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PURPOSE: To evaluate the safety and benefits of the biplanar position technique on operative time, radiation exposure, and screw placement accuracy. METHODS: In this study, we retrospectively evaluated the records of 64 patients with pelvic fractures (Tile B and C) between October 2020 and September 2021. According to the surgical methods selected by the patients, the patients were divided into a biplanar positioning technique group (biplanar group), a Ti-robot navigation group (Ti-robot group), and a traditional fluoroscopy-guided technique group (traditional group). Length of operation, blood loss, intra-operative radiation exposure fracture reduction, and the quality of screw positioning were compared among the three groups. RESULTS: One hundred three screws were implanted in 64 patients (biplanar group 22, Ti-robot group 21, traditional group 21). The average operation time was significantly less in the biplanar group (26.32 ± 6.32 min) than in the traditional group (79.24 ± 11.31 min), but significantly more than in the Ti-robot group (15.81 ± 3.9 min). The radiation exposure was similar in the biplanar group (740.53 ± 185.91 cGy/cm2) and Ti-robot group (678.44 ± 127.16 cGy/cm2), both of which were significantly more than in the traditional group (2034.58 ± 494.54 cGy/cm2). The intra-operative blooding loss was similar in the biplanar group (12.76 ± 3.77 mL) and the Ti-robot group (11.92 ± 4.67 mL), both of which were significantly less than in the traditional group (29.7 ± 8.01 mL). The Screw perforation was slightly lower in the biplanar group (94.1%) than in the Ti-robot group (97.2%) but was significantly higher than in the traditional group (75.7%). CONCLUSIONS: The biplanar positioning technique is as accurate and safe as computer-navigated systems for percutaneous iliosacral screw insertion, associated with shorter surgical time, lower intra-operative radiation exposure, and more accuracy compared to traditional fluoroscopy.
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Fraturas Ósseas , Ossos Pélvicos , Humanos , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/cirurgia , Parafusos Ósseos , Fluoroscopia/métodosRESUMO
Extravasation of Onyx is a rare complication during embolization of arteriovenous malformations (AVM). We present a case of embolization that was complicated by leakage of Onyx into the cerebellum which was later encountered during surgical excision of the AVM. Our goal is to report this rare event and to outline successful treatment of this complication. The patient's records were reviewed for medical history, laboratory and radiologic workup, and outpatient clinical follow-up. A 62-year-old female presented with Hunt Hess grade 2 and modified Fisher grade 2 subarachnoid hemorrhage (SAH) secondary to ruptured left posterior inferior cerebellar artery (PICA) aneurysm associated with a superior cerebellar vermian AVM. Following endovascular intervention, the aneurysm was completely embolized; however, only 75% of the AVM could be safely obliterated. Extravasation of Onyx from the ruptured aneurysm was noted on her initial angiogram. Elective suboccipital craniectomy was subsequently planned for resection of the residual AVM where the extravasated Onyx posed an operative nuisance during resection. Post-op angiogram confirmed complete resection of the AVM, as well as the bulk of the extravasated Onyx. Patient did well post-operatively, remaining neurologically intact throughout her hospital course. Although infrequently reported in the literature, Onyx extravasation is a potential complication that neurosurgeons should be ready to face. Adherence of Onyx to surrounding parenchyma could hinder optimal surgical resection of AVM and increase complications. Therefore, careful surgical dissection should be performed with special care to delicate neurovasculature. In this case, complete resection of the AVM and Onyx mass was safely achieved.
