keyword
https://read.qxmd.com/read/38512424/interleukin-3-inhibits-glutamate-cytotoxicity-in-neuroblastoma-cell-line
#1
JOURNAL ARTICLE
Verónica Matus, Marcos Castro-Guarda, Joaquín Cárcamo-Fierro, Francisco J Morera, Angara Zambrano
Interleukin 3 (IL-3) is a well-known pleiotropic cytokine that regulates the proliferation and differentiation of hematopoietic progenitor cells, triggering classical signaling pathways such as JAK/STAT, Ras/MAPK, and PI3K/Akt to carry out its functions. Interestingly, the IL-3 receptor is also expressed in non-hematopoietic cells, playing a crucial role in cell survival. Our previous research demonstrated the expression of the IL-3 receptor in neuron cells and its protective role in neurodegeneration. Glutamate, a principal neurotransmitter in the central nervous system, can induce cellular stress and lead to neurotoxicity when its extracellular concentrations surpass normal levels...
March 21, 2024: Neurochemical Research
https://read.qxmd.com/read/38487090/diagnostic-utility-of-ras-mutation-testing-for-refining-cytologically-indeterminate-thyroid-nodules
#2
REVIEW
Isabel R Riccio, Alexandra C LaForteza, Mohammad H Hussein, Joshua P Linhuber, Peter P Issa, Jonathan Staav, Manal S Fawzy, Eman A Toraih, Emad Kandil
RAS mutations are prevalent in indeterminate thyroid nodules, but their association with malignancy risk and utility for diagnosis remains unclear. We performed a systematic review and meta-analysis to establish the clinical value of RAS mutation testing for cytologically indeterminate thyroid nodules. PubMed and Embase were systematically searched for relevant studies. Thirty studies comprising 13,328 nodules met the inclusion criteria. Random effects meta-analysis synthesized pooled estimates of RAS mutation rates, risk of malignancy with RAS positivity, and histologic subtype outcomes...
2024: EXCLI Journal
https://read.qxmd.com/read/38480881/time-resolved-cryo-em-of-g-protein-activation-by-a-gpcr
#3
JOURNAL ARTICLE
Makaía M Papasergi-Scott, Guillermo Pérez-Hernández, Hossein Batebi, Yang Gao, Gözde Eskici, Alpay B Seven, Ouliana Panova, Daniel Hilger, Marina Casiraghi, Feng He, Luis Maul, Peter Gmeiner, Brian K Kobilka, Peter W Hildebrand, Georgios Skiniotis
G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by stimulating guanine nucleotide exchange in the Gα subunit1 . To visualize this mechanism, we developed a time-resolved cryo-EM approach that examines the progression of ensembles of pre-steady-state intermediates of a GPCR-G-protein complex. By monitoring the transitions of the stimulatory Gs protein in complex with the β2 -adrenergic receptor at short sequential time points after GTP addition, we identified the conformational trajectory underlying G-protein activation and functional dissociation from the receptor...
March 13, 2024: Nature
https://read.qxmd.com/read/38473335/forchlorfenuron-induced-mitochondrial-respiration-inhibition-and-metabolic-shifts-in-endometrial-cancer
#4
JOURNAL ARTICLE
Kyukwang Kim, Negar Khazan, Rachael B Rowswell-Turner, Rakesh K Singh, Taylor Moore, Myla S Strawderman, John P Miller, Cameron W A Snyder, Ahmad Awada, Richard G Moore
Forchlorfenuron (FCF) is a widely used plant cytokinin that enhances fruit quality and size in agriculture. It also serves as a crucial pharmacological tool for the inhibition of septins. However, the precise target of FCF has not yet been fully determined. This study reveals a novel target of FCF and elucidates its downstream signaling events. FCF significantly impairs mitochondrial respiration and mediates metabolic shift toward glycolysis, thus making cells more vulnerable to glycolysis inhibition. Interestingly, FCF's impact on mitochondrial function persists, even in cells lacking septins...
February 28, 2024: Cancers
https://read.qxmd.com/read/38467862/assessment-and-application-of-non-technical-skills-in-robotic-assisted-surgery-a-systematic-review
#5
REVIEW
Vimaladhithan Mahendran, Laura Turpin, Matthew Boal, Nader K Francis
BACKGROUND: Undeniably, robotic-assisted surgery (RAS) has become very popular in recent decades, but it has introduced challenges to the workflow of the surgical team. Non-technical skills (NTS) have received less emphasis than technical skills in training and assessment. The systematic review aimed to update the evidence on the role of NTS in robotic surgery, specifically focusing on evaluating assessment tools and their utilisation in training and surgical education in robotic surgery...
March 11, 2024: Surgical Endoscopy
https://read.qxmd.com/read/38462034/myotubularin-related-protein-7-inhibits-mutant-g12v-k-ras-by-direct-interaction
#6
JOURNAL ARTICLE
Philip Weidner, Daniel Saar, Michaela Söhn, Torsten Schroeder, Yanxiong Yu, Frank G Zöllner, Norbert Ponelies, Xiaobo Zhou, André Zwicky, Florian N Rohrbacher, Vijaya R Pattabiraman, Matthias Tanriver, Alexander Bauer, Hazem Ahmed, Simon M Ametamey, Philipp Riffel, Rony Seger, Jeffrey W Bode, Rebecca C Wade, Matthias P A Ebert, Birthe B Kragelund, Elke Burgermeister
Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesised that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c-FOS transcription and cancer cell proliferation in vitro...
