Article
Medicine, Research & Experimental
M. Hope Robinson, Nancy Y. Villa, David L. Jaye, Ajay K. Nooka, Alyssa Duffy, Samuel S. McCachren, Julia Manalo, Jeffrey M. Switchenko, Sierra Barnes, Sayalee Potdar, Maryam I. Azeem, Ava A. Horvat, Vaunita C. Parihar, Jingjing Gong, Yan Liang, Geoffrey H. Smith, Vikas A. Gupta, Lawrence H. Boise, Jonathan L. Kaufman, Craig C. Hofmeister, Nisha S. Joseph, Sagar Lonial, Kavita M. Dhodapkar, Madhav V. Dhodapkar
Summary: This study investigates the mechanisms underlying immune infiltration in human multiple myeloma (MM) and its precursor monoclonal gammopathy of undetermined significance (MGUS) using high-dimensional spatial analyses and in vitro and in vivo modeling. The results suggest that MM exhibits clustered tumor growth and spatial heterogeneity with the coexistence of T cell-rich and T cell-sparse regions, as well as areas of T cell exclusion. T cell entry into MM clusters is regulated by agonistic signals and CD2-CD58 interactions, and CLEC9A+ DCs play a role in marking the portals of entry for T cell infiltration.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Cell Biology
Qixin Duan, Shuang Zhang, Yang Wang, Dongming Lu, Yingming Sun, Yongyang Wu
Summary: The Warburg effect refers to the hyperactive glycolysis in tumor cells that provides energy for rapid growth and proliferation even under sufficient oxygen. Proton-coupled monocarboxylate transporters (MCTs) play a crucial role in the metabolic reprogramming and survival of tumor cells, as well as tumor angiogenesis, immune suppression, multidrug resistance, migration and metastasis, ferroptosis resistance, and autophagy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Oncology
Jennifer Sun, Chaelee Park, Nicole Guenthner, Shannon Gurley, Luna Zhang, Berit Lubben, Ola Adebayo, Hannah Bash, Yixuan Chen, Mina Maksimos, Barbara Muz, Abdel Kareem Azab
Summary: MM is a cancer of plasma cells in the bone marrow, with the tumor microenvironment playing a critical role in disease progression. TAMs in the TME have been found to support tumor survival and chemoresistance, highlighting the importance of exploring macrophage-targeted immunotherapy in MM treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Ashley B. B. Zhang, Khashayar Mozaffari, Brian Aguirre, Victor Li, Rohan Kubba, Nilay C. Desai, Darren Wei, Isaac Yang, Madhuri Wadehra
Summary: Glioblastoma, the most common malignant primary brain tumor, has a poor prognosis despite advancements in treatment. Angiogenesis, particularly involving vascular endothelial growth factor-A (VEGF-A), plays a critical role in the growth and invasion of glioblastoma cells. Bevacizumab, a medication targeting VEGF-A, has been approved for recurrent glioblastoma but has not significantly improved survival. Other agents with similar mechanisms of action have also shown unfavorable results. This review explores the current state and future potential of anti-angiogenesis therapeutic agents.
Review
Hematology
Eline Menu, Karin Vanderkerken
Summary: This review summarizes the role of exosomes in multiple myeloma (MM), including their involvement in osteolysis, angiogenesis, immune suppression, and drug resistance. Targeting exosome secretion could potentially block these processes. The review also discusses current treatment strategies to counter these processes and explores how exosomes can be harnessed to deliver toxic payloads. Additionally, the review provides an overview of clinical studies investigating exosome cargo as potential MM biomarkers in liquid biopsies.
