Article
Oncology
Carlotta Guzzetti, Cristina Corno, Elisabetta Vergani, Luca Mirra, Emilio Ciusani, Monica Rodolfo, Paola Perego, Giovanni L. Beretta
Summary: KiSS1, a metastasis suppressor, plays an important role in the development and puberty of melanoma cells. This study found that kisspeptin 54, a cleavage product of KiSS1, can enhance the pro-apoptotic activity of vemurafenib in melanoma cells, including drug-resistant cells. These findings suggest the potential of using KiSS1 to modulate apoptotic response.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell Biology
Heike Niessner, Markus Burkard, Christian Leischner, Olga Renner, Sarah Ploeger, Francisco Meraz-Torres, Matti Boecker, Constanze Hirn, Ulrich M. Lauer, Sascha Venturelli, Christian Busch, Tobias Sinnberg
Summary: High-dose ascorbate has a paradoxical pro-oxidant effect and shows significant therapeutic efficacy against tumor cells, especially melanomas. Combining high-dose ascorbate with vemurafenib can significantly enhance the therapeutic effect of vemurafenib without any adverse effects.
Article
Multidisciplinary Sciences
Lauren Y. Cheng, Lauren E. Haydu, Ping Song, Jianyi Nie, Michael T. Tetzlaff, Lawrence N. Kwong, Jeffrey E. Gershenwald, Michael A. Davies, David Yu Zhang
Summary: The study demonstrates that the NuProbe VarTrace BRAF sequencing technology can detect BRAF V600 mutations down to 0.20% VAF from FFPE lymph node tissue samples, with high concordance among various methods for samples with VAF>=1% BRAF mutations, but with possible false negatives in IHC. The BDA Sanger method is effective for rapid detection and quantitation of multiple low VAF BRAF mutations.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Honey Bokharaie, Walter Kolch, Aleksandar Krstic
Summary: Alternative splicing plays an important role in cancer, and one common mechanism of vemurafenib resistance in malignant melanoma involves alternative splicing of the BRAF gene. Our study shows that alternative splicing in vemurafenib-resistant cells can affect cell motility and melanin synthesis. The results highlight the need for further investigation of aberrant alternative splicing in patients with melanoma.
Article
Cell Biology
Ting Wu, Chengyun Li, Changlong Zhou, Xiaxia Niu, Gege Li, Yali Zhou, Xinsheng Gu, Hongmei Cui
Summary: In this study, repression of USP14 sensitized vemurafenib resistance in melanoma through stabilizing Skp2 and blocking its ubiquitination. The combination of Skp2 inhibitor and USP14/UCHL5 inhibitor significantly inhibited cell proliferation, migration, invasion, and colony formation in vemurafenib-sensitive and vemurafenib-resistant melanoma. The dual treatment also led to enhanced apoptosis and autophagy in melanoma cells.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anne Uebel, Stefanie Kewitz-Hempel, Edith Willscher, Kathleen Gebhardt, Cord Sunderkoetter, Dennis Gerloff
Summary: Activating BRAF mutations are present in 50-60% of malignant melanomas. Inhibiting EZH2 or its downstream target PLK1, in combination with BRAF inhibitors, may provide potential novel therapeutic options for melanomas with BRAF mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Environmental Sciences
Yu-Jen Chiu, Jai-Sing Yang, Fuu-Jen Tsai, Hong-Yi Chiu, Yu-Ning Juan, Yu-Hsiang Lo, Jo-Hua Chiang
Summary: This study identified the resistance of melanoma to vemurafenib and revealed that curcumin can induce apoptosis in vemurafenib-resistant melanoma cells by regulating the EGFR signaling pathway, suggesting curcumin as a potential therapeutic candidate for vemurafenib-resistant melanoma treatment.
ENVIRONMENTAL TOXICOLOGY
(2022)
Article
Oncology
Yufan Tan, Xiaoyu Zhong, Xizhi Wen, Leyi Yao, Zhenlong Shao, Wenshuang Sun, Jiawen Wu, Guanmei Wen, Daolin Tang, Xiaoshi Zhang, Yuning Liao, Jinbao Liu
Summary: A study showed that blood bilirubin levels in BRAF-mutant melanoma patients treated with vemurafenib are inversely correlated with clinical outcomes. Bilirubin can counteract the growth-inhibiting and apoptosis-inducing effects of vemurafenib on melanoma cells by activating the ERK-MNK1 axis. This highlights the negative impact of bilirubin on the effectiveness of vemurafenib in treating BRAF-mutant melanoma.
