Article
Oncology
Masatoshi Takagi, Chitose Ogawa, Tomoko Iehara, Yuki Aoki-Nogami, Eri Ishibashi, Minoru Imai, Toshimi Kimura, Masashi Nagata, Masato Yasuhara, Mitsuko Masutani, Kenichi Yoshimura, Daisuke Tomizawa, Atsushi Ogawa, Kan Yonemori, Aoi Morishita, Satoshi Miyamoto, Junko Takita, Tetsuro Kihara, Kiyoshi Nobori, Kazuhisa Hasebe, Fuyuki Miya, Sadakatsu Ikeda, Yoko Shioda, Kimikazu Matsumoto, Junya Fujimura, Shuki Mizutani, Tomohiro Morio, Hajime Hosoi, Ryuji Koike
Summary: This study evaluated the safety and efficacy of the PARP inhibitor olaparib in pediatric patients with solid tumors, recommending a daily dose for Phase 2 trials. Results showed that olaparib was well tolerated and had potential antitumor effects in DNA damage response-defective pediatric tumors.
Article
Veterinary Sciences
Jacob R. Cawley, Samuel D. Stewart, Jonathan Paul Mochel, Sridhar Veluvolu, Chand Khanna, Joelle M. Fenger
Summary: This study evaluated the pharmacokinetics of sorafenib in tumor-bearing dogs and found that a twice-daily oral dose of 3 mg/kg was well-tolerated without any adverse events.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Abigail Ferreira, Rui Lapa, Nuno Vale
Summary: Gemcitabine, a nucleoside analog used for solid tumors, is limited by factors like metabolic inactivation and rapid clearance. Research aims to improve therapy efficacy and enhance oral bioavailability. Modeling and analysis suggest oral administration may be a viable alternative to traditional IV infusions, with potential for personalized health care and new drug delivery systems.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2021)
Article
Oncology
Andrea Wang-Gillam, Kian-Huat Lim, Robert McWilliams, Rama Suresh, Albert C. Lockhart, Amberly Brown, Marcus Breden, Jad I. Belle, John Herndon, Savannah J. Bogner, Katrina Pedersen, Benjamin Tan, Nicholas Boice, Abhi Acharya, Mina Abdiannia, Feng Gao, Harry H. Yoon, Mojun Zhu, Nikolaos A. Trikalinos, Lee Ratner, Olivia Aranha, William G. Hawkins, Brett H. Herzog, David G. Denardo
Summary: The combination therapy of defactinib, pembrolizumab, and gemcitabine showed good tolerability and safety, promising preliminary efficacy, and biomarker activity in infiltrative T lymphocytes in PDAC patients.
CLINICAL CANCER RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Xu Zhang, Kejian Shi, Jiahui Mao, Kerou Mao, Yangrui Jia, Jiakun Zhang, Qingzhen Wang, Ru Bai, Fene Gao, Shihui Liu, Mengyu Guo, Fenglan Qin, Shengmin Li, Chunying Chen, Huige Zhou, Jing Liu, Fulin Chen
Summary: Compared with vein injection, oral administration is a preferred non-invasive and self-help treatment option for cancer therapy. However, the harsh gastrointestinal tract and biological barriers limit the stability and efficiency of oral drug delivery systems. To overcome these challenges, researchers have developed Cyssome, a drug delivery platform that can maintain stability in harsh environments, penetrate biological barriers, and improve drug release and bioavailability.
