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Article ; Online: Rôle de la succinate déshydrogénase dans le cancer.

Moog, Sophie / Favier, Judith

2022 Volume 38, Issue 3, Page(s) 255–262

Abstract: Succinate dehydrogenase (SDH) is a mitochondrial enzyme that participates in both the tricarboxylic acid cycle and the electron transport chain. Mutations in genes encoding SDH are responsible for a predisposition to pheochromocytomas and paragangliomas, ...

Title translation	Succinate dehydrogenase in cancer.
Abstract	Succinate dehydrogenase (SDH) is a mitochondrial enzyme that participates in both the tricarboxylic acid cycle and the electron transport chain. Mutations in genes encoding SDH are responsible for a predisposition to pheochromocytomas and paragangliomas, and more rarely, to gastrointestinal stromal tumors or renal cell carcinomas. A decrease in SDH activity, not explained by genetics, has also been observed in more common cancers. One of the consequences of the inactivation of SDH is the excessive production of its substrate, succinate, which acts as an oncometabolite by promoting a pseudohypoxic status and an extensive epigenetic rearrangement. Understanding SDH-related oncogenesis now makes it possible to develop innovative diagnostic methods and to consider targeted therapies for the management of affected patients.
MeSH term(s)	Adrenal Gland Neoplasms/genetics ; Gastrointestinal Stromal Tumors/genetics ; Humans ; Paraganglioma/genetics ; Paraganglioma/pathology ; Pheochromocytoma/genetics ; Pheochromocytoma/pathology ; Succinate Dehydrogenase/genetics ; Succinate Dehydrogenase/metabolism
Chemical Substances	Succinate Dehydrogenase (EC 1.3.99.1)
Language	French
Publishing date	2022-03-25
Publishing country	France
Document type	Journal Article
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2022024
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Zs.B 2872: Show issues

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Article ; Online: Epigenetic and metabolic reprogramming of SDH-deficient paragangliomas.

Moog, Sophie / Lussey-Lepoutre, Charlotte / Favier, Judith

Endocrine-related cancer

2020 Volume 27, Issue 12, Page(s) R451–R463

Abstract: Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors arising from the adrenal medulla or extra-adrenal paraganglia. Around 40% of all cases are caused by a germline mutation in a susceptibility gene, half of which being found in an ... ...

Abstract	Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors arising from the adrenal medulla or extra-adrenal paraganglia. Around 40% of all cases are caused by a germline mutation in a susceptibility gene, half of which being found in an SDHx gene (SDHA, SDHB, SDHC, SDHD or SDHAF2). They encode the four subunits and assembly factor of succinate dehydrogenase (SDH), a mitochondrial enzyme involved both in the tricarboxylic acid cycle and electron transport chain. SDHx mutations lead to the accumulation of succinate, which acts as an oncometabolite by inhibiting iron(II) and alpha-ketoglutarate-dependent dioxygenases thereby regulating the cell's hypoxic response and epigenetic processes. Moreover, SDHx mutations induce cell metabolic reprogramming and redox imbalance. Major discoveries in PPGL pathophysiology have been made since the initial discovery of SDHD gene mutations in 2000, improving the understanding of their biology and patient management. It indeed provides new opportunities for diagnostic tools and innovative therapeutic targets in order to improve the prognosis of patients affected by these rare tumors, in particular in the context of metastatic diseases associated with SDHB mutations. This review first describes an overview of the pathophysiology and then focuses on clinical implications of the epigenetic and metabolic reprogramming of SDH-deficient PPGL.
MeSH term(s)	Epigenomics/methods ; Female ; Humans ; Male ; Paraganglioma/genetics ; Succinate Dehydrogenase/genetics
Chemical Substances	Succinate Dehydrogenase (EC 1.3.99.1)
Language	English
Publishing date	2020-10-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1218450-0
ISSN	1479-6821 ; 1351-0088
ISSN (online)	1479-6821
ISSN	1351-0088
DOI	10.1530/ERC-20-0346
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Zs.A 4192: Show issues

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Article: Intraoperative Parathyroid Gland Identification Using Autofluorescence Imaging in Thyroid Cancer Surgery with Central Neck Dissection: Impact on Post-Operative Hypocalcemia.

