Article
Multidisciplinary Sciences
Ke-Jun Chen, Feng-Zeng Li, Qian Ye, Meng Jia, Sheng Fang
Summary: Heat shock protein 105 (HSP105) is overexpressed in cutaneous malignant melanoma (CMM) and is closely associated with different clinicopathological variables. Lesions in exposed sites, recurrent and metastatic lesions, nodular melanoma, and lentigo maligna melanoma show higher HSP105 expression, suggesting HSP105 as a potential target for the diagnosis, treatment, and prognostic prediction of CMM.
Article
Dermatology
Alexis G. Strahan, Ivan Svagelj, Drazen Jukic
Summary: This retrospective study found an association between histopathologic characteristics and gene expression profiles in malignant melanoma. Depth of invasion, melanoma subtype, and presence of ulcer were identified as major histopathologic factors associated with gene expression profiles. Gene expression profiling provides valuable data for evaluating malignant melanoma, but cannot definitively predict its progression.
AMERICAN JOURNAL OF CLINICAL DERMATOLOGY
(2023)
Article
Dermatology
Ida M. Heerfordt, Peter A. Philipsen, Jeppe D. Andersen, Linnea Langhans, Grethe Schmidt, Niels Morling, Hans Christian Wulf
Summary: Using tape strip derived RNA, this study developed a technique to differentiate cutaneous malignant melanoma (CMM) from nevi with 100% sensitivity. The technique reduced the unnecessary surgical removal of benign lesions by one-third without overlooking any CMMs.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexander X. Lozano, Aadel A. Chaudhuri, Aishwarya Nene, Antonietta Bacchiocchi, Noah Earland, Matthew D. Vesely, Abul Usmani, Brandon E. Turner, Chloe B. Steen, Bogdan A. Luca, Ti Badri, Gunsagar S. Gulati, Milad R. Vahid, Farnaz Khameneh, Peter K. Harris, David Y. Chen, Kavita Dhodapkar, Mario Sznol, Ruth Halaban, Aaron M. Newman
Summary: This study provides new insights into the immunological state prior to the development of immune-related adverse events (irAEs) in patients with melanoma treated with immune checkpoint inhibitors (ICIs). The abundance of activated CD4 memory T cells and T cell receptor diversity in the blood samples were found to be associated with severe irAEs, regardless of the affected organ system. The study also investigated the changes in T cell receptor clonality during combination therapy and linked them to the severity and timing of irAE onset. These findings have implications for improved diagnostics and clinical management of irAEs.
Article
Multidisciplinary Sciences
Won-Min Song, Praveen Agrawal, Richard Von Itter, Barbara Fontanals-Cirera, Minghui Wang, Xianxiao Zhou, Lara K. Mahal, Eva Hernando, Bin Zhang
Summary: This study establishes predictive gene network models of molecular alterations in primary melanoma by integrating various types of data, revealing key factors influencing melanoma development. Tumors with high immune infiltrates are associated with good prognosis, potentially due to induced CD8+ T-cell cytotoxicity. Experimental validation shows that 17 key regulators associated with poor prognosis have pro-tumorigenic effects in melanoma.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Viktoria Koroknai, Istvan Szasz, Krisztina Jambor, Margit Balazs
Summary: This study investigated the gene expression patterns of cytokines and chemokine receptors in human melanoma cell lines. The results showed significant differential expression of these genes between cell lines originating from different subtypes of primary melanomas and those from melanoma metastases. The expression levels of certain receptor genes were positively correlated with invasive potential, while others were negatively correlated with BRAF(V600E) mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Juan Tang, Youling Gong, Xuelei Ma
Summary: The discovery of oncogenes and immune checkpoints has revolutionized the treatment of melanoma in the past 10 years. However, the current PD-L1 checkpoints lack specificity for tumors and target normal cells expressing PD-L1, thus reducing the efficacy on malignant melanoma and increasing the side effects. In addition, the treatment options for primary or secondary drug-resistant melanoma are limited. Bispecific antibodies bind tumor cells and immune cells by simultaneously targeting two antigens, enhancing the anti-tumor targeting effect and cytotoxicity and reducing drug-resistance in malignant melanoma, thus representing an emerging strategy to improve the clinical efficacy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Rosy Setiawati, M. S. Suarnata, Paulus Rahardjo, Del Grande Filippo, Giuseppe Guglielmi
Summary: This study aimed to characterize the ADC values of benign, malignant chondrogenic, and malignant non-chondrogenic bone tumors through diffusion-weighted imaging. Results showed significant differences in ADC values among these tumors, improving diagnostic accuracy for bone tumors.