Article
Oncology
Diwakar Davar, Roberta Zappasodi, Hong Wang, Girish S. Naik, Takami Sato, Todd Bauer, David Bajor, Olivier Rixe, Walter Newman, Jingjing Qi, Aliya Holland, Phillip Wong, Lianna Sifferlen, Diane Piper, Cynthia A. Sirard, Taha Merghoub, Jedd D. Wolchok, Jason J. Luke
Summary: TRX518 showed acceptable safety and pharmacodynamic activity in the treatment of advanced solid tumors, but the clinical responses were limited. TRX518 had an impact on regulatory T cells (Treg) with different kinetics depending on the combination regimen.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Christos Fountzilas, Alex Adjei, Mateusz Opyrchal, Rachel Evans, Mohammad Ghasemi, Kristopher Attwood, Adrienne Groman, Wiam Bshara, Andrew Goey, John Wilton, Wen Wee Ma, Renuka Iyer
Summary: Ceritinib in combination with gemcitabine and gemcitabine/cisplatin has manageable toxicity profile, showing potential efficacy in tumors with ALK or ROS1 fusions.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Oncology
Andrew J. Wagner, Paul L. Severson, Anthony F. Shields, Amita Patnaik, Rashmi Chugh, Gabriel Tinoco, Guoxian Wu, Marika Nespi, Jack Lin, Ying Zhang, Todd Ewing, Gaston Habets, Elizabeth A. Burton, Bernice Matusow, James Tsai, Garson Tsang, Rafe Shellooe, Heidi Carias, Katrina Chan, Hamid Rezaei, Laura Sanftner, Adhirai Marimuthu, Wayne Spevak, Prabha N. Ibrahim, Kerry Inokuchi, Oscar Alcantar, Glenn Michelson, Athanasios C. Tsiatis, Chao Zhang, Gideon Bollag, Jonathan C. Trent, William D. Tap
Summary: In this non-randomized phase 1b/2a clinical trial, the type I and type II KIT inhibitors PLX9486 and sunitinib were safely coadministered at recommended doses in patients with refractory GIST, suggesting that targeting two complementary conformational states of the same kinase was associated with clinical benefit.
Article
Oncology
Ke Cheng, Xiao-Yu Li, Yu-Wen Zhou, Zheng-Yin Liao, Meng Qiu, Feng Bi, Li Zheng
Summary: MET overexpression is uncommon, with positive MET immunohistochemistry being an independent positive prognostic factor. Metatinib was well tolerated, safe, and effective in patients with advanced solid tumors.
Article
Oncology
Rolf D. Issels, Stefan Boeck, Uwe Pelzer, Ulrich Mansmann, Pirus Ghadjar, Lars H. Lindner, Markus Albertsmeier, Martin K. Angele, Michael Schmidt, Yujun Xu, Marcus Bahra, Johann Pratschke, Michael Schoenberg, Wolfgang E. Thasler, Christoph Salat, Oliver J. Stoetzer, Wolfram T. Knoefel, Dirk Graf, Rudiger Wessalowski, Verena Keitel-Anselmino, Alfred Koenigsrainer, Michael Bitzer, Daniel Zips, Michael Bamberg, Rainer Fietkau, Oliver Ott, Maciej Kawecki, Lucian Wyrwicz, Piotr Rutkowski, Markus Rentsch, Juliana Ababei, Peter Reichardt, Marco Rigamonti, Bernhard Weber, Sultan Abdel-Rahman, Katharina Tschoep-Lechner, Karl-Walter Jauch, Christiane J. Bruns, Helmut Oettle, Michael von Bergwelt-Baildon, Volker Heinemann, Jens Werner
Summary: In this randomized controlled trial, the addition of cisplatin to gemcitabine with regional hyperthermia did not significantly improve disease-free survival in resected pancreatic ductal adenocarcinoma, but it showed a difference in post-recurrence survival and a trend for improved overall survival.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Rocio Garcia-Carbonero, Miriam Bazan-Peregrino, Marta Gil-Martin, Rafael Alvarez, Teresa Macarulla, Maria C. Riesco-Martinez, Helena Verdaguer, Carmen Guillen-Ponce, Marti Farrera-Sal, Rafael Moreno, Ana Mato-Berciano, Maria Victoria Maliandi, Silvia Torres-Manjon, Marcel Costa, Natalia del Pozo, Jaime Martinez de Villarreal, Francisco X. Real, Noemi Vidal, Gabriel Capella, Ramon Alemany, Emma Blasi, Carmen Blasco, Manel Cascallo, Ramon Salazar
