This study utilized Next-Generation Sequencing (NGS) to explore genetic determinants of survival duration in Glioblastoma Multiforme (GBM) patients. We categorized 30 primary GBM patients into two groups based on their survival periods: extended survival (over two years, N = 17) and abbreviated survival (under two years, N = 13). For identifying pathogenic or likely pathogenic variants, we leveraged the ClinVar database. The cohort, aged 23 to 66 (median: 53), included 17 patients in Group A (survival >2 years, 10 males, 7 females), and 13 patients in Group B (survival <2 years, 8 males, 5 females), with a 60% to 40% male-to-female ratio. Identified mutations included CHEK2 (c.1477 G > A, p.E493K), IDH1 (c.395 G > A, p.R132H), and TP53 mutations. Non-coding regions exhibited variants in the TERT promoter (c.-146C > T, c.-124C > T) and TP53 RNA splicing site (c.376-2 A > C, c.376-2 A > G). While Group A had more mutations, statistical significance wasn't reached, likely due to sample size. Notably, TP53, and ATR displayed a trend toward significance. Surprisingly, TP53 mutations were more prevalent in Group A, contradicting Western findings on poorer GBM prognosis. In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness. EGFR mutations are infrequent, suggesting potential distinctions in carcinogenic pathways. Further research on EGFR mutations and amplifications is essential for refining therapeutic approaches. TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape.
INTRODUCTION: Aneurysmal bone cysts (ABCs) are a rare, vascular, rapidly growing, benign, osteolytic lesions. Most ABCs involve the metaphysis of long bones, vertebrae, or flat bones. In this study, we review the literature to better understand the natural history, clinical presentation, and treatments. PRESENTATION OF CASE: A 34-year-old man who presented with left intermittent otorrhea for months. Yellowish, pus-like discharge was noted. Mild tinnitus, hearing loss, and occasional headache was also found. The initial impression was chronic otitis media and ear drops were prescribed. However, his symptoms did not improve in the following months. The brain MRI with gadolinium enhancement revealed an extra-axial mixed signal intensity lesion on the T2-weighted image, multiloculated cystic components and rim enhancement was noted over the left middle cranial fossa. Left fronto-temporal craniotomy for tumor removal was performed. The pathological reports revealed an aneurysmal bone cyst. CLINICAL DISCUSSION: Typically, ABCs present with localized swelling and pain due to their rapid growth and expansion, with concomitant signs corresponding with the anatomical location of the lesion. MRI studies can reveal the cystic components of the lesion and multiple fluid levels within multiloculated cysts resulting from unclotted blood, separated from the soft tissue and medullary bone. Histopathologic diagnosis of ABC is the presence of multiple blood-filled cystic spaces separated by fibrous septa. The fibrous septa are composed of spindle-celled fibroconnective tissue with occasional osteoclast-type giant cells. CONCLUSION: ABCs are a rare, osteolytic lesions that rarely involve the skull. When the MRI shows a lesion with soap-bubble appearance in the calvaria, an aneurysmal bone cyst should be considered in the differential diagnosis, even if it is an extremely rare entity or the patient is relatively old. Surgical resection of the tumor is the first choice for treatment.
In the present study, the various concentrations of AuNP (1.25, 2.5, 5, 10 ppm) were prepared to investigate the biocompatibility, biological performances and cell uptake efficiency via Wharton's jelly mesenchymal stem cells and rat model. The pure AuNP, AuNP combined with Col (AuNP-Col) and FITC conjugated AuNP-Col (AuNP-Col-FITC) were characterized by Ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and Dynamic Light Scattering (DLS) assays. For in vitro examinations, we explored whether the Wharton's jelly MSCs had better viability, higher CXCR4 expression, greater migration distance and lower apoptotic-related proteins expression with AuNP 1.25 and 2.5 ppm treatments. Furthermore, we considered whether the treatments of 1.25 and 2.5 ppm AuNP could induce the CXCR4 knocked down Wharton's jelly MSCs to express CXCR4 and reduce the expression level of apoptotic proteins. We also treated the Wharton's jelly MSCs with AuNP-Col to investigate the intracellular uptake mechanisms. The evidence demonstrated the cells uptake AuNP-Col through clathrin-mediated endocytosis and the vacuolar-type H+-ATPase pathway with good stability inside the cells to avoid lysosomal degradation as well as better uptake efficiency. Additionally, the results from in vivo examinations elucidated the 2.5 ppm of AuNP attenuated foreign body responses and had better retention efficacy with tissue integrity in animal model. In conclusion, the evidence demonstrates that AuNP shows promise as a biosafe nanodrug delivery system for development of regenerative medicine coupled with Wharton's jelly MSCs.