Article
Cell Biology
Luise Dunsche, Nikita Ivanisenko, Shamala Riemann, Sebastian Schindler, Stefan Beissert, Cristian Angeli, Stephanie Kreis, Mahvash Tavassoli, Inna Lavrik, Dagmar Kulms
Summary: Malignant melanoma is intrinsically chemoresistant, and only a small percentage of cases carry p53 mutations. A specific p53 mutation, E285K, was identified and found to disrupt the function of p53 and confer chemoresistance. Restoring wild-type p53 function or inhibiting AKT-driven survival pathways can re-sensitize cancer cells to chemotherapy, and inducing ferroptosis shows promise as a therapeutic approach for fighting malignant melanoma.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Jana Jandova, Georg T. Wondrak
Summary: The research findings suggest that overexpression of GLO1 in melanoma cells is associated with invasion and metastasis, while its deletion affects glucose metabolism and redox homeostasis, accelerating tumorigenesis. TXNIP, a key regulator of cellular energy metabolism and redox homeostasis, shows significant expression changes after GLO1 deletion.
Article
Agriculture, Dairy & Animal Science
Elzbieta Stefanik, Kamil Gorski, Bernard Turek, Olga Drewnowska-Szczepakowska, Katarzyna Kliczkowska-Klarowicz, Aleksandra Stefanik
Summary: This article describes a case report of a hoof lesion initially diagnosed as a keratoma, but evolved into an anaplastic malignant melanoma over time. Melanomas in horses are typically associated with older, gray horses, but they can rarely affect non-gray horses.
Article
Veterinary Sciences
Tatiany L. Silveira, Lisa Y. Pang, Alexandra Di Domenico, Emerson S. Veloso, Istefani L. D. Silva, Helen L. Del Puerto, Enio Ferreria, David J. Argyle
Summary: Metastatic melanoma is an aggressive form of cancer in humans and dogs, with COX-2 potentially playing a critical role in malignant behavior. The study on canine melanomas showed that COX-2 is overexpressed in both oral and cutaneous melanomas, correlating with poor prognosis markers. The research also established a direct relationship between COX-2 expression and malignant behavior in canine melanoma, providing a powerful molecular tool for further understanding melanoma progression.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Sumei Ren, Xiaodong Wang, Jun Song, Guangyi Jin
Summary: A series of novel ibrutinib analogues were synthesized and evaluated for their proliferation inhibitory activities against various B lymphoma cell lines and solid tumor cells. The compound YL7 showed strong antiproliferative activity in all cell lines, with particularly impressive efficacy in B16 cells. Mechanistic studies revealed that YL7 inhibited proliferation and migration, induced cell cycle arrest, apoptosis, and autophagy in B16 cells, demonstrating potential as an anti-melanoma treatment.
BIOORGANIC CHEMISTRY
(2021)
Article
Oncology
Fernanda Costa Svedman, Ishani Das, Rainer Tuominen, Eva Darai Ramqvist, Veronica Hoiom, Suzanne Egyhazi Brage
Summary: The introduction of targeted therapies and immunotherapies has greatly improved the clinical outcomes for patients with advanced cutaneous melanoma. However, only a subset of patients benefit from these treatments in the long term. This study aims to identify gene signatures that can predict the treatment outcomes in melanoma patients. The findings suggest that up-regulation of immune-related genes is associated with better outcomes in targeted therapy, while down-regulation of proliferation and up-regulation of allograft rejection genes favor patients treated with immune checkpoint inhibitors.
Article
Dermatology
M. Scatolini, A. Patel, E. Grosso, M. Mello-Grand, P. Ostano, R. Coppo, M. Vitiello, T. Venesio, A. Zaccagna, A. Pisacane, I Sarotto, D. Taverna, L. Poliseno, D. Bergamaschi, G. Chiorino
Summary: The study identified a significant association between metastases, BRAF mutation, and low GJB5 expression in melanoma, suggesting a potential prognostic role for GJB5 in cutaneous melanoma.