Summary: The study evaluates the safety and efficacy of VCN-01 adenovirus in patients with advanced cancer. The results show promising biological and clinical activity when administered in combination with nab-paclitaxel plus gemcitabine.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Paul F. Vollebregt, Rebecca E. Burgell, Richard L. Hooper, Charles H. Knowles, S. Mark Scott
Summary: The study revealed that 25% of patients with refractory functional constipation have rectal hyposensitivity. There is a linear relationship between the number of elevated sensory thresholds and the severity of constipation, and RH is significantly associated with defecation symptoms and physiological investigations.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Pharmacology & Pharmacy
Suying Lu, Ye Hong, Huimou Chen, Liuhong Wu, Feifei Sun, Juan Wang, Jia Zhu, Yi Que, Lian Zhang, Zijun Zhen, Xiaofei Sun, Junting Huang, Yizhuo Zhang
Summary: This study evaluated the efficacy and safety of anlotinib in pediatric patients with refractory or recurrent solid tumors. The results showed that anlotinib monotherapy and its combination with chemotherapy may be effective treatment options with tolerable adverse events.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Filip Janku, Halle Huihong Zhang, Abdulmohammad Pezeshki, Sanjay Goel, Ravi Murthy, Andrea Wang-Gillam, Dale R. Shepard, Thorunn Helgason, Tyler Masters, David S. Hong, Sarina A. Piha-Paul, Daniel D. Karp, Mark Klang, Steven Y. Huang, Divya Sakamuri, Anjali Raina, Jean Torrisi, Stephen B. Solomon, Alice Weissfeld, Ernest Trevino, Gary DeCrescenzo, Amanda Collins, Maria Miller, Jennifer L. Salstrom, Ronald L. Korn, Linping Zhang, Saurabh Saha, Alexey A. Leontovich, David Tung, Brent Kreider, Mary Varterasian, Khashayarsha Khazaie, Mrinal M. Gounder
Summary: The first-in-human study on intratumoral injection of Clostridium novyi-NT demonstrated its feasibility with manageable toxicities. The treatment induced antitumor responses and host immune reactions in patients, with most experiencing reduction or stability in injected tumor size. Further studies are warranted to explore the potential of C. novyi-NT in human therapy.
CLINICAL CANCER RESEARCH
(2021)
Article
Dentistry, Oral Surgery & Medicine
Camila Stofella Sodre, Dennis de Carvalho Ferreira, Mayra Stambovsky Vieira, Fernanda Sampaio Cavalcante, Beatriz Stofel Braga, Simone Saintive, Eliane de Dios Abad, Ekaterini Goudouris, Evandro A. Prado, Lucio Souza Goncalves, Katia Regina Netto dos Santos, Marcia Goncalves Ribeiro
Summary: The study found that oral health conditions and diagnosis of caries in atopic dermatitis patients are influenced by multiple factors, including the use of inhaled corticosteroids, type of teething, and brushing quality.
Article
Multidisciplinary Sciences
Robert S. Jansen, Lungelo Mandyoli, Ryan Hughes, Shoko Wakabayashi, Jessica T. Pinkham, Bruna Selbach, Kristine M. Guinn, Eric J. Rubin, James C. Sacchettini, Kyu Y. Rhee
NATURE COMMUNICATIONS
(2020)
Article
Chemistry, Medicinal
John Ginn, Xiuju Jiang, Shan Sun, Mayako Michino, David J. Huggins, Zodwa Mbambo, Robert Jansen, Kyu Y. Rhee, Nancy Arango, Christopher D. Lima, Nigel Liverton, Toshihiro Imaeda, Rei Okamoto, Takanobu Kuroita, Kazuyoshi Aso, Andrew Stamford, Michael Foley, Peter T. Meinke, Carl Nathan, Ruslana Bryk
Summary: The development and effectiveness of novel analogs targeting the mycobacterial lipoamide dehydrogenase in inhibiting the growth of Mycobacterium tuberculosis was discussed in the article. These analogs showed improved permeability, potency, and selectivity, as well as on-target activity within the mycobacteria by increasing intrabacterial pyruvate levels. Improved potency and selectivity were achieved through distinct binding modalities between the mycobacterial and human enzymes.