FRONTIERS IN ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Meng-Ting Chang, Li-Chu Tsai, Kyoko Nakagawa-Goto, Kuo-Hsiung Lee, Lie-Fen Shyur
Summary: This study uncovers the abnormal upregulation of PUFAs and oxylipin metabolism in vemurafenib resistant melanoma cells. DET and DETD-35 induce cell death in sensitive and resistant BRAF(V600E) melanoma cells by reprogramming metabolism and causing mitochondrial damage, targeting GPX4 and ferroptosis.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Dermatology
Mario Mandala, Giuseppe Palmieri, Vienna Ludovini, Sara Baglivo, Francesca Marasciulo, Francesca Castiglione, Alessio Gili, Simona Osella Abate, Marco Rubatto, Rebecca Senetta, Gianluca Avallone, Simone Ribero, Luca Romano, Nicola Pimpinelli, Vincenzo de Giorgi, Fausto Roila, Marina Pisano, Milena Casula, Antonella Manca, Maria Cristina Sini, Daniela Massi, Pietro Quaglino
Summary: The prognostic impact of variant allele frequency (VAF) on clinical outcome in metastatic melanoma patients receiving BRAF and MEK inhibitors is still unclear. This study found that high VAF is an independent poor prognostic factor in these patients.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Oncology
Manali S. Phadke, Zhihua Chen, Jiannong Li, Eslam Mohamed, Michael A. Davies, Inna Smalley, Derek R. Duckett, Vinayak Palve, Brian J. Czerniecki, Peter A. Forsyth, David Noyes, Dennis O. Adeegbe, Zeynep Eroglu, Kimberly T. Nguyen, Kenneth Y. Tsai, Uwe Rix, Christin E. Burd, Yian A. Chen, Paulo C. Rodriguez, Keiran S. M. Smalley
Summary: In mouse models of BRAF- and NRAS-mutant melanoma, upfront immunotherapy enhances responses to targeted therapy. The sequence of IT -> TT modulates the immune environment, increasing infiltration of T cells and decreasing tumor-associated macrophages, leading to improved therapeutic outcomes. Durable responses to the IT -> TT sequence depend on T-cell activity and enrichment of a population of melanoma cells with increased expression of MHC class I and melanoma antigens.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Anna Piotrowska, Renata Zaucha, Oliwia Krol, Michal Aleksander Zmijewski
Summary: Preconditioning of patient-derived melanoma cells with 1,25(OH)(2)D-3 enhances the inhibitory effect of cediranib and vemurafenib and reduces mitochondrial respiration parameters. Moreover, cancer-associated fibroblasts play a crucial role in melanoma growth. Thus, 1,25(OH)(2)D-3 could be considered as an adjuvant agent in the treatment of malignant melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Pawel Rogala, Anna M. Czarnecka, Bozena Cybulska-Stopa, Krzysztof Ostaszewski, Karolina Piejko, Marcin Zietek, Robert Dziura, Ewa Rutkowska, Lukasz Galus, Natasza Kempa-Kaminska, Jacek Calik, Agata Salek-Zan, Tomasz Zemelka, Wieslaw Bal, Agnieszka Kamycka, Tomasz Switaj, Grazyna Kaminska-Winciorek, Rafal Suwinski, Jacek Mackiewicz, Piotr Rutkowski
Summary: Limited data is available on the sequencing of targeted therapy and immunotherapy in patients with BRAF-mutant melanoma. This study demonstrates the effectiveness of BRAFi/MEKi therapy as a second-line treatment for advanced melanoma patients, with similar efficacy observed for all combinations of BRAFi/MEKi.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Nelly Durand, Meline Simsir, Laurie Signetti, Fabien Labbal, Robert Ballotti, Isabelle Mus-Veteau
Summary: The study demonstrated that methiothepin enhances the cytotoxicity of doxorubicin on melanoma cells and overcomes resistance of BRAF(V600E) melanoma cells to vemurafenib and trametinib treatment. This highlights the potential of Ptch1 drug efflux inhibition in improving the effectiveness of anti-cancer treatments for melanoma.
Article
Oncology
Kiran Kumar Reddi, Praveen Guruvaiah, Yvonne J. K. Edwards, Romi Gupta
Summary: The study identified new targets and mechanisms driving resistance to MAPK pathway inhibitors in melanoma cells through unbiased RNA-sequencing and ATAC-seq. Changes in chromatin accessibility affected the expression levels of multiple genes, modulating oncogenic pathways and promoting resistance to inhibitors. This research provides potential new targets for treating melanoma patients resistant to MEK or BRAF inhibitors.
