Use the keywords feature with a free QxMD account.
Use Read by QxMD to access full text via your institution or open access sources.
Read also provides personalized recommendations to keep you up to date in your field.
Existing User
Sign InNew to Read
Sign Up#61
JOURNAL ARTICLE
Xiao-Hong Ding, Yi Xiao, Fenfang Chen, Cheng-Lin Liu, Tong Fu, Zhi-Ming Shao, Yi-Zhou Jiang
Breast cancer is a highly heterogeneous disease with varied subtypes, prognoses and therapeutic responsiveness. Human leukocyte antigen class I (HLA-I) shapes the immunity and thereby influences the outcome of breast cancer. However, the implications of HLA-I variations in breast cancer remain poorly understood. In this study, we established a multiomics cohort of 1156 Chinese breast cancer patients for HLA-I investigation. We calculated four important HLA-I indicators in each individual, including HLA-I expression level, somatic HLA-I loss of heterozygosity (LOH), HLA-I evolutionary divergence (HED) and peptide-binding promiscuity (Pr)...
March 27, 2024: Briefings in Bioinformatics
#62
JOURNAL ARTICLE
John Alexander, Koen Schipper, Sarah Nash, Rachel Brough, Harriet Kemp, Jacopo Iacovacci, Clare Isacke, Rachael Natrajan, Elinor Sawyer, Christopher J Lord, Syed Haider
BACKGROUND: Invasive Lobular Carcinoma (ILC) is a morphologically distinct breast cancer subtype that represents up to 15% of all breast cancers. Compared to Invasive Breast Carcinoma of No Special Type (IBC-NST), ILCs exhibit poorer long-term outcome and a unique pattern of metastasis. Despite these differences, the systematic discovery of robust prognostic biomarkers and therapeutically actionable molecular pathways in ILC remains limited. METHODS: Pathway-centric multivariable models using statistical machine learning were developed and tested in seven retrospective clinico-genomic cohorts (n = 996)...
April 10, 2024: British Journal of Cancer
#63
JOURNAL ARTICLE
Kevin M Cottrell, Kimberly J Briggs, Douglas A Whittington, Haris Jahic, Janid A Ali, Charles B Davis, Shanzhong Gong, Deepali Gotur, Lina Gu, Patrick McCarren, Matthew R Tonini, Alice Tsai, Erik W Wilker, Hongling Yuan, Minjie Zhang, Wenhai Zhang, Alan Huang, John P Maxwell
It has been shown that PRMT5 inhibition by small molecules can selectively kill cancer cells with homozygous deletion of the MTAP gene if the inhibitors can leverage the consequence of MTAP deletion, namely, accumulation of the MTAP substrate MTA. Herein, we describe the discovery of TNG908, a potent inhibitor that binds the PRMT5·MTA complex, leading to 15-fold-selective killing of MTAP -deleted (MTAP-null) cells compared to MTAP intact (MTAP WT) cells. TNG908 shows selective antitumor activity when dosed orally in mouse xenograft models, and its physicochemical properties are amenable for crossing the blood-brain barrier (BBB), supporting clinical study for the treatment of both CNS and non-CNS tumors with MTAP loss...
April 10, 2024: Journal of Medicinal Chemistry
#64
JOURNAL ARTICLE
Vinod Ravasaheb Shinde, Ajinkya Thanekar, Sajmina Khatun, Hima Sree Buddhiraju, Basu Bhattacharjee, Aravind Kumar Rengan
Melanoma is one of the most aggressive and lethal types of cancer owing to its metastatic propensity and chemoresistance property. An alternative therapeutic option is Photodynamic and Photothermal Therapies (PDT/PTT), which employ near-infrared light to generate heat and Reactive Oxygen Species (ROS). As per previous reports, Melanin and its synthetic analogs (i.e., polydopamine nanoparticles) can induce near-infrared (NIR) light-mediated heat energy, thereby selectively targeting and ameliorating cancer cells...