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Miles H. Black, Adam Osinski, Gina J. Park, Marcin Gradowski, Kelly A. Servage, Krzysztof Pawlowski, Vincent S. Tagliabracci
Summary: ADP-ribosyltransferases (ARTs) are a widespread superfamily of enzymes commonly used by bacteria in pathogenic strategies. Legionella pneumophila has a diverse set of 330 translocated effectors, but the ART effectors influencing this bacteria have not been well defined. The discovery of Legionella ADP-Ribosyltransferase 1 (Lart1) targeting a host metabolic enzyme during infection represents a novel mechanism of pathogenicity for this bacterium.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Juliette Coignard, Michael Lush, Jonathan Beesley, Tracy A. O'Mara, Joe Dennis, Jonathan P. Tyrer, Daniel R. Barnes, Lesley McGuffog, Goska Leslie, Manjeet K. Bolla, Muriel A. Adank, Simona Agata, Thomas Ahearn, Kristiina Aittomaeki, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Norbert Arnold, Kristan J. Aronson, Banu K. Arun, Annelie Augustinsson, Jacopo Azzollini, Daniel Barrowdale, Caroline Baynes, Heko Becher, Marina Bermisheva, Leslie Bernstein, Katarzyna Bialkowska, Carl Blomqvist, Stig E. Bojesen, Bernardo Bonanni, Ake Borg, Hiltrud Brauch, Hermann Brenner, Barbara Burwinkel, Saundra S. Buys, Trinidad Caldes, Maria A. Caligo, Daniele Campa, Brian D. Carter, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Wendy K. Chung, Kathleen B. M. Claes, Christine L. Clarke, J. Margriet Collee, Don M. Conroy, Kamila Czene, Mary B. Daly, Peter Devilee, Orland Diez, Yuan Chun Ding, Susan M. Domchek, Thilo Dork, Isabel dos-Santos-Silva, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, A. Heather Eliassen, Christoph Engel, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Henrik Flyger, Florentia Fostira, Eitan Friedman, Lin Fritschi, Debra Frost, Manuela Gago-Dominguez, Susan M. Gapstur, Judy Garber, Vanesa Garcia-Barberan, Montserrat Garcia-Closas, Jose A. Garcia-Saenz, Mia M. Gaudet, Simon A. Gayther, Andrea Gehrig, Vassilios Georgoulias, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Anna Gonzalez-Neira, Mark H. Greene, Pascal Guenel, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Hakansson, Per Hall, Ute Hamann, Patricia A. Harrington, Steven N. Hart, Wei He, Frans B. L. Hogervorst, Antoinette Hollestelle, John L. Hopper, Darling J. Horcasitas, Peter J. Hulick, David J. Hunter, Evgeny N. Imyanitov, Agnes Jager, Anna Jakubowska, Paul A. James, Uffe Birk Jensen, Esther M. John, Michael E. Jones, Rudolf Kaaks, Pooja Middha Kapoor, Beth Y. Karlan, Renske Keeman, Elza Khusnutdinova, Johanna I. Kiiski, Yon-Dschun Ko, Veli-Matti Kosma, Peter Kraft, Allison W. Kurian, Yael Laitman, Diether Lambrechts, Loic Le Marchand, Jenny Lester, Fabienne Lesueur, Tricia Lindstrom, Adria Lopez-Fernandez, Jennifer T. Loud, Craig Luccarini, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, John W. M. Martens, Noura Mebirouk, Alfons Meindl, Austin Miller, Roger L. Milne, Marco Montagna, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Finn C. Nielsen, Katie M. O'Brien, Olufunmilayo I. Olopade, Janet E. Olson, Hakan Olsson, Ana Osorio, Laura Ottini, Tjoung-Won Park-Simon, Michael T. Parsons, Inge Sokilde Pedersen, Beth Peshkin, Paolo Peterlongo, Julian Peto, Paul D. P. Pharoah, Kelly-Anne Phillips, Eric C. Polley, Bruce Poppe, Nadege Presneau, Miquel Angel Pujana, Kevin Punie, Paolo Radice, Johanna Rantala, Muhammad U. Rashid, Gad Rennert, Hedy S. Rennert, Mark Robson, Atocha Romero, Maria Rossing, Emmanouil Saloustros, Dale P. Sandler, Regina Santella, Maren T. Scheuner, Marjanka K. Schmidt, Gunnar Schmidt, Christopher Scott, Priyanka Sharma, Penny Soucy, Melissa C. Southey, John J. Spinelli, Zoe Steinsnyder, Jennifer Stone, Dominique Stoppa-Lyonnet, Anthony Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Mary Beth Terry, Alex Teule, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Alison H. Trainer, Therese Truong, Nadine Tung, Celine M. Vachon, Ana Vega, Joseph Vijai, Qin Wang, Barbara Wappenschmidt, Clarice R. Weinberg, Jeffrey N. Weitzel, Camilla Wendt, Alicja Wolk, Siddhartha Yadav, Xiaohong R. Yang, Drakoulis Yannoukakos, Wei Zheng, Argyrios Ziogas, Kristin K. Zorn, Sue K. Park, Mads Thomassen, Kenneth Offit, Rita K. Schmutzler, Fergus J. Couch, Jacques Simard, Georgia Chenevix-Trench, Douglas F. Easton, Nadine Andrieu, Antonis C. Antoniou
