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BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined. METHODS: We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG). RESULTS: The median age of the 268 patients was 62 years (range: 17-85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% confidence interval [CI], 19.9-29.1), and the median overall survival (OS) was 34.5 months (95% CI, 22.9-46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9 cm3 and 135.0 ± 152.7 g, respectively. Patients with a baseline TMTV ≥17.0 cm3 had significantly shorter OS (12.5 vs. 74.0 months, p=0.011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs. 46.0 months, p=0.001) and OS (median: 21.0 vs. 62.0 months, p=0.002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (p=0.130) or OS (p=0.540). CONCLUSION: Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.
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Objective: Stereoelectroencephalography (SEEG) is increasingly being recognized as an important invasive modality for presurgical evaluation of epilepsy. This study focuses on the clinical and technical considerations of SEEG investigations when using conventional frame-based stereotaxy, drawing on institutional experience and a comprehensive review of relevant literature. Methods: This retrospective observational study encompassed the surgical implantation of 201 SEEG electrodes in 16 epilepsy patients using a frame-based stereotactic instrument at a single tertiary-level center. We provide detailed descriptions of the operative procedures and technical nuances for bilateral and multiple SEEG insertions, along with several illustrative cases. Additionally, we present a literature review on the technical aspects of the SEEG procedure, discussing its clinical implications and potential risks. Results: Frame-based SEEG electrode placements were successfully performed through sagittal arc application, with the majority (81.2%) of cases being bilateral and involving up to 18 electrodes in a single operation. The median skin-to-skin operation time was 162 minutes (interquartile range [IQR], 145-200), with a median of 13 minutes (IQR, 12-15) per electrode placement for time efficiency. There were two occurrences (1.0%) of electrode misplacement and one instance (0.5%) of a postoperative complication, which manifested as a delayed intraparenchymal hemorrhage. Following SEEG investigation, 11 patients proceeded with surgical intervention, resulting in favorable seizure outcomes for nine (81.8%) and complete remission for eight cases (72.7%). Conclusion: Conventional frame-based stereotactic techniques remain a reliable and effective option for bilateral and multiple SEEG electrode placements. While SEEG is a suitable approach for selected patients who are strong candidates for epilepsy surgery, it is important to remain vigilant concerning the potential risks of electrode misplacement and hemorrhagic complications.
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OBJECTIVE: Foraminal and extraforaminal lumbar disc herniation (FELDH) is an important pathological condition that can lead to lumbar radiculopathy. The paraspinal muscle-splitting approach introduced by Reulen and Wiltse is a reasonable surgical technique. Minimally invasive procedures using a tubular retractor system have also been introduced. However, surgical treatment is considered more challenging for FELDH than for central or subarticular lumbar disc herniations (LDHs). Some researchers have proposed uniportal extraforaminal endoscopic lumbar discectomy through a posterolateral approach as an alternative for FELDH, but heterogeneous clinical results have been reported. Recently, the biportal endoscopic (BE) paraspinal approach has been suggested as an alternative. The aim of this study was to compare the clinical outcomes of BE and microscopic tubular (MT) paraspinal approaches for decompressive foraminotomy and lumbar discectomy (paraLD) in patients with FELDH. METHODS: Ninety-one consecutive patients with unilateral lumbar radiculopathy and FELDH underwent paraLD. Demographic and perioperative data were collected. Clinical outcomes were evaluated using the visual analog scale (VAS) for back and leg pain, the Oswestry Disability Index (ODI) for spinal disability, and the modified Macnab criteria for patient satisfaction. Postoperative complications and reoperation rates were also evaluated. RESULTS: In total, 76 patients were included in the final analysis. Among them, 43 underwent BE paraLD (group A) and the remaining 33 underwent MT paraLD (group B). The demographic and preoperative data were not statistically different between the groups. All patients showed significant improvements in VAS back, VAS leg, and ODI scores compared with baseline values (p < 0.05). The improvement in VAS back scores was significantly better in group A than in group B on postoperative day 2 (p < 0.001). However, all clinical parameters were comparable between the two groups after postoperative year 1 (p > 0.05). According to the modified Macnab criteria, 86.1% and 72.7% of the patients had excellent or good outcomes in groups A and B, respectively. No intergroup differences were observed (p = 0.367). In addition, there were no differences in the total operation time or amount of surgical drainage. Postoperative complications were not significantly different between the two groups (p = 0.301); however, reoperation rates were significantly higher in group B (p = 0.035). CONCLUSIONS: BE paraLD is an effective treatment for FELDH and is an alternative to MT paraLD. In particular, BE paraLD has advantages of early improvement in postoperative back pain and low reoperation rates.
