Article
Chemistry, Multidisciplinary
Leran Zhang, Scott Lovell, Elena De Vita, Pravin Kumar Ankush Jagtap, Daniel Lucy, Andrea Goya Grocin, Svend Kjaer, Annabel Borg, Janosch Hennig, Aubry K. Miller, Edward W. Tate
Summary: Pancreatic cancer has the lowest survival rate among common cancers due to late diagnosis and limited treatment options. The kallikreinrelated peptidase (KLK) family of secreted serine proteases, specifically KLK6, has emerged as a potential target for pancreatic ductal adenocarcinoma (PDAC). However, the lack of reliable activity-based probes (ABPs) has hindered the validation of these enzymes as targets or biomarkers. In this study, potent and selective ABPs for KLK6 were developed, enabling the detection of KLK6 activity in PDAC cell lines and providing insights into KLK6-mediated invasion pathways.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Hayet Bouzid, Feryel Soualmia, Katerina Oikonomopoulou, Antoninus Soosaipillai, Francine Walker, Khaoula Louati, Rea Lo Dico, Marc Pocard, Chahrazade El Amri, Natalia A. Ignatenko, Dalila Darmoul
Summary: KLK6 overexpression in colon cancer is associated with poor prognosis and aggressive behavior. KLK6 activates PAR2, leading to calcium flux and ERK1/2 phosphorylation, promoting tumor formation and invasion. Furthermore, KLK6 abnormal expression can be used to differentiate between malignant and benign ascites.
Article
Pathology
Georgios Pampalakis, Eleni Zingkou, Vassilis Zoumpourlis, Georgia Sotiropoulou
Summary: Melanoma is an aggressive form of cancer, but KLK6 may inhibit the growth of melanomas.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Cardiac & Cardiovascular Systems
Aleksandra Boikova, Megan J. Bywater, Gregory A. Quaife-Ryan, Jasmin Straube, Lucy Thompson, Camilla Ascanelli, Trevor D. Littlewood, Gerard I. Evan, James E. Hudson, Catherine H. Wilson
Summary: The study reveals that Myc and HRas can cooperate to induce proliferation in adult mammalian cardiomyocytes, but the activity of HRas also leads to cell death, limiting its potential as a regenerative therapeutic target.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Minhui Yang, Changxiao Hu, Yibo Cao, Wanling Liang, Xiangdong Yang, Tianbao Xiao
Summary: The study explores the biological functions of CCNB1 in COAD and investigates the therapeutic effects of UA on COAD cells. UA effectively inhibits COAD cell proliferation and induces cell cycle arrest in S phase. The molecular mechanisms of UA involve downregulation of CCNB1 and its interacting genes and proteins, contributing to cell cycle blocking and COAD treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Franz Ketzer, Hend Abdelrasoul, Mona Vogel, Ralf Marienfeld, Markus Mueschen, Hassan Jumaa, Thomas Wirth, Alexey Ushmorov
Summary: CCND3 is essential for the proliferation and survival of B-ALL, exceeding the expression levels of CCND1 and CCND2 at the mRNA level. FOXO1 is identified as a CCND3-activating transcription factor in B-ALL, playing a crucial role in cell growth and survival. The anti-apoptotic effect of CCND3 in B-ALL is independent of the kinase activity of the CCND3-CDK4/6 complex.
Article
Pharmacology & Pharmacy
Riham R. E. Abouleisa, Jessica M. Miller, Ahmad Gebreil, Abou Bakr M. Salama, Marc Dwenger, Hania Abdelhafez, Reham M. Wahid, Adeniyi T. Adewumi, Mahmoud E. S. Soliman, Nader E. Abo-Dya, Tamer M. A. Mohamed
Summary: This study identified a small molecule called NDPPC, which can enhance the cell cycle progression of cardiomyocytes and has the potential to be a drug for heart failure treatment.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Betheney R. Pennycook, Alexis R. Barr
Summary: The use of CDK4/6 inhibitors in cancer treatment is a topic of ongoing investigation, with limited understanding of their mechanisms of action. Recent data have raised questions about how these inhibitors arrest cell proliferation, leading to renewed interest in the roles of CDK4/6. Studying the effects of CDK4/6 inhibitors on the cell cycle can have implications for cancer treatment and patient stratification.