Review
Immunology
Ye Jin, Jianming Xing, Kejin Xu, Da Liu, Yue Zhuo
Summary: Exosomes, produced by endosomes, play a crucial role in intercellular communication. Over the past few decades, there has been growing recognition of the importance of exosomes in the tumor microenvironment and their connection to cancer development. This paper discusses the composition, generation, uptake, and roles of exosomes in tumor metastasis, angiogenesis, and immunosuppression. Understanding the biological characteristics of exosomes and their functions in tumor development is significant for identifying new diagnostic biomarkers and therapeutic targets for cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Danfeng Zhang, Jingcao Huang, Fangfang Wang, Hong Ding, Yushan Cui, Yan Yang, Juan Xu, Hongmei Luo, Yuhan Gao, Ling Pan, Yu Wu, Yuping Gong, Liping Xie, Zhigang Liu, Ying Qu, Li Zhang, Weiping Liu, Wenyan Zhang, Sha Zhao, Qing Yi, Ting Niu, Yuhuan Zheng
Summary: Multiple myeloma is a malignancy characterized by plasma cell accumulation in the bone marrow. Within the tumor microenvironment, macrophages in multiple myeloma exhibit pro-myeloma functions, which are modulated by the polycomb-group protein BMI1. Knockout of BMI1 in MM-associated macrophages leads to reduced proliferation, decreased expression of angiogenic factors, and loss of protection against chemotherapy-induced cell death, ultimately negating the pro-myeloma effects of these cells.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Yang Cao, Huizhuang Shan, Meng Liu, Jia Liu, Zilu Zhang, Xiaoguang Xu, Yue Liu, Hanzhang Xu, Hu Lei, Miao Yu, Xingming Zhang, Wanting Liu, Zhilei Bu, Zhixiao Fang, Yanjie Ji, Hua Yan, Weiying Gu, Yingli Wu
Summary: The study demonstrates that anlotinib exhibits significant anti-myeloma effects by inducing cell cycle arrest, apoptosis, and inhibiting multiple signaling pathways. Notably, it also targets c-Myc and enhances ubiquitin proteasomal degradation, leading to apoptosis. Additionally, anlotinib shows cytotoxicity against bortezomib-resistant MM cells, suggesting its potential clinical application for human MM treatment.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Femke A. I. Ehlers, Niken M. Mahaweni, Annet van de Waterweg Berends, Thara Saya, Gerard M. J. Bos, Lotte Wieten
Summary: Multiple myeloma (MM) is an incurable disease characterized by malignant plasma cells in the bone marrow. The tumor microenvironment (TME) plays a crucial role in MM growth and is composed of various tumor-associated cells (TAC) that promote immunosuppression. This study explores the interaction between natural killer (NK) cells and TAC, namely tumor-associated macrophages (TAMs) and M1 macrophages, and investigates the potential enhancement of NK cell anti-tumor functions through an ADCC-triggering antibody targeting macrophages.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Oncology
Mario Rosario D'Andrea, Vittore Cereda, Luigi Coppola, Guido Giordano, Andrea Remo, Elena De Santis
Summary: Neoangiogenesis and various components of the tumor microenvironment are crucial in early metastatic spreading of breast cancer. Understanding the characteristics of the breast tumor environment, especially in correlation with hormone receptors and HER2 status, is important for diagnostic algorithms. The tumor microenvironment, including immune and non-immune cells, as well as cytokines, plays a critical role in breast cancer biology, impacting prognosis and treatment response.
Article
Oncology
Niklas Kehl, Michael Kilian, Julius Michel, Tim R. Wagner, Sebastian Uhrig, Alexander Brobeil, Lilli-Sophie Sester, Sven Blobner, Simon Steiger, Michael Hundemer, Niels Weinhold, Karsten Rippe, Stefan Froehling, Stefan B. Eichmueller, Lukas Bunse, Carsten Mueller-Tidow, Hartmut Goldschmidt, Michael Platten, Marc-Steffen Raab, Mirco J. Friedrich
Summary: Multiple myeloma (MM) is a rare and aggressive hematological malignancy, and its classification and evolution can be deciphered by molecular features. IgE type MM is a subtype with a small percentage but poor prognosis, and currently there is limited genetic and immunological data available. In this study, comprehensive analysis at the genomic and immune repertoire level revealed the pathophysiological mechanisms and potential targeted therapy opportunities for IgE type MM.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Ilaria Saltarella, Concetta Altamura, Carmen Campanale, Paola Laghetti, Angelo Vacca, Maria Antonia Frassanito, Jean-Francois Desaphy
Summary: Angiogenesis is a critical factor in multiple myeloma, affecting patients' prognosis, survival, and drug resistance. Various anti-angiogenic drugs targeting angiogenic cytokines and their receptors have been developed, along with standard antimyeloma drugs that also exhibit anti-angiogenic effects. This review examines the pharmacological profile and in vitro and in vivo anti-angiogenic effects of these therapies. Although direct targeting of angiogenic cytokines/receptors has shown limited efficacy, there is a need for a deeper understanding of the bone marrow angiogenic niche to develop novel multi-targeting anti-angiogenic therapies.
