sinus fistulas (CCF). The patient initially presented with ocular symptoms and was effectively treated with transarterial coil embolization. Five years later, the patient developed recurrent contralateral CCF that required complex endovascular techniques. Genetic testing identified a novel mutation in the COL3A1 gene, confirming the diagnosis of vEDS. This case report provides a near-term perspective on the identification of structural abnormalities in the COL3A1 protein to ensure the safety of endovascular therapy for patients with vEDS.
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Fístula del Seno Cavernoso de la Carótida , Síndrome de Ehlers-Danlos Tipo IV , Síndrome de Ehlers-Danlos , Embolización Terapéutica , Humanos , Fístula del Seno Cavernoso de la Carótida/diagnóstico por imagen , Fístula del Seno Cavernoso de la Carótida/genética , Colágeno Tipo III/genética , Síndrome de Ehlers-Danlos/complicaciones , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , MutaciónRESUMEN
Glioblastoma, a type of brain cancer, is one of the most aggressive and lethal types of malignancy. The present study shows that JCI-20679, an originally synthesized mitochondrial complex I inhibitor, enhances the anti-proliferative effects of suboptimal concentrations of the clinically used chemotherapeutic drug temozolomide in glioblastoma cells. Analysis of the effects of temozolomide combined with JCI-20679 using isobologram and combination index methods demonstrated that the combination had synergistic effects in murine and human glioblastoma cells. We found that JCI-20679 inhibited the temozolomide-mediated induction of autophagy that facilitates cellular survival. The autophagy induced by temozolomide increased ATP production, which confers temozolomide resistance in glioblastoma cells. JCI-20679 blocked temozolomide-mediated increases in ATP levels and increased the AMP/ATP ratio. Furthermore, JCI-20679 enhanced the therapeutic effects of temozolomide in an orthotopic transplantation model of glioblastoma. These results indicate that JCI-20679 may be promising as a novel agent for enhancing the efficacy of temozolomide against glioblastoma.
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Autofagia , Glioblastoma , Temozolomida , Animales , Humanos , Adenosina Trifosfato/metabolismo , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Glioblastoma/patología , Ratones SCID , Temozolomida/farmacologíaRESUMEN
BACKGROUND: Intracerebral hemorrhage (ICH) is a significant cause of death and disabilities. Recently, cell therapies using mesenchymal stem cells have been shown to improve ICH-induced neurobehavioral deficits. Based on these findings, we designed this study to evaluate the therapeutic efficacy and underlying mechanisms by which human amnion-derived stem cells (hAMSCs) would ameliorate neurobehavioral deficits of ICH-bearing hosts. METHODS: hAMSCs were induced from amnia obtained by cesarean section and administered intravenously to ICH-bearing mice during the acute phase. The mice were then subject to multitask neurobehavioral tests at the subacute phase. We attempted to optimize the dosage and timing of the hAMSC administrations. In parallel with the hAMSCs, a tenfold higher dose of human adipose-derived stem cells (ADSCs) were used as an experimental control. Specimens were obtained from the ICH lesions to conduct immunostaining, flow cytometry, and Western blotting to elucidate the underlying mechanisms of the hAMSC treatment. RESULTS: The intravenous administration of hAMSCs to the ICH-bearing mice effectively improved their neurobehavioral deficits, particularly when the treatment was initiated at Day 1 after the ICH induction. Of note, the hAMSCs promoted clinical efficacy equivalent to or better than that of hADSCs at 1/10 the cell number. The systemically administered hAMSCs were found in the ICH lesions along with the local accumulation of macrophages/microglia. In detail, the hAMSC treatment decreased the number of CD11b+CD45+ and Ly6G+ cells in the ICH lesions, while splenocytes were not affected. Moreover, the hAMSC treatment decreased the number of apoptotic cells in the ICH lesions. These results were associated with suppression of the protein expression levels of macrophage-related factors iNOS and TNFα. CONCLUSIONS: Intravenous hAMSC administration during the acute phase would improve ICH-induced neurobehavioral disorders. The underlying mechanism was suggested to be the suppression of subacute inflammation and apoptosis by suppressing macrophage/microglia cell numbers and macrophage functions (such as TNFα and iNOS). From a clinical point of view, hAMSC-based treatment may be a novel strategy for the treatment of ICH.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Amnios/metabolismo , Amnios/patología , Animales , Apoptosis , Hemorragia Cerebral/metabolismo , Cesárea , Femenino , Humanos , Inflamación/metabolismo , Inflamación/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Ratones , EmbarazoRESUMEN