Article
Biochemistry & Molecular Biology
Kei Takuma, Shintaro Fujihara, Koji Fujita, Hisakazu Iwama, Mai Nakahara, Kyoko Oura, Tomoko Tadokoro, Shima Mimura, Joji Tani, Tingting Shi, Asahiro Morishita, Hideki Kobara, Takashi Himoto, Tsutomu Masaki
Summary: This study investigates the antitumor mechanism of regorafenib on hepatocellular carcinoma (HCC) and the impact on microRNA (miRNA) expression. The results suggest that regorafenib inhibits cell proliferation and tumor growth in HCC by altering the cell cycle and miRNA expression, particularly downregulating cyclin D1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Kee-Beom Kim, Dong-Wook Kim, Youngchul Kim, Jun Tang, Nicole Kirk, Yongyu Gan, Bongjun Kim, Bingliang Fang, Jae-ll Park, Yi Zheng, Kwon-Sik Park
Summary: This study characterizes the activity of the WNT pathway in small cell lung cancer (SCLC) and identifies the key role of the WNT5A-RHOA axis in SCLC progression. It provides potential targets for therapeutic interventions and biomarkers to improve patient treatment.
Article
Biochemistry & Molecular Biology
Sunisa Thongsom, Satapat Racha, Zin Zin Ei, Korrakod Petsri, Nithikoon Aksorn, Supakarn Chamni, Vitsarut Panpuang, Hongbin Zou, Pithi Chanvorachote
Summary: Lung cancer is a common malignancy with NSCLC being the most prevalent type. The PI3K/Akt pathway has been implicated in the progression of NSCLC, making it a potential therapeutic target. However, the effects of unsymmetrical N,N'-diarylurea derivatives on the PI3K/Akt pathway in NSCLC cells are not yet known.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Yu-jia Xu, Kun Zeng, Ying Ren, Chen-yu Mao, Ying-hui Ye, Xiao-ting Zhu, Zi-ying Sun, Bi-yin Cao, Zu-bin Zhang, Guo-qiang Xu, Zhen-qian Huang, Xin-liang Mao
Summary: In this study, the deubiquitinase USP10 is identified as the first deubiquitinase of CCND3, and it stabilizes CCND3 and activates the CCND3/CDK4/6 signaling pathway in multiple myeloma cells. Inhibition of USP10 results in CCND3 degradation, and combined with a CDK4/6 inhibitor, it induces cell apoptosis, suggesting it as a potential therapeutic modality for myeloma.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Oncology
Andra S. Martinikova, Miroslav Stoyanov, Anna Oravetzova, Yannick P. Kok, Shibo Yu, Jana Dobrovolna, Pavel Janscak, Marcel van Vugt, Libor Macurek
Summary: Oncogene-induced replication stress is a major cause of genome instability in cancer cells. This study reveals that increased activity of PPM1D exacerbates replication stress caused by cyclin E1 overexpression, leading to abnormal cell cycle progression and accumulation of DNA copy number alterations. Pharmacological inhibition of PPM1D can alleviate replication stress-induced genome instability.