April 9, 2024: Nanotechnology
#65
JOURNAL ARTICLE
Gabriele Picco, Yanhua Rao, Angham Al Saedi, Yang Lee, Sara F Vieira, Shriram Bhosle, Kieron May, Carmen Herranz-Ors, Samantha J Walker, Raynold Shenje, Cansu Dincer, Freddy Gibson, Ruby Banerjee, Zoe Hewitson, Thilo Werner, Joshua E Cottom, Yang Peng, Nanhua Deng, Philip Landis, Daniela Conticelli, Katrina McCarten, Jacob Bush, Mamta Sharma, Howard Lightfoot, David House, Emma Milford, Emma K Grant, Michal P Glogowski, Craig D Wagner, Marcus Bantscheff, Anna Rutkowska-Klute, Cell Model Network Uk Group, Francesca Zappacosta, Jonathan Pettinger, Syd Barthorpe, H Christian Eberl, Brian T Jones, Jessica L Schneck, Dennis J Murphy, Emile E Voest, Joshua P Taygerly, Michael P DeMartino, Matthew A Coelho, Jonathan Houseley, Geeta Sharma, Benjamin J Schwartz, Mathew J Garnett
Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n-dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumours, and WRN inhibitors are in development. Here, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth In vitro and In vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA-repeats and DNA damage...
April 9, 2024: Cancer Discovery
#66
Kyle B Williams, Alex T Larsson, Bryant J Keller, Katherine E Chaney, Rory L Williams, Minu M Bhunia, Garrett M Draper, Tyler A Jubenville, Sue K Rathe, Christopher L Moertel, Nancy Ratner, David A Largaespada
Neurofibromatosis Type 1 (NF1) is a common cancer predisposition syndrome, caused by heterozygous loss of function mutations in the tumor suppressor gene NF1 . Individuals with NF1 develop benign tumors of the peripheral nervous system (neurofibromas), originating from the Schwann cell linage after somatic loss of the wild type NF1 allele, some of which progress further to malignant peripheral nerve sheath tumors (MPNST). There is only one FDA approved targeted therapy for symptomatic plexiform neurofibromas and none approved for MPNST...
March 25, 2024: bioRxiv
#67
JOURNAL ARTICLE
William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John J Krais, Yifan Wang, Umeshkumar M Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang S Chen, Richard T Pomerantz
The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC50 that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism...
April 5, 2024: Nature Communications
#68
JOURNAL ARTICLE
D Lucas Kane, Brendan Burke, Monica Diaz, Christian Wolf, William A Fonzi
The destructive impact of fungi in agriculture and animal and human health, coincident with increases in antifungal resistance, underscores the need for new and alternative drug targets to counteract these trends. Cellular metabolism relies on many intermediates with intrinsic toxicity and promiscuous enzymatic activity generates others. Fuller knowledge of these toxic entities and their generation may offer opportunities of antifungal development. From this perspective our observation of media-conditional lethal metabolism in respiratory mutants of the opportunistic fungal pathogen Candida albicans was of interest...
2024: PloS One
#69
REVIEW
Kyle D Reichl, Esther C Y Lee, Ariamala Gopalsamy
INTRODUCTION: The multi-subunit SWI/SNF chromatin remodeling complex is a key epigenetic regulator for many cellular processes, and several subunits are found to be mutated in human cancers. The inactivating mutations of SMARCA4, the ATPase subunit of the complex, result in cellular dependency on the paralog SMARCA2 for survival. This observed synthetic lethal relationship posits targeting SMARCA2 in SMARCA4-deficient settings as an attractive therapeutic target in oncology. AREAS COVERED: This review covers patent literature disclosed during the 2019-30 June 2023 period which claim ATPase inhibitors and PROTAC degraders that bind to the ATPase domain of SMARCA2 and/or SMARCA4...
April 5, 2024: Expert Opinion on Therapeutic Patents
#70
REVIEW
Sonja Billerbeck, Roy S K Walker, Isak S Pretorius
Killer yeasts secrete protein toxins that are selectively lethal to other yeast and filamentous fungi. These exhibit exceptional genetic and functional diversity, and have several biotechnological applications. However, despite decades of research, several limitations hinder their widespread adoption. In this perspective we contend that technical advances in synthetic biology present an unprecedented opportunity to unlock the full potential of yeast killer systems across a spectrum of applications. By leveraging these new technologies, engineered killer toxins may emerge as a pivotal new tool to address antifungal resistance and food security...
