Article
Oncology
Adar Yaacov, Oriya Vardi, Britny Blumenfeld, Avraham Greenberg, Dashiell J. Massey, Amnon Koren, Sheera Adar, Itamar Simon, Shai Rosenberg
Summary: This study systematically analyzed the mutational landscape of tumors and identified the association between mutational processes and replication timing. A novel method was developed to improve understanding of the etiology of mutational signatures.
Article
Oncology
Mikko Loukovaara, Annukka Pasanen, Ralf Butzow
Summary: The study suggests that MMR protein and MLH1 methylation status can predict the response to adjuvant therapy in endometrial cancer. Whole pelvic radiotherapy and chemotherapy combined with radiotherapy were associated with improved disease-specific survival in certain subgroups, while they were associated with poor disease-specific survival in other subgroups.
Article
Oncology
Katharina Ulreich, May-Britt Firnau, Nina Tagscherer, Sandra Beyer, Anne Ackermann, Guido Plotz, Angela Brieger
Summary: High nuclear/cytoplasmic expression of CK2 alpha in colorectal cancer correlates with enhanced MLH1 phosphorylation and may cause increased mutation rates. These findings suggest important new therapeutic targets.
Article
Oncology
Michael D. Toboni, Sharon Wu, Alex Farrell, Joanne Xiu, Jennifer R. Ribeiro, Matthew J. Oberley, Rebecca Arend, Britt K. Erickson, Thomas J. Herzog, Premal H. Thaker, Matthew A. Powell
Summary: This study aims to identify differential survival outcomes and immune checkpoint inhibitor response in MLH1 hypermethylated versus MLH1 mutated endometrial tumors and determine whether their molecular profiles can elucidate the differential outcomes.
GYNECOLOGIC ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Melania Scarpa, Cesare Ruffolo, Andromachi Kotsafti, Fabio Canal, Francesca Erroi, Silvia Basato, Lucia Dall'Agnese, Alain Fiorot, Anna Pozza, Paola Brun, Nicolo Bassi, Angelo Dei Tos, Carlo Castoro, Ignazio Castagliuolo, Marco Scarpa
Summary: Research has shown that patients with MMR-deficient colorectal cancer have a more favorable prognosis, possibly due to the interplay between MMR genes and TLR4/MyD88 signaling, with TLR4 expression depending on MMR status and correlating directly with MLH1 expression.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Oncology
Camille Evrard, Jerome Alexandre
Summary: Endometrial cancers are highly affected by microsatellite instability, showing sensitivity to immunotherapy and requiring molecular biology for better understanding. The phenotype is poorly understood in ovarian cancer but does exist. Examination of literature reveals the importance of deficient mismatch repair/microsatellite instability in gynecological cancers and the potential therapeutic and prognostic implications.
Article
Biochemistry & Molecular Biology
Katja Kratz, Mariela Artola-Boran, Saho Kobayashi-Era, Gene Koh, Goncalo Oliveira, Shunsuke Kobayashi, Andreia Oliveira, Xueqing Zou, Julia Richter, Masataka Tsuda, Hiroyuki Sasanuma, Shunichi Takeda, Joanna Loizou, Alessandro A. Sartori, Serena Nik-Zainal, Josef Jiricny
Summary: A study revealed a new exonuclease, FAN1, which can efficiently substitute for EXO1 in the mismatch repair process, with its functional complementation modulated by its interaction with MLH1. Loss of FAN1 exacerbates the mutational profile of EXO1-deficient cells, suggesting redundant action of these two nucleases in the same antimutagenic pathway.
MOLECULAR AND CELLULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Antonio Porro, Mohiuddin Mohiuddin, Christina Zurfluh, Vincent Spegg, Jingqi Dai, Florence Iehl, Virginie Ropars, Giulio Collotta, Keri M. Fishwick, Nour L. Mozaffari, Raphael Guerois, Josef Jiricny, Matthias Altmeyer, Jean-Baptiste Charbonnier, Christopher E. Pearson, Alessandro A. Sartori
Summary: The FAN1-MLH1 complex plays a crucial role in the response to ICL damage and repeat stability, with specific amino acid residues identified as critical for MLH1 binding. Disruption of the FAN1-MLH1 interaction may lead to cellular hypersensitivity to ICL damage and defective repair of CAG/CTG slip-outs.
