ABSTRACT
Cerebellar granule neurons are the most abundant neurons in the brain, and a critical element of the circuitry that controls motor coordination and learning. In addition, granule neuron precursors (GNPs) are thought to represent cells of origin for medulloblastoma, the most common malignant brain tumor in children. Thus, understanding the signals that control the growth and differentiation of these cells has important implications for neurobiology and neurooncology. Our previous studies have shown that proliferation of GNPs is regulated by Sonic hedgehog (Shh), and that aberrant activation of the Shh pathway can lead to medulloblastoma. Moreover, we have demonstrated that Shh-dependent proliferation of GNPs and medulloblastoma cells can be blocked by basic fibroblast growth factor (bFGF). But while the mitogenic effects of Shh signaling have been confirmed in vivo, the inhibitory effects of bFGF have primarily been studied in culture. Here, we demonstrate that mice lacking FGF signaling in GNPs exhibit no discernable changes in GNP proliferation or differentiation. In contrast, activation of FGF signaling has a potent effect on tumor growth: treatment of medulloblastoma cells with bFGF prevents them from forming tumors following transplantation, and inoculation of tumor-bearing mice with bFGF markedly inhibits tumor growth in vivo. These results suggest that activators of FGF signaling may be useful for targeting medulloblastoma and other Shh-dependent tumors.
Subject(s)
Cerebellar Neoplasms/pathology , Cerebellum/growth & development , Fibroblast Growth Factor 2/physiology , Medulloblastoma/pathology , Signal Transduction/physiology , Animals , Cell Cycle , Cell Differentiation , Cerebellar Neoplasms/etiology , Hedgehog Proteins/physiology , Medulloblastoma/etiology , Mice , Mice, Inbred C57BL , Neurons/cytology , Receptor, Fibroblast Growth Factor, Type 1/physiology , Stem Cells/cytologyABSTRACT
Takayasu's arteritis, pulseless disease or occlusive thromboaortopathy, is a progressive disease usually of young women. Early morbidity and death result from ischemia of vital organs. The results of surgical revascularization have been disappointing. Two women with Takayasu's arteritis are reported. They underwent transluminal dilatation of serious symptomatic stenoses of the origins of the left carotid, left subclavian, renal and superior mesenteric arteries. Four repeat dilatations were required. There was one complication. Clinical syndromes of transient cerebral ischemia, upper limb claudication, renal failure and intestinal angina have been reversed by transluminal dilatation. Percutaneous transluminal dilatation is a suggested alternative to surgical revascularization in selected patients with Takayasu's arteritis.
Subject(s)
Angioplasty, Balloon , Aortic Arch Syndromes/therapy , Takayasu Arteritis/therapy , Adult , Carotid Arteries , Female , Humans , Mesenteric Arteries , Renal Artery , Subclavian ArteryABSTRACT
A patient with Takayasu's disease and stenoses of the left common carotid and subclavian arteries presenting with unilateral episodic blindness and arm claudication was treated by transluminal angioplasty. Dilatation of the subclavian lesion by the femoral route and the carotid lesion through a carotid arteriotomy has resulted in relief of symptoms without morbidity.
Subject(s)
Angioplasty, Balloon , Aortic Arch Syndromes/therapy , Carotid Arteries , Subclavian Artery , Takayasu Arteritis/therapy , Adult , Female , Humans , Radiography , Takayasu Arteritis/diagnostic imagingABSTRACT
Mediastinoscopy is an efficient method of assessing lymphatic spread in carcinoma of the lung. It is also valuable in providing a definitive diagnosis of other lung diseases. At the Montreal Chest Hospital Centre diagnostic mediastinoscopy was performed in 60 patients with diseases of the lung other than primary carcinoma. All had preoperative radiologic evidence of hilar adenopathy. A definitive diagnosis was obtained in 91.7% of cases. Nonspecific adenitis was diagnosed in four patients and in none was there evidence of serious intrathoracic disease subsequently. Morbidity was minimal and there were no deaths. Mediastinoscopy is a safe, accurate and efficient aid in the evaluation of primary or secondary disease of the anterior intrathoracic lymphatic system.
Subject(s)
Lung Diseases/diagnosis , Mediastinoscopy , Adolescent , Adult , Aged , Breast Neoplasms/pathology , Female , Hodgkin Disease/diagnosis , Humans , Lung Neoplasms/diagnosis , Male , Middle Aged , Neoplasm Metastasis , Sarcoidosis/diagnosisABSTRACT
In a series of 760 patients with adenocarcinoma of the colon and rectum, 103 patients presented with acute obstruction requiring urgent surgical decompression. Obstructed patients were slightly older and had slightly more advanced tumors than the total group. Obstructing lesions of the left colon treated primarily by staged procedures had relatively low mortality and five year survival figures comparable to unobstructed cases. Obstructing lesions of the right colon had a much poorer absolute five year survival rate, mainly because of the high operative mortality associated with primary resection in our institution. Five year survival after curative resection in patients with obstructing tumors of the right colon was considerably less than in patients with nonobstructing tumors. A suggestion is made for consideration of proximal external bowel decompression in association with resection of the right colon.
