Article
Medicine, Research & Experimental
Sameh Saber, Alexandru Madalin Hasan, Osama A. Mohammed, Lobna A. Saleh, Abdullah A. Hashish, Mohannad Mohammad S. Alamri, Ahmed Y. Al-Ameer, Jaber Alfaifi, Ahmed Senbel, Adel Mohamed Aboregela, Tarig Babikir Algak Khalid, Mustafa Ahmed Abdel-Reheim, Simona Cavalu
Summary: Sorafenib is a first-line treatment for advanced hepatocellular carcinoma, but resistance mechanisms limit its long-term effectiveness. Our research shows that HSP90 plays a critical role in conferring resistance to sorafenib through inhibition of necroptosis and stabilization of HIF-1 alpha. By using ganetespib, an HSP90 inhibitor, we found that the combination therapy enhanced the effectiveness of sorafenib by activating necroptosis and destabilizing HIF-1 alpha. Additionally, LAMP2 aids in the degradation of MLKL, the mediator of necroptosis, through chaperone-mediated autophagy. These findings suggest that the combined therapy of ganetespib and sorafenib may offer a promising approach for the treatment of hepatocellular carcinoma.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Ziwen Lu, Zhixin Wang, Zhigang Tu, Hanqing Liu
Summary: The study suggests that the combination of HSP90 inhibitor ganetespib with BTK inhibitor ibrutinib may be an ideal approach for MCL treatment, as it enhances the effects of ibrutinib on MCL cells by promoting cell cycle arrest, inducing cell apoptosis, increasing DNA damage, and inhibiting tumor growth.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Mahmoud E. Youssef, Simona Cavalu, Alexandru Madalin Hasan, Galal Yahya, Marwa A. Abd-Eldayem, Sameh Saber
Summary: Heat-shock proteins are upregulated in cancer and protect client proteins from degradation, contributing to tumorigenesis and cancer metastasis. Inhibiting HSP90 activity with ganetespib is a promising strategy in cancer treatment, as it has shown strong activity against various cancers and low adverse effects. Ganetespib is being tested in phase II clinical trials as a first-line therapy for metastatic breast cancer, and it has been found to induce apoptosis and growth arrest in cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Rui Yuan, Jie Tu, Chunquan Sheng, Xi Chen, Na Liu
Summary: The Hsp90 inhibitor ganetespib shows excellent synergistic antifungal activity in vitro against azole-resistant Candida albicans, significantly inhibiting fungal biofilm formation and down-regulating key resistance genes. In a mouse model, the combination of ganetespib and fluconazole effectively reverses fluconazole resistance and decreases fungal load in the kidneys.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Tetsuro Marunouchi, Takumi Ito, Sumika Onda, Lina Kyo, Kirara Takahashi, Manami Uchida, Emi Yano, Kouichi Tanonaka
Summary: The study shows that the Hsp90 inhibitor 17-AAG can improve cardiac function and reduce cardiac hypertrophy and fibrosis after myocardial infarction. Activation of the RIP1/RIP3/MLKL pathway is a common event in the development of chronic heart failure.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Tetsuro Marunouchi, Chiharu Nishiumi, Saki Iinuma, Emi Yano, Kouichi Tanonaka
Summary: Necroptosis is a programmed form of cell death regulated by necroptosis-regulating proteins. Inhibition of Hsp90 reverses the increases in RIP1, RIP3, and MLKL in failing hearts, attenuating necrotic cell death and preserving cardiac functions. The findings suggest that targeting Hsp90 could be a new therapeutic strategy for chronic heart failure.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Simon Deycmar, Elisabeth Mara, Sylvia Kerschbaum-Gruber, Verena Waller, Dietmar Georg, Martin Pruschy
Summary: The radiosensitizing effect of HSP90 inhibitor ganetespib was investigated for proton irradiation and photon irradiation. It was found that low-dose ganetespib significantly increased the killing effect of proton irradiation on cancer cells, while having minimal effect on photon irradiation. This provides a theoretical basis for future combinatorial approaches with proton radiotherapy.