FRONTIERS IN ONCOLOGY
(2022)
Letter
Hematology
Giovanni Rindone, Andrea Aroldi, Elisa Bossi, Luisa Verga, Giovanni Zambrotta, Sara Tarantino, Rocco Piazza, Lara Mussolin, Roberto Chiarle, Carlo Gambacorti-Passerini
Article
Oncology
Michele Merli, Isacco Ferrarini, Francesco Merli, Alessandro Busca, Roberto Mina, Brunangelo Falini, Riccardo Bruna, Roberto Cairoli, Monia Marchetti, Alessandra Romano, Michele Cavo, Luca Arcaini, Livio Trentin, Chiara Cattaneo, Enrico Derenzini, Nicola Stefano Fracchiolla, Francesco Marchesi, Annamaria Scattolin, Atto Billio, Monica Bocchia, Massimo Massaia, Carlo Gambacorti-Passerini, Francesca Romana Mauro, Massimo Gentile, Sara Mohamed, Matteo Giovanni Della Porta, Elisa Coviello, Daniela Cilloni, Giuseppe Visani, Augusto Bramante Federici, Maria Chiara Tisi, Laura Cudillo, Sara Galimberti, Filippo Gherlinzoni, Livio Pagano, Anna Guidetti, Lorenza Bertu, Paolo Corradini, Francesco Passamonti, Carlo Visco
Summary: A study analyzed data from CLL patients with COVID-19 in Italy and found that male sex, age over 70, recent CLL treatment, and COVID-19 severity were independently associated with poor survival. The study revealed a dismal COVID-related outcome in a significant fraction of CLL patients.
HEMATOLOGICAL ONCOLOGY
(2023)
Article
Virology
Andrea Aroldi, Fabrizio Angaroni, Deborah D'Aliberti, Silvia Spinelli, Ilaria Crespiatico, Valentina Crippa, Rocco Piazza, Alex Graudenzi, Daniele Ramazzotti
Summary: This study presents a large-scale analysis of SARS-CoV-2 genome mutations, identifying three mutational processes governed by reactive oxygen species (ROS), apolipoprotein B editing complex (APOBEC), and adenosine deaminase acting on RNA (ADAR). The study also shows that samples from Africa have a significantly higher number of mutations, likely due to higher APOBEC activity, and that the Omicron variant has a significantly lower number of mutations attributed to APOBEC activity.
Article
Hematology
Marta Biondi, Sarah Tettamanti, Stefania Galimberti, Beatrice Cerina, Chiara Tomasoni, Rocco Piazza, Samantha Donsante, Simone Bido, Vincenzo Maria Perriello, Vania Broccoli, Andrea Doni, Francesco Dazzi, Alberto Mantovani, Gianpietro Dotti, Andrea Biondi, Alice Pievani, Marta Serafini
Summary: Acute myeloid leukemia (AML) is a hematological malignancy characterized by abnormal clonal proliferation and differentiation. The efficacy of chimeric antigen receptor (CAR)-T-cell therapy in AML has been hindered by factors such as poor accumulation in the leukemia bone marrow niche. Overexpression of CXCR4 in CAR-T cells may improve T-cell homing to the bone marrow and enhance their contact with AML cells, potentially increasing their therapeutic potential. In conclusion, arming CAR-T cells with CXCR4 represents a promising strategy for AML treatment.
Review
Oncology
Diletta Fontana, Elena M. Elli, Fabio Pagni, Rocco Piazza
Summary: Myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) are challenging entities to define and diagnose due to the overlap of features from both myelodysplastic syndromes and myeloproliferative neoplasms. The recent WHO 2022 classification and ICC have improved the diagnostic criteria for these disorders. This review focuses on the main entities and highlights the differential diagnosis.
Article
Medicine, Research & Experimental
Erica Dander, Paola Vinci, Stefania Vetrano, Camilla Recordati, Rocco Piazza, Grazia Fazio, Donatella Bardelli, Mattia Bugatti, Francesca Sozio, Andrea Piontini, Sonia Bonanomi, Luca Bertola, Elena Tassistro, Maria Grazia Valsecchi, Stefano Calza, William Vermi, Andrea Biondi, Annalisa Del Prete, Silvano Sozzani, Giovanna D'Amico
Summary: Gastrointestinal graft-versus-host disease (GvHD) is a major complication after allogeneic bone marrow transplantation (allo-BMT). Chemerin, a chemotactic protein, and its receptor CMKLR1 play a role in leukocyte recruitment to inflamed tissues. In this study, chemerin levels were elevated in mice with GvHD, and knockout of CMKLR1 worsened GvHD symptoms and survival. Histological analysis showed severe colitis in CMKLR1 knockout mice, characterized by neutrophil infiltration, tissue damage, and inflammation. Similar findings were observed in transplant recipients and colitis-induced mice. Transferring wild-type monocytes into CMKLR1 knockout mice improved GvHD symptoms by reducing gut inflammation and T cell activation. Furthermore, higher serum chemerin levels were associated with GvHD development in patients. These results suggest that CMKLR1/chemerin pathway may play a protective role in controlling intestinal inflammation and tissue damage in GvHD.
