Article
Oncology
Levin Haeni, Monika Kopcic, Mattia Branca, Alessa Schuetz, Michael Murek, Nicole Soell, Erik Vassella, Andreas Raabe, Ekkehard Hewer, Philippe Schucht
Summary: The methylation status of the MGMT gene is a prognostic marker in glioblastoma patients, with >= 16% methylation predicting better survival.
Review
Oncology
P. Trillo Aliaga, F. Spada, G. Peveri, V. Bagnardi, C. Fumagalli, A. Laffi, M. Rubino, L. Gervaso, E. Guerini Rocco, E. Pisa, G. Curigliano, N. Fazio
Summary: The meta-analysis suggested that MGMT status may predict the efficacy of TEM in NETs patients. Patients with MGMT deficiency showed better response rate, progression free survival, and overall survival compared to those with MGMT proficiency.
CANCER TREATMENT REVIEWS
(2021)
Article
Oncology
Ophelie De Rycke, Thomas Walter, Marine Perrier, Olivia Hentic, Catherine Lombard-Bohas, Romain Coriat, Guillaume Cadiot, Anne Couvelard, Philippe Ruszniewski, Jerome Cros, Louis de Mestier
Summary: The study found that a pause followed by ALK rechallenge after the initial efficacy of ALK treatment may help prolong tumor control, improve quality of life, and limit long-term adverse events. The low efficacy of ALK rechallenge may be explained by increased MGMT expression under ALK.
ENDOCRINE-RELATED CANCER
(2021)
Article
Biochemistry & Molecular Biology
Rajni Shaw, Subhajit Karmakar, Malini Basu, Mrinal K. Ghosh
Summary: The upregulation of DDX5 (p68) is associated with various cancers, especially colon adenocarcinomas. MGMT has been identified as a major contributor to chemoresistance. This study reveals that p68 is a transcriptional co-activator of the MGMT gene and enhances its transcription through interactions with beta-catenin, RelA, and SP1 transcription factors.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Article
Cell Biology
Alessandro Tancredi, Olga Gusyatiner, Pierre Bady, Michelle C. Buri, Remy Lomazzi, Davide Chiesi, Mahmoud Messerer, Monika E. Hegi
Summary: Bromodomain and extra-terminal tail (BET) proteins are potential epigenetic targets in cancer, including glioblastoma. BET inhibitors disrupt the histone code-gene transcription link. BET-induced differential gene expression in glioblastoma derived-spheres revealed 6 distinct response patterns. The O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for glioblastoma treatment, showed consistent downregulation in response to BET inhibitors.
CELL DEATH & DISEASE
(2022)
Review
Oncology
Satya Das, Taymeyah Al-Toubah, Jonathan Strosberg
Summary: The role of cytotoxic chemotherapy in well-differentiated neuroendocrine tumors remains uncertain, with specific focus on certain tumor types, grade, and DNA repair defects affecting chemosensitivity. Chemotherapy shows greater antitumor activity in pancreatic or grade 3 tumors, while its role in lower grade extra-pancreatic NETs is undefined. Efforts to combine chemotherapy with targeted therapy and other treatments are ongoing to improve options for patients with NETs.
Article
Multidisciplinary Sciences
Duyen Thi Do, Ming-Ren Yang, Luu Ho Thanh Lam, Nguyen Quoc Khanh Le, Yu-Wei Wu
Summary: Using a radiomics-based machine learning model, we can predict the O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status in glioblastoma multiforme (GBM) patients preoperatively and noninvasively. The model achieved high accuracy and specificity using a genetic algorithm-based feature selection method, indicating potential wide application in both low- and high-grade gliomas.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Kohei Yagi, Hiroaki Ono, Atsushi Kudo, Yuko Kinowaki, Daisuke Asano, Shuichi Watanabe, Yoshiya Ishikawa, Hiroki Ueda, Keiichi Akahoshi, Shinji Tanaka, Minoru Tanabe
Summary: This study investigated the expression of O6-methylguanine-DNA methyltransferase (MGMT) in pancreatic neuroendocrine tumors (Pan-NET) and its association with treatment efficacy. The results showed that MGMT expression was negatively correlated with treatment outcomes, and MGMT expression was lower in NET-G2 compared to NET-G1. Therefore, MGMT may serve as a better therapeutic target for STZ treatment in NET-G2.
