Article
Pathology
Megumi Nishikubo, Naoe Jimbo, Yugo Tanaka, Motoko Tachihara, Tomoo Itoh, Yoshimasa Maniwa
Summary: The diagnosis of mesothelioma in situ (MIS) is challenging, but genomic analysis can help with diagnosis and prognosis prediction. CDKN2A homozygous deletion and MTAP loss may be poor prognostic factors for the progression of MIS to invasive mesothelioma.
Article
Oncology
Yue Chen, Xuemei Du, Ying Gao, Heliang Wu, Hongyu Zhao, Yandong Su
Summary: This study aims to explore the combination of BAP1 and MTAP in peritoneal mesothelioma and evaluate their diagnostic and prognostic value.
Article
Multidisciplinary Sciences
Patty Sachamitr, Jolene C. Ho, Felipe E. Ciamponi, Wail Ba-Alawi, Fiona J. Coutinho, Paul Guilhamon, Michelle M. Kushida, Florence M. G. Cavalli, Lilian Lee, Naghmeh Rastegar, Victoria Vu, Maria Sanchez-Osuna, Jasmin Coulombe-Huntington, Evgeny Kanshin, Heather Whetstone, Mathieu Durand, Philippe Thibault, Kirsten Hart, Maria Mangos, Joseph Veyhl, Wenjun Chen, Nhat Tran, Bang-Chi Duong, Ahmed M. Aman, Xinghui Che, Xiaoyang Lan, Owen Whitley, Olga Zaslaver, Dalia Barsyte-Lovejoy, Laura M. Richards, Ian Restall, Amy Caudy, Hannes L. Rost, Zahid Quyoom Bonday, Mark Bernstein, Sunit Das, Michael D. Cusimano, Julian Spears, Gary D. Bader, Trevor J. Pugh, Mike Tyers, Mathieu Lupien, Benjamin Haibe-Kains, H. Artee Luchman, Samuel Weiss, Katlin B. Massirer, Panagiotis Prinos, Cheryl H. Arrowsmith, Peter B. Dirks
Summary: The study suggests that PRMT5 inhibitors can block the growth of patient-derived glioblastoma stem cell cultures in vitro and in vivo, indicating that PRMT5 inhibition may be a useful therapeutic strategy.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Yoshiaki Kinoshita, Makoto Hamasaki, Shinji Matsumoto, Masayo Yoshimura, Ayuko Sato, Tohru Tsujimura, Toshiaki Kamei, Kunimitsu Kawahara, Akinori Iwasaki, Kazuki Nabeshima
Summary: NF2 FISH alone or in combination with other diagnostic assays effectively differentiates MPM cells from RMCs in cell blocks prepared from pleural effusions.
CANCER CYTOPATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Simranjit X. Singh, Rui Yang, Kristen Roso, Landon J. Hansen, Changzheng Du, Lee H. Chen, Paula K. Greer, Christopher J. Pirozzi, Yiping He
Summary: This study reveals that the loss of MTAP gene in GBM promotes stemness of tumor cells. By inhibiting purine synthesis, researchers found that low-dose L-Alanosine (ALA) can attenuate the stemness of MTAP-deficient GBM cells by compromising mitochondrial function. Furthermore, ALA is shown to increase sensitivity of GBM cells to temozolomide (TMZ).
Article
Chemistry, Multidisciplinary
Menghua Wang, Katherine S. Ryan
Summary: In this study, two new l-Alanosine-producing strains were discovered through genome mining. These strains lack the aspartate-nitrosuccinate pathway genes found in the original producer and use a unique set of nitrate-nitrite reductases to reduce nitrate instead. The repurposing of enzymes from the nitrogen cycle for specialized metabolite biosynthesis and the potential for the discovery of new nitric-oxide-derived natural products are demonstrated.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Baiqing Tang, Hyung-Ok Lee, Sapna Gupta, Liqun Wang, Alison M. Kurimchak, James S. Duncan, Warren D. Kruger
Summary: MTAP is a key enzyme that converts MTA into methionine, and its inactivation is commonly found in various cancers. Our study confirms that MTAP-deleted cells have increased MTA accumulation and reduced protein sDMAylation. Additionally, we demonstrate that extracellular MTA can inhibit protein sDMAylation, which can affect the function of FUBP proteins.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Oncology
Peter Kalev, Marc L. Hyer, Stefan Gross, Zenon Konteatis, Chi-Chao Chen, Mark Fletcher, Max Lein, Elia Aguado-Fraile, Victoria Frank, Amelia Barnett, Everton Mandley, Joshua Goldford, Yue Chen, Katie Sellers, Sebastian Hayes, Kate Lizotte, Phong Quang, Yesim Tuncay, Michelle Clasquin, Rachel Peters, Jaclyn Weier, Eric Simone, Joshua Murtie, Wei Liu, Raj Nagaraja, Lenny Dang, Zhihua Sui, Scott A. Biller, Jeremy Travins, Kevin M. Marks, Katya Marjon
Summary: In MTAP-deleted cancers, potent MAT2A inhibitors were found to reduce SAM levels and decrease PRMT5 activity, leading to transcriptional perturbations that cause DNA damage and mitotic defects. This provides a rationale for combining MAT2A inhibitors with anti-mitotic drugs for treatment.