April 3, 2024: Trends in Biotechnology
#71
REVIEW
Camille Voros, José Dias, Christopher M Timperley, Florian Nachon, Richard C D Brown, Rachid Baati
The first organophosphorus nerve agent was discovered accidently during the development of pesticides, shortly after the first use of chemical weapons (chlorine, phosgene) on the battlefield during World War I. Despite the Chemical Weapons Convention banning these substances, they have still been employed in wars, terrorist attacks or political assassinations. Characterised by their high lethality, they target the nervous system by inhibiting the acetylcholinesterase (AChE) enzyme, preventing neurotransmission, which, if not treated rapidly, inevitably leads to serious injury or the death of the person intoxicated...
April 2, 2024: Chemico-biological Interactions
#72
JOURNAL ARTICLE
Cicera Maria de Oliveira Xavier, Eduardo Henrique Amorim Silva, Ivaldo Victor Mota de Siqueira, Lucia Oliveira de Macedo, Vanderson Barbosa Bernardo, Henrique Fonseca Goulart, Antônio Euzébio Goulart Santana, Rafael Antonio Nascimento Ramos, Pedro Gregório Vieira Aquino, Gílcia Aparecida de Carvalho
PURPOSE: Rhipicephalus (Boophilus) microplus is one the most significant ectoparasite in cattle farming in tropical and subtropical regions, causing problems to livestock health worldwide. The control of this ectoparasite primarily relies on the use of synthetic acaricides. However, the emergence of acaricide resistance has stimulated the search for new control alternatives, including phytocompounds with acaricidal and insecticidal potential. The aim of this study was to evaluate the acaricidal potential of Lavandula dentata essential oil against the engorged females of R...
April 3, 2024: Acta Parasitologica
#73
Caleb Cheng, Jing Hu, Rahul Mannan, Rupam Bhattacharyya, Nicholas J Rossiter, Brian Magnuson, Jasmine P Wisniewski, Yang Zheng, Lanbo Xiao, Chungen Li, Dominik Awad, Tongchen He, Yi Bao, Yuping Zhang, Xuhong Cao, Zhen Wang, Rohit Mehra, Pietro Morlacchi, Vaibhav Sahai, Marina Pasca di Magliano, Yatrik M Shah, Ke Ding, Yuanyuan Qiao, Costas A Lyssiotis, Arul M Chinnaiyan
Pancreatic ductal adenocarcinoma (PDAC) subsists in a nutrient-deregulated microenvironment, making it particularly susceptible to treatments that interfere with cancer metabolism 1 2 . For example, PDAC utilizes and is dependent on high levels of autophagy and other lysosomal processes 3-5 . Although targeting these pathways has shown potential in preclinical studies, progress has been hampered by the challenge of identifying and characterizing favorable targets for drug development 6 . Here, we characterize PIKfyve, a lipid kinase integral to lysosomal functioning 7 , as a novel and targetable vulnerability in PDAC...
March 20, 2024: bioRxiv
#74
Jean Ching-Yi Tien, Yu Chang, Yuping Zhang, Jonathan Chou, Yunhui Cheng, Xiaoju Wang, Jianzhang Yang, Rahul Mannan, Palak Shah, Xiao-Ming Wang, Abigail J Todd, Sanjana Eyunni, Caleb Cheng, Ryan J Rebernick, Lanbo Xiao, Yi Bao, James Neiswender, Rachel Brough, Stephen J Pettitt, Xuhong Cao, Stephanie J Miner, Licheng Zhou, Yi-Mi Wu, Estefania Labanca, Yuzhuo Wang, Abhijit Parolia, Marcin Cieslik, Dan R Robinson, Zhen Wang, Felix Y Feng, Christopher J Lord, Ke Ding, Arul M Chinnaiyan
Biallelic loss of cyclin-dependent kinase 12 ( CDK12 ) defines a unique molecular subtype of metastatic castration-resistant prostate cancer (mCRPC). It remains unclear, however, whether CDK12 loss per se is sufficient to drive prostate cancer development-either alone, or in the context of other genetic alterations-and whether CDK12 -mutant tumors exhibit sensitivity to specific pharmacotherapies. Here, we demonstrate that tissue-specific Cdk12 ablation is sufficient to induce preneoplastic lesions and robust T cell infiltration in the mouse prostate...