Summary: Breast cancer risk for BRCA1/BRCA2 mutation carriers varies based on genetic factors. A case-only genome-wide association study identified novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Kristoffer von Stedingk, Karl-Johan Stjernfelt, Anders Kvist, Cecilia Wahlstrom, Ulf Kristoffersson, Marie Stenmark-Askmalm, Thomas Wiebe, Lars Hjorth, Jan Koster, Hakan Olsson, Ingrid Ora
Summary: A study found that 10 out of 22 cancer susceptibility genes analyzed had pathogenic variants in pediatric cancer patients, covering 3.8% of the patients. The prevalence of TP53 mutations was significantly lower than in previous studies, partly due to differences in tumor diagnosis distributions. Despite matched family history for relatives, no significant difference in cancer incidence was found in families of children carrying pathogenic variants compared to those who did not.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Ting-Sung Hsieh, Victor A. Lopez, Miles H. Black, Adam Osinski, Krzysztof Pawlowski, Diana R. Tomchick, Jen Liou, Vincent S. Tagliabracci
Summary: During infection, bacterial pathogens can manipulate host cellular membranes by utilizing a self-organizing system involving bacterial kinases and phosphatases, such as the Legionella effector MavQ. This mechanism allows bacteria to hijack host cellular structures for survival by driving rapid turnover of phosphoinositides and inducing vesicle and tubule budding.
Article
Biochemistry & Molecular Biology
Bernhard Luscher, Ivan Ahel, Matthias Altmeyer, Alan Ashworth, Peter Bai, Paul Chang, Michael Cohen, Daniela Corda, Francoise Dantzer, Matthew D. Daugherty, Ted M. Dawson, Valina L. Dawson, Sebastian Deindl, Anthony R. Fehr, Karla L. H. Feijs, Dmitri V. Filippov, Jean-Philippe Gagne, Giovanna Grimaldi, Sebastian Guettler, Nicolas C. Hoch, Michael O. Hottiger, Patricia Korn, W. Lee Kraus, Andreas Ladurner, Lari Lehtio, Anthony K. L. Leung, Christopher J. Lord, Aswin Mangerich, Ivan Matic, Jason Matthews, George-Lucian Moldovan, Joel Moss, Gioacchino Natoli, Michael L. Nielsen, Mario Niepel, Friedrich Nolte, John Pascal, Bryce M. Paschal, Krzysztof Pawlowski, Guy G. Poirier, Susan Smith, Gyula Timinszky, Zhao-Qi Wang, Jose Yelamos, Xiaochun Yu, Roko Zaja, Mathias Ziegler
Summary: ADP-ribosylation, a post-translational modification of proteins, nucleic acids, and metabolites, plays diverse roles in cellular processes such as stress responses, signaling, and transcriptional regulation. Recent advances in research have identified a wide range of cellular pathways regulated by ADP-ribosylation, highlighting the importance of understanding this mechanism in cell biology.
Article
Biochemistry & Molecular Biology
Adam Osinski, Miles H. Black, Krzysztof Pawlowski, Zhe Chen, Yang Li, Vincent S. Tagliabracci
Summary: Studies reveal that Legionella effectors SidJ and its homolog SdjA adopt a kinase fold to regulate the activity of SidE ligases through glutamylation reaction, uncovering the structural and mechanistic basis in which the kinase fold catalyzes non-ribosomal amino acid ligations.
Article
Biochemistry & Molecular Biology
Michel Rasmussen, Charlotte Welinder, Frank Schwede, Per Ekstrom
Summary: This study investigated the stereospecific binding of cGMP analogs to cGMP-binding proteins, revealing crucial parameters for drug design and target specificity in drug development.
CHEMICAL BIOLOGY & DRUG DESIGN
(2022)
Article
Cell Biology
Chunyang Ni, Daniel A. Schmitz, Jeon Lee, Krzysztof Pawlowski, Jun Wu, Michael Buszczak
Summary: This study identifies two functionally uncharacterized genes, C1orf109 and SPATA5, which control a late step of human pre-60S maturation in the cytoplasm along with other factors. Loss of either C1orf109 or SPATA5 impairs global protein synthesis.
