Article
Cell Biology
Thomas M. O'Connell, Lilian Golzarri-Arroyo, Fabrizio Pin, Rafael Barreto, Stephanie L. Dickinson, Marion E. Couch, Andrea Bonetto
Summary: The search for early biomarkers of cancer cachexia is crucial, with amino acids and lipoproteins identified as the earliest significant changes. Metabolic alterations appear before weight loss, providing a new avenue for early detection in clinical settings.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Oncology
Mit Joshi, Bhoomika M. Patel
Summary: Cancer cachexia is a wasting syndrome driven by chronic inflammation and high energy expenditure. Uncoupling proteins (UCPs) play an important role in cancer cachexia by increasing the body's overall energy utilization. This review provides new insights into the role of UCPs in cancer cachexia and highlights their potential as a target for treating this syndrome.
Article
Geriatrics & Gerontology
Haiming Liu, Pu Zang, Ian (In-gi) Lee, Barbara Anderson, Anthony Christiani, Lena Strait-Bodey, Beatrice A. Breckheimer, Mackenzie Storie, Alison Tewnion, Kora Krumm, Theresa Li, Brynn Irwin, Jose M. Garcia
Summary: The study found that the growth hormone secretagogue receptor-1a mediates the effects of ghrelin in attenuating weakness induced by LLC by modulating the autophagy-lysosome pathway, mitophagy, and mitochondrial respiration, but not reducing muscle mass loss.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Review
Oncology
Claudia Bordignon, Bethania S. dos Santos, Daniela D. Rosa
Summary: Cachexia is a common syndrome in cancer patients, especially those with advanced tumors, characterized by weight loss, muscle wasting, and cardiac dysfunction. This review examines the manifestations of cachexia and the potential role of physical exercise in preventing or reversing this syndrome in cancer patients.
Article
Gastroenterology & Hepatology
Zhijun Zhou, Yu Ren, Jingxuan Yang, Mingyang Liu, Xiuhui Shi, Wenyi Luo, Kar-Ming Fung, Chao Xu, Michael S. Bronze, Yuqing Zhang, Courtney W. Houchen, Min Li
Summary: In this study, we found that ACSS2 enhances nonselective macropinocytosis and muscle wasting in pancreatic cancer through metabolic reprogramming, revealing the potential mechanism behind these processes.
Article
Geriatrics & Gerontology
Fabrizio Pin, Marc Beltra, Lorena Garcia-Castillo, Barbara Pardini, Giovanni Birolo, Giuseppe Matullo, Fabio Penna, Denis Guttridge, Paola Costelli
Summary: The study demonstrates that TMVs can influence differentiation and the mitochondrial system in C2C12 cultures, possibly through TMV-contained miRs.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Review
Oncology
Louisa Tichy, Traci L. Parry
Summary: Cancer-induced cardiac cachexia is a major cause of death in cancer patients, characterized by severe cardiac muscle wasting and dysfunction. The exact molecular mechanisms are not fully understood, but researchers have identified different stages of progression and potential biomarkers for detection and monitoring. Current treatment options are limited and there is a need for further research to develop effective interventions.
Review
Cell Biology
Marc Beltra, Fabrizio Pin, Riccardo Ballaro, Paola Costelli, Fabio Penna
Summary: Cancer cachexia is a frequently neglected syndrome with complex pathogenesis impacting patients' quality of life, and no effective therapeutic approach has been identified yet.
Article
Oncology
Andrea David Re Cecconi, Mara Barone, Mara Forti, Martina Lunardi, Alfredo Cagnotto, Mario Salmona, Davide Olivari, Lorena Zentilin, Andrea Resovi, Perla Persichitti, Dorina Belotti, Federica Palo, Nobuyuki Takakura, Hiroyasu Kidoya, Rosanna Piccirillo
Summary: The study aimed to assess the role of apelin in combating muscle loss during cancer cachexia. The results showed that although apelin exhibited beneficial effects against muscle atrophy in in vitro models, it failed to do so in in vivo models due to undesired apelin resistance. This study uncovering apelin resistance highlights potential issues in apelin-based therapy for cancer cachexia.