RADIATION ONCOLOGY
(2022)
Article
Cell Biology
Axel Witt, Tatiana Goncharov, Yujung Michelle Lee, Matthias Kist, Monika Dohse, Jeff Eastham, Debra Dugger, Kim Newton, Joshua D. Webster, Domagoj Vucic
Summary: XIAP is a protein that inhibits caspase, blocking multiple cell death pathways and mediating proper activation of inflammatory NOD2-RIP2 signaling. Absence of XIAP increases sensitivity to cell death mediated by LPS and TNF without affecting NF-kappa B and MAPK signaling. In XIAP deficient mice, inhibition of RIP1 effectively blocks TNF-stimulated cell death, hypothermia, lethality, cytokine/chemokine release, intestinal tissue damage, and granulocyte migration, suggesting an attractive option for patients with XIAP deficiency.
CELL DEATH & DISEASE
(2023)
Article
Microbiology
Sangwoo Nam, Yun Ji Ga, Joo-Youn Lee, Woo-Yeon Hwang, Eunhye Jung, Jin Soo Shin, Weiyi Chen, Gildon Choi, Bin Zhou, Jung-Yong Yeh, Yun Young Go
Summary: The study found that radicicol effectively suppressed CHIKV replication and may serve as a potential drug candidate against CHIKV. It also revealed nsP2 as a putative molecular target of radicicol, with the G641D mutation in nsP2 playing a key role in its interaction with cytoplasmic Hsp90 beta chaperone.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Sujae Yang, Nam Gu Yoon, Min-A Park, Jisu Yun, Jin Young Im, Byoung Heon Kang, Soosung Kang
Summary: TRAP1, overexpressed in many cancer cells, supports tumorigenesis by rewiring vital metabolic and cell death pathways. Compound 6a, a TRAP1-selective inhibitor, shows potent anticancer activity in multiple cancer cell lines and suppresses tumor growth in a nude mouse model.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yong Jin Oh, Sun You Park, Young Ho Seo
Summary: The development of a hydrogen peroxide-activated Hsp90 inhibitor shows promise in selectively targeting cancer cells while minimizing toxicity effects. This novel approach offers an improved therapeutic index and reduced adverse effects, demonstrating potential for clinical application.
BIOORGANIC CHEMISTRY
(2021)
Article
Oncology
Dilay Karademir, Aykut Ozgur
Summary: Combined chemotherapy is recommended as a first-line treatment for cervical cancer. The combination of STA-9090 and Venetoclax synergistically inhibits cervical cancer cell proliferation and induces apoptosis by down-regulating anti-apoptotic markers and upregulating pro-apoptotic markers.
Article
Chemistry, Medicinal
Jing Yu, Chao Zhang, Chun Song
Summary: In the past few decades, the development of Hsp90 inhibitors for cancer treatment has been ongoing. However, many compounds evaluated in clinical trials were not approved by the FDA due to toxic effects and lack of efficacy. Insufficient isoform selectivity has been identified as one of the reasons for these failures. Therefore, the development of isoform-specific Hsp90 inhibitors could lead to significant progress in finding therapeutic agents for cancer and other diseases. This article provides a summary of classic pan-inhibitors of Hsp90 and discusses the design strategies used in drug discovery. It also summarizes current isoform-specific Hsp90 inhibitors, including their discovery processes and potential indications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Aichun Li, Qin Yang, Guohua Lou, Yanning Liu, Hongguang Xia, Zhi Chen
Summary: In this study, F-nec was identified as a novel potent RIP1 inhibitor that efficiently blocked TNF-alpha-induced necroptosis in human and mice cells. Pre-treatment with F-nec prevented hepatic necrosis and attenuated LPS/GalN-induced acute liver failure by suppressing JNK-triggered inflammation, highlighting its potential for use in the treatment of inflammatory liver diseases driven by RIP1.
Article
Biochemistry & Molecular Biology
Vanessa Nguyen, Ethan Ahler, Katherine A. Sitko, Jason J. Stephany, Dustin J. Maly, Douglas M. Fowler
Summary: Hsp90 is a molecular chaperone involved in the refolding and activation of protein substrates. By studying a large number of variants, we identified functionally dependent client variants of the Src kinase and identified the factors driving Hsp90 dependence.