ACS INFECTIOUS DISEASES
(2021)
Article
Microbiology
Cornelia U. Welte, Rob de Graaf, Paula Dalcin Martins, Robert S. Jansen, Mike S. M. Jetten, Julia M. Kurth
Summary: The study found that the non-methanogenic archaeon A. fulgidus has the ability to grow on MACs, converting them to hydroxylated derivatives with CO2 as the main product and sulfate as electron acceptor. Additionally, MACs can enhance the growth of A. fulgidus in the presence of organic substrates.
ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Sarah M. Schrader, Helene Botella, Robert Jansen, Sabine Ehrt, Kyu Rhee, Carl Nathan, Julien Vaubourgeix
Summary: A critical challenge faced by microbiology and medicine is how to cure infections caused by bacteria that survive antibiotic treatment by persistence or tolerance. Research has found that even a single base change in a gene encoding a component of a metabolic pathway can confer multiple forms of resistance to multiple antibiotics with different targets. This extraordinary resilience may help explain why substerilizing exposure to one antibiotic in a regimen can induce resistance to others, and could lead to the development of drugs targeting the mediator of multiform resistance, WhiB7.
Article
Multidisciplinary Sciences
Tiago Beites, Robert S. Jansen, Ruojun Wang, Adrian Jinich, Kyu Y. Rhee, Dirk Schnappinger, Sabine Ehrt
Summary: The pathogen Mycobacterium tuberculosis relies on etfD for fatty acid metabolism, and this protein complex is crucial for its survival.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Kyu Y. Rhee, Robert S. Jansen, Christoph Grundner
Summary: Current tools for annotating protein function cannot keep up with the fast pace of DNA sequencing and the exponentially increasing number of proteins with unknown functions. The lack of high-throughput methods for experimentally determining biochemical activity is a major reason for this mismatch. Activity-based methods offer new opportunities for unbiased and comprehensive annotation of protein function.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Kaj M. Kreutzfeldt, Robert S. Jansen, Travis E. Hartman, Alexandre Gouzy, Ruojun Wang, Inna Krieger, Matthew D. Zimmerman, Martin Gengenbacher, Jansy P. Sarathy, Min Xie, Veronique Dartois, James C. Sacchettini, Kyu Y. Rhee, Dirk Schnappinger, Sabine Ehrt
Summary: The protein CinA in Mycobacterium tuberculosis mediates drug tolerance by cleaving NAD-drug adducts, suggesting it as a potential target for shortening tuberculosis treatment by enhancing the efficacy of currently used antibiotics. By reducing the fraction of drug-tolerant persisters, genetic inactivation of cinA accelerated the killing of Mtb by four antibiotics. Deletion of CinA also increased in vivo killing of Mtb by a combination of pretomanid, bedaquiline, and linezolid.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Veronica L. Li, Yang He, Kevin Contrepois, Hailan Liu, Joon T. Kim, Amanda L. Wiggenhorn, Julia T. Tanzo, Alan Sheng-Hwa Tung, Xuchao Lyu, Peter-James H. Zushin, Robert S. Jansen, Basil Michael, Kang Yong Loh, Andrew C. Yang, Christian S. Carl, Christian T. Voldstedlund, Wei Wei, Stephanie M. Terrell, Benjamin C. Moeller, Rick M. Arthur, Gareth A. Wallis, Koen van de Wetering, Andreas Stahl, Bente Kiens, Erik A. Richter, Steven M. Banik, Michael P. Snyder, Yong Xu, Jonathan Z. Long
Summary: Exercise stimulates the production of a blood-borne metabolite called Lac-Phe, which suppresses feeding and obesity. This metabolite is synthesized in specific cells and controls appetite, reduces fat content, and improves glucose balance. It is also observed in humans and racehorses, suggesting that it is a molecular effector associated with physical activity in multiple species.
