Article
Pharmacology & Pharmacy
Luisa Maresca, Enrica Crivaro, Francesca Migliorini, Giulia Anichini, Alessandro Giammona, Sara Pepe, Federica Poggialini, Chaira Vagaggini, Giuseppe Giannini, Serena Sestini, Lorenzo Borognoni, Andrea Lapucci, Elena Dreassi, Maurizio Taddei, Fabrizio Manetti, Elena Petricci, Barbara Stecca
Summary: Aberrant activation of Hedgehog signaling in cancer can be suppressed by inhibiting the zinc-finger transcription factors GLI1 and GLI2, which are activated by genetic alterations or other oncogenic mechanisms. A novel GLI inhibitor called JC19 was discovered, which showed excellent metabolic stability and high passive permeability. JC19 inhibited GLI1 and GLI2 activities, suppressed cancer cell proliferation, and induced apoptosis, making it a potential anti-cancer agent.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Xiaohua Liu, Yu Zhang, Yalei Li, Juan Wang, Huaqian Ding, Wenjing Huang, Chunyong Ding, Hongchun Liu, Wenfu Tan, Ao Zhang
Summary: Medulloblastoma is a childhood malignant brain tumor with heterogeneous characteristics and lacks effective molecular targeted therapy. Compounds 25 and 35 show high potency in inhibiting hedgehog signaling and interacting with the transcriptional factor GLI, with potential to combat resistant and wild type smoothened receptor.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Oncology
Anke Koeniger, Anna Brichkina, Iris Nee, Lukas Dempwolff, Anna Hupfer, Ilya Galperin, Florian Finkernagel, Andrea Nist, Thorsten Stiewe, Till Adhikary, Wibke Diederich, Matthias Lauth
Summary: Elevated GLI1 expression levels are associated with improved survival in NB patients and GLI1 overexpression exerts tumor-suppressive traits in cultured NB cells. However, NB cells are protected from increased GLI1 levels as they have lost their primary cilia and ability to transduce Hedgehog signals. An isoxazole molecule (ISX) has been identified to activate GLI1 independently of primary cilia, providing a potential therapeutic strategy for NB treatment.
Article
Cell Biology
Jun Yang, Juan Wang, Yuan Liu, Yu Zhang, Wenjing Huang, Yu Zou, Yanyan Qiu, Weiyang Cai, Jing Gao, Hu Zhou, Yingli Wu, Weijun Liu, Qingqing Ding, Yanjie Zhang, Pei-hao Yin, Wenfu Tan
Summary: The study reveals that colorectal cancer cells exploit PGE2 to promote Hh activity in a non-canonical manner, leading to Gli-dependent proliferation. Mechanistically, PGE2 activates JNK, enabling Gli2 to evade degradation by phosphorylating Gli2 at Thr1546.
CELL DEATH & DISEASE
(2021)
Review
Cell Biology
Patricia A. Umberger, Stacey K. Ogden
Summary: SPOP protein serves as a guardian of genome integrity and controls transcriptional regulation by regulating the stability of GLI family members in the Hedgehog signaling pathway. In Drosophila, the protein HIB targets the GLI ortholog Ci for proteolysis through Cul3-directed degradation, but the molecular mechanisms of GLI/Ci targeting differ between Drosophila and vertebrates.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Patricia A. Umberger, Stacey K. Ogden
Summary: SPOP plays a crucial role in maintaining cellular homeostasis by regulating DNA repair and gene expression-related DNA-binding proteins; within the Hedgehog signaling pathway, CUL3-SPOP activity influences stability of GLI transcription factors and the amplitude and duration of HH transcriptional responses; a similar mechanism exists in Drosophila, but HIB and SPOP have different molecular contributions to Drosophila and vertebrate HH signaling pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Erik P. Beadle, Natalie E. Bennett, Julie A. Rhoades
Summary: Liposarcomas are rare soft tissue malignancies with varying clinical prognosis. Well-differentiated and dedifferentiated liposarcomas commonly occur in extremities and the retroperitoneal cavity. Surgical resection and post-operative monitoring are effective treatments, but recurrence is common and chemotherapy may be necessary. Hedgehog signaling is upregulated in dedifferentiated liposarcomas and is associated with reduced immune cell infiltration and increased extracellular matrix protein expression.
Article
Cell Biology
Ping Shi, Jia Tian, Julianne C. Mallinger, Dahao Ling, Loic P. Deleyrolle, Jeremy C. Mcintyre, Tamara Caspary, Joshua J. Breunig, Matthew R. Sarkisian
Summary: This study found that increasing ARL13B expression in glioma cells can promote the accumulation of SMO and GLI2 in cilia, and this accumulation is resistant to SMO inhibitors. Furthermore, the increase in ARL13B also leads to changes in ciliary membrane characteristics and retrograde transport, which further promote SMO and GLI accumulation in glioma cells.