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Aneurisma Roto/cirurgia , Craniotomia/métodos , Dissecação/métodos , Procedimentos Cirúrgicos Eletivos/métodos , Embolização Terapêutica/métodos , Malformações Arteriovenosas Intracranianas/cirurgia , Hemorragia Subaracnóidea/cirurgia , Aneurisma Roto/complicações , Aneurisma Roto/terapia , Craniotomia/efeitos adversos , Dissecação/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/terapia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hemorragia Subaracnóidea/etiologiaRESUMO
Central nervous system infections in immunosuppressed patients are rare but potentially lethal complications that require swift diagnoses and intervention. While the differential diagnosis for new lesions on neuroradiological imaging of immunosuppressed patients typically includes infections and neoplasms, image-based heuristics to differentiate the two has been shown to have variable reliability.The authors describe 2 rare CNS infections in immunocompromised patients with atypical physical and radiological presentations. In the first case, a 59-year-old man, who had recently undergone a renal transplantation, was found to have multifocal Nocardia amikacinitolerans abscesses masquerading as neoplasms on diffusion-weighted imaging (DWI); in the second case, a 33-year-old man with suspected recurrent Hodgkin's lymphoma was found to have a nonpyogenic abscess with cytomegalovirus (CMV) encephalitis.As per review of the literature, this appears to be the first case of brain abscess caused by N. amikacinitolerans, a recently isolated superbug. Despite confirmation through brain biopsy later on in case 1, the initial radiological appearance was atypical, showing subtle diffusion restriction on DWI. Similarly, the authors present a case of CMV encephalitis that presented as a ring-enhancing lesion, which is extremely rare. Both cases draw attention to the reliability of neuroimaging in differentiating an abscess from a neoplasm.
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Abscesso Encefálico/virologia , Neoplasias Encefálicas/cirurgia , Citomegalovirus/patogenicidade , Nocardia/patogenicidade , Adulto , Encéfalo/patologia , Encéfalo/cirurgia , Abscesso Encefálico/diagnóstico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/virologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Reprodutibilidade dos TestesRESUMO
The central nervous system plays an important role in essential hypertension in humans and in animal models of hypertension through modulation of sympathetic activity and Na+ and body fluid homeostasis. Data from animal models of hypertension suggest that the renin-angiotensin system in the subfornical organ (SFO) of the brain is critical for hypertension development. We recently reported that the brain (pro)renin receptor (PRR) is a novel component of the brain renin-angiotensin system and could be a key initiator of the pathogenesis of hypertension. Here, we examined the expression level and cellular distribution of PRR in the SFO of postmortem human brains to assess its association with the pathogenesis of human hypertension. Postmortem SFO tissues were collected from hypertensive and normotensive human subjects. Immunolabeling for the PRR and a retrospective analysis of clinical data were performed. We found that human PRR was prominently expressed in most neurons and microglia, but not in astrocytes, in the SFO. Importantly, PRR levels in the SFO were elevated in hypertensive subjects. Moreover, PRR immunoreactivity was significantly correlated with systolic blood pressure but not body weight, age, or diastolic blood pressure. Interestingly, this correlation was independent of antihypertensive drug therapy. Our data indicate that PRR in the SFO may be a key molecular player in the pathogenesis of human hypertension and, as such, could be an important focus of efforts to understand the neurogenic origin of hypertension. NEW & NOTEWORTHY This study provides evidence that, in the subfornical organ of the human brain, the (pro)renin receptor is expressed in neurons and microglia cells but not in astrocytes. More importantly, (pro)renin receptor immunoreactivity in the subfornical organ is increased in hypertensive humans and is significantly correlated with systolic blood pressure.
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Hipertensão/enzimologia , Receptores de Superfície Celular/análise , Órgão Subfornical/enzimologia , ATPases Vacuolares Próton-Translocadoras/análise , Idoso , Autopsia , Pressão Sanguínea , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Imuno-Histoquímica , Masculino , Microglia/enzimologia , Pessoa de Meia-Idade , Neurônios/enzimologia , Estudos Retrospectivos , Órgão Subfornical/fisiopatologia , Regulação para CimaRESUMO
To investigate the relationship between Eg5 and histopathological grade of astrocytoma, Eg5 expression was evaluated by immunohistochemical examination on 88 specimens including 25 cases of glioblastoma (WHO grade IV), 22 cases of anaplastic astrocytoma (WHO grade III), 20 cases of diffuse astrocytoma (WHO grade II), and 21 cases of pilocytic astrocytoma (WHO grade I). The histopathological characteristics and Eg5 expression level of each tumor were assessed and statistically analyzed. Astrocytic tumors exhibited significant correlation of expression of Eg5 with higher WHO histopathological grades (p < 0.001). Eg5 is expressed in 51-98% (mean 76.88%) of neoplastic cells in glioblastoma, 34-57% (mean 43.59%) of neoplastic cells in anaplastic astrocytoma, 6-36% (mean 18.60%) of neoplastic cells in diffuse astrocytoma, and 2-28% (mean 13.48%) of neoplastic cells in pilocytic astrocytoma. In conclusion, overexpression of Eg5 associates with high-grade astrocytic neoplasm, and it may represent an independent diagnostic and prognostic factor in grading astrocytic tumors and predicting prognosis of astrocytic tumor patients.