Article
Oncology
Qiangsheng Hu, Yi Qin, Shunrong Ji, Xiuhui Shi, Weixing Dai, Guixiong Fan, Shuo Li, Wenyan Xu, Wensheng Liu, Mengqi Liu, Zheng Zhang, Zeng Ye, Zhijun Zhou, Jingxuan Yang, Qifeng Zhuo, Xianjun Yu, Min Li, Xiaowu Xu
Summary: The study reveals that MTAP deficiency drives pancreatic cancer progression by inducing metabolic reprogramming, offering a new target and therapeutic strategy for treating MTAP-deficient disease. The findings also suggest that MTAP status impacts glucose and purine metabolism, identifying multiple novel treatment options against MTAP-deficient pancreatic cancer.
Article
Multidisciplinary Sciences
Omar Alhalabi, Jianfeng Chen, Yuxue Zhang, Yang Lu, Qi Wang, Sumankalai Ramachandran, Rebecca Slack Tidwell, Guangchun Han, Xinmiao Yan, Jieru Meng, Ruiping Wang, Anh G. Hoang, Wei-Lien Wang, Jian Song, Lidia Lopez, Alex Andreev-Drakhlin, Arlene Siefker-Radtke, Xinqiao Zhang, William F. Benedict, Amishi Y. Shah, Jennifer Wang, Pavlos Msaouel, Miao Zhang, Charles C. Guo, Bogdan Czerniak, Carmen Behrens, Luisa Soto, Vassiliki Papadimitrakopoulou, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Jack Lee, Jack Roth, Stephen Swisher, Ignacio Wistuba, John Heymach, Jing Wang, Matthew T. Campbell, Eleni Efstathiou, Mark Titus, Christopher J. Logothetis, Thai H. Ho, Jianjun Zhang, Linghua Wang, Jianjun Gao
Summary: This study demonstrates a synthetic lethal interaction between MTAP(def) and antifolates, and shows that MTAP(def) urothelial carcinoma patients have a higher response rate to pemetrexed.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Julia R. Farkas, Mark Sharobim, Jefree J. Schulte
Summary: This review discusses recent developments in the diagnosis and classification of mesothelioma, including histologic classifications, the use of these classifications and nuclear grading in prognosis, the indispensability of ancillary studies in diagnosis, the application of pleural-based classifications and diagnostic schemes in peritoneal mesothelioma, and the potential for diagnosing in situ mesothelioma.
JOURNAL OF CANCER METASTASIS AND TREATMENT
(2022)
Article
Hematology
Jue Feng, Pei-Feng Hsu, Eduardo Esteva, Rossella Labella, Yueyang Wang, Alireza Khodadadi-Jamayran, Joseph Pucella, Cynthia Z. Liu, Arnaldo A. Arbini, Aristotelis Tsirigos, Stavroula Kousteni, Boris Reizis
Summary: Deletion of the 9p21 locus is associated with reduced survival in cancer patients and can lead to myelodysplastic syndrome/myeloproliferative neoplasm and aberrant bone formation in the bone marrow.
Article
Chemistry, Medicinal
Tuomo Kalliokoski, Henna Kettunen, Esa Kumpulainen, Emilia Kettunen, Gabriel Thieulin-Pardo, Lars Neumann, Maren Thomsen, Ralf Paul, Alina Malyutina, Maria Georgiadou
Summary: This study conducted a structure-based virtual screening on commercially available chemical space, leading to the discovery of two novel MAT2A-inhibitor chemical series. X-ray crystallography confirmed the binding modes of the compounds. Both series exhibited nanomolar activity in the biochemical MAT2A inhibition assay and single-digit micromolar activity in the proliferation assay. These findings and the related structural data could be valuable for drug discovery projects related to MAT2A.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Multidisciplinary Sciences
Santosh Kesari, Feng Wang, Tiffany Juarez, Shashaanka Ashili, C. Pawan K. Patro, Jose Carrillo, Minhdan Nguyen, Judy Truong, Joan Levy, Josh Sommer, Daniel M. Freed, Joanne Xiu, Yuki Takasumi, Eric Bouffet, Jaya M. Gill
Summary: Chordomas are rare tumors that have a high tendency to recur and currently lack effective treatment options. A study found that the drug Pemetrexed, which inhibits enzymes involved in folate metabolism, showed activity against chordomas in preclinical models. Three cases of metastatic chordoma that had poor response to standard therapies showed objective responses when treated with Pemetrexed.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Johanna Rapp, Pascal Rath, Joachim Kilian, Klaus Brilisauer, Stephanie Grond, Karl Forchhammer
Summary: The byproduct 5-Deoxyadenosine is not only an inhibitor of certain enzymes, but can also be used as a growth advantage for organisms to produce antimicrobial and herbicidal compounds from primary metabolism. This challenges the traditional view of bioactive molecules as products of secondary metabolite gene clusters and expands the range of compounds that microorganisms can deploy to compete for ecological niches.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)