Article
Immunology
Nastya Kharlamova, Nicky Dunn, Sahl K. Bedri, Svante Jerling, Malin Almgren, Francesca Faustini, Iva Gunnarsson, Johan Ronnelid, Rille Pullerits, Inger Gjertsson, Karin Lundberg, Anna Manberg, Elisa Pin, Peter Nilsson, Sophia Hober, Katharina Fink, Anna Fogdell-Hahn
Summary: Commercial serological assays for SARS-CoV-2 have poor specificity in patients with chronic inflammatory diseases, leading to a high risk of false positive results, especially among rheumatoid arthritis patients with rheumatoid factor. Therefore, the possibility of false positivity should be considered when interpreting the results of these tests.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Sebastian Havervall, Henry Ng, August Jernbom Falk, Nina Greilert-Norin, Anna Manberg, Ulrika Marking, Ida Lauren, Lena Gabrielsson, Ann-Christin Salomonsson, Katherina Aguilera, Martha Kihlgren, Maja Mansson, Axel Rosell, Cecilia Hellstrom, Eni Andersson, Jennie Olofsson, Lovisa Skoglund, Jamil Yousef, Elisa Pin, Martin Lord, Mikael Aberg, My Hedhammar, Hanna Tegel, Pierre Donnes, Mia Phillipson, Peter Nilsson, Jonas Klingstrom, Sara Mangsbo, Sophia Hober, Charlotte Thalin
Summary: Emerging data suggests detectable immune responses can last for months after SARS-CoV-2 infection or vaccination, but the degree and duration of protection against reinfection remains uncertain. A study on healthcare workers and COVID-19 patients found that the majority of individuals tested positive for anti-spike IgG antibodies remained positive for at least 8 months, with a significantly reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19.
JOURNAL OF INTERNAL MEDICINE
(2022)
Article
Oncology
Lisa Blixt, Gordana Bogdanovic, Marcus Buggert, Yu Gao, Sophia Hober, Katie Healy, Hemming Johansson, Christian Kjellander, Sara Mravinacova, Sandra Muschiol, Peter Nilsson, Marzia Palma, Elisa Pin, C. I. Edvard Smith, Olga Stromberg, Margaret Sallberg Chen, Rula Zain, Lotta Hansson, Anders Osterborg
Summary: The study revealed that severe cases of Covid-19 were equally distributed among CLL patients, regardless of age, gender, BMI, or CLL status, except for the Cumulative Illness Rating Scale (CIRS). The mortality rate was higher in patients aged 75 and above. Despite the high hospitalization rate, there was a numerical reduction in deaths and ICU admissions during different periods of the pandemic. Most convalescent patients showed robust and durable B and/or T cell immunity, with a majority testing positive for anti-SARS-CoV-2 antibodies even six to twelve months after infection.
Article
Biochemical Research Methods
Sara Mravinacova, Malin Jonsson, Wanda Christ, Jonas Klingstrom, Jamil Yousef, Cecilia Hellstrom, My Hedhammar, Sebastian Havervall, Charlotte Thalin, Elisa Pin, Hanna Tegel, Peter Nilsson, Anna Manberg, Sophia Hober
Summary: Highly accurate serological testing is crucial for evaluating the prevalence of SARS-CoV-2 antibodies and population immunity levels, especially in the context of new variants. The newly developed high throughput method enables rapid assessment of antibodies inhibiting the binding between the SARS-CoV-2 spike protein and ACE2, providing valuable insights compared to traditional serological methods.
Article
Multidisciplinary Sciences
Sebastian Havervall, August Jernbom Falk, Jonas Klingstrom, Henry Ng, Nina Greilert-Norin, Lena Gabrielsson, Ann-Christin Salomonsson, Eva Isaksson, Ann-Sofie Rudberg, Cecilia Hellstrom, Eni Andersson, Jennie Olofsson, Lovisa Skoglund, Jamil Yousef, Elisa Pin, Wanda Christ, Mikaela Olausson, My Hedhammar, Hanna Tegel, Sara Mangsbo, Mia Phillipson, Anna Manberg, Sophia Hober, Peter Nilsson, Charlotte Thalin
Summary: Current serological assays for SARS-CoV-2 generate inconsistent results and the longitudinal characteristics of antibodies targeting different antigens after asymptomatic or mild COVID-19 have not been established. This cohort study involving healthcare workers found that antibodies against the SARS-CoV-2 spike antigen remained detectable in 96% of participants at least four months after infection, even if they had no or mild symptoms. The study also confirmed virus neutralization capacity in 91% of participants at least four months after infection.