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Astrócitos/metabolismo , Neoplasias Encefálicas/metabolismo , Cinesinas/metabolismo , Astrócitos/classificação , Astrócitos/patologia , Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Humanos , Antígeno Ki-67 , MasculinoRESUMO
BACKGROUND: Naegleria fowleri is a climate-sensitive, thermophilic ameba found in warm, freshwater lakes and rivers. Primary amebic meningoencephalitis (PAM), which is almost universally fatal, occurs when N. fowleri-containing water enters the nose, typically during swimming, and migrates to the brain via the olfactory nerve. In August 2013, a 4-year-old boy died of meningoencephalitis of unknown etiology in a Louisiana hospital. METHODS: Clinical and environmental testing and a case investigation were initiated to determine the cause of death and to identify potential exposures. RESULTS: Based on testing of cerebrospinal fluid and brain specimens, the child was diagnosed with PAM. His only reported water exposure was tap water; in particular, tap water that was used to supply water to a lawn water slide on which the child had played extensively prior to becoming ill. Water samples were collected from both the home and the water distribution system that supplied the home and tested; N. fowleri was identified in water samples from both the home and the water distribution system. CONCLUSIONS: This case is the first reported PAM death associated with culturable N. fowleri in tap water from a US treated drinking water system. This case occurred in the context of an expanding geographic range for PAM beyond southern states, with recent case reports from Minnesota, Kansas, and Indiana. This case also highlights the role of adequate disinfection throughout drinking water distribution systems and the importance of maintaining vigilance when operating drinking water systems using source waters with elevated temperatures.
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Amebíase/diagnóstico , Amebíase/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/diagnóstico , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Água Potável/parasitologia , Naegleria fowleri/isolamento & purificação , Encéfalo/parasitologia , Líquido Cefalorraquidiano/parasitologia , Pré-Escolar , Evolução Fatal , Humanos , Louisiana , Masculino , OligopeptídeosRESUMO
BACKGROUND: Interleukin-17 (IL-17) has been demonstrated to promote formation and growth of hormone-naïve prostate adenocarcinoma in mice. IL-17's role in development of castration-resistant prostate cancer is unknown. In the present study, we investigated IL-17's role in castration-resistant prostate cancer in a mouse model. METHODS: IL-17 receptor C (IL-17RC) deficient mice were interbred with Pten conditional mutant mice to produce RC(+) mice that maintained IL-17RC expression and RC(-) mice that were IL-17RC deficient. Male RC(+) and RC(-) mice were Pten-null and were castrated at 16 weeks of age when invasive prostate cancer had already formed. At 30 weeks of age, all male mice were analyzed for the prostate phenotypes. RESULTS: RC(-) mice displayed prostates that were smaller than RC(+) mice. Approximately 23% of prostatic glands in RC(-) mice, in contrast to 65% of prostatic glands in RC(+) mice, developed invasive adenocarcinomas. Compared to castrate RC(+) mice, castrate RC(-) mouse prostate had lower rates of cellular proliferation and higher rates of apoptosis as well as lower levels of MMP7, YBX1, MTA1, and UBE2C proteins. In addition, castrate RC(-) mouse prostate had less angiogenesis, which was associated with decreased levels of COX-2 and VEGF. Moreover, castrate RC(-) mouse prostate had fewer inflammatory cells including lymphocytes, myeloid-derived suppressor cells, and macrophages. CONCLUSIONS: Taken together, our findings suggest that IL-17 promotes development of invasive prostate adenocarcinomas under castrate conditions, potentially through creating an immunotolerant and pro-angiogenic tumor microenvironment.