Article
Medicine, General & Internal
Masanao Kaneko, Mitsuko Nakashima, Kiichi Sugiura, Natsuki Ishida, Satoshi Tamura, Shinya Tani, Mihoko Yamade, Yasushi Hamaya, Satoshi Osawa, Kyota Tatsuta, Kiyotaka Kurachi, Satoshi Baba, Yuji Iwashita, Tomio Arai, Haruhiko Sugimura, Masato Maekawa, Ken Sugimoto, Moriya Iwaizumi
Summary: This study aimed to understand the histopathological characteristics of colorectal cancers (CRC) that exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. The findings showed that medullary carcinomas have unique characteristics of harboring the BRAFV600E mutation and expressing dMLH1.
Article
Pathology
Lindsay E. Borden, Tonja M. Locklear, Douglas J. Grider, Janet L. Osborne, Erin J. Saks, Fidel A. Valea, David A. Iglesias
Summary: The study found that patients with hMLH1+ endometrial cancer are typically older, exhibit higher histological grades and presence of lymphovascular space invasion, and are more likely to receive adjuvant treatment. Even in patients traditionally considered low risk for recurrence, early stage hMLH1+ patients are more likely to recur.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2022)
Article
Oncology
Rachel Hodan, Kerry Kingham, Kristina Cotter, Ann K. Folkins, Allison W. Kurian, James M. Ford, Teri Longacre
Summary: This study found that 5.2% of primary ovarian cancer patients had MMR-D, with the majority being endometrioid cancer. The incidence of LS was 66.6% in women with ovarian cancer suggestive of LS.
Article
Oncology
Daniele Fanale, Lidia Rita Corsini, Chiara Brando, Alessandra Dimino, Clarissa Filorizzo, Luigi Magrin, Roberta Sciacchitano, Alessia Fiorino, Tancredi Didier Bazan Russo, Valentina Calo, Juan Lucio Iovanna, Edoardo Francini, Antonio Russo, Viviana Bazan
Summary: Lynch syndrome is a genetic condition associated with an increased predisposition to colorectal cancer and other tumors. The most efficient strategy to identify patients with this syndrome is still unclear. A study found that analyzing tissue microsatellite instability according to the revised Bethesda guidelines is the best selection approach, but using different selection methods as complementary strategies helps reduce underdiagnosis.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Maria Ovejero-Sanchez, Rogelio Gonzalez-Sarmiento, Ana Belen Herrero
Summary: This article reviews the alterations in DNA damage response (DDR) pathways in ovarian cancer (OC), and the therapeutic potential of targeting the DDR for the treatment of OC. Failures in DDR have been associated with the development, progression, and chemoresistance of OC. Defects in DNA repair pathways, such as DNA double-strand break repair by homologous recombination and ARID1A mutations, have been found in different OC subtypes. Preclinical and clinical studies have shown promise in targeting the DDR to fight OC.
Article
Biochemistry & Molecular Biology
Christopher D. Putnam, Richard D. Kolodner
Summary: MutL family proteins have a conserved structure and mediate DNA mismatch repair. The function of the endonuclease active site and the role of the linker motif in regulating the activity are not well understood. This study proposes that the inhibitory cysteine in the FERC sequence sequesters the active site and suggests a functional interaction between the conserved linker motif and the FERC sequence.
