ABSTRACT
The 2016 WHO Classification of Tumours of the Central Nervous System incorporates a new diagnostic entity: the mutant diffuse midline glioma H3K27, a tumor with a characteristic location and special molecular biology. We report the case of a 51-year-old male patient with progressive diplopia. The imaging study showed a mesencephalic tumor; the stereotacic biopsy disclosed an Anaplastic Astrocytoma Isocitrate dehydrogenase (IDH) wild type. The molecular study concludes H3K27 mutation. The patient was treated with radiotherapy with concurrent and adjuvant chemotherapy (temozolomide) with partial recovery of the diplopia.
Subject(s)
Humans , Male , Middle Aged , Brain Neoplasms/genetics , Histones/genetics , Glioma/genetics , Mutation/genetics , Brain Neoplasms/pathology , Brain Neoplasms/diagnostic imaging , Magnetic Resonance Imaging , Biomarkers, Tumor , Genetic Markers , Neuroimaging , Glioma/pathology , Glioma/diagnostic imagingABSTRACT
BACKGROUND: During the last few years it has been shown in several laboratories that Celecoxib (Cx), a non-steroidal anti-inflammatory agent (NSAID) normally used for pain and arthritis, mediates antitumor and antiangiogenic effects. However, the effects of this drug on a tumor cell line resistant to chemotherapeutical drugs used in cancer have not been described. Herein we evaluate the angiogenic and antitumor effects of Cx in the development of a drug-resistant mammary adenocarcinoma tumor (TA3-MTXR). RESULTS: Cx reduces angiogenesis in the chick embryonic chorioallantoic membrane assay (CAM), inhibits the growth and microvascular density of the murine TA3-MTXR tumor, reduces microvascular density of tumor metastases, promotes apoptosis and reduces vascular endothelial growth factor (VEGF) production and cell proliferation in the tumor. CONCLUSION: The antiangiogenic and antitumor Cx effects correlate with its activity on other tumor cell lines, suggesting that Prostaglandins (PGs) and VEGF production are involved. These results open the possibility of using Celecoxib combined with other experimental therapies, ideally aiming to get synergic effects.
Subject(s)
Animals , Female , Chick Embryo , Mice , Pyrazoles/pharmacology , Sulfonamides/pharmacology , Breast Neoplasms/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Apoptosis/drug effects , Drug Resistance, Neoplasm/drug effects , Lung Neoplasms/secondary , Neovascularization, Pathologic/drug therapy , Pyrazoles/administration & dosage , Sulfonamides/administration & dosage , Breast Neoplasms/pathology , Drug Screening Assays, Antitumor , Chickens , In Situ Nick-End Labeling , Angiogenesis Inhibitors/pharmacology , Cell Line, Tumor , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Chorioallantoic Membrane , Cell Proliferation/drug effects , CelecoxibABSTRACT
High-grade gliomas are highly vascularized tumors. Neo-angiogenesis plays a key role in tumor growth and resistance to therapy. A cerebrospinal fluid (CSF) sample could be a useful way to obtain pro-angiogenic predictive or prognostic markers at different stages of the disease. As a first step we looked for pro-angiogenic activity in the CSF of patients with high-grade gliomas. We performed the chicken embryo chorio-allantoic membrane (CAM) assay to study the angiogenic potential of the cerebrospinal fluid (CSF), obtained either by lumbar puncture (LP) or craniotomy from six patients with high-grade brain tumors (three glioblastoma (WHO grade IV), one anaplastic oligodendroglioma (WHO grade III), two anaplastic ganglioglioma (WHO grade III)), and four healthy controls. Significantly increased neo-angiogenesis was observed on the surface of the growing CAM in the 6 patients with high-grade gliomas compared to controls (3.69 ± 1.23 versus 2.16 ± 0.97 capillaries per area (mean ± SD), p<0.005). There was no statistical difference related to the hystological grade of the tumor (WHO grade III or IV), previous treatment (radio-chemotherapy plus temozolomide, temozolomide alone or no treatment), or the site of CSF sample (surgery or lumbar puncture). Our results suggest a pro-angiogenic potential in the CSF of patients with high-grade gliomas.
Subject(s)
Adult , Animals , Chick Embryo , Humans , Male , Middle Aged , Brain Neoplasms/cerebrospinal fluid , Chorioallantoic Membrane/blood supply , Glioma/cerebrospinal fluid , Neovascularization, Pathologic/etiology , Brain Neoplasms/blood supply , Case-Control Studies , Craniotomy , Cerebrospinal Fluid/physiology , Glioma/blood supply , Neoplasm Staging , Predictive Value of Tests , PrognosisABSTRACT
El tratamiento de la Esclerosis Múltiple ha sufrido un desarrollo vertiginoso durante la última década. En esta revisión se analizan estas nuevas terapias en forma paralela al proceso fisiopatológico del cuadro, de manera conocer detalladamente el mecanismo de acción de cada uno de los fármacos actualmente en uso o en estudio,para el manejo de la Esclerosis Múltiple.
The treatment of Multiple Sclerosis has suffered a tremendous development in the past decade. In this article we review the current an new treatment options with a pathophysiology point of view, so readers will can know drugs available and the mechanism of action of each of them.