MOLECULAR ONCOLOGY
(2024)
Article
Biology
Mohamed A. Elkady, Ahmed S. Doghish, Ahmed Elshafei, Mostafa M. Elshafey
Summary: miR-567 is downregulated in A549 NSCLC cells, but its upregulation can inhibit cell proliferation, promote apoptosis, induce cell cycle arrest, and act as a tumor suppressor by regulating CDK8 gene expression.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Oncology
Qing Hua, Tianjiao Li, Yixuan Liu, Xuefang Shen, Xiaoyan Zhu, Pingbo Xu
Summary: The study revealed that KLK8 is up-regulated in PDAC tumor tissues and serves as an independent prognostic factor for PDAC. KLK8 overexpression in Mia-paca-2 and Panc-1 cells promotes cell proliferation and inhibits apoptosis, potentially through activation of the PI3K/Akt/mTOR and Notch pathways. Additionally, KLK8-induced effects can be attenuated by inhibitors for PI3K, Akt, and mTOR, suggesting a potential therapeutic target for PDAC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Maya Hassane, Youenn Jouan, Florent Creusat, Daphnee Soulard, Chloe Boisseau, Loic Gonzalez, Emmanuel C. Patin, Nathalie Heuze-Vourc'h, Jean-Claude Sirard, Christelle Faveeuw, Francois Trottein, Mustapha Si-Tahar, Thomas Baranek, Christophe Paget
MUCOSAL IMMUNOLOGY
(2020)
Review
Pharmacology & Pharmacy
Stephan Ehrmann, Otmar Schmid, Chantal Darquenne, Barbara Rothen-Rutishauser, Josue Sznitman, Lin Yang, Hana Barosova, Laurent Vecellio, Jolyon Mitchell, Nathalie Heuze-Vourc'h
EXPERT OPINION ON DRUG DELIVERY
(2020)
Article
Multidisciplinary Sciences
Nicolas Guyot, Herve Meudal, Sascha Trapp, Sophie Iochmann, Anne Silvestre, Guillaume Jousset, Valerie Labas, Pascale Reverdiau, Karine Loth, Virginie Herve, Vincent Aucagne, Agnes F. Delmas, Sophie Rehault-Godbert, Celine Landon
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Pharmacology & Pharmacy
T. Secher, E. Bodier-Montagutelli, A. Guillon, N. Heuze-Vourc'h
ADVANCED DRUG DELIVERY REVIEWS
(2020)
Review
Immunology
Alexie Mayor, Adelaide Chesnay, Guillaume Desoubeaux, David Ternant, Nathalie Heuze-Vourc'h, Thomas Secher
Summary: Respiratory tract infections (RTIs) are common and life-threatening diseases, involving various microorganisms. The development of novel anti-infective molecules is urgently needed, with antibodies (Abs) becoming increasingly important in respiratory medicine, although progress in developing Abs for infectious diseases lags behind that for cancer and inflammatory diseases.
Article
Biochemistry & Molecular Biology
Marion Lavergne, Audrey Guillon-Munos, Woodys Lenga Ma Bonda, Sylvie Attucci, Thomas Kryza, Aurelia Barascu, Thierry Moreau, Agnes Petit-Courty, Damien Sizaret, Yves Courty, Sophie Iochmann, Pascale Reverdiau
Summary: TFPI-2 is a potent inhibitor of KLK12 and can regulate matrix remodeling and cancer progression mediated by KLK12. The down-regulation of TFPI-2 in human non-small-cell lung tumor tissue suggests its role in cancer development.
BIOLOGICAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Antoine Guillon, Jeoffrey Pardessus, Guillaume L'Hostis, Cindy Fevre, Celine Barc, Emilie Dalloneau, Youenn Jouan, Elsa Bodier-Montagutelli, Yonatan Perez, Camille Thorey, Laurent Mereghetti, Maria Cabrera, Mickael Riou, Laurent Vecellio, Sandrine Le Guellec, Nathalie Heuze-Vourc'h
Summary: By selecting an active phage cocktail and optimizing aerosol delivery conditions, we were able to deliver high phage concentrations in the lungs, resulting in a rapid and marked reduction in P. aeruginosa density (1.5-log reduction, p < .001). No infective phage was detected in the sera and urines throughout the experiment.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Respiratory System
Piotr Szychowiak, Samuel Gensburger, Thomas Bocar, Cassandre Landel, Marion Philippe, Deborah Le Pennec, Maria Cabrera, Lydiane Mordier, Laurent Vecellio, Francois Reminiac, Nathalie Heuze-Vourc'h, Stephan Ehrmann
Summary: The study found that using pressurized metered-dose inhalers (pMDIs) within a nasal high-flow (NHF) therapy circuit can effectively deliver albuterol to the lungs. The use of a spacer and optimal settings can improve drug delivery efficiency, potentially leading to bronchodilation in patients receiving this treatment.
JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY
(2021)
Article
Instruments & Instrumentation
Alexie Mayor, Beatrice Thibert, Sylvain Huille, Renaud Respaud, Heloise Audat, Nathalie Heuze-Vourc'h
Summary: Respiratory infections are life-threatening, and therapeutic antibodies could benefit patients with pneumonia caused by multidrug-resistant bacteria or emergent viruses. Inhalation of anti-infectious antibodies may be more effective than intravenous injection, but challenges remain in preventing protein instability during aerosolization. Repurposing antibody formulations developed for intravenous delivery for inhalation may not be straightforward, highlighting the need for specific formulation development for inhaled antibodies.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Marion Ferreira, Thomas Secher, Nathalie Heuze-Vourc'H, Karen L. Reckamp
Summary: This article summarizes the use of various antibodies in the treatment of non-small cell lung cancer, specifically focusing on the application of anti-angiogenic and immune checkpoint inhibitor antibodies. It introduces the marketed ICI and anti-angiogenic antibodies approved in the EU and US for treating NSCLC, discussing their development in thoracic oncology and comparing pharmacokinetic data and regulatory approvals by the EMA and FDA.
Article
Biochemistry & Molecular Biology
Woodys Lenga Ma Bonda, Marion Lavergne, Virginie Vasseur, Lucie Brisson, Sebastien Roger, Antoine Legras, Antoine Guillon, Serge Guyetant, Pieter S. Hiemstra, Mustapha Si-Tahar, Sophie Iochmann, Pascale Reverdiau
Summary: KLK5 has been identified as a crucial protease in extracellular matrix remodeling and bronchial epithelial repair after injury. It promotes epithelial-to-mesenchymal transition (EMT) and cell migration by activating the mitogen-activated protein kinase signaling pathway, while also delaying wound healing repair.
Article
Microbiology
Adelaide Chesnay, Christophe Paget, Nathalie Heuze-Vourc'h, Thomas Baranek, Guillaume Desoubeaux
Summary: Pneumocystis pneumonia is a severe lung infection that primarily occurs in immunocompromised patients. In order to study diagnosis and treatment strategies, it is important to understand the biology of the Pneumocystis agent and the course of the disease. Animal studies are crucial for researching Pneumocystis pneumonia in the absence of in vitro continuous culture systems. This overview of animal models in the literature highlights the variability in variables studied and provides important information for researchers in choosing experimental parameters.
Article
Immunology
Aubin Pitiot, Marion Ferreira, Christelle Parent, Chloe Boisseau, Laura Bouvart, Christophe Paget, Nathalie Heuze-Vourc'h, Thomas Secher
Summary: Bacterial respiratory infections pose significant threats to human health. Direct mucosal administration of therapeutic antibodies has the potential to effectively treat respiratory infections. Research shows that these antibodies can rapidly contain primary infections and provide long-term protection against secondary infections by recruiting immune effectors.
MUCOSAL IMMUNOLOGY
(2023)
Article
Virology
Sandrine Le Guellec, Jeoffrey Pardessus, Elsa Bodier-Montagutelli, Guillaume L'Hostis, Emilie Dalloneau, Damien Piel, Hakim Chouky Samai, Antoine Guillon, Elvir Mujic, Emmanuelle Guillot-Combe, Stephan Ehrmann, Eric Morello, Jerome Gabard, Nathalie Heuze-Vourc'h, Cindy Fevre, Laurent Vecellio
Summary: Bacteriophages have the potential to treat lung infections in the context of antibiotic resistance, and nebulization during mechanical ventilation is an effective delivery method.
Review
Immunology
Aubin Pitiot, Nathalie Heuze-Vourc'h, Thomas Secher
Summary: This review provides an overview of alternative routes of administration for delivering therapeutic antibodies, highlighting their physical and biological fundamentals, as well as their strengths and limitations. In addition to the commonly used intravenous (IV) route, topical delivery has shown clinical successes in improving drug bioavailability and efficacy while reducing side effects. Further research is needed to understand the impact of biological barriers on local delivery and optimize delivery methods and formulations for antibodies.