SCIENTIFIC REPORTS
(2023)
Article
Clinical Neurology
Sotirios Katsigiannis, Stefan Grau, Boris Krischek, Kadir Er, Bogdan Pintea, Roland Goldbrunner, Pantelis Stavrinou
Summary: Stratifying GBM patients according to their MGMT promoter methylation status revealed different prognostic factors and resection thresholds. Extent of resection was an independent predictor of survival for unmethylated MGMT patients, while residual tumor volume, Karnofsky Performance Score, and age were independent prognostic factors for methylated MGMT patients.
Article
Oncology
Hanna Lagenfelt, Hakon Blomstrand, Nils O. Elander
Summary: This study evaluated the real-world outcomes of GemOx treatment in 121 patients with advanced biliary tract cancer in three hospitals in the South East Region of Sweden. The median overall survival was 8.9 months, with prognostic factors including performance status and primary gallbladder carcinoma. Most patients received a lower dose of oxaliplatin than previous studies suggested, which appeared to be more tolerable.
Review
Pharmacology & Pharmacy
Peiying Bai, Tengjiao Fan, Xin Wang, Lijiao Zhao, Rugang Zhong, Guohui Sun
Summary: Guanine O-6-alkylating agents, as first-line chemotherapeutic drugs, induce cytotoxic DNA damage but face the challenge of chemoresistance caused by O-6-methylguanine-DNA methyltransferase (MGMT) repair pathway. Covalent inhibitors of MGMT have limited utility due to severe delayed hematological toxicity. Therefore, targeting specific cell signaling pathways that regulate MGMT expression emerges as a promising strategy to overcome tumor resistance and enhance the efficacy of DNA alkylating agents in chemotherapy.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Elies Fuster-Garcia, David Lorente Estelles, Maria del Mar Alvarez-Torres, Javier Juan-Albarracin, Eduard Chelebian, Alex Rovira, Cristina Auger Acosta, Jose Pineda, Laura Oleaga, Enrique Molla-Olmos, Silvano Filice, Paulina Due-Tonnessen, Torstein R. Meling, Kyrre E. Emblem, Juan M. Garcia-Gomez
Summary: The study found that MGMT methylation and rCBV provide complementary prognostic information, with MGMT methylation being a positive predictive factor for OS in patients with moderately vascularized tumors, but not showing significant effects in patients with highly vascularized tumors.
EUROPEAN RADIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shao-Wei Feng, Pei-Chi Chang, Hsuan-Yu Chen, Dueng-Yuan Hueng, Yao-Feng Li, Shih-Ming Huang
Summary: Metformin has been shown to effectively reduce cell proliferation and migration, promote cell apoptosis, and disrupt mitochondrial metabolism in glioblastoma cells. Additionally, the combination treatment of metformin and temozolomide has different effects on glioblastoma cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Lucia Cannella, Rosa Della Monica, Antonella Lucia Marretta, Domenico Iervolino, Bruno Vincenzi, Anna Rosaria De Chiara, Ottavia Clemente, Michela Buonaiuto, Maria Luisa Barretta, Annabella Di Mauro, Massimiliano Di Marzo, Michele Guida, Giuseppe Badalamenti, Lorenzo Chiariotti, Salvatore Tafuto
Summary: This retrospective study investigated the correlation between the methylation status of the MGMT promoter and clinical outcomes of dacarbazine-treated patients with leiomyosarcoma (LMS). The results showed better outcomes in patients with unmethylated MGMT, indicating a relationship between MGMT methylation and poor prognosis in LMS.
