Endometrioid Paraovarian Borderline Cystic Tumor in an Infant with Proteus Syndrome

Vásquez, Liliana; Tello, Mariela; Maza, Iván; Oscanoa, Mónica; Dueñas, María; Castro, H Escobar; Latorre, Alan

doi:10.1155/2015/392576

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…The nature of gynaecological lesions and their size have rarely been precisely reported. They include ovarian serous cystadenomas (4 cases) [Cohen, 1993;Skovby, 1993;Cohen, 2002;Gordon, 1995], ovarian cysts (3 cases) [Koussef, 1986;Maassen and Voigtlander, 1991;Bouzas, 1993], uterine leiomyomas [Maassen and Voigtlander, 1991], endometrial carcinoma (1 case) , bilateral paraovarian villoglandular endometrioid cystadenomatous tumours of borderline malignancy with neoplastic perineal implant (1 case) [Raju, 2002], juvenile granulosa cell tumours (1 case) [Ezzeldin, 2002], ovarian dermoid cysts and paratubal cysts (1 case) [Hong, 2010], endometrioid paraovarian borderline cystic tumours (1 case) [Vasquez, 2015] and Müllerian papilloma associated with ovarian serous cystadenoma (1 case) [Smrkolj, 2012]. The most common and specific gynaecological lesion reported in PS is ovarian serous cystadenoma.…”

Section: Discussionmentioning

confidence: 99%

Severe gynaecological involvement in Proteus Syndrome

Sévérino-Freire¹,

Maza²,

Kuentz³

et al. 2019

European Journal of Medical Genetics

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Proteus Syndrome is a rare complex overgrowth syndrome. We report a young female patient with Proteus Syndrome due to AKT1 mutation c.49G > A (p.Glu17Lys), presenting with a severe gynaecological involvement which necessitated a complete hysterectomy and a left adnexectomy. Cases of gynecological involvements in Proteus Syndrome are rare, not well known by physicians while they can be potentially severe.

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Section: Discussionmentioning

confidence: 99%

Severe gynaecological involvement in Proteus Syndrome

Sévérino-Freire¹,

Maza²,

Kuentz³

et al. 2019

European Journal of Medical Genetics

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“…The test was positive for tumor cells, but no other abnormal pathological findings were found. Post-operatory evolution was favorable and received three adjuvant chemotherapies in every 21 days for 3 h. The patient was alive till 2 years with no evidence of disease [56].…”

Section: Keerthimentioning

confidence: 93%

Proteus Syndrome: Need for Patient Centric Therapy

Kuppusamy

Radhakrishnan

Shanmukhan

et al. 2018

Asian J Pharm Clin Res

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Proteus syndrome (PS) is a hamartomatous disorder with multisystem involvement that results from mutation in the AKT1gene. Since the symptoms and severity of PS are unique to each patient, diagnosis and treatment become hard for the physician. This article is concentrated upon the identification and recognition of specific characteristics of the disease, pathophysiology, symptoms, diagnosis, treatment and the necessity of advanced diagnosis, effective generalized and personalized therapy, as well as the requirement of new drugs for the management of PS. Detailed studies on the PS and evidence from the case reports revealed the requirement of intensive care, accurate diagnosis, and an effective treatment for each patient preferably patient-centric drug delivery due to the high degree of variation in the symptoms and clinical features among patients.

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In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS)

et al. 2018

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Postzygotic mutations of the PIK3CA [phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha] gene constitutively activate the PI3K/AKT/mTOR pathway in PIK3CA-related overgrowth spectrum (PROS) patients, causing congenital mosaic tissue overgrowth that even multiple surgeries cannot solve. mTOR inhibitors are empirically tested and given for compassionate use in these patients. PROS patients could be ideal candidates for enrolment in trials with PI3K/AKT pathway inhibitors, considering the “clean” cellular setting in which a unique driver, a PIK3CA mutation, is present. We aimed to assess the effects of blocking the upstream pathway of mTOR on PROS patient-derived cells by using ARQ 092, a potent, selective, allosteric, and experimental orally bioavailable and highly selective AKT-inhibitor with activity and long-term tolerability, currently under clinical development for treatment of cancer and Proteus syndrome. Cell samples (i.e., primary fibroblasts) were derived from cultured tissues obtained from six PROS patients [3 boys, 3 girls; aged 2 to 17 years] whose spectrum of PIK3A-related overgrowth included HHML [hemihyperplasia multiple lipomatosis; n = 1], CLOVES [congenital lipomatosis, overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies, scoliosis; n = 1], and MCAP [megalencephaly capillary malformation syndrome; n = 4]. We performed the following: (a) a deep sequencing assay of PI3K/AKT pathway genes in the six PROS patients’ derived cells to identify the causative mutations and (b) a pathway analysis to assess the phosphorylation status of AKT [Ser473 and Thr308] and its downstream targets [pAKTS1 (Thr246), pRPS6 (Ser235/236), and pRPS6Kβ1 (Ser371)]. The anti-proliferative effect of ARQ 092 was tested and compared to other PI3K/AKT/mTOR inhibitors [i.e., wortmannin, LY249002, and rapamycin] in the six PROS patient-derived cells. Using ARQ 092 to target AKT, a critical node connecting PI3K and mTOR pathways, we observed the following: (1) strong anti-proliferative activity [ARQ 092 at 0.5, 1, and 2.5 μM blunted phosphorylation of AKT and its downstream targets (in the presence or absence of serum) and inhibited proliferation after 72 h; rapamycin at 100 nM did not decrease AKT phosphorylation] and (2) less cytotoxicity as compared to rapamycin and wortmannin. We demonstrated the following: (a) that PROS cells are dependent on AKT; (b) the advantage of inhibiting the pathway immediately downstream of PI3K to circumventing problems depending on multiple classes a PI3K kinases; and (c) that PROS patients benefit from inhibition of AKT rather than mTOR. Clinical development of ARQ 092 in PROS patients is on going in these patients.Electronic supplementary materialThe online version of this article (10.1007/s10048-018-0540-1) contains supplementary material, which is available to authorized users.

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Endometrioid Paraovarian Borderline Cystic Tumor in an Infant with Proteus Syndrome

Cited by 3 publications

References 24 publications

Severe gynaecological involvement in Proteus Syndrome

Severe gynaecological involvement in Proteus Syndrome

Proteus Syndrome: Need for Patient Centric Therapy

In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS)

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