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MTORC1 Inhibition Is an Effective Treatment for Sporadic Renal Angiomyolipoma.

ABSTRACT: Introduction:Renal angiomyolipoma (AML) is the most common benign renal tumor. Despite a generally benign histology, AML can result in significant morbidity, from intra-abdominal hemorrhage and reduction in kidney function. While classically associated with the autosomal dominant disorder tuberous sclerosis complex (TSC) or with pulmonary lymphangioleiomyomatosis, most AMLs are sporadic. Mammalian target of rapamycin complex 1 (mTORC1) inhibitors (e.g., sirolimus) have been found to be effective in treating TSC- or lymphangioleiomyomatosis-associated AML, but to date it is unknown whether this strategy is effective for sporadic AML. Methods:We stained tumor specimens of sporadic AML patients for pS6 to assess for mTORC1 activation. Results:We detected strong activation of the mTORC1 pathway, similar to TSC-associated AML. Consequently, we showed that in vitro treatment with sirolimus results in significant growth inhibition of the human sporadic AML cell line SV7Tert, similar to the effect seen when the same treatment is applied to the human TSC-associated AML cell line UMBSV-tel. To further investigate the potential of mTORC1 inhibition for treating sporadic AML and assess whether the in vitro results are clinically relevant, we identified a patient with sporadic, bilateral AMLs, showing continued tumor growth following a partial nephrectomy. Using immunostaining, we detected strong mTORC1 activation in the patient's AML tissue. Accordingly, upon treatment with sirolimus, we noted significant reduction in the patient's tumor volume and resolution of hydronephrosis, without any significant side effects. Conclusion:We propose mTORC1 inhibition as an effective treatment option for patients with sporadic AML, which represents the vast majority of patients with this tumor.

SUBMITTER: Pleniceanu O

PROVIDER: S-EPMC5762943 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo evaluate the feasibility and effectivity of deep learning (DL) plus three-dimensional (3D) printing in the management of giant sporadic renal angiomyolipoma (RAML).MethodsThe medical records of patients with giant (>15 cm) RAML were retrospectively reviewed from January 2011 to December 2020. 3D visualized and printed kidney models were performed by DL algorithms and 3D printing technology, respectively. Patient demographics and intra- and postoperative outcomes were compared between those with 3D-assisted surgery (3D group) or routine ones (control group).ResultsAmong 372 sporadic RAML patients, 31 with giant ones were eligible for analysis. The median age was 40.6 (18-70) years old, and the median tumor size was 18.2 (15-28) cm. Seventeen of 31 (54.8%) had a surgical kidney removal. Overall, 11 underwent 3D-assisted surgeries and 20 underwent routine ones. A significant higher success rate of partial nephrectomy (PN) was noted in the 3D group (72.7% vs. 30.0%). Patients in the 3D group presented a lower reduction in renal function but experienced a longer operation time, a greater estimated blood loss, and a higher postoperative morbidity. Subgroup analysis was conducted between patients undergoing PN with or without 3D assistance. Despite no significant difference, patients with 3D-assisted PN had a slightly larger tumor size and higher nephrectomy score, possibly contributing to a relatively higher rate of complications. However, 3D-assisted PN lead to a shorter warm ischemia time and a lower renal function loss without significant difference. Another subgroup analysis between patients under 3D-assisted PN or 3D-assisted RN showed no statistically significant difference. However, the nearness of tumor to the second branch of renal artery was relatively shorter in 3D-assisted PN subgroup than that in 3D-assisted RN subgroup, and the difference between them was close to significant.Conclusions3D visualized and printed kidney models appear to be additional tools to assist operational management and avoid a high rate of kidney removal for giant sporadic RAMLs.

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MTORC1 Inhibition Is an Effective Treatment for Sporadic Renal Angiomyolipoma.

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