Article
Biotechnology & Applied Microbiology
Magda A. Rogowska-van der Molen, Dmitrii Nagornii, Silvia Coolen, Rob M. de Graaf, Tom Berben, Theo van Alen, Mathilde A. C. H. Janssen, Floris P. J. T. Rutjes, Robert S. Jansen, Cornelia U. Welte
Summary: Plants have evolved chemical defense mechanisms to deter herbivores, including the production of plant toxins like nitropropionic acid (NPA). In this study, a bacterium isolated from the gut of the Southern green shield bug was found to degrade NPA and its metabolic pathway was identified. The discovery of NPA degradation pathways by environmental bacteria opens up new possibilities for pretreating contaminated food sources and utilizing understudied enzymes in biotechnology.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Femke J. Vermeir, Robert S. Jansen, Laura van Niftrik, Wouter Versantvoort
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Article
Biochemical Research Methods
Stefan Lundkvist, Fatemeh Niaziorimi, Flora Szeri, Matthew Caffet, Sharon F. Terry, Gunnar Johansson, Robert S. Jansen, Koen van de Wetering
Summary: Inorganic pyrophosphate (PPi) is a crucial regulator of extracellular mineralization, but there is currently no reliable assay for its quantification. In this study, we report a new and robust assay that converts PPi into ATP and quantifies it using firefly luciferase-based bioluminescence. The assay shows high sensitivity, precision, and accuracy, and outperforms currently available assays.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Review
Microbiology
Robin A. Dawson, Andrew T. Crombie, Robert S. Jansen, Thomas J. Smith, Tim Nichol, Colin Murrell
Summary: Isoprene, emitted by plants in large quantities each year, interacts with atmospheric compounds and has implications for global warming and local air quality. It has long been known that soil-dwelling bacteria consume a significant amount of isoprene, but the mechanisms underlying this biological sink have been poorly understood. Recent studies have identified bacterial genera that can degrade isoprene through different mechanisms, challenging our understanding of isoprene uptake and the ecology of isoprene-degraders.
ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Niek F. de Jonge, Joris J. R. Louwen, Elena Chekmeneva, Stephane Camuzeaux, Femke J. Vermeir, Robert S. Jansen, Florian Huber, Justin J. J. van der Hooft
Summary: The authors have developed a machine learning approach, MS2Query, to facilitate chemical discovery in mass spectral libraries. This tool increases the annotation rate and aids in assessing novelty in metabolomics datasets. By integrating mass spectral embedding-based chemical similarity predictors and detected precursor masses, MS2Query offers a more reliable and efficient alternative for searching structurally related molecules in metabolomics studies.
NATURE COMMUNICATIONS
(2023)
Review
Microbiology
Magda A. Rogowska-van der Molen, Aileen Berasategui-Lopez, Silvia Coolen, Robert S. Jansen, Cornelia U. Welte
Summary: Plants produce a variety of secondary metabolites in response to different stresses. Microorganisms have the ability to detoxify these toxic metabolites, which benefits their herbivory host. This review focuses on the genes and enzymes involved in the breakdown pathways of toxic alkaloids, glucosinolates, terpenes, and polyphenols and highlights the potential biotechnological applications of insect-associated microbes in pest control strategies.
ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Infectious Diseases
Jodie A. Schildkraut, Jordy P. M. Coolen, Carolien Ruesen, Jeroen J. M. W. van den Heuvel, Laura Edo Acena, Heiman F. L. Wertheim, Robert S. Jansen, Jan B. Koenderink, Lindsey H. M. te Brake, Jakko van Ingen
Summary: The study found that Mycobacterium avium (M. avium) has ABC transporters related to antibiotic efflux, which plays an important role in antibiotic resistance. It was found that ABC transporters are sensitive to certain antibiotics, but only specific ones. In addition, M. avium cannot modify amikacin, which is of significant importance to its activity.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2023)