Article
Biochemistry & Molecular Biology
Mohammed A. Ibrahim Al-Obaide, Viswanath Arutla, Manny D. Bacolod, Wei Wang, Ruiwen Zhang, Kalkunte S. Srivenugopal
Summary: This study identified new regulatory elements in the MGMT gene locus, indicating complex transcriptional and posttranscriptional controls, with potential for new therapeutic avenues.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Michele Flagiello, Matteo Pozzi, Laurent Francois, Ahmed Al Harthy, Julien Forestier, Sara Boccalini, Gilles Rioufol, Thomas Walter, Jean Francois Obadia
Summary: This article presents a rare disease called carcinoid heart disease and discusses its treatment methods, with a successful case of treatment through direct transcatheter pulmonary valve implantation without pre-stenting.
CARDIOVASCULAR REVASCULARIZATION MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Claire Boyer, David Sefrioui, Romain Cohen, Romain Chautard, Marine Perrier, Hugo Lebrun, Gael Goujon, Vincent Hautefeuille, Marie Dior, Thomas Walter, Florence Mary, Silvain Manfredi, Francois-Xavier Caroli-Bosc, Baptiste Cervantes, Romain Coriat, Elise Deluche, Aziz Zaanan, Raphael Olivier, Olivier Bouche, Guillaume Piessen, Thierry Lecomte, Christophe Louvet, Pierre Michel, Thomas Aparicio, Thierry Andre, Julien Taieb, Violaine Randrian, David Tougeron
Summary: This French multicenter study evaluated the overall survival of patients with dMMR/MSI digestive non-colorectal tumors. The results showed that most tumors were oesophago-gastric or small bowel adenocarcinomas and were at a localized stage at diagnosis. Patients with localized tumors and R0 resection had a median overall survival of 134.0 +/- 64.2 months. Overall, dMMR/MSI digestive non-colorectal tumors have a good prognosis, but advanced tumors treated with standard chemotherapy have a poor prognosis.
DIGESTIVE AND LIVER DISEASE
(2023)
Article
Gastroenterology & Hepatology
Adrien Patenotte, Clara Yzet, Timothee Wallenhorst, Fabien Subtil, Sarah Leblanc, Marion Schaefer, Thomas Walter, Thomas Lambin, Tanguy Fenouil, Pierre Lafeuille, Jean-Baptiste Chevaux, Romain Legros, Florian Rostain, Jerome Rivory, Jeremie Jacques, Vincent Lepilliez, Mathieu Pioche
Summary: This study evaluated the feasibility and effectiveness of ESD for lesions with a suspicion of focal deep invasion. It found that ESD is feasible and safe for colorectal lesions with an FDIP <= 15 mm. It achieved high resection and en bloc resection rates, making it a potential valid option for low-risk T1 cancer patients.
Article
Surgery
Antoine Coupier, Yves Gallien, Olivier Boillot, Thomas Walter, Olivier Guillaud, Melanie Vallin, Elsa Thimonier, Domitille Erard, Jerome Dumortier
Summary: This study describes a cohort of liver transplantation recipients who underwent antineoplastic cytotoxic chemotherapy. The results suggest that immunosuppressive drugs and antineoplastic chemotherapy can be managed satisfactorily in most cases.
