Treatment of childhood kaposiform hemangioendothelioma with sirolimus

Blatt, Julie; Stavas, Joseph M.; Moats‐Staats, Billie M.; Woosley, John T.; Morrell, Dean S.

doi:10.1002/pbc.22766

Cited by 140 publications

(129 citation statements)

References 13 publications

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“…In case of signs of disease recurrence, at present, we do not see any other option but to stay on sirolimus for a number of years to come under close monitoring. Our experience with successful use of sirolimus in a patient with a complex VA is supporting previous reports [4][5][6][7] and encourages further research on this field.…”

Section: Figuresupporting

confidence: 88%

“…At present, there is only 1 published retrospective analysis of 6 patients with different VAs and 4 published case reports showing that sirolimus is a potent treatment option for patients with complex VA. [4][5][6][7] In the case of our patient, sirolimus brought a spectacular improvement of his FIGURE 2…”

Section: Discussionmentioning

confidence: 49%

“…3 Recently, successful systemic treatment of such patients with sirolimus has been reported. [3][4][5][6][7] Sirolimus inhibits the mammalian target of rapamycin, which is a master switch of numerous cellular processes leading to cellular proliferation. Therefore, the rationale for use of sirolimus in treatment of children with complex VAs lies in its antiproliferative and antiangiogenic effects.…”

mentioning

confidence: 99%

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Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report

Vlahovic

Haxhija

2015

Pediatrics

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Management of patients with complex vascular anomalies (VAs) is often associated with significant morbidity and mortality because of the lack of effective treatment modalities that may lead to significant improvement of the disease and/or healing. Recently, reports of treatment of patients with complex VAs with sirolimus revealed encouraging results. Sirolimus inhibits the mammalian target of rapamycin, which acts as a master switch of numerous cellular processes. We report a successful use of sirolimus for the treatment of a patient with a complex CLVM of the trunk and the right lower extremity believed to be untreatable. Our patient had 44 hospitalizations during the 10-year period, with various unsuccessful treatments and continuous deterioration of his clinical condition, ending up in a wheelchair. His condition reversed to normal everyday activities 9 months after initiation of sirolimus therapy. We conclude that sirolimus is a very promising therapeutic option for children with complex VAs of capillary-lymphatico-venous type.

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Section: Figuresupporting

confidence: 88%

Section: Discussionmentioning

confidence: 49%

mentioning

confidence: 99%

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Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report

Vlahovic

Haxhija

2015

Pediatrics

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“…Some recent case reports have shown a rapid response of KHE and KMP to sirolimus [71][72][73]. In a case series reported by Kai et al, sirolimus was shown to be effective in children with refractory KHE with KMS.…”

Section: Role Of Mtor Inhibitorsmentioning

confidence: 99%

Clinical Review: Management of Adult Kasabach-Merritt Syndrome Associated with Hemangiomas

Master¹,

Kallam²,

Eo³

et al. 2017

J Blood Disord Transfus

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Kasabach-Merritt syndrome (KMS) consists of a clinical trial of capillary hemangioma, thrombocytopenia and disseminated intravascular coagulation. KMS occurs most commonly in the pediatric population, and its occurrence in adults is rare. Specific guidelines or randomized clinical trials guiding clinical management of KMS in adult patients are lacking. This manuscript provides a comprehensive review of KMS and discusses recent advances in the medical management of KMS. We also propose a systematic therapeutic approach which would serve as a guide in the management of adult patients with KMS caused by hemangiomas.

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“…Bleomycin inhibits the development of HA via inactivation of AKT, which may represent an important therapeutic target for HA (22). Sirolimus, an mTOR inhibitor, has been demonstrated to exert anti-angiogenic activity in kaposifonn hemangioendotheliomas and complicated vascular malformations (23,24). Rapamycin targets the self-renewal and vascular differentiation potential in patient-derived HA stem cells, suggesting a novel therapeutic strategy to prevent formation of HA (25,26).…”

Section: Discussionmentioning

confidence: 99%

Combined Blockade and Akt/Mtor Pathway Inhibits Growth of Human Hemangioma via Downregulation of Proliferating Cell Nuclear Antigen

et al. 2012

Int J Immunopathol Pharmacol

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Protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in the tumorigenesis and progression of multiple tumors, and has been shown to be important therapeutic targets for cancer. The present study aimed to explore the role and molecular mechanisms of AKT/mTOR pathway in human hemangioma (HA). Twenty-five cases of human HA tissues were collected. The expression of AKT, mTOR and proliferating cell nuclear antigen (PCNA) proteins was evaluated using semi-quantitative immunohistochemistry in biopsy samples in different phases of HA. AKT/mTOR pathway was blocked by recombinant small hairpin RNA adenovirus vector rAd5-AKT+mTOR (rAd5-Am), used for infecting proliferating phase HA-derived endothelial cells (HDEC). The expression of AKT, mTOR and PCNA was detected by Real-time PCR and Western blot assays. Cell proliferative activities were determined by MTT assay, and cell cycle distribution and apoptosis were analyzed by flow cytometry. As a consequence, the expression of AKT, mTOR and PCNA was significantly increased in proliferative phase HA, while that was decreased in involutive phase. Combined blockade of AKT/mTOR pathway by rAd5-Am diminished cell proliferative activities, and induced cell apoptosis and cycle arrest with the decreased expression of AKT, mTOR and PCNA in proliferative phase HDEC. In conclusion, the activity of AKT/mTOR pathway was increased in proliferative phase HA, while it was decreased in involutive phase. Combined blockade of AKT/mTOR pathway might suppress cell proliferation via down-regulation of PCNA expression, and induce apoptosis and cycle arrest in proliferative phase HDEC, suggesting thatAKT/mTOR pathway might represent the important therapeutic targets for human HA.

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Treatment of childhood kaposiform hemangioendothelioma with sirolimus

Cited by 140 publications

References 13 publications

Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report

Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report

Clinical Review: Management of Adult Kasabach-Merritt Syndrome Associated with Hemangiomas

Combined Blockade and Akt/Mtor Pathway Inhibits Growth of Human Hemangioma via Downregulation of Proliferating Cell Nuclear Antigen

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