CCL28 induces the migration of IgA Ab-secreting cells (ASCs) via CCR10 and also displays a potent antimicrobial activity in vitro. To explore the role of CCL28 in vivo, we generated CCL28-deficient mice. The mice exhibited a significant reduction and abnormal distribution of IgA ASCs in the lamina propria of the colon. The concentrations of total and Ag-specific IgA in the fecal extracts of CCL28-deficient mice were also drastically reduced. The average amount of IgA secreted by a single IgA ASC derived from the colon was also substantially reduced in CCL28-deficient mice. Furthermore, CCL28 was found to significantly increase the average amount of IgA secreted by a single IgA ASC derived from the colon in vitro. In contrast, the generation of IgA ASCs in Peyer's and cecal patches was not significantly impaired in CCL28-deficient mice. We also found a relative increase in the Class Bacilli in the fecal extracts of CCL28-deficient mice and demonstrated a potent antimicrobial activity of CCL28 against Bacillus cereus and Enterococcus faecalis, both of which belong to Class Bacilli. Thus, CCL28 may also suppress the outgrowth of some bacterial species by its direct antimicrobial activity. Finally, CCL28-deficient mice exhibited a highly aggravated dextran sodium sulfate-induced colitis that was ameliorated by pretreatment with antibiotics. Collectively, CCL28 plays a pivotal role in the homing, distribution, and function of IgA ASCs in the colon and may also affect the intestinal microbiota through its direct antimicrobial activity.
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Quimiocinas CC/deficiencia , Colon/inmunología , Colon/metabolismo , Colon/microbiología , Microbioma Gastrointestinal , Inmunoglobulina A Secretora/inmunología , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Alcadienos , Animales , Quimiocinas CC/metabolismo , Colitis/etiología , Colitis/metabolismo , Colitis/patología , Marcación de Gen , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Ratones , Ratones NoqueadosRESUMEN
Hepatitis B virus (HBV) infects the liver, causing cirrhosis and cancer. In developed countries, five international guidelines have been used to make a decision for the management of patients with chronic HBV infection. In this review, since the guidelines were established by clinical and epidemiological data of developed countries, we aimed to evaluate whether (1) HBV patient profiles of developing countries are similar to developed countries, and (2) which guideline can be applicable to resource-limited developing countries. First, as an example of the most recent data of HBV infections among developing countries, we evaluated the national HBV viral load study in Nepal, which were compared with the data from other developing countries. In Nepal, the highest number of patients had viral loads of 20-2000 IU/mL (36.7%) and belonged to the age group of 21-30 years; HBV epidemiology in Nepal, based on the viral loads, gender, and age groups was similar to those of not only other developing countries but also developed countries. Next, we reviewed five international HBV treatment guidelines of the World Health Organization (WHO), American Association for the Study of Liver Diseases (AASLD), National Institute for Health and Care Excellence (NICE), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). All guidelines require the viral load and alanine aminotransferase (ALT) levels for decision making. Although four guidelines recommend elastography to assess liver cirrhosis, the WHO guideline alternatively recommends using the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), which is inexpensive and conducted routinely in most hospitals. Therefore, in resource-limited developing countries like Nepal, we recommend the WHO guideline for HBV treatment based on the viral load, ALT, and APRI information.
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BACKGROUND: Percutaneous sensitization is associated with various allergic diseases, including asthma and food allergies. However, the immunologic mechanisms underlying how the skin regulates percutaneous sensitization are still unclear. OBJECTIVE: We aimed to investigate whether and how CD4+Foxp3+ regulatory T (Treg) cells residing in the skin regulate percutaneous sensitization in the skin. METHODS: Selective reduction of numbers of cutaneous Treg cells was achieved by means of intradermal injection of diphtheria toxin into the ear skin of Foxp3DTR mice, in which Treg cells specifically express the diphtheria toxin receptor fused with green fluorescent protein. RESULTS: Thirty percent to 40% of cutaneous Treg cells were capable of IL-10 production in both mice and human subjects. Selective reduction of cutaneous Treg cells at the sensitization site promoted migration of antigen-bearing dendritic cells (DCs) to the draining lymph nodes (dLNs). Accordingly, sensitization through the skin with reduced numbers of Treg cells led to enhanced antigen-specific immune responses in the dLNs, including both effector T-cell differentiation and T cell-dependent B-cell responses, such as the development of germinal center B cells expressing IgG1 and IgE. Furthermore, antigen-bearing cutaneous DC migration was enhanced in mice with IL-10 deficiency restricted to the cutaneous Treg cell compartment, suggesting an important role of cutaneous IL-10+ Treg cells in limiting percutaneous sensitization. Treg cells with a skin-homing phenotype in skin dLNs expressed high levels of IL-10, suggesting that they contribute to renewal and maintenance of the cutaneous IL-10+ Treg cell population. CONCLUSION: Skin-resident Treg cells limit percutaneous sensitization by suppressing antigen-bearing DC migration through in situ IL-10 production.
