Neuropathology最新文献_第2页

Neuropilin-1 enhances temozolomide resistance in glioblastoma via the STAT1/p53/p21 axis. 神经蛋白-1通过STAT1/p53/p21轴增强胶质母细胞瘤对替莫唑胺的耐药性

IF 1.3 4区医学

Neuropathology Pub Date : 2024-08-01 Epub Date: 2024-03-06 DOI: 10.1111/neup.12966

Ping Huang, Lixia Zhang, Hongwei Wang, Changwu Dou, Haitao Ju, Peng Yue, Jiaxing Ren

{"title":"Neuropilin-1 enhances temozolomide resistance in glioblastoma via the STAT1/p53/p21 axis.","authors":"Ping Huang, Lixia Zhang, Hongwei Wang, Changwu Dou, Haitao Ju, Peng Yue, Jiaxing Ren","doi":"10.1111/neup.12966","DOIUrl":"10.1111/neup.12966","url":null,"abstract":"Glioblastoma (GBM) is the most prevalent primary intracranial tumor. Temozolomide (TMZ) is the first-line chemotherapy for GBM. Nonetheless, the development of TMZ resistance has become a main cause of treatment failure in GBM patients. Evidence suggests that neuropilin-1 (NRP-1) silencing can attenuate GBM cell resistance to TMZ. This study aims to determine potential mechanisms by which NRP-1 affects TMZ resistance in GBM. The parental U251 and LN229 GBM cells were exposed to increasing concentrations of TMZ to construct TMZ-resistant GBM cells (U251/TMZ, LN229/TMZ). BALB/c nude mice were injected with U251/TMZ cells to establish the xenograft mouse model. Functional experiments were carried out to examine NRP-1 functions. Western blotting and real-time quantitative polymerase chain reaction were used to evaluate molecular protein and mRNA expression, respectively. Immunohistochemical staining showed NRP-1 and STAT1 expression in mouse tumors. The results showed that NRP-1 was highly expressed in TMZ-resistant cells. Moreover, knocking down NRP-1 attenuated the TMZ resistance of U251/TMZ cells, while upregulating NRP-1 enhanced TMZ resistance of the parental cells. NRP-1 silencing elevated GBM cell sensitivity to TMZ in tumor-bearing mice. Depleting NRP-1 reduced STAT1, p53, and p21 expression in U251/TMZ cells. STAT1 depletion offset NRP-1 silencing evoked attenuation of GBM cell resistance to TMZ. Collectively, our study reveals that NRP-1 enhances TMZ resistance in GBM possibly by regulating the STAT1/p53/p21 axis.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140050006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A case of disseminated spinal astroblastoma harboring a MAMLD1::BEND2 fusion. 一例携带 MAMLD1::BEND2 融合基因的播散性脊柱星形母细胞瘤。

IF 1.3 4区医学

Neuropathology Pub Date : 2024-08-01 Epub Date: 2023-12-21 DOI: 10.1111/neup.12960

Erin N Walker, Maxwell T Laws, Francesca Cozzi, Martha Quezado, Desmond A Brown, Eric C Burton

{"title":"A case of disseminated spinal astroblastoma harboring a MAMLD1::BEND2 fusion.","authors":"Erin N Walker, Maxwell T Laws, Francesca Cozzi, Martha Quezado, Desmond A Brown, Eric C Burton","doi":"10.1111/neup.12960","DOIUrl":"10.1111/neup.12960","url":null,"abstract":"Astroblastoma, MN1-altered, is a rare neoplasm of the central nervous system (CNS). This malignancy shares similar histopathological features with other CNS tumors, including ependymomas, making it challenging to diagnose. DNA methylation profiling is a new and robust technique that may be used to overcome this diagnostic hurdle. We report the case of a now 25-year-old female diagnosed with what was initially called an ependymoma located in the cervical spine at the age of 2 years old. After initial resection, the tumor recurred multiple times and within 2 years of diagnosis had disseminated disease throughout the brain and spinal cord. She has now undergone over two decades of treatment, including multiple surgical resections, radiation therapy, and administration of numerous chemotherapeutic agents. In 2021, the patient presented to our institution with lumbosacral radicular symptoms due to enlarging lesions within the lumbosacral spine. Reexamination of formalin-fixed, paraffin-embedded material from the patient's tumor using genomic DNA methylation profiling resulted in a diagnostic change from grade III anaplastic ependymoma to astroblastoma, MN1-altered. This work describes another confirmed case of astroblastoma, MN1-altered, to the growing body of literature.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11190029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From pathological mechanisms in Krabbe disease to cutting-edge therapy: A comprehensive review. 从克拉伯病的病理机制到前沿疗法：全面回顾。