Article
Cell Biology
Mukta Basu, Debalina Mukhopadhyay, Balarko Chakraborty, Sabnam Ghosh, Dilip Kumar Pal, Amlan Ghosh, Chinmay Kumar Panda
Summary: This study aimed to investigate the crosstalk between mismatch repair (MMR) and FA-BRCA pathways and found their importance in the early pathogenesis of primary bladder carcinoma. The genetic alterations of MMR-related genes MLH1 and MSH2 were found to be correlated with the nuclear translocation of FANCD2 protein. Furthermore, inefficiency of MMR proteins in chemotolerant cells was found to restrict FANCD2 nuclear translocation.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Microbiology
Jun Zhang, Jian Chen, Yi-Fei Wu, Zi-Ping Wang, Ji-Guo Qiu, Xiao-Long Li, Feng Cai, Ke-Qing Xiao, Xiao-Xu Sun, Barry P. Rosen, Fang-Jie Zhao
Summary: Arsenic can be biomethylated to form various organic arsenicals with different toxicities and environmental mobilities. The trivalent methylarsenite (MAs(III)) produced in this process is more toxic than inorganic arsenite (As(III) and can also act as a primitive antibiotic. A new enzyme, ArsV, has been identified in Ensifer adhaerens ST2, which plays a role in detoxifying MAs(III) and Sb(III) by oxidizing them to MAs(V) and Sb(V). Genes encoding ArsV are widely present in soil bacteria according to metagenomic analysis.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Microbiology
Jian Chen, Jun Zhang, Barry P. Rosen
Summary: Organoarsenicals enter the environment from biogenic and anthropogenic sources. Microorganisms can methylate trivalent inorganic arsenite to more toxic methylarsenite and oxidize them. Sources include herbicides and antimicrobial growth promoters, with microorganisms such as Sphingobacterium wenxiniae showing resistance and detoxification abilities.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Review
Environmental Sciences
Xi-Mei Xue, Chan Xiong, Masafumi Yoshinaga, Barry Rosen, Yong-Guan Zhu
Summary: This review summarizes the classification, identification, and toxicological properties of organoarsenicals in the environment. The toxicological properties and biological functions of most organoarsenicals are still largely unknown.
CRITICAL REVIEWS IN ENVIRONMENTAL SCIENCE AND TECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ngozi P. Paul, Adriana E. Galvan, Kunie Yoshinaga-Sakurai, Barry P. Rosen, Masafumi Yoshinaga
Summary: Arsenicals, one of the oldest treatments for various human disorders, have been paradoxically used as therapeutic agents since ancient times despite their toxicity. After the discovery of antibiotics, most arsenic-based drugs were abandoned, but recent years have seen a renewed interest in their clinical use. The current applications of arsenicals include antimicrobial, antiviral, antiparasitic, and anticancer uses. With the rise of antibiotic resistance and emerging pathogens, revisiting arsenicals as an effective treatment option is suggested.
Article
Genetics & Heredity
Amy Finch, Kelly Metcalfe, Mohammad Akbari, Eitan Friedman, Nadine Tung, Barry Rosen, Andrea Eisen, Beth Karlan, William Foulkes, Susan L. Neuhausen, Leigha Senter, Wendy McKinnon, Christine Elser, Ping Sun, Steven A. Narod
Summary: Approximately 1% of the Ashkenazi Jewish population carries the BRCA2 6174delT pathogenic variant, which is associated with the risks of breast and ovarian cancer. Women carrying the 6174delT variant have a significantly lower annual risk for developing breast cancer compared to those carrying other variants in the BRCA2 gene, but the difference in ovarian or fallopian tube cancer risk is not significant.
Article
Microbiology
Jun Zhang, Jian Chen, Yi-Fei Wu, Xia Liu, Charles Packianathan, Venkadesh S. Nadar, Barry P. Rosen, Fang-Jie Zhao
Summary: This study identified an arsRM operon in Noviherbaspirillum denitrificans HC18, which can detoxify MAs(III) via further methylation.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Review
Medicine, General & Internal
Y. Tong, E. Orang'o, M. Nakalembe, P. Tonui, P. Itsura, K. Muthoka, M. Titus, S. Kiptoo, A. Mwangi, J. Ong'echa, R. Tonui, B. Odongo, C. Mpamani, B. Rosen, A. Moormann, S. Cu-Uvin, J. A. Bailey, C. Oduor, A. Ermel, C. Yiannoutsos, B. Musick, E. Sang, A. Ngeresa, G. Banturaki, A. Kiragga, J. Zhang, Y. Song, S. Chintala, R. Katzenellenbogen, P. Loehrer, D. R. Brown
Summary: The East Africa Consortium was established to study the epidemiology of HPV infections and cervical cancer, as well as the influence of HIV infection on HPV and cervical cancer. Collaborations between researchers in North America and East African countries have led to a better understanding of the impact of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on HPV detection, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia. Future research will focus on how HPV testing can be integrated into cervical cancer screening programs, the influence of aflatoxin on the immunological control of HIV, and how HPV alters certain genes involved in tumor growth in HIV-infected women.