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Linfocitos B/inmunología , Células Dendríticas/inmunología , Interleucina-10/metabolismo , Piel/inmunología , Linfocitos T Reguladores/inmunología , Administración Cutánea , Animales , Presentación de Antígeno , Movimiento Celular , Células Cultivadas , Factores de Transcripción Forkhead/metabolismo , Humanos , Inmunización , Inmunoglobulina E/metabolismo , Interleucina-10/genética , Activación de Linfocitos , Ratones , Ratones Noqueados , Ratones TransgénicosRESUMEN
INTRODUCTION: The introduction of systemic chemotherapy for advanced hepatocellular carcinoma in recent years has led to the prediction that cases of brain metastases from hepatocellular carcinoma will increase. However, because brain metastases from hepatocellular carcinoma are relatively rare, the characteristics of this pathology are poorly understood. METHODS: We carried out a multicenter retrospective study to verify the characteristics of brain metastases from hepatocellular carcinoma in Japan. RESULTS: A total of 38 patients were enrolled and patient characteristics were poor general condition in many patients due to the progression of primary cancers. Stereotactic radiosurgery/stereotactic radiotherapy alone was the most common treatment (39.5%), with best supportive care provided for 10.5%. Median survival was 6 months, the neurological death rate was 28%, and the rate of brain hemorrhage was high (39.5%). Overall survival was analyzed for correlations with age, etiology of chronic liver disease, albumin-bilirubin (ALBI) grade, RPA classification, control of the primary tumor, number of brain metastases, brain hemorrhage, surgical resection, and radiotherapy. In multivariate analysis, ALBI grade, number of brain metastases and brain hemorrhage showed statistically significant correlation. CONCLUSIONS: A multivariate analysis extracted three items-ALBI grade, number of brain metastases, and brain hemorrhage-as prognostic factors for survival of brain metastases from hepatocellular carcinoma.
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Neoplasias Encefálicas/mortalidad , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/mortalidad , Radiocirugia/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Cartilage tissue is characterized by its poor regenerative properties, and the clinical performance of cartilage grafts to replace cartilage defects has been unsatisfactory. Recently, cartilage regeneration with mature chondrocytes and stem cells has been developed and applied in clinical settings. However, there are challenges with the use of mature chondrocytes and stem cells for tissue regeneration, including the high costs associated with the standard stem cell isolation methods and the decreased cell viability due to cell manipulation. Previous studies demonstrated that cartilage can be regenerated from chondrocyte clusters that contain stem cells. Based upon some of the existing techniques, the goal of this study was to develop a novel and practical method to induce cartilage regeneration. A microslicer device was developed to process cartilage tissues into micron-size cartilage (microcartilage) in a minimally invasive manner. We evaluated microcartilage sizes and demonstrated 100-400 µm as optimal for generating a high cell yield with collagenase digestion. In addition, autologous intrafascial implantation of the composites of microcartilage and an absorbable scaffold with a slow-release system of basic fibroblast growth factor (bFGF) was carried out to induce cartilage regeneration. Our results demonstrated that the extent of bFGF diffusion depends on the size of microcartilage, and that cartilage regeneration was induced most effectively with 100 µm of microcartilage via SOX5 upregulation. These findings suggest that cartilage regeneration is possible with microcartilage as a source of cells without ex vivo cell expansion.
