Efficacy and Safety of Sirolimus for Renal Angiomyolipoma in Patients with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis: A Systematic Review

Peng, Zhou; Yang, Lu; Wang, Tingting; Han, Ping; Liu, Zhenhua; Wang, Qiang

doi:10.1016/j.juro.2014.04.096

Cited by 34 publications

(25 citation statements)

References 28 publications

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“…Although significant progress has been made in characterizing the underlying cause of these conditions and pharmacologically slowing their progression with rapamycin, 23,37 our understanding of their pathogenesis remains incomplete because of the lack of an identified cell of origin. Because the only available bona fide cell lines to study these conditions are AML derived, we elucidated the source of these neoplastic cells by endowing them with TSC2 with the expectation that TSC2 reconstitution can revert the AML cell phenotype to that of its precursor cell type.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical trials with the mTORC1 inhibitor rapamycin, the only US Food and Drug Administrationeapproved drug for the treatment of LAM and AML, have revealed only partial efficacy in the treatment of both conditions 22,37,81,82 ; therefore, combined therapies with rapamycin followed by surgery, 83 in the case of AML, or including an adjuvant drug in addition to rapamycin, particularly in the case of LAM, are currently the focus of much attention. 25,84,85 On the basis of the results obtained with NCTD in the treatment of TSC2…”

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confidence: 99%

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Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2− Tumor Related to Lymphangioleiomyomatosis

Yue

Pacheco

Cheng

et al. 2016

The American Journal of Pathology

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Angiomyolipoma (AML) is a tumor closely related to lymphangioleiomyomatosis (LAM). Both entities are characterized by the proliferation of smooth muscle actin and melanocytic glycoprotein 100 (recognized by antibody HMB-45)epositive spindle-shaped and epithelioid cells. AML and LAM are etiologically linked to mutations in the tsc2 and tsc1 genes in the case of LAM. These genes encode the proteins tuberous sclerosis complex (TSC)-1 and TSC2, which are directly involved in suppressing the mechanistic target of rapamycin cell growth signaling pathway. Although significant progress has been made in characterizing and pharmacologically slowing the progression of AML and LAM with rapamycin, our understanding of their pathogenesis lacks an identified cell of origin. We used an AML-derived cell line to determine whether TSC2 restitution brings about the cell type from which AML arises. We found that AML cells express lymphatic endothelial cell markers consistent with lymphatic endothelial cell precursors in vivo and in vitro. Moreover, on TSC2 correction, AML cells mature into adult lymphatic endothelial cells and have functional attributes characteristic of this cell lineage, suggesting a lymphatic endothelial cell of origin for AML. These effects are dependent on TSC2-mediated mechanistic target of rapamycin inactivation. Finally, we demonstrate the in vitro effectiveness of norcantharidin, a lymphangiogenesis inhibitor, as a potential co-adjuvant therapy in the treatment of AML. (Am J Pathol 2016 http://dx

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2− Tumor Related to Lymphangioleiomyomatosis

Yue

Pacheco

Cheng

et al. 2016

The American Journal of Pathology

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“…Several studies have demonstrated the efficacy of oral rapamycin for treatment of giant cell astrocytomas and angiomyolipomas associated with TSC. 11,12 In 2008, Haemel et al 13 demonstrated a significant reduction in number of facial angiofibromas and associated erythema after 3 months of treatment with topical rapamycin without the systemic toxicity associated with oral administration. Later studies confirmed the profound effect of topical rapamycin on angiofibroma size and erythema and reported a reduction in recurrence rates.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Angiofibromas in a Tuberous Sclerosis Patient Using Topical Timolol 0.5% Gel

Krakowski

Nguyen

2015

Pediatrics

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Angiofibromas are the most recognized cutaneous manifestations of tuberous sclerosis complex. Angiofibromas can be associated with disfigurement, bleeding, pruritus, and erythema and may lead to significant psychosocial consequences for affected patients. Histopathologically, angiofibromas consist of a mixture of vascular and interstitial cells. Traditional treatment options include cryotherapy, electrocoagulation, radiofrequency ablation, dermabrasion, laser treatment, and topical agents such as podophyllotoxin. However, complications such as pain, postinflammatory hyperpigmentation, scarring, and the frequent recurrence rate reduce the utility of these treatment options. The introduction of topical rapamycin marked a turning point for treatment of facial angiofibromas; however, the lack of a standardized formulation, limited insurance coverage, and significant financial cost restrict universal access for patients and their caregivers. Both oral and topical β-blockers have proven extremely effective treatments for superficial vascular tumors such as hemangiomas and pyogenic granulomas. Topical β-blockers may potentially be useful for treatment of angiofibromas considering these lesions also contain a vascular component. Here we present an exploratory case report of a patient with tuberous sclerosis complex who had significant clinical improvement of her facial angiofibromas utilizing a “split-face” comparison protocol of topical timolol 0.5% gel after full-field treatment with ablative fractional laser resurfacing and pulsed-dye laser.