Review
Oncology
Marie-Anne Goyette, Jean-Francois Cote
Summary: Metastasis is a complex process involving the acquisition of specific traits by cancer cells and the cooperation of non-neoplastic cells in the stroma. AXL receptor tyrosine kinase plays a crucial role in multiple steps of the metastatic cascade and contributes to deregulation of the tumor microenvironment. Inhibition of AXL has been shown to be beneficial for the treatment of metastatic cancers, but other roles of AXL in cancer progression are still being explored.
Article
Oncology
Rodrigo Carlini Fernando, Fabricio de Carvalho, Adriana Franco Paes Leme, Gisele Wally Braga Colleoni
Summary: The tumor microenvironment plays a central role in promoting the proliferation, survival, migration, and drug resistance of tumor cells in cancers like multiple myeloma. Understanding and targeting the dysregulated biological pathways in the microenvironment may lead to new therapeutic opportunities for these patients.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Raquel Lopes, Joana Caetano, Bruna Ferreira, Filipa Barahona, Emilie Arnault Carneiro, Cristina Joao
Summary: The interaction between multiple myeloma and immune cells in the bone marrow microenvironment is considered a key aspect of this hematological disease. Understanding how myeloma cells disrupt immune homeostasis is crucial in developing effective treatments, particularly through immunotherapy. Ongoing pre-clinical studies are focused on targeting immune populations within the bone marrow niche, aiming to improve outcomes for patients with multiple myeloma.
Article
Medicine, Research & Experimental
Franco Dammacco, Anna Cirulli, Annalisa Simeone, Patrizia Leone, Raffaele Pulli, Domenico Angiletta, Giuseppe Rubini, Alessandra Di Palo, Angelo Vacca, Rosanna Dammacco
Summary: Takayasu arteritis is a rare granulomatous vasculitis that mainly affects the aorta and its major branches. This study describes the clinical features, diagnostic procedures, pathogenesis, and management of TAK, revealing significant differences in patients from different geographic areas. Treatment is primarily based on glucocorticoids combined with immunosuppressive agents, with biologic drugs used for relapsing or refractory cases.
CLINICAL AND EXPERIMENTAL MEDICINE
(2021)
Review
Medicine, Research & Experimental
Antonio Giovanni Solimando, Nicola Susca, Antonella Argentiero, Oronzo Brunetti, Patrizia Leone, Valli De Re, Rossella Fasano, Markus Krebs, Elisabetta Petracci, Irene Azzali, Oriana Nanni, Nicola Silvestris, Angelo Vacca, Vito Racanelli
Summary: A meta-analysis of second-line therapies for hepatocellular carcinoma (HCC) identified regorafenib and cabozantinib as potential treatment options, showing significant improvement in overall survival and progression-free survival compared with placebo in randomized controlled trials. None of the compared drugs stood out as clearly superior after stratification of patients.
CLINICAL AND EXPERIMENTAL MEDICINE
(2022)
Article
Ophthalmology
Rosanna Dammacco, Walter Lisch, Tero T. Kivela, Evangelos Terpos, Efstathios Kastritis, Dario Sisto, Alberto Mavilio, Roberto Ria, Giovanni Alessio, Angelo Vacca, Franco Dammacco
Summary: The study investigated the ocular manifestations in 91 Waldenstrom's macroglobulinemia (WM) patients, revealing a variety of ocular impairments that can potentially threaten vision. Genetic analysis and treatment have significantly improved ophthalmological outcomes, highlighting the importance of managing both the hematological and ocular aspects of WM patients.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2022)
Article
Rheumatology
Alessandra Bettiol, Maria Letizia Urban, Lorenzo Dagna, Vincent Cottin, Franco Franceschini, Stefano Del Giacco, Franco Schiavon, Thomas Neumann, Giuseppe Lopalco, Pavel Novikov, Chiara Baldini, Carlo Lombardi, Alvise Berti, Federico Alberici, Marco Folci, Simone Negrini, Renato Alberto Sinico, Luca Quartuccio, Claudio Lunardi, Paola Parronchi, Frank Moosig, Georgina Espigol-Frigole, Jan Schroeder, Anna Luise Kernder, Sara Monti, Ettore Silvagni, Claudia Crimi, Francesco Cinetto, Paolo Fraticelli, Dario Roccatello, Angelo Vacca, Aladdin J. Mohammad, Bernhard Hellmich, Maxime Samson, Elena Bargagli, Jan Willem Cohen Tervaert, Camillo Ribi, Davide Fiori, Federica Bello, Filippo Fagni, Luca Moroni, Giuseppe Alvise Ramirez, Mouhamad Nasser, Chiara Marvisi, Paola Toniati, Davide Firinu, Roberto Padoan, Allyson Egan, Benjamin Seeliger, Florenzo Iannone, Carlo Salvarani, David Jayne, Domenico Prisco, Augusto Vaglio, Giacomo Emmi
Summary: Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks proved effective in treating EGPA, with no significant difference between the two doses. Complete response rates reached 30.4% at 12 months and 35.7% at 24 months, with some patients experiencing exacerbations in asthma and ENT.