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Tolerância Imunológica , Interleucina-17/fisiologia , Neovascularização Patológica/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptores de Interleucina-17/fisiologia , Microambiente Tumoral/genética , Animais , Tolerância Imunológica/genética , Interleucina-17/deficiência , Masculino , Camundongos , Camundongos Knockout , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Orquiectomia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/imunologia , Receptores de Interleucina-17/deficiênciaRESUMO
BACKGROUND: Osteosarcoma is a highly invasive bone marrow stromal tumor with limited treatment options. Oxidative stress plays a crucial role in the development and progression of tumors, but the underlying regulatory mechanisms are not fully understood. Recent studies have revealed the significant involvement of UBE2L3 in oxidative stress, but its specific role in osteosarcoma remains poorly investigated. OBJECTIVE: This study aimed to explore the molecular mechanisms by which UBE2L3 promotes oxidative stress-regulated necroptosis to accelerate the progression of osteosarcoma using in vitro cell experiments. METHODS: Human osteoblast hFOB1.19 cells and various human osteosarcoma cell lines (MG-63, U2OS, SJSA-1, HOS, and 143B) were cultured in vitro. Plasmids silencing UBE2L3 and negative control plasmids were transfected into U2OS and HOS cells. The cells were divided into the following groups: U2OS cell group, HOS cell group, si-NC-U2OS cell group, si-UBE2L3-U2OS cell group, si-NC-HOS cell group, and si-UBE2L3-HOS cell group. Cell viability and proliferation capacity were measured using the Tunnel method and clonogenic assay. Cell migration and invasion abilities were assessed by Transwell and scratch assays. Cell apoptosis was analyzed by flow cytometry, and ROS levels were detected using immunofluorescence. The oxidative stress levels in various cell groups and the expression changes of necroptosis-related proteins were assessed by PCR and WB. Through these experiments, we aim to evaluate the impact of oxidative stress on necroptosis and uncover the specific mechanisms by which targeted regulation of oxidative stress promotes tumor cell necroptosis as a potential therapeutic strategy for osteosarcoma. RESULTS: The mRNA expression levels of UBE2L3 in human osteosarcoma cell lines were significantly higher than those in human osteoblast hFOB1.19 cells (p <0.01). UBE2L3 expression was significantly decreased in U2OS and HOS cells transfected with si-UBE2L3, indicating the successful construction of stable cell lines with depleted UBE2L3. Tunnel assay results showed a significant increase in the number of red fluorescent-labeled cells in si-UBE2L3 groups compared to si-NC groups in both cell lines, suggesting a pronounced inhibition of cell viability. Transwell assay demonstrated a significant reduction in invasion and migration capabilities of si-UBE2L3 groups in osteosarcoma cells. The clonogenic assay revealed significant suppression of proliferation and clonogenic ability in both U2OS and HOS cells upon UBE2L3 knockdown. Flow cytometry confirmed that UBE2L3 knockdown significantly enhanced apoptosis in U2OS and HOS cells. Immunofluorescence results showed that UBE2L3 silencing promoted oxidative stress levels in osteosarcoma cells and facilitated tumor cell death. WB analysis indicated a significant increase in phosphorylation levels of necroptosis-related proteins, RIP1, RIP3, and MLKL, in both osteosarcoma cell lines after UBE2L3 knockdown. In addition, the expression of necrosis-associated proteins was inhibited by the addition of the antioxidant N-acetylcysteine (NAC). CONCLUSION: UBE2L3 is upregulated in osteosarcoma cells, and silencing of UBE2L3 promotes oxidative stress in these cells, leading to enhanced necroptosis and delayed progression of osteosarcoma.
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As a public health problem, prostate cancer engenders huge economic and life-quality burden. Developing effective chemopreventive regimens to alleviate the burden remains a major challenge. Androgen signaling is vital to the development and progression of prostate cancer. Targeting androgen signaling via blocking the production of the potent ligand dihydrotestosterone has been shown to decrease prostate cancer incidence. However, the potential of increasing the incidence of high-grade prostate cancers has been a concern. Mechanisms of disease progression after the intervention may include increased expression of androgen receptor (AR) in prostate tissue and expression of the constitutively active AR splice variants (AR-Vs) lacking the ligand-binding domain. Thus, novel agents targeting the receptor, preferentially both the full-length and AR-Vs, are urgently needed. In the present study, we show that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) effectively downregulates the expression and activity of both the full-length AR and AR-Vs. The effects of PPD on AR and AR-Vs are manifested by an immediate drop in proteins followed by a reduction in transcripts, attributed to PPD induction of proteasome-mediated degradation and inhibition of the transcription of the AR gene. We further show that although PPD inhibits the growth as well as AR expression and activity in LNCaP xenograft tumors, the morphology and AR expression in normal prostates are not affected. This study is the first to show that PPD suppresses androgen signaling through downregulating both the full-length AR and AR-Vs, and provides strong rationale for further developing PPD as a promising agent for the prevention and/or treatment of prostate cancer.
