Article
Oncology
Ellen Finnegan, Wei Ding, Ziga Ude, Sara Terer, Tadhg Mcgivern, Anna M. Blumel, Grainne Kirwan, Xinxin Shao, Flavia Genua, Xiaofei Yin, Alexander Kel, Sarinj Fattah, Parvathi A. Myer, Sally-Ann Cryan, Jochen H. M. Prehn, Darran P. O'Connor, Lorraine Brennan, Gregory Yochum, Celine J. Marmion, Sudipto Das
Summary: Belinostat and Cubisbel significantly reduced colon cancer cell growth through HDAC inhibition and apoptosis induction. Cubisbel exhibited a significantly longer in vitro half-life compared to belinostat. Both HDACis showed a significant reduction in cell viability and downregulation of stem cell and proliferation markers in colon cancer patient-derived tumor organoids (PDTOs).
Article
Oncology
Katharine A. Collier, Hugo Valencia, Herbert Newton, Erinn M. Hade, Douglas W. Sborov, Robert Cavaliere, Ming Poi, Mitch A. Phelps, Sophia G. Liva, Christopher C. Coss, Jiang Wang, Soun Khountham, Paul Monk, Charles L. Shapiro, Richard Piekarz, Craig C. Hofmeister, D. Bradley Welling, Amir Mortazavi
Summary: The study investigated the safety and tolerability of the oral histone deacetylase inhibitor AR-42 in patients with advanced solid tumors. AR-42 showed clinical activity with the most common adverse events being cytopenias, fatigue, and nausea. Further studies may explore AR-42 in a larger cohort of patients with NF2 or in combination with other agents for advanced solid tumors.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shunda Li, Chunlong Zhao, Guozhen Zhang, Qifu Xu, Qian Liu, Wei Zhao, C. James Chou, Yingjie Zhang
Summary: The novel pyrrolo[2,3-d]pyrimidine-based HDAC inhibitors demonstrated potent inhibitory activities and selectivities against HDAC6, showing superior antiproliferative activity against human multiple myeloma cell lines while maintaining low cytotoxicity. In addition, one representative compound showed good metabolic stability and in vivo anti-multiple myeloma potency in a xenograft model.
BIOORGANIC CHEMISTRY
(2021)
Article
Parasitology
Ming Jang Chua, Jiahui Tng, Eva Hesping, Gillian M. Fisher, Christopher D. Goodman, Tina Skinner-Adams, Darren Do, Andrew J. Lucke, Robert C. Reid, David P. Fairlie, Katherine T. Andrews
Summary: Research has shown that the anticancer drug HDAC inhibitor AR-42 and its 36 analogues have in vitro activity against Plasmodium parasites, with some compounds showing low cytotoxicity to human cells and high selectivity for the parasites. AR-42 induces hyperacetylation of Plasmodium histone H4 by inhibiting PfHDAC(s), effectively blocking parasite growth inside red blood cells and demonstrating curative properties in oral treatment of experimental mouse malaria.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2021)
Article
Medicine, Research & Experimental
Lin Chen, Azeem Alam, Aurelie Pac-Soo, Qian Chen, You Shang, Hailin Zhao, Shanglong Yao, Daqing Ma
Summary: The study found that VPA prevented EMT in a time- and concentration-dependent manner both in vitro and in vivo, leading to improvement in lung structure. Pretreatment with VPA increased the survival rate and prevented weight loss in mice, associated with Smad2/3 deactivation.
LABORATORY INVESTIGATION
(2021)
Article
Pharmacology & Pharmacy
Zhong Li, Jimin Xu, Yuekun Lang, Xiangmeng Wu, Saiyang Hu, Subodh Kumar Samrat, Anil M. Tharappel, Lili Kuo, David Butler, Yongcheng Song, Qing-Yu Zhang, Jia Zhou, Hongmin Li
Summary: Erythrosin B is an effective antiviral against Zika virus both in vitro and in vivo, and its derivatives are non-toxic to human cells.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Medicine, Research & Experimental
Joana Grand-Guillaume, Rosalba Mansi, Raghuvir H. Gaonkar, Sandra Zanger, Melpomeni Fani, Philippe J. Eugster, Maja Beck Popovic, Eric Grouzmann, Karim Abid
Summary: Pharmacological induction of transporters can enhance the uptake of mIBG, improving imaging and therapy of NB and PHEO cells both in vitro and in vivo.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Maria J. Klomp, Leo J. Hofland, Lilian van den Brink, Peter M. van Koetsveld, Fadime Dogan, Corrina M. A. de Ridder, Debra C. Stuurman, Marian C. Clahsen-van Groningen, Marion de Jong, Simone U. Dalm
Summary: The study aimed to enhance the expression of somatostatin type-2 receptors (SSTR2) using valproic acid (VPA) for peptide receptor radionuclide therapy (PRRT). VPA significantly increased SSTR2 expression in vitro, but in vivo, increased tumor uptake of [Lu-177]Lu-DOTATATE was not caused by SSTR2 upregulation but rather by other mechanisms such as increased radiotracer circulation time and renal toxicity.