Article
Biochemistry & Molecular Biology
Lauren E. Rentz, Marcella A. Whetsell, Stuart A. Clayton, Alan D. Mizener, Ida Holaskova, Matthew G. Chapa, Emily H. Hoblitzell, Timothy D. Eubank, Emidio E. Pistilli
Summary: Breast cancer incidence is rare in men, but the lack of screening results in lower survival rates compared to women. The study found that there are sexually dimorphic responses in skeletal muscle function and molecular composition to breast tumors. The findings provide insights into therapeutic strategies targeting tumor-associated muscle alterations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Wenlan Li, Jennifer Trieu, Ronnie Blazev, Benjamin L. Parker, Kate T. Murphy, Kristy Swiderski, Gordon S. Lynch
Summary: Cancer cachexia is a common condition in cancer patients, where loss of skeletal muscle mass affects treatment response and quality of life. Sulforaphane (SFN), a natural antioxidant found in cruciferous vegetables, has been shown to decrease oxidative stress. This study investigated whether SFN could attenuate muscle wasting induced by cancer cells and chemotherapy, and found that SFN was able to prevent muscle atrophy and activate antioxidant signaling pathways.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elisabeth Wyart, Myriam Y. Hsu, Roberta Sartori, Erica Mina, Valentina Rausch, Elisa S. Pierobon, Mariarosa Mezzanotte, Camilla Pezzini, Laure B. Bindels, Andrea Lauria, Fabio Penna, Emilio Hirsch, Miriam Martini, Massimiliano Mazzone, Antonella Roetto, Simonetta Geninatti Crich, Hans Prenen, Marco Sandri, Alessio Menga, Paolo E. Porporato
Summary: Cachexia is a wasting syndrome characterized by severe muscle atrophy, particularly common in cancer patients, with limited knowledge on its mechanisms. This study found significant alterations in iron metabolism in the skeletal muscle of cancer patients and tumor-bearing mice, with modulation of iron levels directly influencing muscle mass. Iron supplementation was shown to preserve muscle function, mass, and even improve strength in a short time frame, refueling mitochondrial oxidative metabolism and energy production.
Article
Multidisciplinary Sciences
Aneesha Dasgupta, Daniel F. Gibbard, Rebecca E. Schmitt, Paige C. Arneson-Wissink, Alexandra M. Ducharme, Elizabeth S. Bruinsma, John R. Hawse, Aminah Jatoi, Jason D. Doles
Summary: Cancer cachexia is a major hurdle in cancer management, lacking effective therapies. KLF10 upregulation is found in multiple wasting contexts and targeting KLF10 can mitigate cancer-associated muscle wasting. TGF-beta, a known inducer of KLF10, plays a critical role in the etiology of pancreatic cancer-associated muscle wasting.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Oncology
Tania Setiawan, Ita Novita Sari, Yoseph Toni Wijaya, Nadya Marcelina Julianto, Jabir Aliyu Muhammad, Hyeok Lee, Ji Heon Chae, Hyog Young Kwon
Summary: Muscle wasting is the progressive loss of skeletal muscle mass and strength, which can be caused by physiological changes or various diseases. Cancer cachexia is a syndrome characterized by the loss of skeletal muscle mass, leading to functional impairment and reduced quality of life. It is caused by inflammation and an increase in muscle breakdown. This article summarizes the molecular networks that regulate muscle mass, discusses the multi-organ roles in cancer cachexia, and explores potential therapeutic approaches, as there are currently no approved drugs for this condition.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Mengyuan Niu, Shiyu Song, Zhonglan Su, Lulu Wei, Li Li, Wenyuan Pu, Chen Zhao, Yibing Ding, Jinglin Wang, Wangsen Cao, Qian Gao, Hongwei Wang
Summary: The study revealed that enhanced interaction between activated STAT3 and HSP90 in skeletal muscle is crucial for the development of cachectic muscle wasting in cancer patients. Inhibitors of HSP90, such as 17DMAG and PU-H71, were found to alleviate muscle wasting and myotube atrophy induced by C26 conditional medium. Prolonged STAT3 activation triggers muscle wasting in a FOXO1-dependent manner by transactivating FOXO1 in muscle cells.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Massimiliano Gasparrini, Francesca Mazzola, Massimiliano Cuccioloni, Leonardo Sorci, Valentina Audrito, Federica Zamporlini, Carlo Fortunato, Adolfo Amici, Michele Cianci, Silvia Deaglio, Mauro Angeletti, Nadia Raffaelli