Guerlain, Joanne / Breuskin, Ingrid / Abbaci, Muriel / Lamartina, Livia / Hadoux, Julien / Baudin, Eric / Al Ghuzlan, Abir / Moog, Sophie / Marhic, Alix / Villard, Adrien / Obongo, Rais / Hartl, Dana M

Cancers

2023 Volume 16, Issue 1

Abstract: Hypoparathyroidism is the most frequent complication in thyroid surgery. The aim of this study was to evaluate the impact of intraoperative parathyroid gland identification, using autofluorescence imaging, on the rate of post-operative (PO) ... ...

Abstract	Hypoparathyroidism is the most frequent complication in thyroid surgery. The aim of this study was to evaluate the impact of intraoperative parathyroid gland identification, using autofluorescence imaging, on the rate of post-operative (PO) hypoparathyroidism in thyroid cancer surgery. Patients undergoing total thyroidectomy with central neck dissection from 2018 to 2022 were included. A prospective cohort of 77 patients operated on using near-infrared autofluorescence (NIRAF+) with the Fluobeam
Language	English
Publishing date	2023-12-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16010182
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Article ; Online: Alkylating Agent-Induced High Tumor Mutational Burden in Medullary Thyroid Cancer and Response to Immune Checkpoint Inhibitors: Two Case Reports.

Moog, Sophie / Lamartina, Livia / Bani, Mohamed-Amine / Al Ghuzlan, Abir / Friboulet, Luc / Italiano, Antoine / Lacroix, Ludovic / Postel Vinay, Sophie / Tselikas, Lambros / Deschamps, Frédéric / Bonnet, Baptiste / Pani, Fabiana / Baudin, Eric / Hadoux, Julien

Thyroid : official journal of the American Thyroid Association

2023 Volume 33, Issue 11, Page(s) 1368–1373

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Humans ; Alkylating Agents/adverse effects ; Carcinoma, Neuroendocrine/drug therapy ; Carcinoma, Neuroendocrine/genetics ; Immune Checkpoint Inhibitors/therapeutic use ; Thyroid Neoplasms/drug therapy ; Thyroid Neoplasms/genetics
Chemical Substances	Alkylating Agents ; Immune Checkpoint Inhibitors
Language	English
Publishing date	2023-10-09
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1086044-7
ISSN	1557-9077 ; 1050-7256
ISSN (online)	1557-9077
ISSN	1050-7256
DOI	10.1089/thy.2023.0144
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Zs.A 3307: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Impact of lymphovascular invasion on otherwise low-risk papillary thyroid carcinomas: a retrospective and observational study.

Puga, Francisca Marques / Al Ghuzlan, Abir / Hartl, Dana M / Bani, Mohamed-Amine / Moog, Sophie / Pani, Fabiana / Breuskin, Ingrid / Guerlain, Joanne / Faron, Matthieu / Denadreis, Desirée / Baudin, Eric / Hadoux, Julien / Lamartina, Livia

Endocrine

2023 Volume 83, Issue 1, Page(s) 150–159

Abstract: Purpose: Presence of venous vascular invasion is a criterion of intermediate risk of recurrence in papillary thyroid carcinoma (PTC). However, the presence and type of vascular invasion (lymphatic or venous) is often underreported and its impact on PTCs ...

Abstract	Purpose: Presence of venous vascular invasion is a criterion of intermediate risk of recurrence in papillary thyroid carcinoma (PTC). However, the presence and type of vascular invasion (lymphatic or venous) is often underreported and its impact on PTCs without other risk features remains unknown. The aim of this study was to evaluate the impact of both lymphatic and venous invasion on the risk of recurrence/persistence on otherwise low-risk PTCs. Methods: Retrospective study including patients with otherwise low-risk PTCs but with vascular invasion, diagnosed between 2013 and 2019. The persistence/recurrence during the follow-up was evaluated. Pathology was reviewed to confirm the presence of lymphovascular invasion and determine the type of invasion. Results: A total of 141 patients were included. Lymphovascular invasion was confirmed in 20.6%. After surgery, 48.9% (N = 69) of the patients received radioactive iodine (RAI). The median follow-up time was 4 [3-6] years. Overall, 6 (4.2%) patients experienced persistent/recurrent disease in the neck, including 3 with lymphovascular invasion, confirmed as "only lymphatic". Overall, patients with tumors harboring lymphovascular invasion had sensibly more persistent/recurrence disease compared with those without lymphovascular invasion (10.3% vs 2.7%, p = 0.1), especially in the subgroup of patients not treated with RAI (20% vs 1.6%, p = 0.049) [OR 15.25, 95% CI 1.24-187.85, p = 0.033]. Conclusion: Lymphovascular invasion, including lymphatic invasion only, is associated with a sensibly higher risk of persistent/recurrent disease in otherwise low-risk PTCs, namely in patients not treated with RAI. Lymphatic invasion could have a role in risk-stratification systems for decision making.
MeSH term(s)	Humans ; Thyroid Cancer, Papillary/pathology ; Retrospective Studies ; Thyroid Neoplasms/pathology ; Iodine Radioisotopes ; Neck ; Thyroidectomy ; Neoplasm Recurrence, Local/pathology
Chemical Substances	Iodine Radioisotopes
Language	English
Publishing date	2023-08-28
Publishing country	United States
Document type	Observational Study ; Journal Article
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-023-03475-8
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Zs.A 3884: Show issues