INTRODUCTION: Pituicytomas are low-grade glial tumors in the sellar and suprasellar region. They may be easily confused with pituitary lesions. We review the literature in order to better understand and categorize the natural history, clinical presentations, and treatments. PRESENTATION OF CASE: A 45-year-old female patient who complained of left eye blurred vision for 2 months. The imaging study revealed a solid sellar tumor with marked homogeneous enhancement following intravenous administration of gadolinium, and compression of the optic chiasm. Thus, under the preoperative diagnosis of pituitary macroadenoma, the patient underwent endoscope-assisted surgery via the transsphenoidal approach. The patient recovered well after surgery. The histopathological diagnosis was pituicytoma, WHO grade I. CLINICAL DISCUSSION: Pituicytomas are defined as a circumscribed low-grade glial tumor arising from the neurohypophysis or infundibulum with bipolar spindle cells arranged in a fascicular or storiform pattern (a cartwheel). The clinical symptoms are variable depending on the tumor size and location. They usually present due to mass effect. The radiographic characteristics are not nonspecific. The diagnosis of pituicytoma is based on histopathological evidence. Pituicytomas consist of a solid proliferation of elongated spindle cells arranged in interlacing fascicles and/or in a "storiform" pattern. In immunohistochemical studies, pituicytomas was strongly expressed in TTF-1. CONCLUSION: Pituicytomas are benign, slow-growing glial tumors. It is difficult to diagnosed before operation as its clinical presentations and imaging studies resemble those of non-functional pituitary adenomas. The best chance of successful treatment is gross total resection by the endoscopic approach or transcranial approach.
n-butylidenephthalide (BP) has been verified as having the superior characteristic of cancer cell toxicity. Furthermore, gold (Au) nanoparticles are biocompatible materials, as well as effective carriers for delivering bio-active molecules for cancer therapeutics. In the present research, Au nanoparticles were first conjugated with polyethylene glycol (PEG), and then cross-linked with BP to obtain PEG-Au-BP nanodrugs. The physicochemical properties were characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) to confirm the combination of PEG, Au, and BP. In addition, both the size and structure of Au nanoparticles were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), where the size of Au corresponded to the results of DLS assay. Through in vitro assessments, non-transformed BAEC and DBTRG human glioma cells were treated with PEG-Au-BP drugs to investigate the tumor-cell selective cytotoxicity, cell uptake efficiency, and mechanism of endocytic routes. According to the results of MTT assay, PEG-Au-BP was able to significantly inhibit DBTRG brain cancer cell proliferation. Additionally, cell uptake efficiency and potential cellular transportation in both BAEC and DBTRG cell lines were observed to be significantly higher at 2 and 24 h. Moreover, the mechanisms of endocytosis, clathrin-mediated endocytosis, and cell autophagy were explored and determined to be favorable routes for BAEC and DBTRG cells to absorb PEG-Au-BP nanodrugs. Next, the cell progression and apoptosis of DBTRG cells after PEG-Au-BP treatment was investigated by flow cytometry. The results show that PEG-Au-BP could remarkably regulate the DBTRG cell cycle at the Sub-G1 phase, as well as induce more apoptotic cells. The expression of apoptotic-related proteins in DBTRG cells was determined through Western blotting assay. After treatment with PEG-Au-BP, the apoptotic cascade proteins p21, Bax, and Act-caspase-3 were all significantly expressed in DBTRG brain cancer cells. Through in vivo assessments, the tissue morphology and particle distribution in a mouse model were examined after a retro-orbital sinus injection containing PEG-Au-BP nanodrugs. The results demonstrate tissue integrity in the brain (forebrain, cerebellum, and midbrain), heart, liver, spleen, lung, and kidney, as they did not show significant destruction due to PEG-Au-BP treatment. Simultaneously, the extended retention period for PEG-Au-BP nanodrugs was discovered, particularly in brain tissue. The above findings identify PEG-Au-BP as a potential nanodrug for brain cancer therapies.