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PURPOSE: Oligodendrogliomas (ODGs) are a subtype of diffuse lower-grade gliomas with overall survival of > 10 years. This study aims to analyze long-term outcomes and identify prognostic factors in patients with WHO grade 2 ODG. METHODS: We retrospectively reviewed 138 adult patients diagnosed with 1p/19q co-deleted ODG who underwent surgical resection or biopsy between 1994 and 2021, analyzing clinical data, treatment details, and outcomes. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were utilized to identify significant prognostic factors. RESULTS: In the gross total resection (GTR) group, 63 (45.7%) underwent observation and 5 (3.6%) received postoperative treatment; in the non-GTR group, 37 (26.8%) were observed and 33 (23.9%) received postoperative treatment. The median PFS and OS were 6.8 and 18.4 years, respectively. Between adjuvant treatment and observation, there was no significant difference in PFS or OS. However, GTR or STR with less than 10% residual tumor exhibited significantly better PFS and OS compared to PR or biopsy (p = 0.022 and 0.032, respectively). Multivariate analysis revealed that contrast enhancement on MRI was associated with worse PFS (HR = 2.36, p < 0.001) and OS (HR = 5.89, p = 0.001). And the presence of seizures at presentation was associated with improved OS (HR = 0.28, p = 0.006). CONCLUSION: This study underscores favorable long-term outcomes for patients with 1p/19q co-deleted ODG WHO grade 2. Our findings indicate that the EOR plays a crucial role as a significant prognostic factor in enhancing PFS and OS outcomes in WHO grade 2 ODG.
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INTRODUCTION: Cervical cancer presents a significant global health challenge, disproportionately impacting underserved populations with limited access to healthcare. Early detection and effective management are vital in addressing this public health concern. This study focuses on Glyoxalase-1 (GLO1), an enzyme crucial for methylglyoxal detoxification, in the context of cervical cancer. METHODS: We assessed GLO1 expression in cervical cancer patient samples using immunohistochemistry. In vitro experiments using HeLa cells were conducted to evaluate the impact of GLO1 inhibition on cell viability and migration. Single-cell RNA sequencing (scRNA-seq) and gene set variation analysis were utilized to investigate the role of GLO1 in the metabolism of cervical cancer. Additionally, public microarray data were analyzed to determine GLO1 expression across various stages of cervical cancer. RESULTS: Our analysis included 58 cervical cancer patients, and showed that GLO1 is significantly upregulated in cervical cancer tissues compared to normal cervical tissues, independent of pathological findings and disease stage. In vitro experiments indicated that GLO1 inhibition by S-p-bromobenzylglutathione cyclopentyl diester decreased cell viability and migration in cervical cancer cell lines. Analyses of scRNA-seq data and public gene expression datasets corroborated the overexpression of GLO1 and its involvement in cancer metabolism, particularly glycolysis. An examination of expression data from precancerous lesions revealed a progressive increase in GLO1 expression from normal tissue to invasive cervical cancer. CONCLUSIONS: This study highlights the critical role of GLO1 in the progression of cervical cancer, presenting it as a potential biomarker and therapeutic target. These findings contribute valuable insights towards personalized treatment approaches and augment the ongoing efforts to combat cervical cancer. Further research is necessary to comprehensively explore GLO1's potential in clinical applications.