CLINICAL TRANSPLANTATION
(2023)
Article
Medicine, Research & Experimental
David Kryza, Jennifer Wischhusen, Mathieu Richaud, Maeva Hervieu, Jacqueline Sidi Boumedine, Jean-Guy Delcros, Sophie Besse, Thomas Baudier, Pierre-Alexandre Laval, Silvia Breusa, Erwan Boutault, Hugo Clermidy, Nicolas Rama, Benjamin Ducarouge, Mojgan Devouassoux-Shisheboran, Jean-Michel Chezal, Anne-Laure Giraudet, Thomas Walter, Patrick Mehlen, David Sarrut, Benjamin Gibert
Summary: Targeted radionuclide therapy is a revolutionary tool for treating metastatic cancers. This study identifies netrin-1, a molecule known to promote cancer progression, as a potential target for radiotherapy. The development of a therapeutic anti-netrin-1 antibody and an imaging contrast agent allows for the specific detection and treatment of netrin-1-positive tumors. Preclinical studies demonstrate the effectiveness of the therapy in tumor mouse models. These findings suggest that netrin-1 may be a promising target for advanced solid cancers.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Nicola Fazio, Lorenzo Gervaso, Thorvardur R. Halfdanarson, Mohamad Sonbol, Rachel A. Eiring, Sara Pusceddu, Natalie Prinzi, Benedetta Lombardi Stocchetti, Simona Grozinsky-Glasberg, David J. Gross, Thomas Walter, Patrick Robelin, Catherine Lombard-Bohas, Samuele Frassoni, Vincenzo Bagnardi, Lorenzo Antonuzzo, Clotilde Sparano, Sara Massironi, Fabio Gelsomino, Alberto Bongiovanni, Nicoletta Ranallo, Salvatore Tafuto, Maura Rossi, Mauro Cives, Ibrahim Rasul Kakil, Hytam Hamid, Alessandra Chirco, Michela Squadroni, Anna La Salvia, Jorge Hernando, Johannes Hofland, Anna Koumarianou, Sabrina Boselli, Darina Tamayo, Cristina Mazzon, Manila Rubino, Francesca Spada
Summary: This study investigated patients with neuroendocrine neoplasms (NENs) and confirmed SARS-CoV-2 positivity at the molecular level through a retrospective/prospective worldwide study. The findings indicate a decreasing trend in the incidence of COVID-19 over the years, with older age, non-gastroenteropancreatic primary sites, and diabetes mellitus associated with increased severity and mortality of COVID-19.
ENDOCRINE-RELATED CANCER
(2023)
Review
Endocrinology & Metabolism
Clemence Delhomme, Thomas Walter, Dimitri Arangalage, Gaspard Suc, Olivia Hentic, Agnes Cachier, Soleiman Alkhoder, Laurent Francois, Catherine Lombard-Bohas, Bernard Iung, Philippe Ruszniewski, Louis de Mestier
Summary: Carcinoid heart disease (CHD) is a major complication of carcinoid syndrome (CS) associated with metastatic small intestine neuroendocrine tumors (NETs). The formation of fibrous plaques involving the right side of the heart is mainly caused by vasoactive hormones secreted by NETs, particularly serotonin. Diagnosis of CHD can be delayed as patients are often asymptomatic despite severe heart valve involvement. Treatment of CHD requires a multidisciplinary approach, including antitumor treatment, control of CS, and surgical valve replacement in severe cases.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Pathology
Tanguy Fenouil, Pierre Marie Lavrut, Maud Rabeyrin, Mustapha Adham, Kayvan Mohkam, Jean Yves Mabrut, Thomas Walter, Valerie Hervieu
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a major public health issue with a high incidence/mortality ratio. Only a small percentage of patients with PDAC can have surgery, and even after surgery, there is a high risk of recurrence. Necrosis is found to have a significant impact on overall survival in patients with PDAC.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Article
Surgery
Lea Robin, Alain Sauvanet, Thomas Walter, Haythem Najah, Massimo Falconi, Francois Pattou, Sebastien Gaujoux
Summary: Gastrinoma can be cured by complete resection, but the surgical management for sporadic nonmetastatic gastrinoma is still controversial. This retrospective study analyzed patients who underwent surgery for nonmetastatic sporadic gastrinoma between 2000 and 2020. The study identified predictive factors for overall survival and disease-free survival. The results showed that tumor size and grade were independent predictors of recurrence, and surgical procedures did not significantly affect overall survival and disease-free survival for duodenal gastrinomas.
