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Cancer Imaging : the Official... Oct 2023The glymphatic system actively exchanges cerebrospinal fluid (CSF) and interstitial fluid (ISF) to eliminate toxic interstitial waste solutes from the brain parenchyma....
BACKGROUND
The glymphatic system actively exchanges cerebrospinal fluid (CSF) and interstitial fluid (ISF) to eliminate toxic interstitial waste solutes from the brain parenchyma. Impairment of the glymphatic system has been linked to several neurological conditions. Glioblastoma, also known as Glioblastoma multiforme (GBM) is a highly aggressive form of malignant brain cancer within the glioma category. However, the impact of GBM on the functioning of the glymphatic system has not been investigated. Using dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) and advanced kinetic modeling, we examined the changes in the glymphatic system in rats with GBM.
METHODS
Dynamic 3D contrast-enhanced T1-weighted imaging (T1WI) with intra-cisterna magna (ICM) infusion of paramagnetic Gd-DTPA contrast agent was used for MRI glymphatic measurements in both GBM-induced and control rats. Glymphatic flow in the whole brain and the olfactory bulb was analyzed using model-derived parameters of arrival time, infusion rate, clearance rate, and residual that describe the dynamics of CSF tracer over time.
RESULTS
3D dynamic T1WI data identified reduced glymphatic influx and clearance, indicating an impaired glymphatic system due to GBM. Kinetic modeling and quantitative analyses consistently indicated significantly reduced infusion rate, clearance rate, and increased residual of CSF tracer in GBM rats compared to control rats, suggesting restricted glymphatic flow in the brain with GBM. In addition, our results identified compromised perineural pathway along the optic nerves in GBM rats.
CONCLUSIONS
Our study demonstrates the presence of GBM-impaired glymphatic response in the rat brain and impaired perineural pathway along the optic nerves. Reduced glymphatic waste clearance may lead to the accumulation of toxic waste solutes and pro-inflammatory signaling molecules which may affect the progression of the GBM.
Topics: Rats; Animals; Glioblastoma; Brain; Glymphatic System; Magnetic Resonance Imaging; Contrast Media
PubMed: 37904254
DOI: 10.1186/s40644-023-00628-w -
Neuroscience Bulletin Nov 2023Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy, characterized by late diagnosis, aggressive growth, and therapy resistance, leading to... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy, characterized by late diagnosis, aggressive growth, and therapy resistance, leading to a poor overall prognosis. Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape. The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets. In this review, we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC, summarize the potential signaling pathways modulating the neuronal-cancer interaction, and discuss the current and future therapeutic possibilities for this condition.
Topics: Humans; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Signal Transduction; Peripheral Nerves; Tumor Microenvironment
PubMed: 37347365
DOI: 10.1007/s12264-023-01082-1 -
International Journal of Molecular... Sep 2023Adenoid cystic carcinoma (ACC) has a worldwide incidence of three to four cases per million population. Although more cases occur in the minor and major salivary glands,... (Review)
Review
Adenoid cystic carcinoma (ACC) has a worldwide incidence of three to four cases per million population. Although more cases occur in the minor and major salivary glands, it is the most common lacrimal gland malignancy. ACC has a low-grade, indolent histological appearance, but is relentlessly progressive over time and has a strong proclivity to recur and/or metastasise. Current treatment options are limited to complete surgical excision and adjuvant radiotherapy. Intra-arterial systemic therapy is a recent innovation. Recurrent/metastatic disease is common due to perineural invasion, and it is largely untreatable as it is refractory to conventional chemotherapeutic agents. Given the rarity of this tumour, the molecular mechanisms that govern disease pathogenesis are poorly understood. There is an unmet, critical need to develop effective, personalised targeted therapies for the treatment of ACC in order to reduce morbidity and mortality associated with the disease. This review details the evidence relating to the molecular underpinnings of ACC of the lacrimal gland, including the chromosomal translocations, -signalling pathway aberrations, DNA damage repair gene mutations and epigenetic modifications.
Topics: Humans; Carcinoma, Adenoid Cystic; Lacrimal Apparatus; Salivary Gland Neoplasms; Neoplasm Recurrence, Local; Salivary Glands
PubMed: 37762061
DOI: 10.3390/ijms241813755 -
Frontiers in Oncology 2023Adenoid cystic carcinoma (ACC) is an aggressive tumor with a high propensity for distant metastasis and perineural invasion. This tumor is more commonly found in regions... (Review)
Review
Adenoid cystic carcinoma (ACC) is an aggressive tumor with a high propensity for distant metastasis and perineural invasion. This tumor is more commonly found in regions of the head and neck, mainly the salivary glands. In general, the primary treatment modality for ACC is surgical resection and, in some cases, postoperative radiotherapy. However, no effective systemic treatment is available for patients with advanced disease. Furthermore, this tumor type is characterized by recurrent molecular alterations, especially rearrangements involving the , and genes. In addition, they also reported copy number alterations (CNAs) that impact genes. One of them is , mutations that affect signaling pathways such as NOTCH, PI3KCA, and PTEN, as well as alterations in chromatin remodeling genes. The identification of new molecular targets enables the development of specific therapies. Despite ongoing investigations into immunotherapy, tyrosine kinase inhibitors, and anti-angiogenics, no systemic therapy is approved by the FDA for ACC. In this review, we report the genetic and cytogenetic findings on head and neck ACC, highlighting possible targets for therapeutic interventions.
PubMed: 37476370
DOI: 10.3389/fonc.2023.1191218