Publications by authors named "Pashayar P Lookian"

Background: Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.

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  • Reversible Cerebral Vasoconstriction Syndrome (RCVS) is characterized by the constriction and dilation of cerebral blood vessels, but its underlying causes are not fully understood.
  • Two cases of RCVS linked to the drug teprotumumab were reported, involving two women with Graves' eye disease who experienced symptoms like leg weakness and severe headaches after starting the medication.
  • Both patients showed improvement after treatment with verapamil, leading to concerns about the potential role of teprotumumab in triggering RCVS, warranting further research into this connection.
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Background: Growing evidence indicates fractal analysis (FA) has potential as a computational tool to assess tumor microvasculature in glioblastoma (GBM). As fractal parameters of microvasculature have shown to be reliable quantitative biomarkers in brain tumors, there has been similar success in measuring the architecture of tumor tissue using FA in other tumor types. However, evaluating fractal parameters of tissue structure in relation to the microvasculature has not yet been implemented in GBM.

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Understanding physiologic and pathologic central nervous system function depends on our ability to map the entire cranial vasculature and neurovascular interfaces. To accomplish this, we developed a non-invasive workflow to visualize murine cranial vasculature via polymer casting of vessels, iterative sample processing and micro-computed tomography, and automatic deformable image registration, feature extraction, and visualization. This methodology is applicable to any tissue and allows rapid exploration of normal and altered pathologic states.

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  • Researchers have discovered a previously unknown transtentorial venous system (TTVS) that connects venous drainage in the human brain, challenging earlier beliefs that this part was mainly avascular.
  • The study used mice as a model to investigate the TTVS and found that it is present in adult mice and can be traced back to an embryonic stage where it aids in draining the choroid plexus.
  • The findings suggest that the TTVS is conserved between humans and mice, making mice a suitable model for further research into the development and implications of this venous system in brain physiology.
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  • The inner ear, located within the petrous bone of the skull, plays a critical role in transmitting sound and balance signals to the brain through cranial nerves, developing from neural crest during early growth stages.
  • While the anatomy of the inner ear in mice has been well-studied only up to day 6 after birth, both mice and humans continue to develop their inner ear and skull base into early adulthood.
  • Traditional methods for studying the inner ear structure have limitations, particularly as the bone hardens after birth, but modern imaging techniques like high-resolution Micro-CT and MRI now enable detailed 3D visualization of this complex anatomy, resulting in the creation of a new atlas for the murine inner ear.
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The foundation of precision immunotherapy in oncology is rooted in computational biology and patient-derived sample sequencing to enrich for and target immunogenic epitopes. Discovery of these tumor-specific epitopes through tumor sequencing has revolutionized patient outcomes in many types of cancers that were previously untreatable. However, these therapeutic successes are far from universal, especially with cancers that carry high intratumoral heterogeneity such as glioblastoma (GBM).

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Tumor resistance to cytotoxic therapeutics coupled with dose-limiting toxicity is a serious hurdle in the field of medical oncology. In the face of this obstacle, nitric oxide has emerged as a powerful adjuvant for the hypersensitization of tumors to more traditional chemo- and radio-therapeutics. Furthermore, emerging evidence indicates that nitric oxide donors have the potential to function independently in the clinical management of cancer.

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