Tuberous sclerosis complex

TSC1.2 Tuberous sclerosis complex hamartomas of the brain, heart, kidneys, skin, lungs, and eyes... 

Manning, B. D., and Cantley, L. C. (2003). United at last The tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signaling. Biochem. Soc. Trans. 31, 573-578. 

Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J., and Candey, L. C. (2002). Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 10, 151—162. 

Rolfe, M., McLeod, L. E., Pratt, P. F., and Proud, C. G. (2005). Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2). Biochem. J. 388, 973-984. 

Extensive preclinical studies have shown that sensitivity to mTOR inhibition may correlate with aberrant activation of the PI3K pathway or loss of functional tuberous sclerosis complex (TSC), as occurred in patients with tuberous sclerosis syndrome [151,152]. Rapamycin (compound 31, Fig. 6), which was the first compound shown to inhibit mTOR kinase activity, is an approved drug for prevention of allograft rejection. Rapamycin is a macrocyclic... 

The mammalian target of rapamycin complex 1 (mTORCl) system as it is affected by increased nutrients (f AA). The increased AA may interact with the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2), which inhibit Ras homologue enriched in brain (Rheb). The increased AA may also act on Rheb or mTOR directly. Rapamycin inhibits mTOR in this complex, which includes Raptor and the G protein, GpL, which binds to the kinase domain of mTOR both facilitate mTOR signaling. Output from the Raptor protein in mTORCl includes the activation of the ribosomal subunit, S6K, and inhibition of the 4E-binding protein (4E-BP), both of which lead to protein synthesis and cellular hypertrophy. mTOR directly stimulates ribosome synthesis and inhibits autophagy. Arrows indicate stimulatory effects, T-bars indicate inhibition... 

About 5% to 10% of GI neuroendocrine tumors are associated with a hereditary disease. The inherited syndromes and their associated genes include multiple endocrine neoplasia type I MENl gene), neurofibromatosis type 1 NFl gene), von Hippel-Lindau disease VHL gene), and the tuberous sclerosis complex TSCl or TSC2 gene).406... 

A 6-month-old boy with infantile spasms and tuberous sclerosis complex was treated with vigabatrin for 1 month. A routine follow-up MRI demonstrated asymptomatic diffusion abnormalities in bilateral thalami. Similar abnormalities were also identified in globi pallidi and brainstem. 

Lymphangioleiomyomatosis (LAM) is a rare interstitial lung disease that affects women of childbearing age exclusively. The tuberous sclerosis complex (TSC), an autosomal dominant inherited disorder, is associated with parenchymal lung changes identical to LAM (Pallisa etal.2002). 

Fig. 26. 17a,b. A 30-year-old woman with tuberous sclerosis complex, a Axial CT image shows multiple thin-walled cysts in a uniform distribution. The cysts adjacent to the upper right mediastinum tend to conflate (white arrows), b Coronal CT image displays the uniform and bilateral distribution of the cysts throughout both lungs. The lung parenchyma between the cysts is inconspicuous... 

Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary lymphangio-leiomyomatosis in women with tuberous sclerosis complex. Mayo CUn Proc 2000 75(6) 591-594. 

Moss J, Avila NA, Barnes PM, et al. Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex. Am J Respir Crit Care Med 2001 164(4) 669 71. 

Miyake M, Tateishi U, Maeda T, et al. Pulmonary lymphangioleiomyomatosis in a male patient with tuberous sclerosis complex. Radiat Med 2005 23(7) 525-527. Aubry MC, Myers JL, Ryu JH, et al. Pulmonary lymphangioleiomyomatosis in a man. Am J Respir Crit Care Med 2000 162(2 pt l) 749-752. 

Tapon N, Ito N, Dickson BJ, et al. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 2001 105(3) 345 355. 

Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A 2000 97(ll) 6085-6090. 

Henske EP. Metastasis of benign tumor cells in tuberous sclerosis complex. Genes Chromosomes Cancer 2003 38(4) 376-381. 

Avila NA, Dwyer AJ, Rabel A, et al. Sporadic lymphangioleiomyomatosis and tuberous sclerosis complex with lymphangioleiomyomatosis comparison of CT features. Radiology 2007 242(l) 277-285. 

Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference revised clinical diagnostic criteria. J Child Neurol 1998 13(12) 624-628. 

Ess KC. (2010) Tuberous sclerosis complex a brave new world Curr Opin Neurol 23(2), 189-193. 

Koenig MK, Butler U, Northrup H. (2008) Regression of subependymal giant cell astrocytoma with rapamy-cin in tuberous sclerosis complex. J Child Neurol 23 (10), 1238-1239. 

Von Hippel-Lindau disease predisposes to the development of various tumors (hemangioblastomas of the neuraxis and retina, tumors of the membranous labyrinth, renal clear cell carcinomas or cysts, pheochromocytomas, pancreatic cysts or tumors, and epididymal cystadenomas). Renal cancer constitutes one of the main causes of death (Richard et al. 1998). Conversely, meta-analysis of cases of coincident tuberous sclerosis complex shows that the risk of malignancy is comparable with the normal population (Tello et al. 1998). 

Casper KA, Donnelly LF, Chen B et al (2002) Tuberous sclerosis complex renal imaging findings. Radiology 225(2) 451-456... 

Tello R, Blickman G, Buonomo C et al (1998) Meta analysis of the relationship between tuberous sclerosis complex and renal cell carcinoma. Eur J Radiol 27(2) 131-138... 

---