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Article ; Online: DietSee: An on-hand, portable, strip-type biosensor for lipolysis monitoring via real-time amperometric determination of glycerol in blood.

Degrelle, Séverine A / Delile, Sébastien / Moog, Sophie / Mouisel, Etienne / O'Gorman, Donal / Moro, Cédric / Denechaud, Pierre-Damien / Torre, Cyril

Analytica chimica acta

2021 Volume 1155, Page(s) 338358

Abstract: Glycerol is a clinical biomarker of lipolysis that is mainly produced by adipose tissues. Blood glycerol content increases in pathological conditions such as metabolic and cardiovascular diseases or cancer cachexia, but also in response to energetic ... ...

Abstract	Glycerol is a clinical biomarker of lipolysis that is mainly produced by adipose tissues. Blood glycerol content increases in pathological conditions such as metabolic and cardiovascular diseases or cancer cachexia, but also in response to energetic stress such as physical exercise. Accurate glycerol monitoring is therefore important in a range of healthcare contexts. However, current methods available for the quantification of glycerol are expensive, time-consuming, and require the extraction of plasma from blood, from which blood glycerol content is then extrapolated. Here, we report the development of a new point-of-care glycerometer device, DietSee, based on a strip-type biosensor that enables the quantification of glycerol directly from whole blood in 6 s. The performance of the biosensor was first evaluated using buffer solutions and spiked human and mouse plasma samples, and its response was compared with that of the gold-standard colorimetric method. The results obtained using DietSee correlated strongly with those from the reference method and demonstrated a linear response to glycerol levels across a wide range of concentrations (40-750 μM) that were representative of those in the human body. Next, the biosensor was validated using spiked human blood samples over a range of 30-55% hematocrit; it also demonstrated a strong correlation with reference measurements under these conditions (R
MeSH term(s)	Animals ; Biosensing Techniques ; Colorimetry ; Glycerol ; Lipolysis ; Mice
Chemical Substances	Glycerol (PDC6A3C0OX)
Language	English
Publishing date	2021-02-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1483436-4
ISSN	1873-4324 ; 0003-2670
ISSN (online)	1873-4324
ISSN	0003-2670
DOI	10.1016/j.aca.2021.338358
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Article ; Online: Patterns of Treatment Failure After Selective Rearranged During Transfection (RET) Inhibitors in Patients With Metastatic Medullary Thyroid Carcinoma.

Hadoux, Julien / Al Ghuzlan, Abir / Lamartina, Livia / Bani, Mohamed-Amine / Moog, Sophie / Attard, Marie / Scoazec, Jean Yves / Hartl, Dana / Aldea, Mihaela / Friboulet, Luc / Jules-Clement, Gerome / Italiano, Antoine / Besse, Benjamin / Lacroix, Ludovic / Baudin, Eric

JCO precision oncology

2023 Volume 7, Page(s) e2300053

Abstract: Purpose: Medullary thyroid cancer (MTC) harbors frequent mutations in RET oncogene. Selective RET inhibitors (RETi) have emerged as effective treatments. However, resistance almost invariably occurs.: Methods: MTC patients who were initiated on RETi ... ...

