Article
Pharmacology & Pharmacy
Anton Amadeus Hormann, Maximilian Klingler, Christine Rangger, Christian Mair, Lieke Joosten, Gerben M. Franssen, Peter Laverman, Elisabeth von Guggenberg
Summary: By modifying the C-terminal receptor-specific region, the therapeutic potential of minigastrin (MG) analogs for the treatment of CCK2R-expressing cancers was improved. Further investigations on N-terminal peptide modifications led to the design of two novel MG analogs that showed enhanced stability, strong receptor binding, and high tumor uptake.
Article
Agriculture, Dairy & Animal Science
Yiping Wan, Qiuyang Deng, Zhichun Zhou, Yue Deng, Jiannan Zhang, Juan Li, Yajun Wang
Summary: In this study, the expression and functionality of CCK and its receptors in chicken tissues were investigated. The results showed that chicken CCK1R could be activated by cCCK-8S but not cCCK-4, while cCCK2R could be activated by cCCK-8S and cCCK-4. CCK was abundantly expressed in the testis, ileum, and several brain regions, while CCK1R was highly expressed in the pancreas and moderately expressed in various intestinal regions and the pituitary gland, and CCK2R expression was primarily restricted to the brain. These findings contribute to the understanding of the physiological functions of CCK/CCKRs in birds.
Article
Biochemistry & Molecular Biology
Jill P. Smith, Hong Cao, Elijah F. Edmondson, Siva Sai Krishna Dasa, Stephan T. Stern
Summary: A new fluorescent nanoparticle targeting pancreatic intraepithelial neoplasia (PanIN) lesions has been developed, showing tissue specificity in both mouse and human pancreatic tissues. This imaging tool has the potential for early detection of pancreatic cancer in high-risk individuals.
Article
Endocrinology & Metabolism
Hannah Gilliam-Vigh, Tina Jorsal, Jens F. Rehfeld, Jens Pedersen, Steen S. Poulsen, Tina Vilsboll, Filip K. Knop
Summary: The study found that both healthy individuals and patients with type 2 diabetes showed a gradual decrease in CCK mRNA expression and density of CCK cells along the small intestine, with lower levels in the large intestine. There were no significant differences observed in the expression of CCK receptors in the intestines between the two groups.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Kaleeckal G. Harikumar, Thomas Coudrat, Aditya J. Desai, Maoqing Dong, Daniela G. Dengler, Sebastian G. B. Furness, Arthur Christopoulos, Denise Wootten, Eduard A. Sergienko, Patrick M. Sexton, Laurence J. Miller
Summary: This study proposes a new strategy for improving obesity treatment by enhancing the action of the CCK receptor, reducing the likelihood of side effects and toxicity. By identifying positive allosteric modulators (PAMs) with minimal intrinsic agonist activity and studying their mechanisms of action, it is possible to correct abnormal signaling in high-cholesterol environments and develop more effective drugs. The research focuses on compound 1, a weak partial agonist with PAM activity, which enhances CCK signaling without inducing receptor internalization, providing a potential avenue for developing targeted therapies for metabolic regulation.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Chemistry, Medicinal
Nadine Holzleitner, Thomas Guenther, Roswitha Beck, Constantin Lapa, Hans-Jurgen Wester
Summary: In this study, simultaneous F-18 and Lu-177 labelling of the same molecule was achieved. The introduction of a silicon-based fluoride acceptor enhanced the CCK-2R affinity and improved tumour retention, but also resulted in elevated kidney retention, which needs to be addressed in future studies.
Article
Oncology
Nathalie M. Grob, Roger Schibli, Martin Behe, Thomas L. Mindt
Summary: Several radiolabeled peptides targeting CCK2R-positive cancers have been investigated, with some showing promising tumor-targeting properties. By applying chemical modifications to the peptide Lu-177-PP-F11N, improved radiolabeled peptidomimetics were developed with enhanced tumor uptake and retention, making them promising candidates for imaging and therapy of CCK2R-positive tumors. The use of stable 1,2,3-triazoles as amide bond bioisosteres proved to be a successful strategy in improving the tumor-targeting properties of the peptides.
Article
Microbiology
Shengya Geng, Qian Li, Xue Zhou, Junkang Zheng, Huimin Liu, Jie Zeng, Ruizhi Yang, Herui Fu, Fanrui Hao, Qianxu Feng, Bin Qi
Summary: This study uncovers the role of bacterial outer membrane proteins in regulating animal nutrient uptake and supports the key role of innate immunity in digestion.