Article
Cell Biology
Raphael Carapito, Richard Li, Julie Helms, Christine Carapito, Sharvari Gujja, Veronique Rolli, Raony Guimaraes, Jose Malagon-Lopez, Perrine Spinnhirny, Alexandre Lederle, Razieh Mohseninia, Aurelie Hirschler, Leslie Muller, Paul Bastard, Adrian Gervais, Qian Zhang, Francois Danion, Yvon Ruch, Maleka Schenck, Olivier Collange, Thien-Nga Chamaraux-Tran, Anne Molitor, Angelique Pichot, Alice Bernard, Ouria Tahar, Sabrina Bibi-Triki, Haiguo Wu, Nicodeme Paul, Sylvain Mayeur, Annabel Larnicol, Geraldine Laumond, Julia Frappier, Sylvie Schmidt, Antoine Hanauer, Cecile Macquin, Tristan Stemmelen, Michael Simons, Xavier Mariette, Olivier Hermine, Samira Fafi-Kremer, Bernard Goichot, Bernard Drenou, Khaldoun Kuteifan, Julien Pottecher, Paul-Michel Mertes, Shweta Kailasan, M. Javad Aman, Elisa Pin, Peter Nilsson, Anne Thomas, Alain Viari, Damien Sanlaville, Francis Schneider, Jean Sibilia, Pierre-Louis Tharaux, Jean-Laurent Casanova, Yves Hansmann, Daniel Lidar, Mirjana Radosavljevic, Jeffrey R. Gulcher, Ferhat Meziani, Christiane Moog, Thomas W. Chittenden, Seiamak Bahram
Summary: In this study, multi-omics analysis and artificial intelligence were used to examine the differences in biological factors between critical and non-critical COVID-19 patients in a young and otherwise healthy cohort. The study identified ADAM9 as a driver of disease severity and a potential therapeutic target.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Pablo Juanes-Velasco, Norma Galicia, Elisa Pin, Ricardo Jara-Acevedo, Javier Carabias-Sanchez, Rodrigo Garcia-Valiente, Quentin Lecrevisse, Carlos Eduardo Pedreira, Rafael Gongora, Jose Manuel Sanchez-Santos, Hector Lorenzo-Gil, Alicia Landeira-Vinuela, Halin Bareke, Alberto Orfao, Peter Nilsson, Manuel Fuentes
Summary: Exploring potential protein biomarkers through proteomics can aid in the early diagnosis and prognosis of leptomeningeal disease.
Article
Immunology
Ida Lauren, Sebastian Havervall, Henry Ng, Martin Lord, Aleksandra Pettke, Nina Greilert-Norin, Lena Gabrielsson, Aikaterini Chourlia, Catarina Amoedo-Leite, Vijay S. Josyula, Mohamed Eltahir, Iliana Kerzeli, August J. Falk, Jonathan Hober, Wanda Christ, Anna Wiberg, My Hedhammar, Hanna Tegel, Joachim Burman, Feifei Xu, Elisa Pin, Anna Manberg, Jonas Klingstrom, Gustaf Christoffersson, Sophia Hober, Peter Nilsson, Mia Philipson, Pierre Donnes, Robin Lindsay, Charlotte Thalin, Sara Mangsbo
Summary: This study investigates the correlation between symptomology and cellular immune responses post seroconversion to COVID-19. The findings demonstrate that the severity of the disease and specific COVID-19 symptoms are correlated with the magnitude of SARS-CoV-2-specific memory T cell responses. The study highlights the importance of cellular immune memory in understanding the immune response to COVID-19.