Article
Pharmacology & Pharmacy
Peiran Song, Gang Bai, Shingpan Chan, Tao Zhang, Linjiang Tong, Yi Su, Yanyan Shen, Yi Chen, Yingqiang Liu, Mengzhen Lai, Yi Ning, Haotian Tang, Yan Fang, Yi Chen, Ke Ding, Jian Ding, Hua Xie
Summary: This study demonstrated that the novel drug ASK120067 exhibited potent anti-tumor activity against B-/T-cell malignancies by targeting BTK/ITK. It inhibited the phosphorylation of BTK and ITK, induced apoptosis in B-lymphoma cells, and caused growth arrest in T-cell leukemia cells. Oral administration of ASK120067 also led to significant tumor regression in xenograft models.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Otorhinolaryngology
D. Bradley Welling, Katharine A. Collier, Sarah S. Burns, Janet L. Oblinger, Edina Shu, Beth A. Miles-Markley, Craig C. Hofmeister, Mina S. Makary, H. Wayne Slone, Jaishri O. Blakeley, S. Alireza Mansouri, Brian A. Neff, Robert K. Jackler, Amir Mortazavi, Long-Sheng Chang
Summary: Two pilot studies of AR-42 in NF2, VS, and meningiomas showed good efficacy and safety. Tumor volumes and growth rates varied in response to treatment. At a 40-mg dose, AR-42 concentrated in tumors and suppressed growth pathways, indicating potential effectiveness.
LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY
(2021)
Article
Infectious Diseases
Snehal Palwe, Yamuna Devi Bakthavatchalam, Kshama Khobragadea, Arun S. Kharat, Kamini Walia, Balaji Veeraraghavan
Summary: This study revealed the development of ceftazidime/avibactam resistance in K. pneumoniae expressing OXA-48-like beta-lactamases, with mutations in proteins associated with efflux, membrane permeability, and stress response pathways. The mutants selected for ceftazidime/avibactam resistance still maintained pathogenicity in mice models, highlighting the need for vigilant monitoring of resistance development in clinical settings. Additional combinations of beta-lactams with beta-lactamase inhibitors or enhancers showed potential for overcoming ceftazidime/avibactam resistance.
Review
Biochemistry & Molecular Biology
Ailin Zhao, Hui Zhou, Jinrong Yang, Meng Li, Ting Niu
Summary: Hematologic malignancies are common and incurable cancers that have been increasing in incidence. The epigenetic regulation, including DNA modifications, histone modifications, and noncoding RNA-mediated targeting, plays a vital role in hematologic oncogenesis. Abnormal methylation profiles and histone deacetylase expression are frequently found in leukemia and lymphoma. Hypomethylating agents and histone deacetylase inhibitors have shown effectiveness in treating certain hematologic malignancies. This review comprehensively discusses the role of epigenetic regulators in normal and oncogenic hematopoiesis and their implications in targeted treatment.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Multidisciplinary Sciences
Thomas Heerde, Matthies Rennegarbe, Alexander Biedermann, Dilan Savran, Peter B. Pfeiffer, Manuel Hitzenberger, Julian Baur, Ioana Puscalau-Girtu, Martin Zacharias, Nadine Schwierz, Christian Haupt, Matthias Schmidt, Marcus Faendrich
Summary: In this study, cryo-electron microscopy and other methods were used to analyze the ability of SAA1.1-derived amyloid fibrils to seed solutions of recombinant SAA1.1 protein. The seeded fibrils were found to remodel the main ex vivo fibril morphology and were more stable than unseeded fibrils.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Yajing Xing, Weikai Guo, Min Wu, Jiuqing Xie, Dongxia Huang, Pan Hu, Miaoran Zhou, Lin Zhang, Qiansen Zhang, Peili Wang, Xin Wang, Guixue Wang, Huangan Wu, Cili Zhou, Yihua Chen, Mingyao Liu, Zhengfang Yi, Zhenliang Sun
Summary: Researchers have identified a small molecule compound named WK500B that can block the inhibition of BCL6, reactivate target genes, kill DLBCL cells, and display strong anti-tumor effects in animal models. Therefore, WK500B holds promise as an effective orally available therapeutic agent for DLBCL.