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Biomarcadores de Tumor , Lactoilglutatión Liasa , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Femenino , Lactoilglutatión Liasa/metabolismo , Lactoilglutatión Liasa/genética , Lactoilglutatión Liasa/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Células HeLa , Progresión de la Enfermedad , Movimiento Celular , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Persona de Mediana Edad , Supervivencia Celular/efectos de los fármacos , Adulto , Línea Celular TumoralRESUMEN
The objective of standard guideline for utilization of human lung organoids is to provide the basic guidelines required for the manufacture, culture, and quality control of the lung organoids for use in non-clinical efficacy and inhalation toxicity assessments of the respiratory system. As a first step towards the utilization of human lung organoids, the current guideline provides basic, minimal standards that can promote development of alternative testing methods, and can be referenced not only for research, clinical, or commercial uses, but also by experts and researchers at regulatory institutions when assessing safety and efficacy.
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BACKGROUND: In vitro disease modeling enables translational research by providing insight into disease pathophysiology and molecular mechanisms, leading to the development of novel therapeutics. Nevertheless, in vitro systems have limitations for recapitulating the complexity of tissues, and a single model system is insufficient to gain a comprehensive understanding of a disease. RESULTS: Here we explored the potential of using several models in combination to provide mechanistic insight into hereditary hemorrhagic telangiectasia (HHT), a genetic vascular disorder. Genome editing was performed to establish hPSCs (H9) with ENG haploinsufficiency and several in vitro models were used to recapitulate the functional aspects of the cells that constitute blood vessels. In a 2D culture system, endothelial cells showed early senescence, reduced viability, and heightened susceptibility to apoptotic insults, and smooth muscle cells (SMCs) exhibited similar behavior to their wild-type counterparts. Features of HHT were evident in 3D blood-vessel organoid systems, including thickening of capillary structures, decreased interaction between ECs and surrounding SMCs, and reduced cell viability. Features of ENG haploinsufficiency were observed in arterial and venous EC subtypes, with arterial ECs showing significant impairments. Molecular biological approaches confirmed the significant downregulation of Notch signaling in HHT-ECs. CONCLUSIONS: Overall, we demonstrated refined research strategies to enhance our comprehension of HHT, providing valuable insights for pathogenic analysis and the exploration of innovative therapeutic interventions. Additionally, these results underscore the importance of employing diverse in vitro systems to assess multiple aspects of disease, which is challenging using a single in vitro system.
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OBJECTIVE: Petroclival meningiomas invade Meckel's cave through the porus trigeminus, leading to secondary trigeminal neuralgia. Microsurgery and stereotactic radiosurgery (SRS) are the typical treatment options. This study investigated symptom control, outcomes, and surgical strategies for PC meningioma-induced TN. METHODS: We retrospectively analyzed 28 TN patients with PC meningiomas who underwent microsurgical nerve decompression between January 2021 and February 2023. In all patients undergoing a transpetrosal approach, the porus trigeminus was opened to enable the removal of the entire tumor within Meckel's cave. Clinical outcomes were assessed using the Barrow Neurologic Institute (BNI) pain intensity scale. Risk factors for poor TN outcomes and poor facial numbness were analyzed. RESULTS: Among 28 patients, 21 (75%) underwent the transpetrosal approach, 5 (17.9%) underwent the retrosigmoid approach, and 2 (7.1%) underwent the Dolenc approach. Following microsurgery, 23 patients (82.1%) experienced TN relief without further medication (BNI I or II). TN recurrence occurred in 2 patients (7.1%), and 3 patients (10.7%) did not achieve TN relief. Cavernous sinus invasion was significantly correlated with poor TN outcomes (P = 0.047). A history of previous SRS (P = 0.011) and upper clivus type tumor (P = 0.018) were significantly associated with poor facial numbness. CONCLUSIONS: Microsurgical nerve decompression is effective in improving BNI scores in patients with TN associated with PC meningiomas. Considering the results of our study, the opening of the porus trigeminus can be considered as a suggested procedure in the treatment of PC meningiomas, especially in cases accompanied by TN.