Article
Biology
Aleksander Giwercman, K. Barbara Sahlin, Indira Pla Parada, Krzysztof Pawlowski, Carl Fehninger, Yvonne Lundberg Giwercman, Irene Leijonhufvud, Roger Appelqvist, Gyoergy Marko-Varga, Aniel Sanchez, Johan Malm
Summary: This study aimed to identify new protein biomarkers of testosterone activity and assess their predictive value in relation to testosterone levels and androgen deficiency-related pathologies. Through mass spectrometry analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6), and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm based on levels of 4HPPD and IGFBP6, were identified as the most accurate predictors of low testosterone levels. They were also found to be more strongly associated with metabolic syndrome and diabetes compared to testosterone levels. Further investigations are needed to determine the clinical potential of these biomarkers.
Article
Multidisciplinary Sciences
Gina J. Park, Adam Osinski, Genaro Hernandez, Jennifer L. Eitson, Abir Majumdar, Marco Tonelli, Katie Henzler-Wildman, Krzysztof Pawlowski, Zhe Chen, Yang Li, John W. Schoggins, Vincent S. Tagliabracci
Summary: In this study, we reconstituted the formation mechanism of the SARS-CoV-2 RNA cap and identified key domains and interactions involved. This finding reveals a new target for the treatment of COVID-19.
Article
Multidisciplinary Sciences
Madeleine Johansson, Hong Yan, Charlotte Welinder, Akos Vegvari, Viktor Hamrefors, Magnus Back, Richard Sutton, Artur Fedorowski
Summary: This study used proteomics to identify plasma protein biomarkers of postural orthostatic tachycardia syndrome (POTS) and revealed differentially regulated proteomic pathways in POTS. The findings suggest that POTS may be an autoimmune, inflammatory, and hyperadrenergic disorder, characterized by a hypercoagulable state, proinflammatory state, enhanced cardiac contractility and hypertrophy, skeletal muscle expression, and increased adrenergic activity.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Jiaming Zhou, Charlotte Welinder, Per Ekstroem
Summary: Retinitis pigmentosa (RP) is a common genetic disease that leads to the death of photoreceptor cells and blindness in industrial countries. Although gene therapy for certain mutations has been approved, there is currently no effective treatment available. This study explored the cGMP-PKG downstream signaling in degenerating retinas from a mouse model and identified potential substrates and kinases. Further investigation revealed the possible involvement of the RAS/RAF1/MAPK/ERK pathway in retinal degeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Michel Rasmussen, Arianna Tolone, Francois Paquet-Durand, Charlotte Welinder, Frank Schwede, Per Ekstroem
Summary: RP is an inherited eye disease with an unknown cell death mechanism. Rp-8-Br-PET-cGMPS, a modified cGMP analog, selectively inhibits PKG and slows down photoreceptor death. Through affinity chromatography and mass spectrometry, it was found that Rp-8-Br-PET-cGMPS interacts with seven known cGMP-binding proteins and an additional 28 proteins. In summary, Rp-8-Br-PET-cGMPS is more target-specific compared to regular cGMP.
JOURNAL OF COMPARATIVE NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Shashank Shekhar, Andrew T. Moehlman, Brenden Park, Michael Ewnetu, Charles Tracy, Iris Titos, Krzysztof Pawlowski, Vincent S. Tagliabracci, Helmut Kramer
Summary: The study reveals that Allnighter (Aln), a pseudokinase, plays a crucial role in maintaining normal sleep and neuronal structural plasticity in Drosophila photoreceptors by regulating proteostasis. Aln protein is secreted by different neurons but not expressed in photoreceptors, yet it is retrogradely endocytosed by photoreceptors. Inhibition of photoreceptor synaptic release reduces Aln levels in lamina neurons, indicating the involvement of secreted Aln in a feedback loop. Moreover, aln mutants exhibit reduced night time sleep, suggesting a molecular link between dysregulated proteostasis and sleep, which are characteristics of ageing and neurodegenerative diseases.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Komal Umashankar Rao, Ping Li, Charlotte Welinder, Erik Tenland, Pontus Gourdon, Erik Sturegard, James C. S. Ho, Gabriela Godaly
Summary: Multidrug-resistant tuberculosis (MDR) remains a threat to public health. A cationic host defense peptide has been identified with activity against M. tuberculosis and bactericidal effect against MDR M. tuberculosis. The peptide induces tube-shaped membranous structures, vesicle formation, and cell death in M. tuberculosis, and changes in secondary structure and aggregation in liposomes. It also targets essential proteins involved in mycolic acid synthesis and protein folding, impacting bacterial proliferation.