IF 1.3 4区医学

Neuropathology Pub Date : 2024-08-01 Epub Date: 2024-03-06 DOI: 10.1111/neup.12967

Imen Ketata, Emna Ellouz

{"title":"From pathological mechanisms in Krabbe disease to cutting-edge therapy: A comprehensive review.","authors":"Imen Ketata, Emna Ellouz","doi":"10.1111/neup.12967","DOIUrl":"10.1111/neup.12967","url":null,"abstract":"Since its initial documentation by Knud Krabbe in 1916, numerous studies have scrutinized the characteristics of Krabbe disease (KD) until the identification of the mutation in the GALC gene. In alignment with that, we investigated the natural history of KD spanning eight decades to gain a deeper understanding of the evolutionary trajectory of its mechanisms. Through our comprehensive analysis, we unearthed additional novel elements in molecular biology involving the micropathological mechanism of the disease. This review offers an updated perspective on the metabolic disorder that defines KD. Recently, extracellular vesicles (EVs), autophagy impairment, and α-synuclein have emerged as pivotal players in the neuropathological processes. EVs might serve as a cellular mechanism to avoid or alleviate the detrimental impacts of excessive toxic psychosine levels, and extracting EVs could contribute to synapse dysfunction. Autophagy impairment was found to be independent of psychosine and reliant on AKT and B-cell lymphoma 2. Additionally, α-synuclein has been recognized for inducing cellular death and dysfunction in common biological pathways. Our objective is to assess the effectiveness of advanced therapies in addressing this particular condition. While hematopoietic stem cells have been a primary treatment, its administration proves challenging, particularly in the presymptomatic phase. In this review, we have compiled information from over 10 therapy trials, comparing them based on their benefits and disadvantage.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Giant cell glioblastoma with lipogenic differentiation in a patient with neurofibromatosis type 1: A case report. 一名神经纤维瘤病 1 型患者的脂肪源性分化巨细胞胶质母细胞瘤：病例报告。

IF 1.3 4区医学

Neuropathology Pub Date : 2024-08-01 Epub Date: 2024-01-10 DOI: 10.1111/neup.12961

Masayuki Shintaku, Tetsuo Hashiba, Masahiro Nonaka, Akio Asai, Koji Tsuta

引用次数: 0

Malignancy arising in adamantinomatous craniopharyngioma: Report of a rare case with unusual morphologic features. 金刚瘤性颅咽管瘤中的恶性肿瘤：一例形态特征异常的罕见病例报告。

IF 1.3 4区医学

Neuropathology Pub Date : 2024-08-01 Epub Date: 2024-02-27 DOI: 10.1111/neup.12962

Sumanta Das, Mehar Chand Sharma, Vaishali Suri, Saumya Sahu, Ajay Garg, Rajinder Kumar Laythalling

{"title":"Malignancy arising in adamantinomatous craniopharyngioma: Report of a rare case with unusual morphologic features.","authors":"Sumanta Das, Mehar Chand Sharma, Vaishali Suri, Saumya Sahu, Ajay Garg, Rajinder Kumar Laythalling","doi":"10.1111/neup.12962","DOIUrl":"10.1111/neup.12962","url":null,"abstract":"Adamantinomatous craniopharyngioma is a grade 1 tumor that arises in a sellar/suprasellar location. Despite being a grade 1 tumor, there is high recurrence and endocrinal insufficiency. Malignancy arising in craniopharyngioma is extremely rare, has a dismal prognosis, and is currently not included as a separate entity in the World Health Organization Classification of Central Nervous System 5th edition. Here we describe a case of adamantinomatous craniopharyngioma and its malignant counterpart. The malignant part had unique histomorphology and basaloid cells with pseudoglandular architecture and a myxoid background. It bore a striking resemblance to adenoid cystic carcinoma. Both the benign and malignant counterparts were beta-catenin and SOX-2 positive, providing proof of the malignant part arising from the benign part. Tumors like squamous cell carcinoma and odontogenic ghost cell carcinoma have been described in cranipharyngioma. This case study is the first to describe this unique morphology of adenoid cystic carcinoma-like features. The possibility of adenoid cystic carcinoma was excluded by immunohistochemistry.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spinal astroblastoma, MN1 altered in 3-year-old child: An uncommon tumor at an unusual site. 3岁儿童脊柱星形母细胞瘤，MN1改变：不常见部位的不常见肿瘤

IF 1.3 4区医学

Neuropathology Pub Date : 2024-08-01 Epub Date: 2024-02-26 DOI: 10.1111/neup.12965

Arun Kumar Panda, Sumanta Das, Anuj Singh, Sandeep Vaishya, Rakesh Kumar Gupta, Mehar Chand Sharma, Sunita Ahlawat