Summary: This study investigated the interaction between the enzyme NAMPT and the receptor TLR4, and found that specific regions of NAMPT play a key role in TLR4 binding and impact the initiation of inflammatory response and the signaling pathway.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Fabrizio Pin, Alexander J. Jones, Joshua R. Huot, Ashok Narasimhan, Teresa A. Zimmers, Lynda F. Bonewald, Andrea Bonetto
Summary: This study demonstrates that patients with ovarian cancer exhibit evidence of cachexia and increased bone turnover, with high levels of RANKL potentially causing skeletal muscle atrophy and bone resorption. Treatment with antiresorptive and anti-RANKL therapies benefits muscle mass and function in cancer cachexia.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Lorena Quirico, Francesca Orso, Stefania Cucinelli, Mladen Paradzik, Dora Natalini, Giorgia Centonze, Alberto Dalmasso, Sofia La Vecchia, Martina Coco, Valentina Audrito, Chiara Riganti, Paola Defilippi, Daniela Taverna
Summary: miRNAs play a crucial role in cancer progression by regulating gene expression. They can impact cell behaviors such as adhesion and migration by modulating metabolic gene expression. This review focuses on how miRNA alterations interfere with cancer cell movement and analyzes the signaling pathways connecting metabolism and adhesion/migration.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Massimiliano Gasparrini, Valentina Audrito
Summary: NAMPT plays a crucial role in both intracellular and extracellular functions, which are essential for tumor growth and survival. Over-expression of NAMPT affects various tumor cellular processes, including DNA repair, gene expression, signaling pathways, proliferation, and metastasis. Thus, NAMPT has emerged as a promising anti-cancer strategy.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Joshua R. Huot, Dryden Baumfalk, Aridai Resendiz, Andrea Bonetto, Ashley J. Smuder, Fabio Penna
Summary: Cancer is often accompanied by cachexia, a wasting syndrome. Cachexia can develop as a result of tumor progression or as a side effect of anticancer treatments. It is characterized by severe loss of muscle mass and function, making it a subject of extensive investigation.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Sara Boumya, Silvia Fallarini, Sonia Siragusa, Giovanni Petrarolo, Silvio Aprile, Valentina Audrito, Concettina La Motta, Silvia Garavaglia, Laura Moro, Giulia Pinton
Summary: Aldehyde dehydrogenase 1A3 (ALDH1A3) has been linked to poor prognosis in malignant pleural mesothelioma (MPM). Inhibition of ALDH1A3 using NR6 resulted in the accumulation of toxic aldehydes, DNA damage, CDKN2A expression, and cell growth arrest. NR6 treatment also affected the tumor microenvironment by altering IL6, CXCL8, and IL-8 levels, and shifting cell fate from senescence to apoptosis. Understanding the role of ALDH1A3 in MPM cells and the tumor microenvironment could lead to potential new treatments for this cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Beatrice Foglia, Marc Beltra, Salvatore Sutti, Stefania Cannito
Summary: Hepatocellular carcinoma (HCC) is a common primary liver cancer, ranking third in cancer-related mortality worldwide. Metabolic rewiring has emerged as a key factor in HCC progression, affecting cancer cell behavior and immune responses. This review focuses on recent studies exploring HCC's metabolic traits, specifically alterations in glucose, fatty acid, and amino acid metabolism. Additionally, it examines how metabolic reprogramming can impact the tumor microenvironment and immune cell populations, enabling tumor escape from immunosurveillance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Marc Beltra, Noora Pollanen, Claudia Fornelli, Kialiina Tonttila, Myriam Y. Hsu, Sandra Zampieri, Lucia Moletta, Samantha Corra, Paolo E. Porporato, Riikka Kivelae, Carlo Viscomi, Marco Sandri, Juha J. Hulmi, Roberta Sartori, Eija Pirinen, Fabio Penna
