Renal angiomyolipomas, cysts, and cancer in tuberous sclerosis complex

Neumann, Hartmut P. H.; Schwarzkopf, Georg; Henske, Elizabeth P.

doi:10.1016/s1071-9091(98)80005-3

Cited by 65 publications

(38 citation statements)

References 35 publications

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“…Angiomyolipomas consist of smooth muscle cells, adipose tissue, and disorganized thick-walled vascular channels (3). Their abnormal vasculature may lead to spontaneous life-threatening bleeding (4). Angiomyolipomas increase in size and/or number in about 60% of children affected by TSC, highlighting the need for close surveillance of the kidneys and the entire abdomen (5).…”

Section: Introductionmentioning

confidence: 99%

Survivin Expression in Tuberous Sclerosis Complex Cells

Carelli

Lesma

Paratore

et al. 2007

Mol Med

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Tuberous Sclerosis Complex (TSC) is a tumor suppressor gene disorder with mutations of TSC1/TSC2 genes. This leads to the development of hamartomas that most frequently affect central nervous system, kidney, and skin. Angiomyolipomas are abdominal masses made up of muscle vessels and adipose tissues that grow mostly in proximity to kidneys and liver. Bleeding and kidney failure are the major justification for surgery. This study shows that angiomyolipoma-derived human smooth muscle TSC2 -/-cells express the apoptosis inhibitor protein survivin when exposed to IGF-1. Survivin expression is also triggered whenever culture conditions perturb normal TSC2-/-cell function, such as the omission of EGF from the growth medium, the supplementation of anti-EGFR, blockade of PI3K and ERK, or inhibition of mTOR. Interestingly, single or simultaneous inhibition of PI3K by LY294002 and ERK by PD98059 does not prevent IGF-1-mediated survivin expression. Apoptogenic Smac/DIABLO, which is constitutively expressed by TSC2 -/-A + cells, is down-regulated by IGF-1 even in the presence of LY294002 and PD98059. These cells release IGF-1 by means of a negative feedback-regulated mechanism that is overrun when they are exposed to antibodies to IGF-1R, which increases the released amount by more than 400%. The autocrine release of IGF-1 may therefore be a powerful mechanism of survival of the tightly packed cells in the thick-walled vessels of TSC angiomyolipoma and in lymphangioleiomyomatosis (LAM) nodules. Future experimental therapies for TSC and LAM may result from the targeted inhibition of survivin, which may enhance sensitivity to TSC2 therapy.

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Section: Introductionmentioning

confidence: 99%

Survivin Expression in Tuberous Sclerosis Complex Cells

Carelli

Lesma

Paratore

et al. 2007

Mol Med

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“…Of those with tuberous sclerosis, 50% develop renal AML. [33,34,35] Renal AML is also more often bilateral and multifocal in this group. In tuberous sclerosis patients renal AML occurs at a 2:1 female: male ratio.…”

Section: Renal Angiomyolipomamentioning

confidence: 68%

“…[33] Growth of this neoplasm may be hormone dependent, which is suggested by both its predominance in the female and adult population. [33,34] 20% to 30% of AMLs are found in patients with tuberous sclerosis syndrome, an autosomal dominant disorder characterized by mental retardation, epilepsy, and adenoma sebaceum (distinctive skin lesion). Of those with tuberous sclerosis, 50% develop renal AML.…”

Section: Renal Angiomyolipomamentioning

confidence: 99%

“…In tuberous sclerosis patients renal AML occurs at a 2:1 female: male ratio. [34,35] In the absence of the tuberous sclerosis complex the lesion occurs more often in female patients, with most patients presenting later in life, during the fifth or sixth decade. [33,34] Though non-malignant, renal AML may still be of concern in that they can be associated with serious or fatal hemorrhage.…”

Section: Renal Angiomyolipomamentioning

confidence: 99%

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Radiologic Imaging of Renal Masses

Bird¹,

Bird²

2011

Renal Cell Carcinoma

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“…3 TSC-associated angiomyolipomas typically present at a younger age (mean age 30 years); and usually they are multiple, bilateral, and symptomatic tumors. [4][5][6] Extrarenal presentations of angiomyolipoma are rare and have been reported in the hilar lymph nodes, retroperitoneum, liver, and with direct extension into the venous system. We present a histopathologically proven rare case of renal angiomyolipoma with regional lymph node involvement in patient with tuberous sclerosis complex.…”

Section: Introductionmentioning

confidence: 99%