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Neoplasias Meníngeas , Meningioma , Neuralgia del Trigémino , Humanos , Neuralgia del Trigémino/cirugía , Neuralgia del Trigémino/etiología , Meningioma/cirugía , Meningioma/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias Meníngeas/cirugía , Neoplasias Meníngeas/complicaciones , Estudios Retrospectivos , Adulto , Nervio Trigémino/cirugía , Microcirugia/métodos , Neoplasias de la Base del Cráneo/cirugía , Neoplasias de la Base del Cráneo/complicaciones , Procedimientos Neuroquirúrgicos/métodos , Radiocirugia/métodos , Descompresión Quirúrgica/métodos , Resultado del TratamientoRESUMEN
Cisplatin is a chemotherapy drug that causes a plethora of DNA lesions and inhibits DNA transcription and replication, resulting in the induction of apoptosis in cancer cells. However, over time, patients develop resistance to cisplatin due to repeated treatment and thus the treatment efficacy is limited. Therefore, identifying an alternative therapeutic strategy combining cisplatin treatment along with targeting factors that drive cisplatin resistance is needed. CRISPR/Cas9 system-based genome-wide screening for the deubiquitinating enzyme (DUB) subfamily identified USP28 as a potential DUB that governs cisplatin resistance. USP28 regulates the protein level of microtubule-associated serine/threonine kinase 1 (MAST1), a common kinase whose expression is elevated in several cisplatin-resistant cancer cells. The expression level and protein turnover of MAST1 is a major factor driving cisplatin resistance in many cancer types. Here we report that the USP28 interacts and extends the half-life of MAST1 protein by its deubiquitinating activity. The expression pattern of USP28 and MAST1 showed a positive correlation across a panel of tested cancer cell lines and human clinical tissues. Additionally, CRISPR/Cas9-mediated gene knockout of USP28 in A549 and NCI-H1299 cells blocked MAST1-driven cisplatin resistance, resulting in suppressed cell proliferation, colony formation ability, migration and invasion in vitro. Finally, loss of USP28 destabilized MAST1 protein and attenuated tumor growth by sensitizing cells to cisplatin treatment in mouse xenograft model. We envision that targeting the USP28-MAST1 axis along with cisplatin treatment might be an alternative therapeutic strategy to overcome cisplatin resistance in cancer patients.
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Cisplatino , Neoplasias , Animales , Humanos , Ratones , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica , Cisplatino/farmacología , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos , Proteínas Asociadas a Microtúbulos , Microtúbulos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proteínas Serina-Treonina Quinasas/genética , Ubiquitina TiolesterasaRESUMEN
OBJECTIVES: Currently, no approved stem cell-based therapies for preserving ovarian function during aging. To solve this problem, we developed a long-term treatment for human embryonic stem cell-derived mesenchymal progenitor cells (hESC-MPCs). We investigated whether the cells retained their ability to resist ovarian aging, which leads to delayed reproductive senescence. MATERIALS AND METHODS: In a middle-aged female model undergoing natural aging, we analyzed whether hESC-MPCs benefit the long-term maintenance of reproductive fecundity and ovarian reservoirs and how their transplantation regulates ovarian function. RESULTS: The number of primordial follicles and mice with regular estrous cycles were increased in perimenopausal mice who underwent multiple introductions of hESC-MPCs compared to age-matched controls. The estradiol levels in the hESC-MPCs group were restored to those in the young and adult groups. Embryonic development and live birth rates were higher in the hESC-MPC group than in the control group, suggesting that hESC-MPCs delayed ovarian senescence. In addition to their direct effects on the ovary, multiple-treatments with hESC-MPCs reduced ovarian fibrosis by downregulating inflammation and fibrosis-related genes via the suppression of myeloid-derived suppressor cells (MDSCs) produced in the bone marrow. CONCLUSIONS: Multiple introductions of hESC-MPCs could be a useful approach to prevent female reproductive senescence and that these cells are promising sources for cell therapy to postpone the ovarian aging and retain fecundity in perimenopausal women.
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Células Madre Embrionarias Humanas , Células Madre Mesenquimatosas , Adulto , Embarazo , Persona de Mediana Edad , Femenino , Humanos , Animales , Ratones , Perimenopausia , Fertilidad , Envejecimiento , FibrosisRESUMEN
Human induced pluripotent stem cell (hiPSC)-derived macrophages provide a valuable tool for disease modeling and drug discovery. Here, we present a protocol to generate functional macrophages from hiPSCs using a feeder-free hematopoietic differentiation technique. We describe steps for preparing hiPSCs, mesodermal differentiation, hematopoietic commitment, and macrophage differentiation and expansion. We then detail assays to characterize their phenotype, polarization, and phagocytic functions. The functional macrophages generated here could be used to generate organoids for disease modeling and drug discovery studies. For complete details on the use and execution of this protocol, please refer to Jeong et al.1 and Heo et al.2.