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Cartílago Articular/efectos de los fármacos , Cartílago Articular/fisiología , Preparaciones de Acción Retardada/química , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Regeneración/efectos de los fármacos , Andamios del Tejido/química , Animales , Cartílago Articular/ultraestructura , Condrogénesis/efectos de los fármacos , Perros , Femenino , Factor 2 de Crecimiento de Fibroblastos/farmacología , Ingeniería de Tejidos/métodosRESUMEN
BACKGROUND: In experimental models, inhibition of high-mobility group box-1 (HMGB1) signaling has been reported to protect against the sequelae of ischemic stroke. Here, we determined the clinical significance of serum HMGB1 levels in patients with acute ischemic stroke. METHODS: We enrolled 183 patients (114 men, 69 women; mean age: 72.7 years) over 6 consecutive months. On admission and day 7, we recorded the National Institutes of Health Stroke Scale scores and measured serum high-sensitivity C-reactive protein (hs-CRP) and HMGB1 levels. Stroke volumes were estimated using diffusion-weighted magnetic resonance imaging performed on admission. One year later, clinical outcome was assessed using the modified Rankin Scale (mRS). RESULTS: Serum hs-CRP and HMGB1 levels in patients with ischemic stroke were increased relative to healthy controls (both P < .01). On day 7, hs-CRP, but not HMBG1, levels had increased significantly relative to levels at admission (P < .01 and .54, respectively). Higher HMGB1, but not hs-CRP, levels at day 7 correlated with larger stroke volumes (P < .01 and .28, respectively). HMGB1 levels did not significantly differ between stroke subtypes. Multiple logistic regression analysis indicated that a serum HMGB1 level higher than 7.5 ng/mL was an independent risk factor for poor prognosis, defined as a 1-year mRS score of 3-6 (odds ratio, 2.34; 95% confidence interval, 1.02-5.38). CONCLUSIONS: Acute ischemic stroke is associated with elevated serum HMGB1 levels, and HMGB1 levels at admission independently predict poor outcome at 1 year. These results suggest that HMGB1 quantification provides more accurate prognostic information after ischemic stroke.
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Isquemia Encefálica/sangre , Proteína HMGB1/sangre , Accidente Cerebrovascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Encéfalo/diagnóstico por imagen , Isquemia Encefálica/diagnóstico por imagen , Proteína C-Reactiva/metabolismo , Imagen de Difusión por Resonancia Magnética , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
BACKGROUND: We verified the effectiveness of training in endoscopic endonasal transsphenoidal surgery (eETSS) techniques using chicken eggs and a skull model. METHODS: We verified the area of eggshell removed by drilling when five residents and four experts used the chicken eggs and a skull model. RESULTS: When residents performed drilling on 10 eggs, a mean (± standard deviation [SD]) area of 31.2 ± 17.5 mm2 was removed from the first egg, and 104.8 ± 3.3 mm2 from the tenth and final egg, representing an increase in area and a decrease in SD. The experts performed the same drilling operation on a single egg, and removed a mean area of 257± 31.7 mm2. These results demonstrated that skills improved as a result of this training, and suggested that this method was also capable of overcoming the initial individual differences in the amount of force applied and ability. An obvious difference between residents and experts was seen in the area removed (p = 0.00011); however, this was attributed to differences in endoscopic manipulation, rather than drilling skill. CONCLUSION: Our findings suggest that this training method could be adequate for acquiring eETSS techniques. Although experts showed superior endoscopic manipulation, residents may also be able to acquire adequate endoscopic skills through further training, and our training method appears to offer an effective means of improving eETSS techniques.
