The role of contextual signal TGF-ß1 inducer of epithelial mesenchymal transition in metastatic lung adenocarcinoma patients with brain metastases: an update on its pathological significance and therapeutic potential.

Lung adenocarcinoma (LA) is the most common cause of cancer-related death worldwide. Despite the advances over last decade in new targeted therapies, cancer genetics, diagnostics, staging, and surgical techniques as well as new chemotherapy and radiotherapy protocols, the death rate from LA remains high. The tumour microenvironment is composed of several cytokines, one of which is transforming growth factor ß1 (TGF-ß1), which modulates and mediates the expression of epithelial-mesenchymal transition (EMT), correlated with invasive growth in LAs, and exhibits its pleiotropic effects through binding to transmembrane receptors TßR-1 (also termed activin receptor-like kinases - ALKs) and TßR-2. Accordingly, there is an urgent need to elucidate the molecular mechanisms associated with the tumoural spreading process and therapeutic resistance of this serious pathology. In this review, we briefly discuss the current role of contextual signal TGF-ß1 inducer of epithelial mesenchymal transition in metastatic lung adenocarcinoma patients with brain metastases, and give an overview of our current mechanistic understanding of the TGF-ß1-related pathways in brain metastases progression, TGF-ß1 pathway inhibitors that could be used for clinical treatment, and examination of models used to study these processes. Finally, we summarise the current progress in the therapeutic approaches targeting TGF-ß1.

Rosette-forming glioneuronal tumour of the fourth ventricle. Not always a foreseeable development.

AIM OF THE STUDY: Rosette-forming glioneuronal tumour (RGNT) of the fourth ventricle is an uncommon tumour. The management is not consensual. Most of the published cases show stable outcome with and without gross total resection and are regarded as having a relatively indolent behaviour. MATERIAL AND METHODS: We present a 32-year-old man with a tumour in the fourth ventricle. He underwent midline suboccipital craniectomy with gross total removal. RESULTS: The histopathological diagnosis was RGNT grade I. Four years later he presented a radiological progression and received stereotactic radiosurgery. At the last follow-up seven years after surgery, the MRI showed no recurrence. CONCLUSIONS: RGNT should be considered in the differential diagnosis of a posterior fossa tumour and has to be differentiated from other lesions for its indolent course and favourable prognosis. Surgical procedures should be carefully performed to avoid serious surgical morbidities. Stereotactic radiosurgery treatment appears to be a useful treatment in recurrence episodes.

Immunophenotypic features of dedifferentiated skull base chordoma: An insight into the intratumoural heterogeneity.

Chordomas are rare and low-grade malignant solid tumours, despite their histologically benign appearance, that arise in the bone from embryonic notochordal vestiges of the axial skeleton, a mesoderm-derived structure that is involved in the process of neurulation and embryonic development. Chordomas occurring in the skull base tend to arise in the basiocciput along the clivus. Three major morphological variants have been described (classical, chondroid, and atypical/dedifferentiated). The pathogenesis and molecular mechanisms involved in chordoma development remain uncertain. From a pathological standpoint, the microenvironment of a chordoma is heterogeneous, showing a dual epithelial-mesenchymal differentiation. These tumours are characterised by slow modality of biologic growth, local recurrence, low incidence of metastasis rates, and cancer stem cell (CSC) phenotype. The main molecular findings are connected with brachyury immunoexpression and activation of the downstream Akt and mTOR signalling pathways. The differentiation between typical and atypical chordomas is relevant because the tumoural microenvironment and prognosis are partially different. This review provides an insight into the recent and relevant concepts and histochemical markers expressed in chordomas, with special emphasis on dedifferentiated chordomas and their prognostic implications.

Mesenchymal/proangiogenic factor YKL-40 related to glioblastomas and its relationship with the subventricular zone.

Glioblastoma is the most common primary brain tumor. Despite multimodality therapy with aggressive microsurgical resection and adjuvant chemotherapy and radiotherapy, the median survival is below 15 months. Glioblastomas are heterogeneous tumors with high resistance to most chemotherapeutic drugs. According to reliable evidence, YKL-40, one of the best investigated chitinase-like protein, may facilitate invasion, migration and angiogenesis, and could be also responsible for temozolomide resistance in glioblastoma, thus conferring a dismal prognosis. Previous studies have demonstrated that glioblastoma stem cells give rise to endothelial cells through an YKL-40 influence. Such factor is closely related to the subventricular zone. This review focuses on the most recent theories involving the possible relationship between topographic gliomagenesis related to the subventricular zone and YKL-40..