IMMUNITY INFLAMMATION AND DISEASE
(2022)
Article
Clinical Neurology
Klara Asplund Hogelin, Nicolas Ruffin, Elisa Pin, Sophia Hober, Peter Nilsson, Chiara Starvaggi Cucuzza, Mohsen Khademi, Tomas Olsson, Fredrik Piehl, Faiez Al Nimer
Summary: This study found that the presence of B cells and/or rituximab in the blood better predicts seroconversion in multiple sclerosis patients treated with anti-CD20. Detectable rituximab levels were negatively associated with seroconversion, while the presence of >0.5% B cells increased the probability of seroconversion. In addition, levels of naive and memory IgG(+) B cells correlated with antibody levels. Interferon-gamma and/or interleukin-13 T-cell responses to the spike S1 domain were observed in most patients, but did not correlate with spike antibody levels.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Correction
Immunology
Hassan Alkharaan, Shaghayegh Bayati, Cecilia Hellstrom, Soo Aleman, Annika Olsson, Karin Lindahl, Gordana Bogdanovic, Katie Healy, Georgios Tsilingaridis, Patricia De Palma, Sophia Hober, Anna Manberg, Peter Nilsson, Elisa Pin, Margaret Sallberg Chen
JOURNAL OF INFECTIOUS DISEASES
(2023)
Letter
Hematology
Lisa Blixt, Yu Gao, David Wullimann, Hanna Muren Ingelman-Sundberg, Sandra Muschiol, Katie Healy, Gordana Bogdanovic, Elisa Pin, Peter Nilsson, Christian Kjellander, Alba Grifoni, Alessandro Sette, Margaret Sallberg Chen, Hans -Gustaf Ljunggren, Marcus Buggert, Lotta Hansson, Anders Osterborg
Article
Immunology
Martina Frodlund, Per Nived, Aikaterini Chatzidionysiou, Anna Sodergren, Eva Klingberg, Anders Bengtsson, Monika Hansson, Sophie Olsson, Elisa Pin, Lars Klareskog, Meliha C. Kapetanovic
Summary: This study aimed to investigate antibody responses in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs) after the second and third dose of COVID-19 vaccine. The results showed that the percentage of patients with positive antibody response was significantly lower after two doses in patients receiving rituximab or abatacept treatment. However, the antibody response improved after the third dose.
Article
Biochemistry & Molecular Biology
Federica Mescia, Shaghayegh Bayati, Elisabeth Brouwer, Peter Heeringa, Erik J. M. Toonen, Marijke Beenes, Miriam J. Ball, Andrew J. Rees, Renate Kain, Paul A. Lyons, Peter Nilsson, Elisa Pin
Summary: This study aimed to analyze the autoantibody repertoire of AAV patients using antigen arrays and identified previously unreported antibodies linked to the disease and observed possible associations between anti-kinesin antibodies and clinically relevant features within AAV patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Rheumatology
Martina Frodlund, Katerina Chatzidionysiou, Anna Soedergren, Eva Klingberg, Anders A. Bengtsson, Monika Hansson, Sophie Ohlsson, Elisa Pin, Lars Klareskog, Meliha Kapetanovic
ARTHRITIS & RHEUMATOLOGY
(2022)
Article
Medicine, Research & Experimental
Katie Healy, Elisa Pin, Puran Chen, Gunnar Soderdahl, Piotr Nowak, Stephan Mielke, Lotta Hansson, Peter Bergman, C. I. Edvard Smith, Per Ljungman, Davide Valentini, Ola Blennow, Anders Osterborg, Giorgio Gabarrini, Khaled Al-Manei, Hassan Alkharaan, Michal Jacek Sobkowiak, Jamil Yousef, Sara Mravinacova, Angelica Cuapio, Xinling Xu, Mira Akber, Karin Lore, Cecilia Hellstrom, Sandra Muschiol, Gordana Bogdanovic, Marcus Buggert, Hans-Gustaf Ljunggren, Sophia Hober, Peter Nilsson, Soo Aleman, Margaret Sallberg Chen
Summary: This study found that the mRNA BNT162b2 vaccine can induce immune responses in the saliva of immunocompromised individuals to SARS-CoV-2 spike antigens. Salivary responses were correlated with specific IgG titers and neutralizing capacity in serum, and had a high predictive power for identifying vulnerable groups for revaccination.