TGFbeta acts as a tumor suppressor in normal epithelial cells and early-stage tumors and becomes an oncogenic factor in advanced tumors. The molecular mechanisms involved in the malignant function of TGFbeta are not fully elucidated. We demonstrate that high TGFbeta-Smad activity is present in aggressive, highly proliferative gliomas and confers poor prognosis in patients with glioma. We discern the mechanisms and molecular determinants of the TGFbeta oncogenic response with a transcriptomic approach and by analyzing primary cultured patient-derived gliomas and human glioma biopsies. The TGFbeta-Smad pathway promotes proliferation through the induction of PDGF-B in gliomas with an unmethylated PDGF-B gene. The epigenetic regulation of the PDGF-B gene dictates whether TGFbeta acts as an oncogenic factor inducing PDGF-B and proliferation in human glioma.

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A 73-year-old male came to our institution with a history of right ptosis and intermittent double vision of 1 week's duration. He had been diagnosed with diabetes mellitus 5 years earlier and had chronic smoking and alcohol abuse history. Physical examination revealed right ptosis and outward ocular deviation with no evidence of pupillary asymmetry. There were no others abnormal findings on neurologic examination. With these finding, a third nerve palsy caused by an ischemic lesion of the nerve because of diabetes was suspected. Emergent computed tomography (CT) of the head revealed cortical-subcortical atrophy and no ischemic lesions. A cranial magnetic resonance showed a mass with a soft tissue component invading the right cavernous sinus. The mass displace the carotide and the intraselar structures (Figs. 1 and 2). With these results, a tumoral disease was suspected and for thus extensive systemic workup was initiated. Chest X-ray, routine blood values, and urinalysis results were normal. The serum PSA level was elevated (1000 ng/mL). Abdomen and chest CT detected hepatic and bone metastases. Findings on bone scintigraphy were compatible with extensive diffuse metastases throughout the skeleton, including the cranial lesion. Prostatic FNAB was indicated based on these findings, the result of which was prostatic adenocarcinoma (Fig. 3). Hormone therapy treatment was initiated with LH-RH agonist and Flutamide followed by Bifosfonates.Prostate carcinoma can metastasize to any organ especially bone but cranial nerve palsies secondary to metastatic prostate to the base of the skull are uncommon situations, most of them presented several years after the diagnosed is made. 1 The cause of the neuropathy is the direct compression of nerves by tumor in this strategic location. The involvement of the cavernous sinus area by malignant neoplasm may occur generally through local extension of a nearby locally advanced primary head and neck tumor or more rarely, through hematogenus spread of tumors located outside including breast and prostate cancer. 2 In most of the previous reports the cranial nerve palsy appears in the context of a widespread metastatic prostate disease diagnosed several years before. 3 The initial diagnosed is usually established by magnetic resonance images. 3 Treatment of skull metastases depends largely of patient symptoms as well as the radiologic findings. Two therapeutic approaches can be performed: systemic treatment with hormonal therapy; and a local therapy with surgery or radiotherapy. It has been reported that hormone therapy treatment can decrease the mass and improve the symptoms. 4 Radiation therapy often is performed in an attempt to palliate symptoms and surgery is occasionally necessary. 3 In conclusion, we describe an uncommon presentation of a metastatic prostate cancer. It should be mention that as more effective therapy for advanced prostate cancer becomes available and patients live longer, skull metastases can be expected to be encountered more frequently. Clinicians caring for pat...

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