Article
Anatomy & Morphology
Li Xu, Caixia Ji, Tingting Yu, Jinyong Luo
Summary: Diseases such as bone nonunion and osteoporosis seriously impact people's quality of life, and bone tissue engineering using mesenchymal stem cells is an effective solution. Previous studies have shown the efficacy of BMP9 in promoting osteogenic differentiation of MSCs, but the underlying mechanisms remain unclear. This study investigated the role of Gli1 and Gli2 in BMP9-induced osteogenic differentiation of MSCs. The results demonstrated that inhibition of Gli1 and Gli2 weakened BMP9-induced osteogenic differentiation and reduced the expression of key osteogenic markers, as well as the activation of p-Smad1/5/8 and p-p38 induced by BMP9. In conclusion, this study highlights the importance of Gli1 and Gli2 in BMP9-induced osteogenic differentiation.
Article
Immunology
Guido Hernan Falduto, Annika Pfeiffer, Qunshu Zhang, Yuzhi Yin, Dean Darrel Metcalfe, Ana Olivera
Summary: The GLI proteins play a critical role in regulating the survival and proliferation of mast cells. Inhibition of GLI activity leads to increased apoptosis and reduced mast cell numbers. GLI silencing also inhibits the proliferation of neoplastic mast cell lines.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Elisabeth Peer, Sophie Karoline Aichberger, Filip Vilotic, Wolfgang Gruber, Thomas Parigger, Sandra Grund-Groeschke, Dominik Patrick Elmer, Florian Rathje, Andrea Ramspacher, Mirko Zaja, Susanne Michel, Svetlana Hamm, Fritz Aberger
Summary: Inhibition of CSNK1D represents a novel therapeutic approach for both SMO inhibitor-sensitive and -resistant tumors, suppressing oncogenic HH-GLI signaling and reducing malignant properties of tumor-initiating cells. This study provides a basis for the development of efficient CSNK1D inhibitors as a potential therapy for HH-GLI-associated cancers.
Review
Oncology
Justin T. Avery, Ruowen Zhang, Rebecca J. Boohaker
Summary: GLI1, a transcriptional effector in the Hedgehog signaling pathway, is tightly regulated during normal tissue development but aberrant activation in cancer can promote hallmarks such as proliferation, metastasis, and chemoresistance. Its oncogenic activities mainly involve regulating cell cycle, DNA replication, and DNA damage repair processes. Understanding the mechanisms of GLI1 dysregulation can provide prognostic and diagnostic biomarkers for targeted therapy in cancer treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Shu Ichimiya, Hideya Onishi, Shinjiro Nagao, Satoko Koga, Kukiko Sakihama, Kazunori Nakayama, Akiko Fujimura, Yasuhiro Oyama, Akira Imaizumi, Yoshinao Oda, Masafumi Nakamura
Summary: This study revealed that GLI2 is involved in various aspects of GBC, such as cell proliferation, invasion, and sensitivity to treatment, suggesting it could be a novel therapeutic target for GBC. The results provide significant insights for the development of new treatment options for refractory GBC.
Article
Oncology
Fan Yang, Jezabel Rodriguez-Blanco, Jun Long, Marzena Swiderska-Syn, Daniel T. Wynn, Bin Li, Chen Shen, Anmada Nayak, Yuguang Ban, Xiaodian Sun, Robert K. Suter, Heather J. McCrea, Anthony J. Capobianco, Nagi G. Ayad, David J. Robbins
Summary: Dysregulation of SHH signaling contributes to the growth of cancer subtypes, and resistance to current SHH inhibitors is a common issue. A novel UHRF1/DNMT1/GLI complex has been identified as a potential target for regulating SHH-dependent tumor growth, with an FDA-approved drug capable of disrupting this complex to attenuate tumor growth.
MOLECULAR CANCER RESEARCH
(2022)
Review
Oncology
Laura Grumetti, Rita Lombardi, Federica Iannelli, Biagio Pucci, Antonio Avallone, Elena Di Gennaro, Alfredo Budillon
Summary: This review focuses on the role of histone deacetylase inhibitors (HDACis) in the metabolism and resistance mechanisms of fluoropyrimidines. Studies have shown that HDACis can enhance the antitumor efficacy of fluoropyrimidines and overcome drug resistance. However, clinical studies have not fully confirmed these observations.