ARTHRITIS & RHEUMATOLOGY
(2022)
Review
Medicine, Research & Experimental
Antonio Giovanni Solimando, Angelo Vacca, Franco Dammacco
Summary: Giant cell arteritis, polymyalgia rheumatica, and Takayasu's arteritis are characterized by extensive vascular remodeling resulting in occlusion and stenosis. Despite hypothetical pathophysiological mechanisms, similarities and differences in immunopathology and clinical phenotypes suggest a potential link between these diseases.
CLINICAL AND EXPERIMENTAL MEDICINE
(2022)
Review
Medicine, General & Internal
Vanessa Desantis, Francesco Domenico Savino, Antonietta Scaringella, Maria Assunta Potenza, Carmela Nacci, Maria Antonia Frassanito, Angelo Vacca, Monica Montagnani
Summary: Multiple myeloma relies on the bone marrow microenvironment for its development, and the immune regulation of the microenvironment may contribute to tumor cell escape and drug resistance. Besides traditional treatments, new strategies aim to restore the immune balance by targeting key components of the immune regulation process. Immune checkpoints and specific proteins have been identified as important targets for immunotherapy.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Oncology
Ilaria Saltarella, Benedetta Apollonio, Aurelia Lamanuzzi, Vanessa Desantis, Maria Addolorata Mariggio, Jean-Francois Desaphy, Angelo Vacca, Maria Antonia Frassanito
Summary: This article discusses the role of long non-coding RNAs in multiple myeloma, highlighting their regulation of cancer hallmarks and their potential as biomarkers for clinical diagnosis, patient stratification, and therapeutic targeting.
Review
Biochemistry & Molecular Biology
Ilaria Saltarella, Concetta Altamura, Aurelia Lamanuzzi, Benedetta Apollonio, Angelo Vacca, Maria Antonia Frassanito, Jean-Francois Desaphy
Summary: Ion channels play a critical role in multiple myeloma by modulating intracellular pathways that promote tumor cell survival, proliferation, and drug resistance, making them a potential therapeutic target for MM treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, General & Internal
Assunta Melaccio, Antonia Reale, Ilaria Saltarella, Vanessa Desantis, Aurelia Lamanuzzi, Sebastiano Cicco, Maria Antonia Frassanito, Angelo Vacca, Roberto Ria
Summary: Multiple myeloma (MM) is an incurable hematological malignancy. Researchers are actively searching for early and non-invasive biomarkers to predict clinical outcomes and therapeutic responses. The interaction between malignant plasma cells and bone marrow stromal cells plays a crucial role in MM progression. This article discusses the roles of cytokines and growth factors in the pathogenesis of MM and their potential as prognostic and predictive biomarkers. It also explores the potential of targeted drugs that can simultaneously block plasma cell proliferation and survival, plasma cell-bone marrow stromal cell interactions, and bone marrow stromal cell activity, which may be the future goal of MM therapy.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Gerardo Cazzato, Eliano Cascardi, Anna Colagrande, Caterina Foti, Alessandra Stellacci, Maricla Marrone, Giuseppe Ingravallo, Francesca Arezzo, Vera Loizzi, Antonio Giovanni Solimando, Paola Parente, Eugenio Maiorano, Gennaro Cormio, Angelo Vacca, Leonardo Resta
Summary: The SARS-CoV-2 pandemic has disrupted global health systems and brought the entire globe to its knees. Although born as a disease of the respiratory system, COVID-19 can affect different parts of the body, including the skin. Researchers conducted immunohistochemical investigations and literature reviews to investigate the association between SARS-CoV-2, ACE2, TMPRSS2, and skin manifestations. They found no statistically significant differences in the immune expression of ACE2 and TMPRSS2 between SARS-CoV-2-positive patients and healthy controls. ACE2 appears to be a target of SARS-CoV-2, and further studies are needed to understand the mechanisms underlying skin manifestations.