Letter
Hematology
Giulia Zamprogna, Anna Maria Frustaci, Giovanna Travi, Chiara Borella, Gianluigi Reda, Marina Motta, Marina Deodato, Elisa Bossi, Veronica Mattiello, Maria Beatrice Ferrari, Giulia Cotilli, Carlo Gambacorti-Passerini, Roberto Cairoli, Massimo Puoti, Alessandra Tedeschi
Letter
Hematology
Federica Malighetti, Giulia Arosio, Chiara Manfroni, Mario Mauri, Matteo Villa, Beatrice Manghisi, Elena Inzoli, Giovanni Rindone, Giovanni P. M. Zambrotta, Ivan Civettini, Veronica Guglielmana, Daniele Ramazzotti, Giovanni Giudici, Silvia Bombelli, Roberto Perego, Rocco Piazza, Luca Mologni, Carlo Gambacorti-Passerini
Article
Biology
Valentina Crippa, Federica Malighetti, Matteo Villa, Alex Graudenzi, Rocco Piazza, Luca Mologni, Daniele Ramazzotti
Summary: Cancer patients exhibit diverse phenotypes and outcomes, making it necessary to comprehensively characterize cancer phenotypes. The generation of large omics datasets now allows us to decipher cancer heterogeneity and implement personalized therapeutic strategies.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Oncology
Laura Mazzera, Manuela Abeltino, Guerino Lombardi, Anna Maria Cantoni, Stefano Jottini, Attilio Corradi, Micaela Ricca, Elena Rossetti, Federico Armando, Angelo Peli, Anna Ferrari, Giovanni Martinelli, Maria Teresa Scupoli, Carlo Visco, Massimiliano Bonifacio, Alessia Ripamonti, Carlo Gambacorti-Passerini, Antonio Bonati, Roberto Perris, Paolo Lunghi
Summary: Resistance to TKIs in Ph-positive variants of chronic myeloid leukemia is a clinical challenge. This study reveals a signaling loop driven by MEK1/2/BCR::ABL1/BCR/ABL1 that determines the efficacy of ATO in TKI-resistant leukemia. Pharmacological blockade of MEK1/2 restores anti-tumor activity and sensitizes leukemic cells to ATO.
Article
Oncology
T. Ottone, G. Silvestrini, R. Piazza, S. Travaglini, C. Gurnari, F. Marchesi, A. M. Nardozza, E. Fabiani, E. Attardi, L. Guarnera, M. Divona, P. Ricci, M. A. Irno Consalvo, S. Ienzi, R. Arcese, A. Biagi, L. Fiori, M. Novello, A. Mauriello, A. Venditti, L. Anemona, M. T. Voso
Summary: By analyzing the transcriptome profile of AML patients, researchers found that TWIST1, ECM-receptor interaction, and focal-adhesion pathways were significantly deregulated. The study also showed that metformin can interfere with these processes.
Article
Biochemistry & Molecular Biology
Silvia Diviccaro, Lucia Cioffi, Rocco Piazza, Donatella Caruso, Roberto Cosimo Melcangi, Silvia Giatti
Summary: The pathological consequences of type 2 diabetes mellitus (T2DM) on the central nervous system include learning and memory disabilities and increased risk of dementia. This study investigates the impact of neuroactive steroids and the gut microbiome on brain pathophysiology in T2DM using a rat model. The results show that T2DM worsens memory abilities, with increased corticosterone levels in the blood and decreased allopregnanolone levels in the hippocampus, where neuroinflammation, oxidative stress, and mitochondrial dysfunction are present. The analysis also identifies specific taxa in the gut microbiome that are closely related to memory impairment and neuroactive steroid levels, suggesting their potential as therapeutic targets.
Article
Biochemistry & Molecular Biology
Nicoletta Cordani, Luca Mologni, Rocco Piazza, Pietro Tettamanti, Viola Cogliati, Mario Mauri, Matteo Villa, Federica Malighetti, Camillo Di Bella, Marta Jaconi, Maria Grazia Cerrito, Guido Cavaletti, Marialuisa Lavitrano, Marina Elena Cazzaniga
Summary: CDK4/6 inhibitors have shown significant improvement in the progression-free survival of hormone-receptor-positive and HER2-negative metastatic breast cancer. However, there is a high percentage of patients who are unresponsive or refractory to these inhibitors, and no reliable biomarkers have been identified to predict patients' response to treatment. This study focused on palbociclib, a selective CDK4/6 inhibitor, and found that TWIST1 could be a potential target for reversing resistance to palbociclib. This study provides new insights into the mechanisms of resistance to CDK4/6 inhibitors and identifies potential markers for patient follow-up during treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)