Abstract	Purpose: Medullary thyroid cancer (MTC) harbors frequent mutations in RET oncogene. Selective RET inhibitors (RETi) have emerged as effective treatments. However, resistance almost invariably occurs. Methods: MTC patients who were initiated on RETi between 2018 and 2022 were included. Baseline characteristics, RET mutational status, RETi response, available tumor tissue and molecular profiles sampled pre- and post-RETi were analyzed. Results: Among 46 MTC patients on RETi during the study period, 26 patients had discontinued at data cut-off because of progression (n = 16), death (n = 4), and toxicity (n = 6). The most frequent RET mutations at baseline were p.M918T (n = 29), and p.C634X (n = 6). Pre- and post-RETi molecular profiles were available in 14 patients. There was no primary resistance on pre-RETi samples. Post-RETi profiles revealed a bypass mechanism of resistance in 75% of the cases including RAS genes mutations (50%), FGFR2 and ALK fusions and and MYC p.P44L. RET solvent from and hinge region mutations was the only resistance mechanisms in 25% of the cases. Tumor samples from initial thyroidectomy, pre- and post-RETi, from six patients, showed an increase of the mean Ki 67-index of 7%, 17% and 40% respectively (P = 0.037) and a more aggressive poorly differentiated histology in three patients. Discussion: Bypass resistance may be the most frequent mechanism of progression under RETi. A more aggressive histology may arise following RETi and warrants further investigation.
MeSH term(s)	Humans ; Carcinoma, Medullary/genetics ; Carcinoma, Medullary/pathology ; Carcinoma, Medullary/surgery ; Proto-Oncogene Proteins c-ret/genetics ; Thyroid Neoplasms/drug therapy ; Thyroid Neoplasms/genetics ; Protein Kinase Inhibitors ; Treatment Failure ; Transfection
Chemical Substances	Proto-Oncogene Proteins c-ret (EC 2.7.10.1) ; Protein Kinase Inhibitors ; RET protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-11-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.23.00053
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Article: Strategies for Radioiodine Treatment: What's New.

Sparano, Clotilde / Moog, Sophie / Hadoux, Julien / Dupuy, Corinne / Al Ghuzlan, Abir / Breuskin, Ingrid / Guerlain, Joanne / Hartl, Dana / Baudin, Eric / Lamartina, Livia

Cancers

2022 Volume 14, Issue 15

Abstract: Radioiodine treatment (RAI) represents the most widespread and effective therapy for differentiated thyroid cancer (DTC). RAI goals encompass ablative (destruction of thyroid remnants, to enhance thyroglobulin predictive value), adjuvant (destruction of ... ...

Abstract	Radioiodine treatment (RAI) represents the most widespread and effective therapy for differentiated thyroid cancer (DTC). RAI goals encompass ablative (destruction of thyroid remnants, to enhance thyroglobulin predictive value), adjuvant (destruction of microscopic disease to reduce recurrences), and therapeutic (in case of macroscopic iodine avid lesions) purposes, but its use has evolved over time. Randomized trial results have enabled the refinement of RAI indications, moving from a standardized practice to a tailored approach. In most cases, low-risk patients may safely avoid RAI, but where necessary, a simplified protocol, based on lower iodine activities and human recombinant TSH preparation, proved to be just as effective, reducing overtreatment or useless impairment of quality of life. In pediatric DTC, RAI treatments may allow tumor healing even at the advanced stages. Finally, new challenges have arisen with the advancement in redifferentiation protocols, through which RAI still represents a leading therapy, even in former iodine refractory cases. RAI therapy is usually well-tolerated at low activities rates, but some concerns exist concerning higher cumulative doses and long-term outcomes. Despite these achievements, several issues still need to be addressed in terms of RAI indications and protocols, heading toward the RAI strategy of the future.
Language	English
Publishing date	2022-08-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14153800
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Article ; Online: Preclinical evaluation of targeted therapies in Sdhb-mutated tumors.

Moog, Sophie / Salgues, Betty / Braik-Djellas, Yasmine / Viel, Thomas / Balvay, Daniel / Autret, Gwennhael / Robidel, Estelle / Gimenez-Roqueplo, Anne-Paule / Tavitian, Bertrand / Lussey-Lepoutre, Charlotte / Favier, Judith

Endocrine-related cancer

2022 Volume 29, Issue 6, Page(s) 375–388

Abstract: Therapies for metastatic SDHB-dependent pheochromocytoma and paraganglioma (PPGL) are limited and poorly efficient. New targeted therapies and identification of early non-invasive biomarkers of response are thus urgently needed for these patients. We ... ...