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“…Sirolimusa bağlı gözlenen en sık yan etkiler stomatit, solunum yolu enfeksiyonu, deri lezyonları ve hiperlipidemi olarak bildirilmiştir. Çalışmanın sonunda sirolimus tedavisi sırasında AML'nin tedaviye cevap verdiği ancak tedavi kesilmesi ile tümörün yeniden büyüme eğilimine geçtiği, genel olarak da sporadik lenfanjiyomiyomatozisli ya da TSC ilişkili AML'li hastalarda efektif ve güvenli bir tedavi olduğu kanaatine varılmıştır (32).…”

Section: Tedaviunclassified

Renal Angiomyolipoma, Review

Ulukaradağ¹,

Memik²,

Özkan³

2015

uob

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GirişAnjiyomiyolipom (AML) perivasküler epiteloid hücre tümörlerinin epiteloid diferansiyasyonu olan tümör ailesinin alt grubudur (1). Perivasküler epiteloid hücre tümörleri kan damarları etrafındaki epiteloid hücrelerin klonal proliferasyonu ile ortaya çıkmaktadırlar (2). Renal AML, tüberoz skleroz (TSC) veya pulmoner lenfanjiyoleiomiyomatozis (LAM) ile birlikte görülebildiği gibi, sporadik olarak her ikisi olmadan da ortaya çıkabilir. AML'lerin %80'i sporadiktir ve herhangi bir genetik sendromla ilişkileri yoktur. Ancak tanı konan renal AML'nin yaklaşık %10'unda TSC bulunduğu düşünülmektedir (3). EpidemiyolojiRenal AML otopside %0,3 ile %2,1 oranında saptanırken (4), görüntüleme yöntemlerindeki gelişmeler ve görüntüleme sayılarının artışına paralel olarak genel popülasyonda insidental saptanma sıklığı giderek artmaktadır (3,4,5,6,7,8,9). Fittschen ve ark.'nın (10) çalışmasında altmış binden fazla hasta abdominal ultrason (US) ile taranmış, AML prevelansı %0,44 (n=270/61389) saptanmıştır. Yapılan değerlendirmede AML'nin kadınlarda (%0,60) erkeklere göre (%0,28) daha sık görüldüğü ortaya konulmuştur. Hastaların %57'sinde sağ böbrek, %43'ünde sol böbrekte tutulum saptanmıştır. Japonyada ultrasonografi (USG) kullanılarak yapılan bir prevalans çalışmasında AML'nin kadınlarda prevalansı %0,2 erkeklerde %0,1 olarak saptanmıştır. Bu bulgular da Fittschen ve ark.'nın (10) çalışmasını destekler niteliktedir (8). Potansiyel böbrek donörü olan 1948 hastanın bilgisayarlı tomografi (BT) ile görüntülendiği bir çalışmada AML prevalansı %2,2 saptanırken ortalama tümör boyutu 5 mm olarak raporlanmıştır (9). US ile yapılmış çalışmalara göre prevelansın Ya z›fl ma Ad re si/Ad dress for Cor res pon den ce: Dr. Emre Ulukaradağ, Kocaeli Derince Eğitim ve Araştırma Hastanesi, Üroloji Kliniği, Kocaeli, Türkiye

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Efficacy and Safety of Sirolimus for Renal Angiomyolipoma in Patients with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis: A Systematic Review

Abstract: This study shows that renal angiomyolipoma shrank during sirolimus therapy but tended to regrow after the therapy was stopped. In general, sirolimus is an effective and safe therapy for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.

Cited by 34 publications

References 28 publications

Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2− Tumor Related to Lymphangioleiomyomatosis

Evidence Supporting a Lymphatic Endothelium Origin for Angiomyolipoma, a TSC2− Tumor Related to Lymphangioleiomyomatosis

Inhibition of Angiofibromas in a Tuberous Sclerosis Patient Using Topical Timolol 0.5% Gel

Renal Angiomyolipoma, Review

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