DEFINITION
Tuberous sclerosis is a rare, multi-system genetic disease that causes benign tumours to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin.
EPIDEMIOLOGY
The live-birth prevalence is estimated to be between 10 and 16 cases per 100,000
age, sex, seasonality, etc
SYMPTOMS
Angiomyolipomata: challenges, solutions, and future prospects based on over 100 cases treated. 2009
DIAGNOSIS
histopathology
radiology
NMR
laboratory tests
PATHOGENESIS
Kinases meet at TSC 2007
Rapamycin and Metformin can replace TSC1 and TSC2 effect on mTor?
Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. 2007
Furthermore, translation in MDA-MB-231 cells, which lack the AMPK kinase LKB1, and in tuberous sclerosis complex 2 null (TSC2) mouse embryonic fibroblasts was unaffected by metformin, indicating that LKB1 and TSC2 are involved in the mechanism of action of metformin . These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth.
PATIENT RISK FACTORS
Vascular
Genetic
Acquired
Hormonal
Genetic
Acquired
TISSUE SPECIFIC RISK FACTORS
anatomical (due its structure)
vascular (due to the local circulation)
physiopathological (due to tissue function and activity)
COMPLICATIONS
Regione Lombardia - Associazione Sclerosi Tuberosa
Sclerosi Tuberosa
Questa Seconda Edizione dell'Unica Pubblicazione in Lingua Italiana
sulla Sclerosi Tuberosa (ST) e' Stata Fortemente Voluta da Tutti i
Membri, Soci e Medici, dell'Associazione per Rispondere all'Esigenza
di Fornire Informazioni Mediche Aggiornate e Condivise che Aiutino
nella Diagnosi di Questa Malattia Genetica Rara, nella Gestione
Clinica della Persona Affetta da Sclerosi Tuberosa Attraverso le Linee
Guida ma Anche nella Comprensione della Patologia da Parte di chi
ne e' Affetto e di chi lo Ricorda
- Aspetti Clinici
- Introduzione
- Cenni Storici
- Incidenza e Prevalenza
- Segni Clinici
- Cute
- Lesioni Orali
- Cuore
- Sistema Vascolare
- Rene
- Sistema Nervoso Centrale
- Occhio
- Apparato Respiratorio
- Altri Organi ed Apparati
- Genetica
- Geni Responsabili e Proteine
- Come si Trasmette la Sclerosi Tuberosa
- Consulenza Genetica e Test Genetici
- Diagnosi
- Follow-Up
- Terapia
- Per Approfondire
Dimensione Del File PDF = 4.1 MB - Pagine = 83
Therapy
Rapamycin (sirolimus) in tuberous sclerosis associated pediatric central nervous system tumors. 2009
Clin Transplant. 2009 Nov 16. [Epub ahead of print]
Sirolimus-induced signaling modifications in Kaposi's sarcoma with resolution in a liver transplant recipient. 2009
Ho CM, Huang SF, Hu RH, Ho MC, Wu YM, Lee PH.
Department of Surgery, National Taiwan UniversityHospital, Taipei.
Sirolimus is one treatment option in transplant recipients with Kaposi's sarcoma (KS), which involves dysregulation of Akt-mammalian target of rapamycin (mTOR) signaling pathway. Signal modifications after sirolimus therapy in organ recipients with KS are largely unknown and not verified. We reported a case of KS found two yr after liver transplantation in which the immunosuppression was changed from tacrolimus, MMF, and steroid to sirolimus alone. In skin, which was found to have persistent KS after a two-month treatment of sirolimus and was removed completely one yr later, KS was no longer present. The patient went well without graft rejection. Tumor biopsies were performed before, two months, and one yr after the start of sirolimus. Immunohistochemical staining of vascular endothelial growth factor (VEGF), p-Akt, p-mTOR, p-p70 S6 kinase, and Western blot for p-tuberin/ tuberous sclerosis complex (TSC)2 was performed. VEGF was suppressed thoroughly in two-month use of sirolimus. In addition, p-Akt and p-mTOR, which were decreased at two months, could not be detected after one yr of treatment. Moreover, p-p70 S6 kinase, expressed strongly in overlying epidermis initially, was suppressed completely after two months of treatment. However, p-tuberin/TSC2, contrary to suggested theoretically, was not detected through all specimens, implying not to be a significant event. Suppressed expression of VEGF, p-Akt, and p-mTOR was the major event of signaling modification through the long-term use of sirolimus.