Summary: NAD(+) loss is associated with muscle mitochondrial dysfunction in cancer hosts. Niacin supplementation improves mitochondrial metabolism and reduces muscle wasting in mouse models of cachexia. Downregulation of muscle NRK2 is correlated with metabolic abnormalities in cancer patients, highlighting the significance of NAD(+) in the pathophysiology of human cancer cachexia.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Hannah Savage, Sumedha Pareek, Jonghae Lee, Riccardo Ballaro, Darlan Conterno Minussi, Karma Hayek, Mumina Sadullozoda, Brooke S. Lochmann, Jennifer L. McQuade, Emily C. LaVoy, Enrica Marmonti, Hetal Patel, Guangyu Wang, Masaki Imanishi, Sivareddy Kotla, Jun-ichi Abe, Keri Schadler
Summary: Exercise modifies the tumor microenvironment by remodeling blood vessels and increasing infiltration of cytotoxic immune cells. This study reveals that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in melanoma mouse models. Exercise suppresses tumor growth and increases CD8 T-cell infiltration in one melanoma model but not in another. The study also shows that exercise modulates the phenotype of tumor-infiltrating cells and that ERK5 signaling plays a crucial role in exercise-induced tumor microenvironment changes.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Geriatrics & Gerontology
Alessio Molfino, Marc Beltra, Maria Ida Amabile, Roberta Belli, Giovanni Birolo, Elena Belloni, Serena De Lucia, Lorena Garcia-Castillo, Fabio Penna, Giovanni Imbimbo, Giuseppe Nigri, Barbara Pardini, Paola Costelli, Maurizio Muscaritoli
Summary: This study analyzed small non-coding RNAs (sncRNAs) in patients with gastrointestinal cancer and found dysregulation of muscle-specific microRNAs in cancer-induced muscle wasting. The study also discovered an association between changes in circulating microRNAs and the level of muscularity at body composition analysis. SncRNAs in muscle were assessed by RNAseq, while circulating microRNAs were evaluated by qPCR.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Review
Cell Biology
Irene Fiorilla, Simona Martinotti, Alberto Maria Todesco, Gregorio Bonsignore, Maria Cavaletto, Mauro Patrone, Elia Ranzato, Valentina Audrito
Summary: Malignant pleural mesothelioma (MPM) is a lethal and rare cancer with increasing incidence worldwide. Asbestos exposure causes MPM through mechanisms including chronic inflammation, oxidative stress, and aberrant signaling. The tumor microenvironment characteristics, such as chronic inflammation, hypoxia, and metabolic changes, support tumor aggressiveness and modulate immune responses. Understanding these interactions provides potential therapeutic targets in MPM.
Article
Biochemistry & Molecular Biology
April Rees, Zoe Edwards-I-Coll, Oliver Richards, Molly E. Raikes, Roberto Angelini, Catherine A. Thornton
Summary: Novel mass spectrometry techniques were used to monitor lipid changes in pregnant women and their potential as biomarkers of inflammation. The ratio of phosphatidylcholine (PC) to lysophosphatidylcholine (LPC) was identified as a reliable indicator of inflammation. This method shows promise for clinical application.
Review
Biochemistry & Molecular Biology
Lorenzo Nevi, Noora Pollanen, Fabio Penna, Giuseppina Caretti
Summary: Epigenetic changes are associated with muscle wasting in various pathological conditions, and targeting HDACs and BET proteins may be a promising strategy to reverse this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Chandler S. Callaway, Lila M. Mouchantat, Benjamin G. Bitler, Andrea Bonetto
Summary: Cancer-associated cachexia is a common occurrence in cancer patients, including those with ovarian cancer. Reduced skeletal muscle mass in ovarian cancer patients is associated with worse outcomes. Mouse models show characteristics of cachexia in ovarian cancer, but there is limited research on ovarian cancer-associated cachexia compared to other cancer types. Certain soluble factors may serve as therapeutic targets for mitigating cachexia in ovarian cancer. However, more research is needed to determine the translational relevance of these findings due to the relatively low number of studies.
Article
Medieval & Renaissance Studies
Roberto Angelini
Summary: This study examines the letters written by Bishop Hildebert to noblewomen, highlighting the portrayal of women in the Middle Ages, particularly the praise for virgins in monasteries.