It's not a mystery, it's in the history: Multidisciplinary management of multiple endocrine neoplasia type 1

Shirali, Aditya S.; Pieterman, Carolina R. C.; Lewis, Mark A.; Hyde, Samuel M.; Makawita, Shalini; Dasari, Arvind; Thosani, Nirav; Ikoma, Naruhiko; McCutcheon, Ian E.; Waguespack, Steven G.; Perrier, Nancy D.

doi:10.3322/caac.21673

Cited by 4 publications

(4 citation statements)

References 69 publications

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“…Given the existing use of nontargeted NIRF dyes with commercially available surgical robotic systems, similar integration of MMC(FNIR-Tag)-TOC is feasible and could facilitate quicker recovery after GEP-NET surgery. 56 Finally, our FGS strategy could potentially extend beyond GEP-NETs by facilitating the conversion of other radiolabeled peptides and small molecules into tumor-targeted fluorescent analogues. Thus, new imaging capabilities would become available for a variety of tumor types that rely on surgery as their primary treatment modality.…”

Section: Discussionmentioning

confidence: 99%

“…This capability could reduce unnecessarily wide surgical margins that can cause pancreatic insufficiency in up to 40% of patients and impair quality of life. − Furthermore, adding real-time tumor imaging to minimally invasive (robotic) surgery may compensate for its lack of tactile feedback. Given the existing use of nontargeted NIRF dyes with commercially available surgical robotic systems, similar integration of MMC(FNIR-Tag)-TOC is feasible and could facilitate quicker recovery after GEP-NET surgery . Finally, our FGS strategy could potentially extend beyond GEP-NETs by facilitating the conversion of other radiolabeled peptides and small molecules into tumor-targeted fluorescent analogues.…”

Section: Discussionmentioning

confidence: 99%

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High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

et al. 2022

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Dye design can influence the ability of fluorescently labeled imaging agents to generate tumor contrast and has become an area of significant interest in the field of fluorescence-guided surgery (FGS). Here, we show that the charge-balanced nearinfrared fluorescent (NIRF) dye FNIR-Tag enhances the imaging properties of a fluorescently labeled somatostatin analogue. In vitro studies showed that the optimized fluorescent conjugate MMC-(FNIR-Tag)-TOC bound primarily via somatostatin receptor subtype-2 (SSTR2), whereas its negatively charged counterpart with IRDye 800CW had higher off-target binding. NIRF imaging in cell line-and patient-derived xenograft models revealed markedly higher tumor contrast with MMC(FNIR-Tag)-TOC, which was attributed to increased tumor specificity. Ex vivo staining of surgical biospecimens from primary and metastatic tumors, as well as involved lymph nodes, demonstrated binding to human tumors. Finally, in an orthotopic tumor model, a simulated clinical workflow highlighted our unique ability to use standard preoperative nuclear imaging for selecting patients likely to benefit from SSTR2-targeted FGS. Our findings demonstrate the translational potential of MMC(FNIR-Tag)-TOC for intraoperative imaging and suggest broad utility for using FNIR-Tag in fluorescent probe development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

et al. 2022

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“…The identification of these neoplasms in someone with an MEN1-associated endocrine tumor can help to detect a patient with MEN1 ( 15 , 30 ). In the study of patients with gastrinoma (with and without MEN1), the presence of > three angiofibromas and any collagenoma had high sensitivity (75%) and specificity (95%) for identifying patients with MEN1 ( 15 ).…”

Section: Cutaneous Tumors (Angiofibromas and Collagenomas)mentioning

confidence: 99%

Beyond the “3 Ps”: A critical appraisal of the non-endocrine manifestations of multiple endocrine neoplasia type 1

Waguespack

2022

Front. Endocrinol.

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Multiple endocrine neoplasia type 1 (MEN1), an autosomal-dominantly inherited tumor syndrome, is classically defined by tumors arising from the “3 Ps”: Parathyroids, Pituitary, and the endocrine Pancreas. From its earliest descriptions, MEN1 has been associated with other endocrine and non-endocrine neoplastic manifestations. High quality evidence supports a direct association between pathogenic MEN1 variants and neoplasms of the skin (angiofibromas and collagenomas), adipose tissue (lipomas and hibernomas), and smooth muscle (leiomyomas). Although CNS tumors, melanoma, and, most recently, breast cancer have been reported as MEN1 clinical manifestations, the published evidence to date is not yet sufficient to establish causality. Well-designed, multicenter prospective studies will help us to understand better the relationship of these tumors to MEN1, in addition to verifying the true prevalence and penetrance of the well-documented neoplastic associations. Nevertheless, patients affected by MEN1 should be aware of these non-endocrine manifestations, and providers should be encouraged always to think beyond the “3 Ps” when treating an MEN1 patient.

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“…MEN1 deficiency occurs in sporadic neuroendocrine tumors, and germline mutations in the gene are the basis for cancer predisposition in the human multiple endocrine neoplasia (MEN1) syndrome 1 , 2 . Such patients are at high risk for the development of a variety of neuroendocrine neoplasms, including pancreatic neuroendocrine carcinomas, which are often not amenable for curative surgical resection and account for the mortality of MEN1 patients 3 .…”

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confidence: 99%

Targeting MEN1-deficient tumors with DHODH inhibitor

2022

Journal of the National Cancer Center

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It's not a mystery, it's in the history: Multidisciplinary management of multiple endocrine neoplasia type 1

Cited by 4 publications

References 69 publications

High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Beyond the “3 Ps”: A critical appraisal of the non-endocrine manifestations of multiple endocrine neoplasia type 1

Targeting MEN1-deficient tumors with DHODH inhibitor

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