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Células Madre Pluripotentes Inducidas , Humanos , Diferenciación Celular/genética , MacrófagosRESUMEN
Pleomorphic xanthoastrocytomas (PXA) are rare, accounting for < 1% of all astrocytomas. Literature on the clinical course and treatment outcomes of PXAs is limited. The study aimed to determine prognosis and treatment strategies for PXAs. Patients who had PXAs surgery between 2000-2021 were retrospectively analyzed for demographics and radiological characteristics. Initial and salvage treatment outcomes were recorded. Overall, 40 and 9 patients had grade 2 and 3 PXAs; their 5-year progression-free survival (PFS) rates were 75.8% and 37.0%, respectively (p = 0.003). Univariate analysis revealed that strong T1 enhancement (p = 0.036), infiltrative tumor margins (p < 0.001), peritumoral edema (p = 0.003), WHO grade (p = 0.005), and gross total resection (p = 0.005) affected the PFS. Multivariate analysis revealed that the WHO grade (p = 0.010) and infiltrative tumor margins (p = 0.008) influenced the PFS. The WHO grade (p = 0.027) and infiltrative tumor margins (p = 0.027) also affected the overall survival (OS). Subgroup analysis for grade 2 PXAs revealed no significant associations between adjuvant radiation therapy and the PFS and OS. This study highlighted the heterogeneous nature of PXAs and its impact on patient prognosis. Infiltrative tumor margins emerged as a key prognostic factor. Our findings have emphasized the prognostic relevance of radiological features and the need for larger studies on comprehensive management.
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Astrocitoma , Neoplasias Encefálicas , Humanos , Pronóstico , Estudios Retrospectivos , Neoplasias Encefálicas/patología , Astrocitoma/diagnóstico por imagen , Astrocitoma/terapia , Astrocitoma/patología , Resultado del TratamientoRESUMEN
Chronic respiratory diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and respiratory infections injure the alveoli; the damage evoked is mostly irreversible and occasionally leads to death. Achieving a detailed understanding of the pathogenesis of these fatal respiratory diseases has been hampered by limited access to human alveolar tissue and the differences between mice and humans. Thus, the development of human alveolar organoid (AO) models that mimic in vivo physiology and pathophysiology has gained tremendous attention over the last decade. In recent years, human pluripotent stem cells (hPSCs) have been successfully employed to generate several types of organoids representing different respiratory compartments, including alveolar regions. However, despite continued advances in three-dimensional culture techniques and single-cell genomics, there is still a profound need to improve the cellular heterogeneity and maturity of AOs to recapitulate the key histological and functional features of in vivo alveolar tissue. In particular, the incorporation of immune cells such as macrophages into hPSC-AO systems is crucial for disease modeling and subsequent drug screening. In this review, we summarize current methods for differentiating alveolar epithelial cells from hPSCs followed by AO generation and their applications in disease modeling, drug testing, and toxicity evaluation. In addition, we review how current hPSC-AOs closely resemble in vivo alveoli in terms of phenotype, cellular heterogeneity, and maturity.
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INTRODUCTION: Recent advancements in stereotactic neurosurgical techniques have become increasingly reliant on image-based target planning. We devised a case-phantom comparative analysis to evaluate the target registration errors arising during the magnetic resonance imaging (MRI)-computed tomography (CT) image fusion process. METHODS: For subjects whose preoperative MRI and CT images both contained fiducial frame localizers, we investigated discrepancies in target coordinates derived from frame registration based on either MRI or CT. We generated a phantom target through an image fusion process, merging the framed CT images with their corresponding reference MRIs after masking their fiducial indicators. This phantom target was then compared with the original during each instance of target planning. RESULTS: In our investigative study with 26 frame registrations, a systematic error in the y-axis was observed as -0.89 ± 0.42 mm across cases using either conventional CT and/or cone-beam CT (O-arm). For the z-axis, errors varied on a case-by-case basis, recording at +0.64 ± 1.09 mm with a predominant occurrence in those merged with cone-beam CT. Collectively, these errors resulted in an average Euclidean error of 1.33 ± 0.93 mm. CONCLUSION: Our findings suggest that the accuracy of frame-based stereotactic planning is potentially compromised during MRI-CT fusion process. Practitioners should recognize this issue, underscoring a pressing need for strategies and advancements to optimize the process.