Assuntos
Processamento Alternativo/genética , Regulação para Baixo/efeitos dos fármacos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Sapogeninas/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/prevenção & controle , Complexo de Endopeptidases do Proteassoma/metabolismo , Sapogeninas/uso terapêuticoRESUMO
Obesity is a chronic inflammation with increased serum levels of insulin, insulin-like growth factor 1 (IGF1), and interleukin-17 (IL-17). The objective of this study was to test a hypothesis that insulin and IGF1 enhance IL-17-induced expression of inflammatory chemokines/cytokines through a glycogen synthase kinase 3ß (GSK3B)-dependent mechanism, which can be inhibited by melatonin. We found that insulin/IGF1 and lithium chloride enhanced IL-17-induced expression of C-X-C motif ligand 1 (Cxcl1) and C-C motif ligand 20 (Ccl20) in the Gsk3b(+/+) , but not in Gsk3b(-/-) mouse embryonic fibroblast (MEF) cells. IL-17 induced higher levels of Cxcl1 and Ccl20 in the Gsk3b(-/-) MEF cells, compared with the Gsk3b(+/+) MEF cells. Insulin and IGF1 activated Akt to phosphorylate GSK3B at serine 9, thus inhibiting GSK3B activity. Melatonin inhibited Akt activation, thus decreasing P-GSK3B at serine 9 (i.e., increasing GSK3B activity) and subsequently inhibiting expression of Cxcl1 and Ccl20 that was induced either by IL-17 alone or by a combination of insulin and IL-17. Melatonin's inhibitory effects were only observed in the Gsk3b(+/+) , but in not Gsk3b(-/-) MEF cells. Melatonin also inhibited expression of Cxcl1, Ccl20, and Il-6 that was induced by a combination of insulin and IL-17 in the mouse prostatic tissues. Further, nighttime human blood, which contained high physiologic levels of melatonin, decreased expression of Cxcl1, Ccl20, and Il-6 in the PC3 human prostate cancer xenograft tumors. Our data support our hypothesis and suggest that melatonin may be used to dampen IL-17-mediated inflammation that is enhanced by the increased levels of insulin and IGF1 in obesity.
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Quinase 3 da Glicogênio Sintase/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Insulina/farmacologia , Interleucina-17/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Humanos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Cloreto de Lítio/farmacologia , Melatonina/metabolismo , Melatonina/farmacologia , Camundongos , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de SinaisRESUMO
BACKGROUND: Osteosarcoma is the most common type of primary malignant bone tumor. INTRODUCTION: This study aimed to explore potential key prognostic genes and their roles in osteosarcoma. METHODS: Three microarray datasets for osteosarcoma were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened by the Limma package. Functional enrichment analysis was performed based on DAVID, GeneMANIA, and Metascape databases. Prognostic value of DEGs was elevated by survival analysis. CIBERSORT was used to assess the infiltrating abundance of 22 immune cells, followed by the Pearson correlation analysis between immune cells and prognosis-related genes. Gene set enrichment analysis and drug-gene interactions prediction were performed for prognosis-related genes. RESULTS: A total of 8 common up-regulated DEGs and 13 common down-regulated DEGs were screened in the GSE36001 and GSE56001 datasets. Enrichment analysis showed these DEGs were implicated in platelet activation, SMAD protein phosphorylation, lymphocyte/leukocyte/T cells activation, and cell migration. Survival analysis indicated that elevated expression of ADAM19 and TUBB1 were associated with a favorable prognosis. CIBERSORT algorithm revealed the higher infiltrating level of CD8 T cells, macrophages M0, and M2 in osteosarcoma. ADAM19 expression positively correlated with naïve B cells and negatively correlated with activated dendritic cells infiltrating abundance. TUBB1 expression positively correlated with gamma delta T cells while negatively correlated with helper follicular T cells infiltrating abundance. A total of 56 drugs were found to target TUBB1. CONCLUSION: ADAM19 and TUBB1 could be prognostic biomarkers in osteosarcoma. Both their expression correlates with tumor infiltrating immune cells. TUBB1 was a multi-drug target that might be a therapeutic target in osteosarcoma.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Osteossarcoma/diagnóstico , Osteossarcoma/genética , Movimento Celular , Algoritmos , Bases de Dados Factuais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Proteínas ADAM , Tubulina (Proteína)RESUMO