March 21, 2024: bioRxiv
#75
Shaonil Binti, Phil T Edeen, David S Fay
The conserved C. elegans protein kinases NEKL-2 and NEKL-3 regulate multiple steps of membrane trafficking and are required for larval molting. Through a forward genetic screen we identified a loss-of-function mutation in catp-1 as a suppressor of molting defects in synthetically lethal nekl-2; nekl-3 double mutants. catp-1 is predicted to encode a membrane- associated P4-type ATPase involved in Na + -K + exchange. Moreover, a mutation predicted to abolish CATP-1 ion-pump activity also suppressed nekl-2; nekl-3 mutants...
March 20, 2024: bioRxiv
#76
JOURNAL ARTICLE
Feng Liu, Minhang Xin, Huiheng Feng, Wentao Zhang, Ziyan Liao, Tao Sheng, Ping Wen, Qing Wu, Tingxizi Liang, Jiaqi Shi, Ruyi Zhou, Kaixin He, Zhen Gu, Hongjun Li
Although CRISPR-mediated genome editing holds promise for cancer therapy, inadequate tumor targeting and potential off-target side effects hamper its outcomes. In this study, we present a strategy using cryo-shocked lung tumor cells as a CRISPR-Cas9 delivery system for cyclin-dependent kinase 4 ( CDK4 ) gene editing, which initiates synthetic lethal in KRAS-mutant non-small cell lung cancer (NSCLC). By rapidly liquid nitrogen shocking, we effectively eliminate the pathogenicity of tumor cells while preserving their structure and surface receptor activity...
March 29, 2024: Science Advances
#77
JOURNAL ARTICLE
Danel Olaverri-Mendizabal, Luis V Valcárcel, Naroa Barrena, Carlos J Rodríguez, Francisco J Planes
Cancer metabolism is a marvellously complex topic, in part, due to the reprogramming of its pathways to self-sustain the malignant phenotype in the disease, to the detriment of its healthy counterpart. Understanding these adjustments can provide novel targeted therapies that could disrupt and impair proliferation of cancerous cells. For this very purpose, genome-scale metabolic models (GEMs) have been developed, with Human1 being the most recent reconstruction of the human metabolism. Based on GEMs, we introduced the genetic Minimal Cut Set (gMCS) approach, an uncontextualized methodology that exploits the concepts of synthetic lethality to predict metabolic vulnerabilities in cancer...
March 27, 2024: Briefings in Bioinformatics
#78
REVIEW
Laetitia Collet, Brunhilde Hanvic, Margherita Turinetto, Isabelle Treilleux, Nicolas Chopin, Olivia Le Saux, Isabelle Ray-Coquard
BRCA1/2 genes are part of homologous recombination (HR) DNA repair pathways in charge of error-free double-strand break (DSB) repair. Loss-of-function mutations of BRCA1/2 genes have been associated for a long time with breast and ovarian cancer hereditary syndrome. Recently, polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) have revolutionized the therapeutic landscape of BRCA1/2 -mutated tumors, especially of BRCA1/2 high-grade serous ovarian cancer (HGSC), taking advantage of HR deficiency through the synthetic lethality concept...
2024: Frontiers in Oncology
#79
JOURNAL ARTICLE
Jingwen Wu, Shuaihui Dang, Yan Zhang, Sha Zhou
The meta-diamide ( m -diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA receptors. In accordance with the principles of drug molecular design, easily derivable sulfur with diverse bioactivities was introduced while leading with the parent Broflanilide. Twelve novel m -diamide target compounds containing sulfide derivatives were synthesized through exploration guided by the literature. Their structures were confirmed by melting points, 1 H NMR, 13 C NMR and HRMS...
March 17, 2024: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
#80
JOURNAL ARTICLE
Shivar Simbu, Ané Orchard, Sandy van Vuuren
Antimicrobial resistance has emerged as a significant threat to public health, prompting novel combinations comprising of natural sources such as essential oil compounds with conventional antibiotics. This study aimed to determine the possible interactions between six essential oil compounds with eight antibiotics/antifungals against six pathogens ( Staphylococcus aureus , Staphylococcus epidermidis , Pseudomonas aeruginosa , Acinetobacter baumannii , Cutibacterium acnes , and Candida albicans ) commonly implicated in skin infections...
March 8, 2024: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Make the most of Read.
Download the mobile app.
Download the mobile app.
Fetching more papers... 
