No abstract

Despite the intensive recent research in cancer therapy, the prognosis in patients affected by high-grade gliomas is still very unfavorable. The efficacy of classical anti-cancer strategies is seriously limited by lack of specific therapies against malignant cells. The extracellular matrix plays a pivotal role in processes such as differentiation, apoptosis, and migration in both the normal and the pathologic nervous system. Glial tumors seem to be able to create a favorable environment for the invasion of glioma cells in cerebral parenchyma when they combine with the extracellular matrix via cell surface receptors. Glioma cells synthesize matrix proteins, such as tenascin, laminin, fibronectin that facilitate the tumor cell's motility. New treatments have shown to hit the acting molecules in the tumor growth and to increase the efficacy and minimize the toxicity. Antisense oligonucleotides are synthetic stretches of DNA which hybridize with specific mRNA strands. The specificity of hybridization makes antisense method an interesting strategy to selectively modulate the expression of genes involved in tumorigenesis. In this review we will focus on the mechanisms of action of antisense oligonucleotides and report clinical and experimental studies on the treatment of high-grade gliomas. We will also report the patents of preclinical and/or clinical studies that adopt the antisense oligonucleotide therapy list in cerebral gliomas.

Meningiomas represent the most common benign histological tumor of the central nervous system. Usually, meningiomas are intracranial, showing a typical dural tail sign on brain MRI with Gadolinium, but occasionally they can infiltrate the skull or be sited extracranially. We present a systematic review of the literature on extracranial meningiomas of the head and neck, along with an emblematic case of primary extracranial meningioma (PEM), which provides further insights into PEM management. A literature search according to the PRISMA statement was conducted from 1979 to June 2021 using PubMed, Web of Science, Google Scholar, and Scopus databases, searching for relevant Mesh terms (primary extracranial meningioma) AND (head OR neck). Data for all patients were recorded when available, including age, sex, localization, histological grading, treatment, possible recurrence, and outcome. A total of 83 published studies were identified through PubMed, Google Scholar, and Scopus databases, together with additional references list searches from 1979 to date. A total of 49 papers were excluded, and 34 manuscripts were considered for this systematic review, including 213 patients. We also reported a case of a 45-year-old male with an extracranial neck psammomatous meningioma with sizes of 4 cm × 3 cm × 2 cm. Furthermore, whole-body 68Ga-DOTATOC PET/CT was performed, excluding tumor spread to other areas. Surgical resection of the tumor was accomplished, as well as skin flap reconstruction, obtaining radical removal and satisfying wound healing. PEMs could suggest an infiltrative and aggressive behavior, which has never found a histopathological correlation with a malignancy (low Ki-67, <5%). Whole-body 68Ga-DOTATOC PET/CT should be considered in the patient’s global assessment. Surgical removal is a resolutive treatment, and the examination of frozen sections can confirm the benignity of the lesion, reducing the extension of the removal of healthy tissue surrounding the tumor.

Cancers originate as the result of hereditary or somatic alterations in genes that control critical biological processes. The accumulation of such genetic damage over time permits the survival and progressive transformation of abnormal cell populations that eventually lead to the formation of a tumor. Consistent with their high malignant potential, gliomas exhibit a vast array of well-documented genetic changes that likely contribute to their phenotype. Gliomagenesis is characterized by several biological events, such as activated growth factor receptor signaling pathways, downregulation of many apoptotic mechanisms and unbalance among proangiogenic and antiangiogenic factors. Several growth factor receptors, such epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDRGF), C-Kit, vascular endhotelial growth factor receptor (VEGFR) and others growth factors receptors, are overexpressed, amplified and/or mutated in gliomas. Features of the glioma cells are the loss of tumor suppressor genes, which are critical for the cell growth, differentiation and function.

The development and commercialization of new drugs is an articulated, lengthy, and very expensive process that proceeds through several steps, starting from target identification, screening new leading compounds for testing in preclinical studies, and subsequently in clinical trials to reach the final approval for therapeutic use. Preclinical studies are usually performed using both cell cultures and animal models, although they do not completely resume the complexity of human diseases, in particular neurodegenerative conditions. To this regard, stem cells represent a powerful tool in all steps of drug discovery. The recent advancement in induced Pluripotent Stem Cells (iPSCs) technology has opened the possibility to obtain patient-specific disease models for drug screening and development. Here, we report the use of iPSCs as a disease model for drug development in the contest of neurological disorders, including Alzheimer’s (AD) and Parkinson’s disease (PD), Amyotrophic lateral Sclerosis (ALS), and Fragile X syndrome (FRAX).