Molecular alterations found in gliomas are now considered entity-defining features. The World Health Organization (WHO) classification system currently classifies the vast majority of gliomas utilizing an integrated genotype-phenotype approach. We present a case of diffuse astrocytoma with a mosaic isocitrate dehydrogenase (IDH)1-R132H-mutant immunophenotype and low subclonal allele frequency. A 35-year-old patient with a history of IDH1-R132H mutated diffuse astrocytoma in 20014 presented to the hospital again in 2019. MRI examination showed a non-enhancing abnormal signal in the periphery of her previous surgical cavity. Histopathological examination revealed that the tumor was hypercellular and without high grade histopathological features. The neoplastic cells were immunohistologically positive for GFAP, Olig2, and ATRX. However, only some scattered tumor cells were positive for IDH1-R132H. Cytogenetic studies revealed a lack of chromosomal 1p/19q co-deletion. Further next-generation sequencing (NGS) demonstrated a low-level IDH1-R132H mutation and allele frequency. Based on these findings, the diagnosis of diffuse astrocytoma with mosaic IDH1- R132H-mutant immunophenotype and low subclonal allele frequency (WHO grade II) was generated. This case indicates that gliomas may have heterogeneous molecular profile and the intra-tumoral molecular heterogeneity highlights the need to further characterize the molecular profile for glioma classification and clinical management.
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A case of myofibrosarcoma of breast is reported. A female patient aged 81 years presented with a mammary mass lesion. Histologically, the tumor consisted of neoplastic spindle cells arranged in fascicles and with variably cellularity and hyalinization. Immunohistochemical studies showed expression of vimentin, smooth-muscle actin, and Bcl-2, but not desmin, S-100, C-kit, or CD34. Proliferative index identified by Ki67 was approximately 30%. Electron microscopy revealed variable amount of rough endoplasmic reticulum, myofilaments, fibronexus junctions, and fibronectin fibrils. The histological, immunohistochemical, and ultrastructural features of this tumor were consistent with myofibrosarcoma. This case will be one of the very few cases of ultrastructurally confirmed mammary myofibrosarcoma reported in the literature and contributes to the recognition of this rare mammary malignant neoplasm. The literature on mammary myofibrosarcoma and its differential diagnosis is also reviewed.
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Neoplasias da Mama/patologia , Fibrossarcoma/patologia , Miossarcoma/patologia , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Microscopia EletrônicaRESUMO
Sarcomas are a heterogeneous group of malignant mesenchymal neoplasms. This study aimed to investigate the immune-related prognostic gene signatures in the tumor microenvironment of sarcoma. The RNA-sequencing data and clinical phenotype data of 260 sarcoma samples and two normal samples were downloaded from The Cancer Genome Atla (TCGA) database. Tumor purity and immune cells infiltration were evaluated by Estimation of Stromal and Immune cells in Malignant Tumors using Expression data (ESTIMATE) deconvolution algorithm. Differentially expressed genes (DEGs) were screened in high vs. low immune score groups. Survival analysis was performed using Kaplan-Meier curve with log-rank test. Tumor infiltrating of immune cells was analyzed by Tumor Immune Estimation Resource (TIMER). High immune score and ESTIMATE score were associated with favorable prognosis. A total of 623 immune DEGs were screened. The majority of these genes (532 genes accounting for 85% of the DEGs) were up-regulated, and these genes were significantly enriched in various immune related biological processed and pathways, such as neutrophil activation, T cell activation, antigen processing and presentation. A total of 146 prognosis-related immune DEGs, and seven hub genes were identified, including B2M, HLA-DRB1, HLA-DRA, HLA-E, LCK, HLA-DPA1, and VAV1. Survival analysis showed that high expression of these genes was associated with a favorable prognosis. There were negative correlations between the expression of these hub genes and tumor purity, while positive correlations between expression of these hub genes and f infiltration levels of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages and dendritic cells. These results help to stratify patients with different immune subtypes and help to design immunotherapy strategies for these patients in sarcoma.