Review
Biochemistry & Molecular Biology
Vanessa Desantis, Maria Assunta Potenza, Luca Sgarra, Carmela Nacci, Antonietta Scaringella, Sebastiano Cicco, Antonio Giovanni Solimando, Angelo Vacca, Monica Montagnani
Summary: The pathophysiology of atrial fibrillation (AF) may involve atrial fibrosis/remodeling and dysfunctional endothelial activities. miRNAs regulate gene expression at the post-transcriptional level and may represent novel and attractive biomarker candidates in AF due to their ease of accessibility in biofluids and prognostic and diagnostic properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Ilaria Saltarella, Concetta Altamura, Carmen Campanale, Paola Laghetti, Angelo Vacca, Maria Antonia Frassanito, Jean-Francois Desaphy
Summary: Angiogenesis is a critical factor in multiple myeloma, affecting patients' prognosis, survival, and drug resistance. Various anti-angiogenic drugs targeting angiogenic cytokines and their receptors have been developed, along with standard antimyeloma drugs that also exhibit anti-angiogenic effects. This review examines the pharmacological profile and in vitro and in vivo anti-angiogenic effects of these therapies. Although direct targeting of angiogenic cytokines/receptors has shown limited efficacy, there is a need for a deeper understanding of the bone marrow angiogenic niche to develop novel multi-targeting anti-angiogenic therapies.
Article
Health Care Sciences & Services
Margherita Zen, Mariele Gatto, Roberto Depascale, Francesca Regola, Micaela Fredi, Laura Andreoli, Franco Franceschini, Maria Letizia Urban, Giacomo Emmi, Fulvia Ceccarelli, Fabrizio Conti, Alessandra Bortoluzzi, Marcello Govoni, Chiara Tani, Marta Mosca, Tania Ubiali, Maria Gerosa, Enrica P. Bozzolo, Valentina Canti, Paolo Cardinaletti, Armando Gabrielli, Giacomo Tanti, Elisa Gremese, Ginevra De Marchi, Salvatore De Vita, Serena Fasano, Francesco Ciccia, Giulia Pazzola, Carlo Salvarani, Simone Negrini, Andrea Di Matteo, Rossella De Angelis, Giovanni Orsolini, Maurizio Rossini, Paola Faggioli, Antonella Laria, Matteo Piga, Alberto Cauli, Salvatore Scarpato, Francesca Wanda Rossi, Amato De Paulis, Enrico Brunetta, Angela Ceribelli, Carlo Selmi, Marcella Prete, Vito Racanelli, Angelo Vacca, Elena Bartoloni, Roberto Gerli, Elisabetta Zanatta, Maddalena Larosa, Francesca Saccon, Andrea Doria, Luca Iaccarino
Summary: This study assessed the efficacy of belimumab in treating joint and skin manifestations in a nationwide cohort of SLE patients. The results showed that belimumab significantly improved joint and skin symptoms and reduced the use of glucocorticoids. A significant proportion of patients who did not achieve complete remission initially achieved remission during follow-up.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Medicine, General & Internal
Sebastiano Cicco, Marialuisa Sveva Marozzi, Carmen Alessandra Palumbo, Elisabetta Sturda, Antonio Fusillo, Flavio Scarilli, Federica Albanese, Claudia Morelli, Davide Fiore Bavaro, Lucia Diella, Annalisa Saracino, Fabrizio Pappagallo, Antonio Giovanni Solimando, Gianfranco Lauletta, Roberto Ria, Angelo Vacca
Summary: Lung ultrasound (LUS) can effectively evaluate and follow lung involvement in COVID-19 patients, and early treatment leads to better recovery and reduced lung involvement after three months.
MEDICINA-LITHUANIA
(2023)
Article
Medicine, General & Internal
Antonio Giovanni Solimando, Giuseppe Coniglio, Vanessa Desantis, Gianfranco Lauletta, Davide Fiore Bavaro, Lucia Diella, Anna Cirulli, Giuseppe Iodice, Piero Santoro, Sebastiano Cicco, Giuseppe Ingravallo, Fabio Signorile, Roberto Ria, Monica Montagnani, Annalisa Saracino, Angelo Vacca
Summary: Leishmaniasis is a disease caused by parasitic infection, with various clinical syndromes depending on the site of infection. The disease phenotype is mainly determined by the biological characteristics of the parasite and the host's immune status.