CELL HOST & MICROBE
(2022)
Article
Biochemistry & Molecular Biology
Marco Verona, Sara Rubagotti, Stefania Croci, Sophia Sarpaki, Francesca Borgna, Marianna Tosato, Elisa Vettorato, Giovanni Marzaro, Francesca Mastrotto, Mattia Asti
Summary: The study synthesized an indium-111-labeled IP-001, which showed high radiotracer uptake in implanted A549 xenograft tumors. In a BALB/c nude mouse model, it was found that while some radiotracer also appeared in the liver, kidneys, and spleen, tumor imaging was achieved rapidly.
Article
Pharmacology & Pharmacy
Amandine Bernard, Aurore Danigo, Mohamad Mroue, Amandine Rovini, Laurence Richard, Angelique Nizou, Alexis Desmouliere, Franck Sturtz, Claire Demiot, Sylvie Bourthoumieu
Summary: In this study, the researchers evaluated the effect of CCK2R blockade on the onset of VIPN and found that it could prevent the development of VIPN. Additionally, CCK2R blockade did not affect the anticancer efficacy of VCR.
Article
Pharmacology & Pharmacy
Shota Tanase, Takayoshi Mamiya, Shogo Nagata, Yusuke Ikawa, Ya-Ping Tang, Masayuki Hiramatsu, Toshitaka Nabeshima
Summary: In this study, the researchers found that galantamine improved social interaction impairments, but failed to attenuate anxiety-like behavior. This effect was mediated by alpha 7 nAChR and blocked by an alpha 7 nAChR antagonist, methyllycaconitine.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Anton Amadeus Hoermann, Elisabeth Plhak, Maximilian Klingler, Christine Rangger, Joachim Pfister, Gert Schwach, Herbert Kvaternik, Elisabeth von Guggenberg
Summary: This study presents a new minigastrin analog, DOTA-MGS8, targeting the cholecystokinin-2 receptor (CCK2R). Ga-68-labeled DOTA-MGS8 was successfully synthesized using an automated synthesis module, and preclinical studies demonstrated its high receptor-specific cell internalization and favorable biodistribution profile. This suggests that stabilized MG analogs like DOTA-MGS8 have the potential for high-sensitivity positron emission tomography in patients with CCK2R-related malignancies.
Article
Oncology
Jaya Nigam, Hasan Raza Kazmi, Leena Khare, Meenu Srivastava, Abhijit Chandra
Summary: This study investigates the expression and heterodimerization of CCK1R and CCK2R in gallbladder cancer cells, and finds that they play a significant role in the development of gallbladder cancer.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Daniela G. G. Dengler, Kaleeckal G. G. Harikumar, Alice Yen, Eduard A. A. Sergienko, Laurence J. J. Miller
Summary: In an effort to develop a drug for obesity, researchers performed a high throughput screening of small molecules to find candidates that can enhance the action of CCK. The study focused on a specific scaffold of tetracyclic molecules and expanded it with commercially available analogs, eliminating off-target effects while retaining its activity as a positive allosteric modulator of CCK1R. These findings provide valuable insights for the future development of potential therapeutic candidates.
Article
Multidisciplinary Sciences
Jiqin Zhang, Yongxian Hu, Jiaxuan Yang, Wei Li, Mingming Zhang, Qingcan Wang, Linjie Zhang, Guoqing Wei, Yue Tian, Kui Zhao, Ang Chen, Binghe Tan, Jiazhen Cui, Deqi Li, Yi Li, Yalei Qi, Dongrui Wang, Yuxuan Wu, Dali Li, Bing Du, Mingyao Liu, He Huang
Summary: A two-in-one approach to generate non-viral, gene-specific targeted CAR-T cells through CRISPR-Cas9 was successfully developed, demonstrating feasibility and efficacy in a preclinical study. An innovative type of anti-CD19 CAR-T cell with PD1 integration showed superior ability to eradicate tumor cells.