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Sarcoma , Microambiente Tumoral , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Mapas de Interação de Proteínas , Sarcoma/genética , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: This study hoped to explore the potential biomarkers and associated metabolites during osteosarcoma (OS) progression based on bioinformatics integrated analysis. METHODS: Gene expression profiles of GSE28424, including 19 human OS cell lines (OS group) and 4 human normal long bone tissue samples (control group), were downloaded. The differentially expressed genes (DEGs) in OS vs. control were investigated. The enrichment investigation was performed based on DEGs, followed by protein-protein interaction network analysis. Then, the feature genes associated with OS were explored, followed by survival analysis to reveal prognostic genes. The qRT-PCR assay was performed to test the expression of these genes. Finally, the OS-associated metabolites and disease-metabolic network were further investigated. RESULTS: Totally, 357 DEGs were revealed between the OS vs. control groups. These DEGs, such as CXCL12, were mainly involved in functions like leukocyte migration. Then, totally, 38 feature genes were explored, of which 8 genes showed significant associations with the survival of patients. High expression of CXCL12, CEBPA, SPARCL1, CAT, TUBA1A, and ALDH1A1 was associated with longer survival time, while high expression of CFLAR and STC2 was associated with poor survival. Finally, a disease-metabolic network was constructed with 25 nodes including two disease-associated metabolites cyclophosphamide and bisphenol A (BPA). BPA showed interactions with multiple prognosis-related genes, such as CXCL12 and STC2. CONCLUSION: We identified 8 prognosis-related genes in OS. CXCL12 might participate in OS progression via leukocyte migration function. BPA might be an important metabolite interacting with multiple prognosis-related genes.
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Biomarcadores Tumorais/análise , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Osteossarcoma/genética , Osteossarcoma/mortalidade , Compostos Benzidrílicos/metabolismo , Linhagem Celular Tumoral , Quimiocina CXCL12/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Fenóis/metabolismo , Prognóstico , Mapas de Interação de Proteínas/genética , Análise de Sobrevida , Transcriptoma/genéticaRESUMO
BACKGROUND: Intramedullary spinal cord metastasis (ISCM) account for a minority of all spinal cord tumors. Rarely, symptoms from ISCM may be the initial presentation of an unknown primary carcinoma. Intramedullary metastasis from a second malignancy or from an unknown neuroendocrine malignancy is extremely rare and has never been reported in the literature. Because of the rarity of these tumors and the low volume of cases, well-defined treatment guidelines do not exist for the management of ISCM. Here we present a rare and one of the first reports of an intramedullary metastatic neuroendocrine tumor. CASE DESCRIPTION: A 66-year-old woman with a history of breast cancer presented with worsening bilateral lower extremity numbness for 2 months. Imaging revealed an intramedullary spinal cord tumor at the T4 level. The patient underwent microsurgical resection of the intramedullary spinal cord tumor. At operation, the tumor had an exophytic component. Subtotal resection was achieved. Pathology revealed a neuroendocrine metastasis, likely pulmonary in origin. She achieved partial resolution of neurologic symptoms at follow-up. CONCLUSIONS: Neuroendocrine ISCM are rare and lack well-defined treatment guidelines. Care should be individualized in these cases. Whenever feasible, surgical resection should be considered. Despite multidisciplinary care, the prognosis is dismal with limited life expectancy. Larger, multiinstitutional, or national database studies are needed that compare treatment modalities in the management of ISCM to identify the therapy with the best outcomes.