Editorial Material
Oncology
Mariano Catello Di Donna, Giuseppe Cucinella, Giulia Zaccaria, Antonio Simone Lagana, Giovanni Scambia, Vito Chiantera
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Oncology
Paul DiSilvestro, Susana Banerjee, Nicoletta Colombo, Giovanni Scambia, Byoung-Gie Kim, Ana Oaknin, Michael Friedlander, Alla Lisyanskaya, Anne Floquet, Alexandra Leary, Gabe S. Sonke, Charlie Gourley, Amit Oza, Antonio Gonzalez-Martin, Carol Aghajanian, William Bradley, Cara Mathews, Joyce Liu, John McNamara, Elizabeth S. Lowe, Mei-Lin Ah-See, Kathleen N. Moore
Summary: Maintenance therapy with olaparib showed sustained progression-free survival benefit in newly diagnosed advanced ovarian cancer patients with a BRCA mutation. After a 7-year follow-up, there was a clinically meaningful improvement in overall survival. The incidence of myelodysplastic syndrome and acute myeloid leukemia was low.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Letter
Oncology
Claudia Marchetti, Anna Fagotti, Giovanni Scambia
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Alejandra Martinez, Fabrice Lecuru, Nicolo Bizzarri, Cyrus Chargari, Anne Ducassou, Anna Fagotti, Francesco Fanfani, Giovanni Scambia, David Cibula, Berta Diaz-Feijoo, Antonio Gil Moreno, Martina Aida Angeles, Mustafa Zelal Muallem, Christhardt Kohler, Mathieu Luyckx, Frederic Kridelka, Agnieszka Rychlik, K. G. Gerestein, Viola Heinzelmann, Pedro T. Ramirez, Michael Frumovitz, Gwenael Ferron, Sarah Betrian, Thomas Filleron, Christina Fotopoulou, Denis Querleu
Summary: This is an international multicenter, randomized, phase III study aims to demonstrate that surgical staging followed by tailored chemoradiation can improve the 3-year disease-free survival compared to PET/CT staging alone in patients with FIGO stage IIIC1 cervical cancer. The primary endpoint is disease-free survival, and the estimated sample size is 510 eligible patients. The estimated dates for completing accrual and presenting results are Q2 2027 and Q4 2030, respectively.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Oncology
Giorgio Bogani, Isabelle Ray-Coquard, Nicole Concin, Natalie Yan Li Ngoi, Philippe Morice, Giuseppe Caruso, Takayuki Enomoto, Kazuhiro Takehara, Hannelore Denys, Domenica Lorusso, Robert Coleman, Michelle M. Vaughan, Masashi Takano, Diane Michele Provencher, Satoru Sagae, Pauline Wimberger, Robert Poka, Yakir Segev, Se Ik Kim, Jae-Weon Kim, Francisco Jose Candido dos Reis, Pedro T. Ramirez, Andrea Mariani, Mario Leitao, Vicky Makker, Nadeem R. Abu-Rustum, Ignace Vergote, Gianfranco Zannoni, David Tan, Mary McCormack, Biagio Paolini, Marta Bini, Francesco Raspagliesi, Pierluigi Benedetti Panici, Violante Di Donato, Ludovico Muzii, Nicoletta Colombo, Sandro Pignata, Giovanni Scambia, Bradley J. Monk
Summary: Endometrial carcinosarcoma is a rare and aggressive type of cancer, with clinical presentation and diagnostic methods similar to the more common endometrioid carcinoma. It is characterized by the presence of both carcinomatous and sarcomatous elements, and the majority of cases have p53 abnormalities. Treatment involves a multimodal approach for non-metastatic disease and palliative chemotherapy for metastatic or recurrent disease.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Oncology
Nicolo Bizzarri, Vito Chiantera, Matteo Loverro, Giulio Sozzi, Emanuele Perrone, Salvatore Gueli Alletti, Barbara Costantini, Valerio Gallotta, Lucia Tortorella, Anna Fagotti, Francesco Fanfani, Alfredo Ercoli, Giovanni Scambia, Giuseppe Vizzielli
Summary: This study compared the disease-free survival, cancer-specific survival, and peri-operative morbidity between patients undergoing open and minimally invasive pelvic exenteration. The results showed no significant difference in survival rates and complications, but a higher intra-operative transfusion rate was seen in the open group.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Oncology
Elisa De Paolis, Ida Paris, Bruno Tilocca, Paola Roncada, Laura Foca, Giordana Tiberi, Tatiana D'Angelo, Francesco Pavese, Margherita Muratore, Luisa Carbognin, Giorgia Garganese, Riccardo Masetti, Alba Di Leone, Alessandra Fabi, Giovanni Scambia, Andrea Urbani, Daniele Generali, Angelo Minucci, Concetta Santonocito
Summary: Breast cancer is the leading cause of cancer-related death in women worldwide, with BRCA1 and BRCA2 genes accounting for a significant portion of hereditary breast cancer. Classifying variants accurately is important for risk-reducing surgeries, treatment planning, and familial surveillance.