Article
Biochemical Research Methods
Hanwen Zhang, Ananda Kumar Kanduluru, Pooja Desai, Afruja Ahad, Sean Carlin, Nidhi Tandon, Wolfgang A. Weber, Philip S. Low
BIOCONJUGATE CHEMISTRY
(2018)
Article
Biochemical Research Methods
Loganathan Rangasamy, Venkatesh Chelvam, Ananda Kumar Kanduluru, Madduri Srinivasarao, N. Achini Bandara, Fei You, Esteban A. Orellana, Andrea L. Kasinski, Philip S. Low
BIOCONJUGATE CHEMISTRY
(2018)
Article
Biochemical Research Methods
Jyoti Roy, Miranda Kaake, Madduri Sriniyasarao, Philip S. Low
BIOCONJUGATE CHEMISTRY
(2018)
Article
Medicine, Research & Experimental
Isaac S. Marks, Spencer S. Gardeen, Sarah J. Kurdziel, Sonia T. Nicolaou, J. Evan Woods, Sumith A. Kularatne, Philip S. Low
MOLECULAR PHARMACEUTICS
(2018)
Article
Medicine, Research & Experimental
Sakkarapalayam M. Mahalingam, Fernando Dip, Marco Castillo, Mayank Roy, Steven D. Wexner, Raul J. Rosenthal, Philip S. Low
MOLECULAR PHARMACEUTICS
(2018)
Article
Chemistry, Multidisciplinary
Jeffery J. Nielsen, Stewart A. Low, Neal T. Ramseier, Rahul Hadap, Nicholas A. Young, Mingding Wang, Philip S. Low
Summary: The study aimed to improve bone fracture management by continuously applying bone anabolic agents to the fracture surface. Short oligopeptides of acidic amino acids were found to significantly increase localization of peptide payload to bone fractures, offering a promising strategy for enhancing fracture healing.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Ioannis Tsamesidis, Karine Reybier, Giuseppe Marchetti, Maria Carmina Pau, Patrizia Virdis, Claudio Fozza, Francoise Nepveu, Philip S. Low, Francesco Michelangelo Turrini, Antonella Pantaleo
Article
Biochemical Research Methods
Xin Liu, Weichuan Luo, Boning Zhang, Yong Gu Lee, Imrul Shahriar, Madduri Srinivasarao, Philip S. Low
Summary: In this study, a modified influenza virus neuraminidase inhibitor, zanamivir, was utilized for diagnostic, imaging, and therapeutic purposes in influenza virus infections. Different conjugates like the zanamivir-conjugated rhodamine dye and zanamivir99 mTc radioimaging conjugate were designed for visual monitoring of virus-infected cells. Moreover, targeted cytotoxic drugs and CAR T cells were developed specifically for viral neuraminidase-expressing cells, showing potential for improved treatment of influenza virus infections.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sakkarapalayam M. Mahalingam, Karson S. Putt, Madduri Srinivasarao, Philip S. Low
Summary: The inadvertent severing of a ureter during colorectal surgeries is a common issue, leading to the development of new near-infrared dyes to help surgeons identify ureter location. The new PEGylated UreterGlow derivatives show promising optical and biodistribution characteristics, making them good candidates for translation into the clinic.
Article
Chemistry, Multidisciplinary
John Victor Napoleon, Boning Zhang, Qian Luo, Madduri Srinivasarao, Philip S. Low
Summary: Administering a CAR-targeted TLR7 agonist can reverse CAR T cell exhaustion and successfully treat solid tumors.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Oncology
Qian Luo, John Napoleon, Xin Liu, Boning Zhang, Suilan Zheng, Philip S. Low
Summary: This study describes a strategy to reverse CAR T-cell exhaustion by using a universal anti-fluorescein CAR that engages multiple cancer cell clones and acts as a drug-internalizing receptor. By attaching a Toll-like receptor 7 agonist to the anti-fluorescein CAR, they downregulate exhaustion markers and reactivate exhausted CAR-T cells, leading to regression of solid tumors.
MOLECULAR CANCER RESEARCH
(2022)
Article
Engineering, Biomedical
Yun Chang, Gyuhyung Jin, Weichuan Luo, Qian Luo, Juhyung Jung, Sydney N. Hummel, Sandra Torregrosa-Allen, Bennett D. Elzey, Philip S. Low, Xiaojun Lance Lian, Xiaoping Bao
Summary: Adoptive CAR-engineered NK cells have potential for cancer treatment, but limited immunological memory and donor cell availability hinder their applications. We evaluated different CAR constructs to enhance NK cell proliferation and anti-tumor cytotoxicity. We genetically engineered hPSCs with optimized CARs and differentiated them into dual CAR-NK cells. The memory-like hPSC-NK cells showed enhanced anti-tumor activity through antigen-dependent activation of signaling pathways. Our modular hPSC CAR-NK engineering platform is a realistic strategy for off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy.
BIOACTIVE MATERIALS
(2023)
Article
Immunology
Huynh Dinh Chien, Antonella Pantaleo, Kristina R. Kesely, Panae Noomuna, Karson S. Putt, Tran Anh Tuan, Philip S. Low, Francesco M. Turrini
Summary: The coadministration of imatinib with standard of care (SOC) in uncomplicated P. falciparum malaria patients led to a faster decline in parasite density and fever, without any delayed parasite clearance. The improvements were most significant in patients with the highest parasite density, where serious complications and death are most common.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Xin Liu, Boning Zhang, Yingcai Wang, Hanan S. Haymour, Fenghua Zhang, Le-cun Xu, Madduri Srinivasarao, Philip S. Low
NATURE COMMUNICATIONS
(2020)
Article
Chemistry, Multidisciplinary
Sakkarapalayam M. Mahalingam, Josue D. Ordaz, Philip S. Low