引用次数: 0

Diffuse leptomeningeal glioneuronal tumor with distinct neuronal and glial components but identical diagnostic molecular and genetic features. 弥漫性脑膜胶质细胞瘤，具有不同的神经元和胶质成分，但诊断分子和遗传特征相同。

IF 1.3 4区医学

Neuropathology Pub Date : 2024-07-28 DOI: 10.1111/neup.12996

Andrew J Witten, Carson Dougherty, Chunhai Hao

{"title":"Diffuse leptomeningeal glioneuronal tumor with distinct neuronal and glial components but identical diagnostic molecular and genetic features.","authors":"Andrew J Witten, Carson Dougherty, Chunhai Hao","doi":"10.1111/neup.12996","DOIUrl":"https://doi.org/10.1111/neup.12996","url":null,"abstract":"The 2021 World Health Organization (WHO) classification of the central nervous system (CNS) tumors has classified diffuse leptomeningeal glioneuronal tumor (DLGNT) as a mixed neuronal and glial tumor. Here, we report a DLGNT with two distinct morphological tumor components but identical molecular features. A four-year-old female child presented with progressive right upper extremity weakness. Magnetic resonance imaging (MRI) revealed the leptomeningeal enhancement over the brain stem and cervicothoracic spine. The histological examination of surgical specimens revealed two distinct tumor components: approximately half of the tumor is composed of oligodendroglioma-like tumor intermingled with nodules of ganglioglioma-like tumor. Immunohistochemistry confirmed the oligodendroglioma and ganglioglioma features. The molecular genetic studies demonstrated the features of DLGNT, including fusion of KIAA1549::BRAF, deletion of chromosome 1p, and absence of isocitrate dehydrogenase 1/2 (IDH1/2) mutation in both tumor components. Interestingly, the genetic studies also revealed the distinct chromosomal abnormalities of the loss of chromosome 4 only in oligodendroglioma-like tumor and copy neutral loss of heterozygosity of 7Q34Q36.3 in the ganglioglioma-like tumor component. This case highlights the critical role of molecular testing in the diagnosis of rare cases of DLGNT with diverse morphological components as well as in the identification of unique molecular alternations responsible for morphological phenotypes of the distinct tumors in DLGNT.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increase in cathepsin K gene expression in Duchenne muscular dystrophy skeletal muscle. 杜兴氏肌肉萎缩症骨骼肌中 cathepsin K 基因表达的增加。

IF 1.3 4区医学

Neuropathology Pub Date : 2024-07-16 DOI: 10.1111/neup.12995

Shigemi Kimura, Noriko Miyake, Shiro Ozasa, Hiroe Ueno, Yoshinobu Ohtani, Yutaka Takaoka, Ichizo Nishino

{"title":"Increase in cathepsin K gene expression in Duchenne muscular dystrophy skeletal muscle.","authors":"Shigemi Kimura, Noriko Miyake, Shiro Ozasa, Hiroe Ueno, Yoshinobu Ohtani, Yutaka Takaoka, Ichizo Nishino","doi":"10.1111/neup.12995","DOIUrl":"https://doi.org/10.1111/neup.12995","url":null,"abstract":"Dystrophinopathy is caused by alterations in the dystrophin gene. The severe phenotype, Duchenne muscular dystrophy (DMD), is caused by a lack of dystrophin in skeletal muscles, resulting in necrosis and regenerating fibers, inflammatory cells, and muscle fibrosis. Progressive muscle weakness is a characteristic finding of this condition. Here, we encountered a rare case of a 10-year-old patient with asymptomatic dystrophinopathy with no dystrophin expression and investigated the reason for the absence of muscle weakness to obtain therapeutic insights for DMD. Using RNA-seq analysis, gene expression in skeletal muscles was compared among patients with asymptomatic dystrophinopathy, three patients with typical DMD, and two patients without dystrophinopathy who were leading normal daily lives. Cathepsin K (CTSK), myosin heavy chain 3 (MYH3), and nodal modulator 3-like genes exhibited a >8-fold change, whereas crystallin mu gene (CRYM) showed a <1/8-fold change in patients with typical DMD compared with their expression in the patient with asymptomatic dystrophinopathy. Additionally, CTSK and MYH3 expression exhibited a >16-fold change (P < 0.01), whereas CRYM expression showed a <1/16-fold change (P < 0.01) in patients with typical DMD compared with their expression in those without dystrophinopathy. CTSK plays an essential role in skeletal muscle loss, fibrosis, and inflammation in response to muscles injected with cardiotoxin, one of the most common reagents that induce muscle injury. Increased CTSK expression is associated with muscle injury or necrosis in patients with DMD. The lack of muscle weakness in the patient with asymptomatic dystrophinopathy might be attributed to the low CTSK expression in the muscles. To the best of our knowledge, this is the first report to demonstrate that CTSK expression was significantly higher in the skeletal muscles of patients with DMD with a typical phenotype than in those without dystrophinopathy.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuropathologic findings in a patient with hemiparkinsonism and hemiatrophy syndrome. 一名患有半帕金森症和半萎缩综合征的患者的神经病理学发现。