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Competencia Clínica , Huevos , Endoscopía/métodos , Cavidad Nasal/cirugía , Neurocirugia/educación , Procedimientos Neuroquirúrgicos/métodos , Cráneo/cirugía , Hueso Esfenoides/cirugía , Animales , Pollos , Cáscara de Huevo , Humanos , Internado y ResidenciaRESUMEN
Nattokinase (NK), also known as subtilisin NAT (EC 3.4.21.62), is a serine protease produced by Bacillus subtilis natto that has anti-inflammatory and fibrinolytic properties. To study whether NK prevents the progression of pathological changes in diabetes as an inflammatory disease, we examined the effect of NK on pathological conditions in streptozotocin (STZ)-induced diabetic rats using the following parameters: fasting blood glucose (glucose), total plasma protein (TP), creatinine, histopathology of renal corpuscles and tubules, advanced glycation end products (AGEs), and C-reactive protein (CRP). STZ-administered rats were maintained on a basic diet (CE-2) as control, low-NK diet (containing 0.2 mg NK/g diet), and high-NK diet (0.6 mg NK/g diet) for 14 days. High-dose NK significantly inhibited both glycogen deposition in the renal tubules and increase in the circulating AGE levels without downregulating glucose levels. Compared with the control group, the group treated with the high-NK diet presented a significant inhibition of the increase in the circulating CRP level on day 7 after the beginning of the treatment. However, the CRP level in the NK-H group reached the same level as that in the control group on Day 14. AGEs are known to induce CRP expression in hepatocytes, but the increase in CRP levels in our animal model was independent on the circulating AGE levels. In contrast, low-dose NK did not suppress changes in these parameters. Our present study suggests that NK suppresses glycogen deposition in renal tubules in a dose-dependent manner by the downregulation of AGE formation under hyperglycaemia in the rats with STZ-induced short-term diabetes. However, it is unclear whether this downregulation is caused by intact NK or peptides derived from NK during its digestion in the digestive tract.
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BACKGROUND/AIM: Resection of brain metastases is a well-established treatment modality that can prolong the survival of patients for whom surgery is indicated. Whole-brain radiotherapy (WBRT) has been the standard postoperative therapy. In recent years, however, clinicians have increasingly avoided WBRT due to its associated adverse events. This study investigated the impact of postoperative WBRT and systemic chemotherapy as prognostic factors on the survival of patients who had undergone resection of brain metastases. PATIENTS AND METHODS: The study subjects were 172 patients who underwent surgical resection for brain metastases. Comparative analyses of survival after WBRT and systemic chemotherapy were performed. RESULTS: Postoperative WBRT had no survival-prolonging effect, whereas postoperative systemic chemotherapy prolonged survival. A comparison based on the number of systemic chemotherapy regimens administered prior to surgery showed that fewer regimens correlated with a better prognosis. CONCLUSION: The addition of WBRT after surgical resection of brain metastases is no longer a standard treatment strategy and systemic chemotherapy after surgery is a positive prognostic factor.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/radioterapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Pronóstico , Irradiación Craneana/métodos , Terapia Combinada , Anciano de 80 o más AñosRESUMEN
BACKGROUND/AIM: Glioblastoma is the most frequent type of adult-onset malignant brain tumor and has a very poor prognosis. Glioblastoma stem cells have been shown to be one of the mechanisms by which glioblastoma acquires therapy resistance. Therefore, there is a need to establish novel therapeutic strategies useful for inhibiting this cell population. γ-Glutamylcyclotransferase (GGCT) is an enzyme involved in the synthesis and metabolism of glutathione, which is highly expressed in a wide range of cancer types, including glioblastoma, and inhibition of its expression has been reported to have antitumor effects on various cancer types. The aim of this study was to clarify the function of GGCT in glioblastoma stem cells. MATERIALS AND METHODS: We searched for pathways affected by GGCT overexpression in mouse embryonic fibroblasts NIH-3T3 by comprehensive gene expression analysis. Knockdown of GGCT and overexpression of desert hedgehog (DHH), a representative ligand of the pathway, were performed in glioblastoma stem cells derived from a mouse glioblastoma model. RESULTS: GGCT overexpression activated the hedgehog pathway. Knockdown of GGCT inhibited proliferation of glioblastoma stem cells and reduced expression of DHH and the downstream target GLI family zinc finger 1 (GLI1). DHH overexpression significantly restored the growth-suppressive effect of GGCT knockdown. CONCLUSION: High GGCT expression is important for expression of DHH and activation of the hedgehog pathway, which is required to maintain glioblastoma stem cell proliferation. Therefore, inhibition of GGCT function may be useful in suppressing stemness of glioblastoma stem cells accompanied by activation of the hedgehog pathway.