FRONTIERS IN ONCOLOGY
(2023)
Article
Medicine, General & Internal
Nicolo Bizzarri, Antonella Biscione, Francesca Moro, Luigi Pedone Anchora, Valeria Catinella, Camilla Certelli, Elena Teodorico, Anna Fagotti, Francesco Fanfani, Ali Kucukmetin, Denis Querleu, Gabriella Ferrandina, Giovanni Scambia, Antonia Carla Testa
Summary: The aim of the study was to investigate the prognostic impact of ultrasound tumor parameters and patients' anthropometric parameters on cervical cancer. The study found that low body mass index (BMI) and ultrasound tumor volume were associated with a higher risk of recurrence. Additionally, the study identified a significant relation between ultrasound characteristics and pathological parametrial infiltration. These findings suggest that these parameters can be useful in pre-operative workup for a patient-tailored treatment in early-stage cervical cancer.
Article
Health Care Sciences & Services
Marianna Mazza, Carla Avallone, Georgios Demetrios Kotzalidis, Giuseppe Marano, Lorenzo Moccia, Anna Maria Serio, Marta Balocchi, Ilenia Sessa, Delfina Janiri, Ilaria De Luca, Caterina Brisi, Maria Chiara Spera, Laura Monti, Angela Gonsalez del Castillo, Gloria Angeletti, Daniela Chieffo, Lucio Rinaldi, Luigi Janiri, Antonio Lanzone, Giovanni Scambia, Eugenio Maria Mercuri, Gabriele Sani
Summary: This study aimed to examine the incidence of depressive symptomatology during pregnancy and to evaluate the role of affective temperament traits and psychosocial risk factors in predicting them. The prevalence of depressive symptomatology in our sample was 41.45% and the prevalence of depression was 9.85%, with 6.75% experiencing mild depression and 3.10% experiencing moderate depression. Several factors were found to be significantly associated with the development of depressive symptoms during pregnancy.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Review
Oncology
Giorgio Bogani, Alessandro Ghelardi, Francesco Sopracordevole, Marco Annoni, Andrea Ciavattini, Luca Giannella, Rosa De Vincenzo, Paolo Cattani, Maggiorino Barbero, Paolo Vercellini, Francesco Raspagliesi, Paolo Bonanni, Giovanni Scambia
Summary: Human papillomavirus (HPV) is a common sexually transmitted infection that can cause various diseases, including cervical cancer. Prophylactic HPV vaccines have been developed to prevent the spread of HPV and reduce the prevalence of HPV-related diseases. Despite their high efficacy, HPV vaccines are underutilized in Italy, with decreasing coverage rates. Action is needed to improve HPV awareness and education to promote widespread adoption of HPV vaccination.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Review
Biochemistry & Molecular Biology
Silvia D'Ippolito, Greta Barbaro, Carmela Paciullo, Chiara Tersigni, Giovanni Scambia, Nicoletta Di Simone
Summary: The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by persistent presence of autoantibodies against phospholipid-binding proteins, leading to thrombosis and/or obstetrical complications. Vascular APS (VAPS) and obstetric APS (OAPS) have been recognized as two distinct clinical entities. VAPS is explained by the interference of antiphospholipid antibodies with the coagulation cascade, while OAPS involves additional mechanisms such as direct damage to trophoblast cells by anti-beta 2 glycoprotein-I.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
A. Rosati, V. Vargiu, C. Certelli, M. Arcieri, E. Vizza, F. Legge, F. Cosentino, G. Ferrandina, F. Fanfani, G. Scambia, G. Corrado
Summary: This study aimed to evaluate the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS) in patients with uterine carcinosarcomas (UCSs). The results showed that the heterologous sarcomatous component had a significant negative impact on the prognosis of early-stage UCSs.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Oncology
Pasquale Lombardi, Marco Filetti, Rosa Falcone, Valeria Altamura, Francesco Paroni Sterbini, Emilio Bria, Alessandra Fabi, Diana Giannarelli, Giovanni Scambia, Gennaro Daniele
Summary: Trop-2 is a glycoprotein that is widely expressed on different types of tumors and is associated with both oncogenic and tumor suppressor roles. The therapeutic potential of Trop-2 has been recognized, and clinical studies with drug-antibody conjugates have been initiated in various cancer types. This review provides an overview of the pre-clinical and clinical activities of anti-Trop-2 therapy, highlighting the future developments of these therapies.
Review
Oncology
Ilaria Capasso, Angela Santoro, Emanuela Lucci Cordisco, Emanuele Perrone, Francesca Tronconi, Ursula Catena, Gian Franco Zannoni, Giovanni Scambia, Francesco Fanfani, Domenica Lorusso, Simona Duranti
Summary: Lynch syndrome is a genetic condition that increases the risk of various tumors, including endometrial and ovarian cancers. Universal screening is recommended for detecting Lynch syndrome. Surgery, chemoprevention, and immunotherapy are viable options for treatment.
Editorial Material
Oncology
Federica Perelli, Alberto Mattei, Giovanni Scambia, Anna Franca Cavaliere
FRONTIERS IN ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)