IF 1.3 4区医学

Neuropathology Pub Date : 2024-07-07 DOI: 10.1111/neup.12994

Masataka Nakamura, Ayako Tsuge, Kosuke Miyake, Takenobu Kunieda, Hirofumi Kusaka, Yusuke Yakushiji

{"title":"Neuropathologic findings in a patient with hemiparkinsonism and hemiatrophy syndrome.","authors":"Masataka Nakamura, Ayako Tsuge, Kosuke Miyake, Takenobu Kunieda, Hirofumi Kusaka, Yusuke Yakushiji","doi":"10.1111/neup.12994","DOIUrl":"https://doi.org/10.1111/neup.12994","url":null,"abstract":"The first postmortem neuropathological findings of a hemiparkinsonism and hemiatrophy (HPHA) patient are presented. A 50-year-old man developed resting tremors affecting the right hand and leg, followed by mild clumsiness of the right hand. On examination, he exhibited muscle atrophy of the right leg extremity, accompanied by right-sided parkinsonism. Brain magnetic resonance imaging was normal. Based on the clinical and radiological findings, HPHA syndrome was diagnosed, showing a good response to L-DOPA. He gradually developed muscular atrophy of the right distal upper extremity. Thirteen years after the onset of the disease, left-sided parkinsonism appeared. The patient died of Trousseau's syndrome associated with a rapidly emerging pancreatic tumor. The total duration of the disease was 14 years. Neuropathologically, the substantia nigra showed markedly left-predominant neuronal loss, along with almost symmetrical Lewy body (LB) pathology. These findings indicated that the patient originally had fewer neurons in the left substantia nigra than in the right, probably caused by congenital or childhood cerebral injury, followed by the development of unilateral parkinsonism due to the progression of LB pathology. Despite our extensive neuropathological analysis, we could not specify the etiology or anatomical substrate responsible for the development of right upper and lower extremity atrophy. Further clinicopathological studies are needed to elucidate the pathoanatomical areas causing hemiparkinsonism and hemiatrophy.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenotypic and genotyping spectrum of two Iranian cases with RBCK1-associated polyglucosan body myopathy. 两例伊朗 RBCK1 相关多聚糖体肌病患者的表型和基因分型谱。

IF 1.3 4区医学

Neuropathology Pub Date : 2024-06-23 DOI: 10.1111/neup.12993

Marzieh Babaee, Yalda Nilipour, Sahar Alijanpour, Aida Ghasemi, Mohammad Mehdi Taghdiri, Payam Sarraf, Mohammad Miryounesi, Mahtab Ramezani

{"title":"Phenotypic and genotyping spectrum of two Iranian cases with RBCK1-associated polyglucosan body myopathy.","authors":"Marzieh Babaee, Yalda Nilipour, Sahar Alijanpour, Aida Ghasemi, Mohammad Mehdi Taghdiri, Payam Sarraf, Mohammad Miryounesi, Mahtab Ramezani","doi":"10.1111/neup.12993","DOIUrl":"https://doi.org/10.1111/neup.12993","url":null,"abstract":"Glycogen storage diseases (GSDs) are a group of metabolic disorders affecting glycogen metabolism, with polyglucosan body myopathy type 1 (PGBM1) being a rare variant linked to RBCK1 gene mutations. Understanding the clinical diversity of PGBM1 aids in better characterization of the disease. Two unrelated Iranian families with individuals exhibiting progressive muscle weakness underwent clinical evaluations, genetic analysis using whole exome sequencing (WES), and histopathological examinations of muscle biopsies. In one case, a novel homozygous RBCK1 variant was identified, presenting with isolated myopathy without cardiac or immune involvement. Conversely, the second case harbored a known homozygous RBCK1 variant, displaying a broader phenotype encompassing myopathy, cardiomyopathy, inflammation, and immunodeficiency. Histopathological analyses confirmed characteristic skeletal muscle abnormalities consistent with PGBM1. Our study contributes to the expanding understanding of RBCK1-related diseases, illustrating the spectrum of phenotypic variability associated with distinct RBCK1 variants. These findings underscore the importance of genotype-phenotype correlations in elucidating disease mechanisms and guiding clinical management. Furthermore, the utility of next-generation sequencing techniques in diagnosing complex neurogenetic disorders is emphasized, facilitating precise diagnosis and enabling tailored genetic counseling for affected individuals and their families.","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0