Abstract	Therapies for metastatic SDHB-dependent pheochromocytoma and paraganglioma (PPGL) are limited and poorly efficient. New targeted therapies and identification of early non-invasive biomarkers of response are thus urgently needed for these patients. We characterized an in vivo allograft model of spontaneously immortalized murine chromaffin cells (imCC) with inactivation of the Sdhb gene by dynamic contrast-enhanced MRI (DCE-MRI) and 18FDG-PET. We evaluated the response to several therapies: IACS-010759 (mitochondrial respiratory chain complex I inhibitor), sunitinib (tyrosine kinase inhibitor with anti-angiogenic activity), talazoparib (poly ADP ribose polymerase (PARP) inhibitor) combined or not to temozolomide (alkylating agent), pharmacological inhibitors of HIF2a (PT2385 and PT2977 (belzutifan)) and molecular inactivation of HIF2a (imCC Sdhb-/- shHIF2a). Multimodal imaging was performed, including magnetic resonance spectroscopy (1H-MRS) to monitor the level of succinate in vivo. The allografted model of Sdhb-/- imCC reflected SDHB-deficient tumors, with increased angiogenesis and a particular avidity for 18FDG. After 14 days of treatment, IACS-010759, sunitinib and talazoparib at high doses allowed a significant reduction of the tumor volumes. In contrast to the tumor growth inhibition observed in Sdhb-/- shHIF2a imCC tumors, pharmacological inhibitors of HIF2a (PT2385 and belzutifan) showed no antitumor action in this model, alone or in combination with sunitinib. 1H-MRS, but not DCE-MRI, enabled the monitoring response to sunitinib, which was the best treatment in this study, promoting a decrease in succinate levels detected in vivo. This study paves the way for new therapeutic options and reveals a potential new early biomarker of response to treatment in SDHB-dependent PPGL.
MeSH term(s)	Adrenal Gland Neoplasms/genetics ; Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Fluorodeoxyglucose F18/therapeutic use ; Humans ; Mice ; Mutation ; Paraganglioma/drug therapy ; Paraganglioma/genetics ; Paraganglioma/pathology ; Pheochromocytoma/genetics ; Succinate Dehydrogenase/genetics ; Succinate Dehydrogenase/metabolism ; Succinates/therapeutic use ; Sunitinib/therapeutic use
Chemical Substances	Antineoplastic Agents ; Succinates ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; SDHB protein, human (EC 1.3.5.1) ; Succinate Dehydrogenase (EC 1.3.99.1) ; Sunitinib (V99T50803M)
Language	English
Publishing date	2022-05-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1218450-0
ISSN	1479-6821 ; 1351-0088
ISSN (online)	1479-6821
ISSN	1351-0088
DOI	10.1530/ERC-22-0030
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Zs.A 4192: Show issues

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Article ; Online: New endpoints in adrenocortical carcinoma studies: a mini review.

Faron, Matthieu / Lamartina, Livia / Hescot, Segolene / Moog, Sophie / Deschamps, Frederic / Roux, Charles / Libe, Rosella / Durand-Labrunie, Jerome / Al Ghuzlan, Abir / Hadoux, Julien / Baudin, Eric

Endocrine

2022 Volume 77, Issue 3, Page(s) 419–424

Abstract: Purpose: Adrenocortical carcinoma (ACC) is a very rare and aggressive malignant disease. Therefore, overall survival (OS) has long been considered as the best endpoint. Yet, a unique endpoint is not optimal to take into account the heterogeneity in ... ...

Abstract	Purpose: Adrenocortical carcinoma (ACC) is a very rare and aggressive malignant disease. Therefore, overall survival (OS) has long been considered as the best endpoint. Yet, a unique endpoint is not optimal to take into account the heterogeneity in tumor profile and the diversification of therapeutic option. The purpose of this mini review was to describe endpoints used in the past, present and future in the field of ACC. Methods: Pubmed and Clinicaltrial.gov were used to identify relevant studies. Results: Before year 2000 only three endpoints were regularly used: OS, recurrence-free survival (RFS) and response rate. These endpoints were used because ACC was seen as a homogeneous diseases with a high recurrence rate and low rate of long-term survival. Since 2000; along with the apparition of new class of drug, progression-free survival (PFS) has been more and more used. Other endpoints as "time to chemotherapy" or "Progression-free survival 2" were used to evaluate multimodal therapies or treatment with a delayed action. Finally, there is a hope that in the near future, quality of life along with other patient-reported outcomes may be used more frequently. Conclusion: While OS and PFS are currently the most used endpoints in ACC, new endpoints are needed to better take into account the challenges offered by different situations and treatment strategies.
MeSH term(s)	Adrenal Cortex Neoplasms/therapy ; Adrenocortical Carcinoma/therapy ; Disease-Free Survival ; Humans ; Quality of Life
Language	English
Publishing date	2022-07-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-022-03128-2
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