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Cirugía Asistida por Computador , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Imagenología Tridimensional/métodos , Cirugía Asistida por Computador/métodos , Técnicas Estereotáxicas , Imagen por Resonancia Magnética/métodosRESUMEN
Objective: Several clinical studies have explored the feasibility and efficacy of radiosurgical treatment for mesial temporal lobe epilepsy, but the long-term safety of this treatment has not been fully characterized. This study aims to report and describe radiation-induced cavernous malformation as a delayed complication of radiosurgery in epilepsy patients. Methods: The series includes 20 patients with mesial temporal lobe epilepsy who underwent Gamma Knife radiosurgery (GKRS). The majority received a prescribed isodose of 24 Gy as an adjuvant treatment after anterior temporal lobectomy. Results: In this series, we identified radiation-induced cavernous malformation in three patients, resulting in a cumulative incidence of 18.4% (95% CI, 6.3 to 47.0%) at an eight-year follow-up. These late sequelae of vascular malformation occurred between 6.9 and 7.6 years after GKRS, manifesting later than other delayed radiation-induced changes, such as radiation necrosis. Neurological symptoms attributed to intracranial hypertension were present in those three cases involving cavernous malformation. Of these, two cases, which initially exhibited an insufficient response to radiosurgery, ultimately demonstrated seizure remission following the successful microsurgical resection of the cavernous malformation. Conclusion: All things considered, the development of radiation-induced cavernous malformation is not uncommon in this population and should be acknowledged as a potential long-term complication. Microsurgical resection of cavernous malformation can be preferentially considered in cases where the initial seizure outcome after GKRS is unsatisfactory.
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(1) Objective: This study aimed to explore the efficacy of conventional invasive techniques in confirming unilateral seizure onset localization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to investigate the association between electrode type and intracranial electroencephalography (EEG) pattern. (2) Methods: This retrospective study encompasses patients diagnosed with MTLE-HS who underwent an invasive study prior to an anterior temporal lobectomy (ATL). Intracranial EEG features were assessed for 99 seizure events from 25 selected patients who achieved seizure remission with ATL after an invasive study using bilateral combined depth and subdural electrodes. Their findings were compared to those of 21 seizure events in eight patients who exhibited suboptimal seizure outcomes. (3) Results: For the distribution of electrodes that recorded the ictal onset, hippocampal depth electrodes recorded 96% of all seizure events, while subdural electrodes recorded 52%. Among the seizures recorded in subdural electrodes, 49% were localized in medial electrodes, with only 8% occurring in lateral electrodes. The initiation of seizures exclusively detected in hippocampal depth electrodes was associated with successful seizure remission, whereas those solely recorded in the lateral strip electrodes were often linked to refractory seizures after ATL. (4) Conclusions: These findings emphasize the importance of employing a combination of depth and subdural electrodes in invasive studies for patients with MTLE-HS to enhance the accuracy of lateralization. This also cautions against sole reliance on subdural electrodes without depth electrodes, which could lead to inaccurate localization.