Article
Biochemistry & Molecular Biology
Jakub Ptacek, Ivan Snajdr, Jiri Schimer, Zsofia Kutil, Jana Mikesova, Petra Baranova, Barbora Havlinova, Werner Tueckmantel, Pavel Majer, Alan Kozikowski, Cyril Barinka
Summary: This article compares hydroxamate-based HDAC6-selective inhibitors commonly used in the treatment of neurological and psychiatric disorders with a novel HDAC6 inhibitor containing the difluoromethyl-1,3,4-oxadiazole function (compound 7). In vitro screening revealed HDAC10 as a primary off-target for hydroxamate-based HDAC6 inhibitors, while compound 7 showed exquisite selectivity over all other HDAC isoforms. Cell-based assays showed lower potency for all compounds when using tubulin acetylation as a surrogate readout. Additionally, the limited selectivity of some HDAC6 inhibitors was shown to be linked to cytotoxicity in RPMI-8226 cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Vikas A. Gupta, Benjamin G. Barwick, Shannon M. Matulis, Ryosuke Shirasaki, David L. Jaye, Jonathan J. Keats, Benjamin Oberlton, Nisha S. Joseph, Craig C. Hofmeister, Leonard T. Heffner, Madhav Dhodapkar, Ajay K. Nooka, Sagar Lonial, Constantine S. Mitsiades, Jonathan L. Kaufman, Lawrence H. Boise
Summary: This study found that Venetoclax sensitivity is closely associated with the expression of B-cell genes and genomic features identified in transposase-accessible chromatin sequencing, and there are potential novel biomarkers associated with Venetoclax sensitivity.
Article
Biochemical Research Methods
Maryam Baniasad, Andrew J. Reed, Stella M. Lai, Liwen Zhang, Kathleen Q. Schulte, Alan R. Smith, Danielle S. LeSassier, Katharina L. Weber, F. Curtis Hewitt, August E. Woerner, Myles W. Gardner, Vicki H. Wysocki, Michael A. Freitas
Summary: The study optimized protein extraction and digestion methods for mass spectrometry-based proteomics analysis of human skin samples. By systematically varying digestion parameters, the study aimed to enhance repeatability and increase the identification of peptides and proteins, particularly genetically variable peptides (GVPs). The research demonstrated the potential for forensic laboratories to employ proteomics sample preparation for GVP analysis to facilitate human identification, complementing traditional DNA profiling methods.
JOURNAL OF PROTEOMICS
(2021)
Article
Biochemistry & Molecular Biology
Liudmila Popova, Prabakaran Nagarajan, Callie M. Lovejoy, Benjamin D. Sunkel, Miranda L. Gardner, Meng Wang, Michael A. Freitas, Benjamin Z. Stanton, Mark R. Parthun
Summary: In this study, it was found that the loss of HAT1 during replication resulted in inaccessibility of specific heterochromatin regions, which make up a significant portion of the genome. Additionally, HAT1 was shown to have a global repression effect on H3 K9 me3 levels and overlap with a subset of Lamin-Associated Domains.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Felice Pepe, Laura Z. Rassenti, Yuri Pekarsky, Jadwiga Labanowska, Tatsuya Nakamura, Giovanni Nigita, Thomas J. Kipps, Veronica Balatti, Carlo M. Croce
Summary: Chronic lymphocytic leukemia (CLL) is a common adult leukemia characterized by chromosomal aberrations. This study found that some CLL patients have undetected microdeletions, which are closely associated with chromosomal alterations in cancer. These findings may have clinical relevance for successful stratification of patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Aleksandra Adamovich, Mariame Diabate, Tapahsama Banerjee, Gregory Nagy, Nahum Smith, Kathryn Duncan, Erika Mendoza Mendoza, Gisselle Prida, Michael A. Freitas, Lea M. Starita, Jeffrey D. Parvin
Summary: Pathogenic variants in BRCA1 are associated with an increased risk of hereditary breast and ovarian cancer. This study used functional assays to evaluate a large number of BRCA1 variants, finding consistent results in terms of repair function and drug resistance. These results are valuable for characterizing variants that are individually detected too infrequently in the population.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Oncology
Ajay K. Nooka, Uma Shanmugasundaram, Narayana Cheedarla, Hans Verkerke, Venkata V. Edara, Rajesh Valanparambil, Jonathan L. Kaufman, Craig C. Hofmeister, Nisha S. Joseph, Sagar Lonial, Maryam Azeem, Julia Manalo, Jeffrey M. Switchenko, Andres Chang, Susanne L. Linderman, John D. Roback, Kavita M. Dhodapkar, Rafi Ahmed, Mehul S. Suthar, Andrew S. Neish, Madhav Dhodapkar
Summary: For patients with multiple myeloma, the ability of vaccine-induced antibodies to neutralize SARS CoV-2 or its variants varies and may be influenced by factors such as race, disease, and treatment.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Matthew S. Conrad, Miranda L. Gardner, Christine Miguel, Michael A. Freitas, Kara M. Rood, Marwan Ma'ayeh
Summary: Fetal growth restriction and pre-eclampsia alter the structure and composition of the umbilical cord, with significant differences in proteins related to extracellular matrix, cellular process, inflammation, and angiogenesis pathways. Further research on these protein differences may help identify therapeutic targets for FGR and FGR with PreE.