ANNALS OF MEDICINE
(2022)
Article
Oncology
Joanne Kotsopoulos, Jan Lubinski, Jacek Gronwald, Janusz Menkiszak, Jeanna McCuaig, Kelly Metcalfe, William D. Foulkes, Susan L. Neuhausen, Sophie Sun, Beth Y. Karlan, Andrea Eisen, Nadine Tung, Olufunmilayo Olopade, Fergus J. Couch, Tomasz Huzarski, Leigha Senter, Louise Bordeleau, Christian F. Singer, Charis Eng, Robert Fruscio, Tuya Pal, Ping Sun, Steven A. Narod
Summary: The study suggests that bilateral oophorectomy is unlikely to determine the risk of breast cancer in BRCA1 mutation carriers, but it should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Microbiology
Jun Zhang, Yan-Ning Li, Jian Chen, Yu Yan, Barry P. Rosen, Fang-Jie Zhao
Summary: This study investigates the molecular mechanisms behind the MAs(III) resistance of Ensifer adhaerens ST2. The results show that the gene arsZ encodes a novel MAs(III) oxidase, which oxidizes highly toxic MAs(III) to relatively nontoxic MAs(V) and confers resistance.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Microbiology
Jian Chen, Adriana E. Galvan, Venkadesh Sarkarai Nadar, Masafumi Yoshinaga, Barry P. Rosen
Summary: Arsenic resistance operons encode genes for arsenic resistance and biotransformation. Fusion of ars genes is not uncommon, and a four-gene operon with two fused arsR-arsC genes has been identified. This fusion mechanism overcomes the limitation of inducers and provides an evolutionary advantage for detoxification of inorganic arsenate.
ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Microbiology
Yi-Fei Wu, Jian Chen, Wan-Ying Xie, Chao Peng, Shi-Tong Tang, Barry P. P. Rosen, Andreas Kappler, Jun Zhang, Fang-Jie Zhao
Summary: We isolated a photosynthetic purple bacteria, Rhodobacter strain CZR27, from an arsenic-contaminated paddy soil and demonstrated its capacity to oxidize As(III) to As(V) using malate as a carbon source photosynthetically. Our study revealed the presence of anaerobic photosynthesis-coupled As(III) oxidation in paddy soils, highlighting the importance of light-dependent, microbe-mediated arsenic redox changes in paddy arsenic biogeochemistry.
ENVIRONMENTAL MICROBIOLOGY
(2023)
Article
Engineering, Environmental
Jian Chen, Barry P. Rosen
Summary: In this study, the broad diversity of structural domains in ArsMs was revealed through comparative analysis. The differences in the ArsM structure lead to variations in methylation efficiency and substrate selectivity. The C-terminal domain was found to play a role in modulating the rate of catalysis. Additionally, the relationship between arsenite efflux systems and methylation was examined.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ngozi P. P. Paul, Thiruselvam Viswanathan, Jian Chen, Masafumi Yoshinaga, Barry P. P. Rosen
Summary: AST is a pentavalent organoarsenical synthesized by Burkholderia gladioli GSRB05, which is effective against carbapenem-resistant Enterobacter cloacae. It inhibits bacterial glutamine synthetase and is a non-proteogenic amino acid and glutamate mimetic. ArsQ is an efflux permease that is proposed to transport AST or related species out of the cells, but the chemical nature of the actual transport substrate is unclear.
MOLECULAR MICROBIOLOGY
(2023)
Article
Microbiology
Masafumi Yoshinaga, Guodong Niu, Kunie Yoshinaga-Sakurai, Venkadesh S. S. Nadar, Xiaohong Wang, Barry P. P. Rosen, Jun Li
Summary: Malaria caused by Plasmodium parasites is a major disease with high morbidity and mortality rates. The Plasmodium parasite has a complex life cycle involving both human and mosquito hosts. Most current antimalarials only target the blood stage of the parasite, requiring the development of new drugs that can target multiple stages of the life cycle.
Article
Engineering, Environmental
Shi-Tong Tang, Xin-Wei Song, Jian Chen, Jie Shen, Bin Ma, Barry P. Rosen, Jun Zhang, Fang-Jie Zhao
Summary: This study identified a previously unknown gene, arsO, which encodes an enzyme called ArsO that oxidizes Sb(III) to Sb(V) under aerobic conditions. The enzyme plays a significant role in the detoxification of Sb(III) in the environment. The arsO gene is widely distributed and abundant in various environments affected by human activities.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