Article
Endocrinology & Metabolism
Vincent Hautefeuille, Thomas Walter, Christine Do Cao, Romain Coriat, Sophie Dominguez, Laurent Mineur, Guillaume Cadiot, Eric Terrebonne, Iradj Sobhani, Delphine Gueguen, Aude Houchard, Charbel Mouawad, Amelie Anota, Pascal Hammel
Summary: This study aimed to evaluate the change in patient's perceptions of information level at LAN treatment initiation for GEP-NETs vs after 6 months. The results showed that there was no significant change in patient's perceptions of disease, treatment, and supportive care information provided over the first 6 months of LAN treatment, suggesting that physicians provided adequate information at the treatment initiation.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Lucie Duponchelle, Eric Baudin, Fabien Subtil, Christine Do Cao, Eric Dansin, Marine Perrier, Marie-Pierre Teissier, Magalie Haissaguerre, Xavier Cansouline, Julien Hadoux, Galina Jepiral, Catherine Lombard-Bohas, Olaf Mercier, Francois Tronc, Thomas Walter
Summary: This retrospective study investigated the outcomes of surgery for patients with metastatic primary lung neuroendocrine tumors, and found that surgery was associated with a higher rate of improvement in pulmonary symptoms compared to nonoperative treatment. Furthermore, the study found no postoperative mortality and a low rate of major complications in the operative group. These results suggest that surgery may be a safe option for selected patients in order to improve their quality of life.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Gregory Kaltsas, Thomas Walter, Ulrich Knigge, Christos Toumpanakis, Ana P. Santos, Nehara Begum, Ulrich F. Pape, Marco Volante, Andrea Frilling, Anne Couvelard
Summary: The aim of this guidance paper is to provide up-to-date practical guidance for the diagnosis and management of well differentiated appendiceal neuroendocrine tumors (NET). The paper addresses controversial issues and areas of uncertainty, offering recommendations based on the best available evidence and the authors' experiences.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Gastroenterology & Hepatology
Marine Perrier, Charbel Mouawad, Delphine Gueguen, Benoit Thom, Maryse Lapeyre-Mestre, Thomas Walter
Summary: This study used the French national health care data system to describe healthcare resource utilization and costs among patients with neuroendocrine tumors and carcinoid syndrome (CS). The first year following diagnosis and the year preceding death were found to be the periods with the highest costs for CS care in France. Successful disease management may contribute to lower costs in the intermediate period.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2023)
Review
Oncology
Marine Perrier, Jean-Yves Scoazec, Thomas Walter
Summary: According to the characteristics of neuroendocrine tumors (NET), there are 3 to 7 different treatment options, corresponding to 6 to 5,040 theoretical different sequences. Despite heterogeneity in NET characteristics, this review discusses main sequences and proposes a case-by-case basis for treating metastatic NET (mNET). Each treatment should be discussed in multi-disciplinary meetings, and clinical trials should be favored. The first-line treatment should be chosen based on treatment aim, taking into account efficacy, safety, and patient preferences. Real-world data using long follow-up durations are necessary to improve knowledge regarding effectiveness and risk of cumulative toxicities for different sequences.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2023)
Article
Oncology
Thomas Walter, Astrid Lievre, Romain Coriat, David Malka, Farid Elhajbi, Frederic Di Fiore, Olivia Hentic, Denis Smith, Vincent Hautefeuille, Guillaume Roquin, Marine Perrier, Laetitia Dahan, Victoire Granger, Iradj Sobhani, Laurent Mineur, Patricia Niccoli, Eric Assenat, Jean-Yves Scoazec, Karine Le Malicot, Come Lepage, Catherine Lombard-Bohas
Summary: This study evaluates the efficacy of FOLFIRI plus bevacizumab and FOLFIRI alone as second-line treatment for gastroenteropancreatic neuroendocrine carcinoma. The addition of bevacizumab did not seem to improve overall survival compared to FOLFIRI alone, suggesting that FOLFIRI could be considered as the standard second-line treatment for this type of cancer.