Assuntos
Carcinoma Neuroendócrino/secundário , Neoplasias Pulmonares/patologia , Neoplasias da Medula Espinal/secundário , Idoso , Neoplasias da Mama/patologia , Humanos , Masculino , Segunda Neoplasia Primária/patologiaRESUMO
BACKGROUND AND IMPORTANCE: Intramedullary spinal cord cavernous malformations represent 5% to 12% of spinal vascular disease. Most patients present with acute or progressive neurological symptoms, including motor weakness or sensory loss. Surgical resection is the only definitive management and is recommended for symptomatic lesions that are surgically accessible. CLINICAL PRESENTATION: A 35-yr-old woman presented with a sudden onset of pain and temperature sensation loss in the left lower extremity. Magnetic resonance imaging of the spine showed a hemorrhage located ventral and slightly lateral to the right of the midline of the spinal cord from C7 through T3. Ultimately, a right lateral myelotomy between the ventral and dorsal roots was performed, and the cavernous malformation was removed. Postoperative imaging confirmed gross total resection of the cavernous malformation. CONCLUSION: In this article, we report a highly unusual case of a multisegment, ruptured intramedullary cavernous malformation that was ultimately resected through a lateral myelotomy approach. This case demonstrates that a lateral approach to the spinal cord substance can be utilized for ruptured cavernous malformation, especially if there is hemorrhage at the surface of the spinal cord. This can be used as an entry into the anterolateral compartment of the spinal cord, which would otherwise be regarded as a highly morbid approach due to the sensory deficits induced. We believe this entry point to the spinal cord is feasible in highly select cases such as this.
Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central , Neoplasias da Medula Espinal , Feminino , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Humanos , Imageamento por Ressonância Magnética , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/cirurgia , Coluna VertebralRESUMO
Robust patient-derived platforms that recapitulate the cellular and molecular fingerprints of glioblastoma are crucial for developing effective therapies. Here, we describe a chemically defined protocol for 3D culture and propagation of glioblastoma in 3D gliospheres, patient-derived organoids (PDOs), mouse brain orthotopic xenografts (PDOXs), and downstream drug and immunofluorescence assays. This simple-to-follow protocol allows assessing drug sensitivity, on-target activity, and combined drug synergy. Promising therapies can then be validated in PDOXs for translation in precision medicine oncology trials. For complete details on the use and execution of this protocol, please refer to Chadwick et al. (2020) and Patrizii et al. (2018).
Assuntos
Neoplasias Encefálicas , Encéfalo , Glioblastoma , Organoides , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Organoides/metabolismo , Organoides/patologia , Organoides/transplante , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Pilocytic astrocytomas are tumors of the central nervous system mostly during the first two decades of life. Although they are mostly common in the midline structures of children, pilocytic astrocytoma within the ventricular system of an adult is extremely rare. We report a case of a 38-year old woman with obstructive hydrocephalus secondary to a brain tumor within the third ventricle. On histological examination, the tumor exhibited biphasic growth pattern comprising compacted cellular areas with Rosenthal fibers and loose textured microcystic areas with eosinophilic granular bodies. Mitosis or necrosis was not present. Immunohistochemical studies demonstrated glial fibrillary acid protein (GFAP), Olig2, and ATRX positivity as well as NeuN and EMA negativity. Ki67 labeling index was less than 1%. Molecular studies revealed that there are no isocitrate dehydrogenase (IDH) gene mutation and H3F3A mutation. This clinical presentation along with the histologic and molecular findings is consistent with a pilocytic astrocytoma arising in the third ventricle of this adult brain, which indicates that pilocytic astrocytoma can present as an intraventricular tumor in an adult patient and should be routinely included in the differential diagnosis of intraventricular brain neoplasm.
RESUMO
Angiolipomas are slow-growing, soft tissue tumors consisting of mature adipocytes and thin-walled blood vessels. While most angiolipomas are subcutaneous lesions in the trunk and upper extremities, intraosseous angiolipomas are rare at cranial site. We present the case of a 61-year-old female with an enlarging lesion in the left frontoparietal skull following minor head trauma. Radiography confirmed an expansile, enhancing, spiculated bony lesion in the left frontoparietal calvarium with extension outside the cortex into the soft tissues. She underwent a craniectomy for complete resection of the calvarial mass, which was histologically composed of mature adipocytes and disorganized blood vessels highlighted by an immunophenotype positive for S100 and CD34, respectively, consistent with a cranial intraosseous angiolipoma. The review of the literature that reported five cases of cranial intraosseous angiolipoma with our case representing the sixth case is discussed.