Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma

Science, Год журнала: 2014, Номер 344(6190), С. 1396 - 1401

Опубликована: Июнь 13, 2014

Human cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to profile 430 from five primary glioblastomas, which we found be inherently variable their expression diverse transcriptional programs related oncogenic signaling, proliferation, complement/immune response, hypoxia. also observed a continuum stemness-related states that enabled us identify putative regulators stemness vivo. Finally, show established glioblastoma subtype classifiers variably expressed across individual within demonstrate the potential prognostic implications such intratumoral heterogeneity. Thus, reveal previously unappreciated heterogeneity regulatory central biology, prognosis, therapy.

Язык: Английский

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Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment

PubMed, Год журнала: 2017, Номер 18(1), С. 3 - 9

Опубликована: Янв. 1, 2017

Glioblastoma multiforme (GBM) is one of the most malignant types central nervous system tumors. Despite advances in treatment modalities it remains largely incurable. The objective our review to provide a holistic picture GBM epidemiology, etiology, pathogenesis, clinical findings and treatment. A literature search was conducted for at PubMed Google Scholar, with relevant key words like glioblastoma multiforme, signs symptoms, etc., papers published until 2015 were reviewed. It found that radiation certain genetic syndromes are only risk factors identified date GBM. Depending on tumor site patients may present clinic varying symptoms. To confirm presence extent tumor, various invasive non-invasive imaging techniques require employment. survey revealed pathogenesis involve aberrations multiple signaling pathways through mutations altered gene expression. Although several options available, including surgery, along adjuvant chemo- radio-therapy, disease has poor prognosis generally succumb within 14 months diagnosis.

Язык: Английский

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Advancing the understanding of autism disease mechanisms through genetics

Nature Medicine, Год журнала: 2016, Номер 22(4), С. 345 - 361

Опубликована: Апрель 1, 2016

Язык: Английский

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Acetate Is a Bioenergetic Substrate for Human Glioblastoma and Brain Metastases

Cell, Год журнала: 2014, Номер 159(7), С. 1603 - 1614

Опубликована: Дек. 1, 2014

Язык: Английский

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Adult Glioblastoma

Journal of Clinical Oncology, Год журнала: 2017, Номер 35(21), С. 2402 - 2409

Опубликована: Июнь 22, 2017

Glioblastoma (GBM) is a rare tumor and one of the most challenging malignancies to treat in all oncology. Although advances have been made treatment GBM, encouraging outcomes typically are not observed; patients diagnosed with these tumors generally dismal prognosis poor quality life as disease progresses. This review summarizes clinical presentation diagnostic methods, evidentiary basis for current standards care, investigational approaches or manage GBM. Because track record developing effective therapies GBM has dismal, we also challenges successful therapeutic biomarker development.

Язык: Английский

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A Three-Dimensional Organoid Culture System Derived from Human Glioblastomas Recapitulates the Hypoxic Gradients and Cancer Stem Cell Heterogeneity of Tumors Found In Vivo

Cancer Research, Год журнала: 2016, Номер 76(8), С. 2465 - 2477

Опубликована: Фев. 20, 2016

Many cancers feature cellular hierarchies that are driven by tumor-initiating cancer stem cells (CSC) and rely on complex interactions with the tumor microenvironment. Standard cell culture conditions fail to recapitulate original architecture or microenvironmental gradients not designed retain heterogeneity of parental tumors. Here, we describe a three-dimensional system supports long-term growth expansion organoids derived directly from glioblastoma specimens, including patient-derived primary cultures, xenografts, genetically engineered glioma models, patient samples. Organoids multiple regions tumors selective tumorigenic potential. Furthermore, could be established brain metastases typically amenable in vitro culture. Once formed, grew for months displayed regional rapidly dividing outer region SOX2(+), OLIG2(+), TLX(+) surrounding hypoxic core primarily non-stem senescent diffuse, quiescent CSCs. Notably, within were sensitive radiotherapy, whereas adjacent CSCs radioresistant. Orthotopic transplantation resulted displaying histologic features, single-cell invasiveness, more representative compared those formed sphere cultures. In conclusion, present new ex vivo model which phenotypically diverse populations can simultaneously cultured explore facets influences CSC biology. Cancer Res; 76(8); 2465-77. ©2016 AACR.

Язык: Английский

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Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies

Oncogene, Год журнала: 2018, Номер 37(12), С. 1561 - 1575

Опубликована: Янв. 8, 2018

Язык: Английский

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PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma

Oncotarget, Год журнала: 2016, Номер 7(22), С. 33440 - 33450

Опубликована: Март 7, 2016

// Xiaoman Li 1,* , Changjing Wu Nianci Chen 2 Huadi Gu 3 Allen Yen 4 Liu Cao 1 Enhua Wang 3,5 and Liang Key Laboratory of Medical Cell Biology, Ministry Education, China University, Shenyang, Class 9 the 97th Clinical Medicine Seven-Year Program, Department Pathology, The College Basic Sciences, School Medicine, University Texas Southwestern Center, Dallas, Texas, United States America 5 First Affiliated Hospital * These authors have contributed equally to this work Correspondence to: Wang, email: Keywords : glioblastoma, EGFR, PI3K/Akt/mTOR pathway, targeted therapy Received December 05, 2015 Accepted February 24, 2016 Published March 07, Abstract Glioblastoma multiform (GBM) is most common malignant glioma all brain tumors currently effective treatment options are still lacking. GBM frequently accompanied with overexpression and/or mutation epidermal growth factor receptor (EGFR), which subsequently leads activation many downstream signal pathways such as phosphatidylinositol 3-kinase (PI3K)/Akt/rapamycin-sensitive mTOR-complex (mTOR) pathway. Here we explored reason why inhibition pathway may serve a compelling therapeutic target for disease, provided an update data EFGR inhibitors in clinical trials.

Язык: Английский

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Extracellular vesicles: Novel promising delivery systems for therapy of brain diseases

Journal of Controlled Release, Год журнала: 2017, Номер 262, С. 247 - 258

Опубликована: Июль 4, 2017

Язык: Английский

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Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma

Nature reviews. Cancer, Год журнала: 2015, Номер 15(5), С. 302 - 310

Опубликована: Апрель 9, 2015

Язык: Английский

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