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Proliferación Celular , Regulación hacia Abajo , Glioblastoma , Proteínas Hedgehog , Células Madre Neoplásicas , gamma-Glutamilciclotransferasa , Animales , Glioblastoma/patología , Glioblastoma/genética , Glioblastoma/metabolismo , Ratones , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , gamma-Glutamilciclotransferasa/metabolismo , gamma-Glutamilciclotransferasa/genética , Humanos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Técnicas de Silenciamiento del Gen , Regulación Neoplásica de la Expresión Génica , Transducción de SeñalRESUMEN
BACKGROUND/AIM: The prognosis of patients with brain metastases (BMs) originating from lung cancer remains poor, despite advancements in treatment strategies. The role of tertiary lymphoid structures (TLSs) within the tumor immune microenvironment of BMs has not been extensively explored. PATIENTS AND METHODS: This study utilized patient-derived clinical samples from 17 patients with histologically confirmed BMs of lung cancer, undergoing surgical resection. Immunohistochemistry was employed to analyze the presence and characteristics of TLS and tumor-infiltrating lymphocytes (TILs) within BM tissues, correlating these with clinical outcomes. RESULTS: TLSs, albeit in their immature form, were identified within BM tissues, distinguishing them from their mature counterparts in primary lung cancer tissues. A significant correlation between TLS density (but not TIL density) and improved postoperative survival was observed, underscoring the potential of TLS density as an independent prognostic marker. Furthermore, TLS density did not correlate with the Graded Prognostic Assessment (GPA) index, suggesting its unique prognostic value beyond conventional predictors. CONCLUSION: Our findings reveal the presence of TLSs in lung cancer-derived BMs and highlight their prognostic significance, independent of the GPA index. The identification of TLS within the unique central nervous system tumor microenvironment offers new insights into the immune landscape of BMs and suggests potential avenues for immunotherapeutic interventions targeting these structures to improve patient outcomes.
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Neoplasias Encefálicas , Neoplasias Pulmonares , Linfocitos Infiltrantes de Tumor , Estructuras Linfoides Terciarias , Microambiente Tumoral , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/inmunología , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Pronóstico , Masculino , Femenino , Persona de Mediana Edad , Microambiente Tumoral/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , AncianoRESUMEN
BACKGROUND/AIM: Individuals with Down syndrome (DS), attributed to triplication of human chromosome 21 (Hsa21), exhibit a reduced incidence of solid tumors. However, the prevalence of glioblastoma among individuals with DS remains a contentious issue in epidemiological studies. Therefore, this study examined the gliomagenicity in Ts1Cje mice, a murine model of DS. MATERIALS AND METHODS: We employed the Sleeping Beauty transposon system for the integration of human oncogenes into cells of the subventricular zone of neonatal mice. RESULTS: Notably, Sleeping Beauty-mediated de novo murine gliomagenesis was significantly suppressed in Ts1Cje mice compared to wild-type mice. In glioblastomas of Ts1je mice, we observed an augmented presence of M1-polarized tumor-associated macrophages and microglia, known for their anti-tumor efficacy in the early stage of tumor development. CONCLUSION: Our findings in a mouse model of DS offer novel perspectives on the diminished gliomagenicity observed in individuals with DS.
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Síndrome de Down , Ratones , Animales , Humanos , Síndrome de Down/genética , Síndrome de Down/patología , Modelos Animales de EnfermedadRESUMEN
BACKGROUND/AIM: Glioblastoma is the most common and aggressive malignant brain tumor in adults, and glioblastoma stem cells (GSCs) contribute to treatment resistance and recurrence. Inhibition of Stat5b in GSCs suppresses cell proliferation and induces apoptosis. Herein, we investigated the mechanisms of growth inhibition by Stat5b knockdown (KD) in GSCs. MATERIALS AND METHODS: GSCs were established from a murine glioblastoma model in which shRNA-p53 and EGFR/Ras mutants were induced in vivo using a Sleeping Beauty transposon system. Microarray analyses were performed on Stat5b-KD GSCs to identify genes that are differentially expressed downstream of Stat5b. RT-qPCR and western blot analyses were used to determine Myb levels in GSCs. Myb-overexpressing GSCs were induced by electroporation. Proliferation and apoptosis were evaluated by a trypan blue dye exclusion test and annexin-V staining, respectively. RESULTS: MYB, which is involved in the Wnt pathway, was identified as a novel gene whose expression was down-regulated by Stat5b-KD in GSCs. Both MYB mRNA and protein levels were down-regulated by Stat5b-KD. Overexpression of Myb rescued cell proliferation that was suppressed by Stat5b-KD. Furthermore, Stat5b-KD-induced apoptosis in GSCs was significantly inhibited by Myb overexpression. CONCLUSION: Down-regulation of Myb mediates Stat5b-KD-induced inhibition of proliferation and induction of apoptosis in GSCs. This may represent a promising novel therapeutic strategy against glioblastoma.
