Obstacles to Glioblastoma Treatment Two Decades after Temozolomide.

Glioblastomas are considered the most common and aggressive primary brain tumor in adults, with an average of 15 months' survival rate. The treatment is surgery resection, followed by chemotherapy with temozolomide, and/or radiotherapy. Glioblastoma must have wild-type IDH gene and some characteristics, such as TERT promoter mutation, EGFR gene amplification, microvascular proliferation, among others. Glioblastomas have great heterogeneity at cellular and molecular levels, presenting distinct phenotypes and diversified molecular signatures in each tumor mass, making it difficult to define a specific therapeutic target. It is believed that the main responsibility for the emerge of these distinct patterns lies in subcellular populations of tumor stem cells, capable of tumor initiation and asymmetric division. Studies are now focused on understanding molecular mechanisms of chemoresistance, the tumor microenvironment, due to hypoxic and necrotic areas, cytoskeleton and extracellular matrix remodeling, and in controlling blood brain barrier permeabilization to improve drug delivery. Another promising therapeutic approach is the use of oncolytic viruses that are able to destroy specifically glioblastoma cells, preserving the neural tissue around the tumor. In this review, we summarize the main biological characteristics of glioblastoma and the cutting-edge therapeutic targets that are currently under study for promising new clinical trials.

Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies.

Lysophosphatidic acid (LPA) is an abundant bioactive phospholipid, with multiple functions both in development and in pathological conditions. Here, we review the literature about the differential signaling of LPA through its specific receptors, which makes this lipid a versatile signaling molecule. This differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis; and also, how it can act as a powerful mediator of pathological conditions, such as neuropathic pain, neurodegenerative diseases, and cancer progression. Ultimately, we review the preclinical and clinical uses of Autotaxin, LPA, and its receptors as therapeutic targets, approaching the most recent data of promising molecules modulating both LPA production and signaling. This review aims to summarize the most update knowledge about the mechanisms of LPA production and signaling in order to understand its biological functions in the central nervous system both in health and disease.

Fibular Nerve Repair by Lateral Sural Cutaneous Nerve Graft: Anatomic Feasibility Study and Clinical Results.

OBJECTIVE: The common fibular nerve (CFN) is the most frequently injured nerve in the lower limbs. Surgical management is necessary in approximately two thirds of patients and includes neurolysis, suture, graft repair, or nerve transfer. The distal sural nerve is the preferred donor for grafting, but it is not without complications and requires a second incision. We sought to study the surgical anatomy of the lateral sural cutaneous nerve (LSCN) with the aim of repairing CFN injuries through the same incision and as a potential source for grafting in other nerve injuries. METHODS: The popliteal fossa was dissected in 11 lower limbs of embalmed cadavers to study LSCN variations. Four patients with CFN injuries then underwent surgical repair by LSCN grafting using the same surgical approach. RESULTS: At the medial margin of the biceps femoris, the LSCN emerged from the CFN approximately 8.15 cm above the fibular head. The LSCN ran longitudinally to the long axis of the popliteal fossa, with an average of 3.2 cm medial to the fibular head. The mean LSCN length and diameter were 9.61 cm and 3.6 mm, respectively. The LSCN could be harvested in all patients for grafting. The mean graft length was 4.4 cm. Motor function was consistently recovered for foot eversion but was recovered to a lesser extent for dorsiflexion and toe extension. All patients recovered sensitive function (75% of S3). Hypoesthesia was recognized at the calf. CONCLUSIONS: LSCN harvest is a viable alternative for nerve grafting, especially for repairing short CFN injuries, thereby avoiding the need for a second incision.