Brain Neoplasms , Metal Nanoparticles , Animals , Apoptosis Regulatory Proteins/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Cell Line, Tumor , Gold/chemistry , Gold/pharmacology , Humans , Metal Nanoparticles/chemistry , Mice , Phthalic Anhydrides , Polyethylene Glycols/chemistry
Chitosan (Chi) is a natural polymer that has been demonstrated to have potential as a promoter of neural regeneration. In this study, Chi was prepared with various amounts (25, 50, and 100 ppm) of gold (Au) nanoparticles for use in in vitro and in vivo assessments. Each as-prepared material was first characterized by UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), and Dynamic Light Scattering (DLS). Through the in vitro experiments, Chi combined with 50 ppm of Au nanoparticles demonstrated better biocompatibility. The platelet activation, monocyte conversion, and intracellular ROS generation was remarkably decreased by Chi-Au 50 pm treatment. Furthermore, Chi-Au 50 ppm could facilitate colony formation and strengthen matrix metalloproteinase (MMP) activation in mesenchymal stem cells (MSCs). The lower expression of CD44 in Chi-Au 50 ppm treatment demonstrated that the nanocomposites could enhance the MSCs undergoing differentiation. Chi-Au 50 ppm was discovered to significantly induce the expression of GFAP, ß-Tubulin, and nestin protein in MSCs for neural differentiation, which was verified by real-time PCR analysis and immunostaining assays. Additionally, a rat model involving subcutaneous implantation was used to evaluate the superior anti-inflammatory and endothelialization abilities of a Chi-Au 50 ppm treatment. Capsule formation and collagen deposition were decreased. The CD86 expression (M1 macrophage polarization) and leukocyte filtration (CD45) were remarkably reduced as well. In summary, a Chi polymer combined with 50 ppm of Au nanoparticles was proven to enhance the neural differentiation of MSCs and showed potential as a biosafe nanomaterial for neural tissue engineering.
Chitosan , Mesenchymal Stem Cells , Metal Nanoparticles , Nanocomposites , Animals , Chitosan/chemistry , Chitosan/pharmacology , Gold/chemistry , Gold/pharmacology , Metal Nanoparticles/chemistry , Nanocomposites/chemistry , Rats
BACKGROUND: Trigeminal neuralgia (TN) is a disease characterized by recurring, short-lived, electric shock-like pain experienced on one side of the face. Microvascular decompression (MVD) is one of the most effective surgical interventions for resolving TN caused by neurovascular compression. This study aimed to determine the predictive and prognostic factors of surgical outcomes. METHODS: This retrospective cohort study enrolled patients diagnosed with TN who underwent MVD at our hospital during 2013-2019. The demographic information, pain character, peri-operative Barrow Neurological Institute (BNI) scale, medication, operative finding were recorded. And the outcome was Outcomes were divided into drug-free and drug-dependent group. Predisposing factors for each outcome were analyzed by one-way analysis of variance, followed by a Mann-Whitney U test or Kruskal-Wallis test. RESULTS: A total of 104 consecutive patients received MVD to treat TN, and 88 patients were enrolled in this study. The overall postoperative drug-free outcome was 72.7%. A significant difference in drug-free outcomes was observed for patients with typical TN (80.8%) compared with patients with atypical TN (33.33%, p = 0001). When severe venous compression was encountered during MVD, the drug-free outcome fell to 50% (10/20, p = 0.009). The Mann-Whitney U test indicated typical TN as a positive predictive factor of a drug-free outcome, whereas severe venous compression was a negative predictive factor. The patients with preoperative BNI score of 4 had better improvement than others (p = 0.045). Age, onset duration, and arterial loop had no specific difference in this study. CONCLUSION: In our study, atypical TN and severe venous compression were associated with poor outcomes. Regrouping atypical TN into precise diagnosis represents an immediate priority according to our result. The preoperative BNI score could be used as an effective predictive tool for the outcome of MVD surgery.
Microvascular Decompression Surgery , Outcome Assessment, Health Care , Trigeminal Neuralgia/physiopathology , Trigeminal Neuralgia/surgery , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies
BACKGROUND: In this study, our major aim is to using multiple-steps bioinformatic analysis to predict cardiogenic genes with targeting mRNA profiling for predicting cardiogenic HoxA11 gene. METHODS: We first analyzed the microarray data with bioinformatic measurement, including combining with panel module 1 (mouse embryonic stem cells), panel module 2 (mouse induced pluripotent stem cells), and panel module 3 (gene list form literature of heart development). A literature-based comparison of the two microarrays and a software-based (Targetscan program, www.targetscan.org) comparative analysis of the two datasets. Furthermore, we select the common central pathways and potential candidate genes involved in the cardiomyocyte-lineaged differentiation and development. RESULTS: Schematic presentation of a putative miR181a target site in Hox-A11 3'UTR. The bioinformatic result showed that potential interacted cardiogenic targets of Tbx5, Tbx20, Mal2c, Nkx2.5, cTNT, Cx43, MHC, and MCK in different treatment groups of pluripotent stem cells by using a literature-based comparison of the two microarrays and a software-based gene-lineage system. CONCLUSION: Our findings support that mir181a is an up-stream regulating microRNA to target the 3'UTR of HoxA11 mRNA during the process of cardiomyocyte differentiation.