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Glioblastoma , Adulto , Humanos , Animales , Ratones , Encéfalo , Apoptosis , Proliferación Celular , Células Madre , Factor de Transcripción STAT5RESUMEN
Background Coronavirus disease 2019 and other viruses are transmissible by aerosols and droplets from infected persons. This study aimed to develop a portable device that can trap droplets and deactivate viruses, and verify whether the device in an enclosed room can suction droplets and sanitize them using a filter and an ultraviolet-C (UVC) light-emitting diode. Materials and methods The portable device was evaluated by placing it 50 cm away from the droplet initiation point. A particle image velocimetry laser dispersed into a sheet form was used to visualize the droplets splashed on the irradiated sagittal plane and captured using a charge-coupled device camera at 60 frames per second. The images were overlaid and calculated to determine the percentage of the droplets beyond the portable device. Droplets with a particle size larger than 50 µm that dispersed and were deposited more than 100 cm away were measured using a water-sensitive paper. The effect of UVC sanitization on viruses captured by a high-efficiency particulate air (HEPA) filter was determined using a plaque assay. Results The percentage of droplets was 13.4% and 1.1% with the portable device OFF and ON, respectively, indicating a 91.8% reduction. The deposited droplets were 86 pixels and 26 pixels with the portable device OFF and ON, respectively, indicating a 68.7% reduction. The UVC deactivated more than 99% of the viruses on the HEPA filter surface in 5 minutes. Conclusions Our novel portable device can suck and fall the dispersed droplets, and an active virus was not observed on the exhaust side.
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How often do intracranial epidermoid cysts occur?Is a coronary incision necessary?What are the steps of the procedure, difficulties encountered, and process for circumventing those difficulties?What is the follow-up protocol and outcome?
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Preoperative angiography in glioblastoma (GBM) often shows arteriovenous shunts and early venous filling (EVF). Here, we investigated the clinical implications of EVF in GBM as a prognostic and vascular mimicry biomarker. In this retrospective multicenter study, we consecutively enrolled patients who underwent angiography with a GBM diagnosis between 1 April 2013 and 31 March 2021. The primary and secondary endpoints were the differences in overall survival (OS) and progression-free survival (PFS), respectively, between cases with and without EVF. Of the 133 initially enrolled patients, 91 newly diagnosed with GBM underwent preoperative angiography and became the study population. The 6-year OS and PFS were significantly worse in the EVF than in the non-EVF group. Moreover, 20 GBM cases (10 with EVF and 10 without EVF) were randomly selected and evaluated for histological vascular mimicry. Except for two cases that were difficult to evaluate, the EVF group had a significantly higher frequency of vascular mimicry than the non-EVF group (0/8 vs. 5/10, p = 0.04). EVF on preoperative angiography is a robust prognostic biomarker for GBM and may help detect cases with a high frequency of histological vascular mimicry.
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BACKGROUND/AIM: In pathology, the digitization of tissue slide images and the development of image analysis by deep learning have dramatically increased the amount of information obtainable from tissue slides. This advancement is anticipated to not only aid in pathological diagnosis, but also to enhance patient management. Deep learning-based image cytometry (DL-IC) is a technique that plays a pivotal role in this process, enabling cell identification and counting with precision. Accurate cell determination is essential when using this technique. Herein, we aimed to evaluate the performance of our DL-IC in cell identification. MATERIALS AND METHODS: Cu-Cyto, a DL-IC with a bit-pattern kernel-filtering algorithm designed to help avoid multi-counted cell determination, was developed and evaluated for performance using tumor tissue slide images with immunohistochemical staining (IHC). RESULTS: The performances of three versions of Cu-Cyto were evaluated according to their learning stages. In the early stage of learning, the F1 score for immunostained CD8+ T cells (0.343) was higher than the scores for non-immunostained cells [adenocarcinoma cells (0.040) and lymphocytes (0.002)]. As training and validation progressed, the F1 scores for all cells improved. In the latest stage of learning, the F1 scores for adenocarcinoma cells, lymphocytes, and CD8+ T cells were 0.589, 0.889, and 0.911, respectively. CONCLUSION: Cu-Cyto demonstrated good performance in cell determination. IHC can boost learning efficiencies in the early stages of learning. Its performance is expected to improve even further with continuous learning, and the DL-IC can contribute to the implementation of precision oncology.