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Toxocara spp. is a zoonotic soil-transmitted parasite that infects canids and felids, which causes toxocariasis in humans, migrating to organ systems, including the lungs, the ocular system, and the central nervous system. Since Toxocara spp. is usually transmitted through soil, children tend to be more susceptible to infection. In order to monitor contamination with Toxocara spp. in children's play facilities in the Republic of Korea, we investigated 11,429 samples of soil from daycare centers, kindergartens, elementary schools, and parks across the country from January 2016 to December 2021. Since the Environmental Health Act in the Republic of Korea was enacted in March 2008, there have been sporadic reports of contamination by Toxocara spp. in children's activity zones. In this study, soil from children's play facilities in regions across the Republic of Korea was monitored according to the Korean standardized procedure to use it as basic data for preventive management and public health promotion. The national average positive rate was 0.16% (18/11,429), and Seoul showed a higher rate of 0.63% (2/318) than any other regions while Incheon, Daegu, Ulsan, Kangwon-do, Jeollabuk-do, and Jeollanam-do were negative (p < 0.05). The positive rates were as follows: 0.37% (4/1089) in daycare centers, 0.13% (3/2365) in kindergartens, 0.2% (7/4193) in elementary schools, 0.09% (1/1143) in apartments, and 0.14% (3/2198) in parks. In addition, it was confirmed that 0.2% (1/498) of elementary schools and 1.17% (2/171) of parks were re-contaminated among play facilities managed with the establishment of a regular inspection cycle. Consequently, there is an essential need for continuous monitoring of Toxocara spp. contamination and regular education for preschool and school children in order to prevent soil-borne parasite infections.
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The solute carrier family 35 F2 (SLC35F2) belongs to membrane-bound carrier proteins that are associated with multiple cancers. The main factor that determines cancer progression is the expression level of SLC35F2. Thus, identifying the E3 ligase that controls SLC35F2 protein abundance in cancer cells is critical. Here, we identified ßTrCP1 interacting with and reducing the SLC35F2 protein level. ßTrCP1 signals SLC35F2 protein ubiquitination and reduces SLC35F2 protein half-life. The mRNA expression pattern between ßTrCP1 and SLC35F2 across a panel of cancer cell lines showed a negative correlation. Additionally, the depletion of ßTrCP1 accumulated SLC35F2 protein and promoted SLC35F2-mediated cell growth, migration, invasion, and colony formation ability in HeLa cells. Overall, we demonstrate that ßTrCP1 acts as a tumor suppressor by controlling SLC35F2 protein abundance in cancer cells. The depletion of ßTrCP1 promotes SLC35F2-mediated carcinogenesis. Thus, we envision that ßTrCP1 may be a potential target for cancer therapeutics.
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Neoplasias , Ubiquitina-Proteína Ligasas , Humanos , Células HeLa , Ubiquitinación , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ciclo Celular , Línea Celular Tumoral , Neoplasias/genética , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismoRESUMEN
BACKGROUND: The solute carrier family 35 F2 (SLC35F2), belongs to membrane-bound carrier proteins that control various physiological functions and are activated in several cancers. However, the molecular mechanism regulating SLC35F2 protein turnover and its implication in cancer progression remains unexplored. Therefore, screening for E3 ligases that promote SLC35F2 protein degradation is essential during cancer progression. METHODS: The immunoprecipitation and Duolink proximity ligation assays (PLA) were used to determine the interaction between APC/CCdh1 and SLC35F2 proteins. A CRISPR/Cas9-mediated knockdown and rescue experiment were used to validate the functional significance of APC/CCdh1 on SLC35F2 protein stabilization. The ubiquitination function of APC/CCdh1 on SLC35F2 protein was validated using in vitro ubiquitination assay and half-life analysis. The role of APC/CCdh1 regulating SLC35F2-mediated tumorigenesis was confirmed by in vitro oncogenic experiments in HeLa cells. RESULTS: Based on the E3 ligase screen and in vitro biochemical experiments, we identified that APC/CCdh1 interacts with and reduces SLC35F2 protein level. APC/CCdh1 promotes SLC35F2 ubiquitination and decreases the half-life of SLC35F2 protein. On the other hand, the CRISPR/Cas9-mediated depletion of APC/CCdh1 increased SLC35F2 protein levels. The mRNA expression analysis revealed a negative correlation between APC/CCdh1 and SLC35F2 across a panel of cancer cell lines tested. Additionally, we demonstrated that depletion in APC/CCdh1 promotes SLC35F2-mediated cell proliferation, colony formation, migration, and invasion in HeLa cells. CONCLUSION: Our study highlights that APC/CCdh1 is a critical regulator of SLC35F2 protein turnover and depletion of APC/CCdh1 promotes SLC35F2-mediated tumorigenesis. Thus, we envision that APC/CCdh1-SLC35F2 axis might be a therapeutic target in cancer.