Article
Biochemical Research Methods
Gordon T. Luu, Michael A. Freitas, Itzel Lizama-Chamu, Catherine S. McCaughey, Laura M. Sanchez, Mingxun Wang
Summary: In this paper, we present TIMSCONVERT, a high-throughput data conversion workflow that converts timsTOF Pro/fleX mass spectrometer raw data files to mzML and imzML formats while incorporating ion mobility data and maintaining compatibility with popular data analysis tools.
Article
Genetics & Heredity
August E. Woerner, Benjamin Crysup, F. Curtis Hewitt, Myles W. Gardner, Michael A. Freitas, Bruce Budowle
Summary: Forensic genetic investigations often rely on DNA analysis, but when the DNA is limited, protein can be used as an alternative target. However, interpreting protein polymorphisms in a forensic context requires addressing certain complexities. This study presents a novel approach that converts genomic information into proteomic information to overcome these complexities. The results show that this method performs well in simulated samples.
FORENSIC SCIENCE INTERNATIONAL-GENETICS
(2022)
Letter
Oncology
Michael Slade, Thomas G. Martin, Nitya Nathwani, Mark A. Fiala, Michael P. Rettig, Feng Gao, Abhinav Deol, Francis K. Buadi, Jonathan L. Kaufman, Craig C. Hofmeister, Tara K. Gregory, Jesus Berdeja, Ajai Chari, Ashley Rosko, Ravi Vij
Biographical-Item
Oncology
Gary S. Stein, Carlo M. Croce
Article
Oncology
Alessandro La Ferlita, Nipin Sp, Marina Goryunova, Giovanni Nigita, Raphael E. Pollock, Carlo M. Croce, Joal D. Beane
Summary: Soft-tissue sarcomas (STS), a rare and diverse group of tumors, have various subtypes characterized by differences in tumor biology and clinical outcomes. Small non-coding RNAs (sncRNAs), including miRNAs and tRNA-derived ncRNAs, play important roles in STS tumorigenesis and differentiation. However, the translation of these findings into clinical applications, such as biomarkers or therapeutic targets, remains challenging. This review summarizes the current understanding of sncRNAs in STS, with a focus on liposarcoma, and discusses their potential as novel biomarkers and therapeutic targets.
MOLECULAR CANCER RESEARCH
(2023)
Letter
Oncology
Kathryn T. T. Maples, Kevin H. H. Hall, Nisha S. S. Joseph, Craig C. C. Hofmeister, Vikas Gupta, Madhav V. V. Dhodapkar, Jonathan L. L. Kaufman, Ajay K. K. Nooka, Sagar Lonial
BLOOD CANCER JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Henry R. Kilgore, Peter G. Mikhael, Kalon J. Overholt, Ann Boija, Nancy M. Hannett, Catherine Van Dongen, Tong Ihn Lee, Young-Tae Chang, Regina Barzilay, Richard A. Young
Summary: This research reveals that different types of intracellular condensates have distinct chemical environments that affect molecular distribution. Machine learning approaches can predict the selective partitioning of molecules in condensates, providing insights for the development of small molecule therapeutics with optimal subcellular distribution and therapeutic benefits.
NATURE CHEMICAL BIOLOGY
(2023)
Letter
Oncology
Sara A. Scott, Ellen M. Marin, Kathryn T. Maples, Nisha S. Joseph, Craig C. Hofmeister, Vikas A. Gupta, Madhav V. Dhodapkar, Jonathan L. Kaufman, Sagar Lonial, Ajay K. Nooka
BLOOD CANCER JOURNAL
(2023)