Computational Biology/methods , Homeodomain Proteins/genetics , MicroRNAs/physiology , Animals , Connexin 43/metabolism , Mice , Mice, Inbred C57BL
BACKGROUND: Particulate matter (PM) has been associated with increased pulmonary and cardiovascular mortality and morbidity. Additionally, PM is known to exacerbate asthma. However, whether ambient PM exposure contributes to the onset of asthma, especially in non-atopic children and adults, is less conclusive. The current study aimed to evaluate the effects of size-fractioned PM on lung immune responses in healthy BALB/c mice. METHODS AND PRINCIPAL FINDINGS: We collected PM10, PM2.5, PM1 and PM0.1 samples from October 2012 to August 2013 in the Taipei Basin. These PM samples were representative of urban traffic pollution. The samples were extracted and sonicated in phosphate-buffered saline (PBS). Female BALB/c mice were exposed to the samples via intratracheal instillation at three different doses: 1.75 mg/kg (35 µg/per mouse), 5 mg/kg (100 µg/per mouse), and 12.5 mg/kg (250 µg/per mouse). The mice were exposed on days 0 and 7, and PBS alone was used as a control. Following the exposures, the expression profiles of inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were assessed. Exposure to PM10 resulted in inflammatory responses, including the recruitment of neutrophils and the induction of T helper 1 (Th1) cell-related cytokine release, such as TNF-α and IFN-γ. Furthermore, an allergic immune response, including the recruitment of eosinophils and the up-regulation of T helper 2 (Th2) cell-related cytokine release, such as IL-5 and IL-13, was also observed in the BALF of mice exposed to PM10. CONCLUSIONS: Our study showed that exposure to PM alone caused mixed Th1/Th2 inflammatory responses in healthy mice. These findings support the hypothesis that PM may contribute to the onset of asthma.
Asthma/immunology , Particulate Matter/toxicity , Th1 Cells/immunology , Th2 Cells/immunology , Air Pollutants/toxicity , Animals , Asthma/chemically induced , Bronchoalveolar Lavage Fluid , Female , Interleukin-13/metabolism , Interleukin-5/metabolism , Mice , Mice, Inbred BALB C , Th1 Cells/drug effects , Th2 Cells/drug effects
BACKGROUND: Gunshot accidents are not uncommon in Taiwan, but involvement limited to the ocular region and sphenoid sinus is rare. Minimal invasive treatment by endonasal transsphenoidal endoscopy-assisted procedure should be considered if there are no additional injuries in the craniocerebral region. CASE DESCRIPTION: A 39-year-old man had severe pain in the left eye with resulting blindness after being accidentally hit in the left eye by a gunshot pellet while walking in a wooded area. He was referred from another hospital with the impression of left eyeball rupture. There was no severe neurologic deficit except for blindness of the left eye when he arrived at the emergency department of our hospital. Brain and orbits CT scans showed a round metallic foreign body at the right sphenoid sinus without predominant damages of brain parenchyma. Endonasal transsphenoidal endoscopy-assisted procedure was used to remove the shotgun pellet, and the patient had good clinical outcomes. CONCLUSION: Herein we present this rare case to show the possibility of a shotgun pellet injury remaining in the sphenoid sinus. The role of radiological studies such as CT scans and intraoperative C-arm fluoroscope plain films in diagnosis and management of this case is affirmed. The strategy of minimally invasive treatment by endonasal transsphenoidal endoscopy-assisted procedure for those limited injuries is a good choice for treatment.
Endoscopy , Foreign Bodies/surgery , Minimally Invasive Surgical Procedures , Nasal Cavity , Sphenoid Sinus/surgery , Wounds, Gunshot/surgery , Fluoroscopy , Humans , Male , Middle Aged , Monitoring, Intraoperative , Tomography, X-Ray Computed