March 8, 2024: Cancer Letters
https://read.qxmd.com/read/38461567/evolving-survival-gains-in-patients-with-young-onset-colorectal-cancer-and-synchronous-resectable-liver-metastases
#7
JOURNAL ARTICLE
Harufumi Maki, Antony Haddad, Mateo Lendoire, Timothy E Newhook, Oliver Peacock, Brian K Bednarski, Tsuyoshi Konishi, Jean-Nicolas Vauthey, Y Nancy You
We aimed to evaluate the practice and the associated outcomes of surgical treatment for young-onset colorectal cancer (YOCRC) patients presenting with synchronous liver metastases. The study cohort was divided into two groups according to surgery date: 131 patients in the early era (EE, 1998-2011) and 179 in the contemporary era (CE, 2012-2020). The CE had a higher rate of node-positive primary tumors, higher carcinoembryonic antigen level, and lower rate of RAS/BRAF mutations. The CE had higher rates of reverse or combined resection, multi-drug prehepatectomy chemotherapy, and two-stage hepatectomy...
February 23, 2024: European Journal of Surgical Oncology
https://read.qxmd.com/read/38457483/dft-and-molecular-simulation-validation-of-the-binding-activity-of-pde%C3%AE-inhibitors-for-repression-of-oncogenic-k-ras
#8
JOURNAL ARTICLE
Taghreed A Majrashi, Ahmed Sabt, Hadia Almahli, Mahmoud A El Hassab, Mahmoud A Noamaan, Eslam B Elkaeed, Mohamed Farouk Hamissa, Abdalkareem Nael Maslamani, Moataz A Shaldam, Wagdy M Eldehna
The development of effective drugs targeting the K-Ras oncogene product is a significant focus in anticancer drug development. Despite the lack of successful Ras signaling inhibitors, recent research has identified PDEδ, a KRAS transporter, as a potential target for inhibiting the oncogenic KRAS signaling pathway. This study aims to investigate the interactions between eight K-Ras inhibitors (deltarazine, deltaflexin 1 and 2, and its analogues) and PDEδ to understand their binding modes. The research will utilize computational techniques such as density functional theory (DFT) and molecular electrostatic surface potential (MESP), molecular docking, binding site analyses, molecular dynamic (MD) simulations, electronic structure computations, and predictions of the binding free energy...
2024: PloS One
https://read.qxmd.com/read/38452582/emerging-role-of-tumor-suppressing-micrornas-as-therapeutics-in-managing-non-small-cell-lung-cancer
#9
REVIEW
Shubham Singh, Sangeeta Saxena, Himani Sharma, Keshav Raj Paudel, Amlan Chakraborty, Ronan MacLoughlin, Brian G Oliver, Gaurav Gupta, Poonam Negi, Sachin Kumar Singh, Kamal Dua
Lung cancer (LC) is the second leading cause of death across the globe after breast cancer. There are two types of LC viz. small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of all LC cases. NSCLC affects smokers and people who do not smoke and mainly arises in bronchi and peripheral lungs tissue. LC is often characterized by the alterations of key genes such as EGFR, Wnt/β-catenin signaling, ALK, MET, K-Ras and p53 and downstream signaling pathways associated with tumor growth, differentiation, and survival...
February 23, 2024: Pathology, Research and Practice
https://read.qxmd.com/read/38451376/evaluation-of-different-approaches-to-define-expert-benchmark-scores-for-new-robotic-training-simulators-based-on-the-medtronic-hugo%C3%A2-ras-surgical-robot-experience
#10
JOURNAL ARTICLE
Mark Brentnall, John Lenihan, Christopher Simmonds, Anand Malpani, Antonio R Gargiulo, Martin Martino, Jeffrey S Levy
New robot-assisted surgery platforms being developed will be required to have proficiency-based simulation training available. Scoring methodologies and performance feedback for trainees are currently not consistent across all robotic simulator platforms. Also, there are virtually no prior publications on how VR simulation passing benchmarks have been established. This paper compares methods evaluated to determine the proficiency-based scoring thresholds (a.k.a. benchmarks) for the new Medtronic Hugo™ RAS robotic simulator...
March 7, 2024: Journal of Robotic Surgery
https://read.qxmd.com/read/38450537/targeting-the-egfr-ras-raf-signaling-pathway-in-anticancer-research-a-recent-update-on-inhibitor-design-and-clinical-trials-2020-2023
#11
REVIEW
Rima Hajjo, Dima A Sabbah, Sanaa K Bardaweel, Haizhen A Zhong
INTRODUCTION: Recent years have seen significant strides in drug developmenttargeting the EGFR/RAS/RAF signaling pathway which is critical forcell growth and proliferation. Protein-protein interaction networksamong EGFR, RAS, and RAF proteins offer insights for drug discovery. This review discusses the drug design and development efforts ofinhibitors targeting these proteins over the past 3 years, detailingtheir structures, selectivity, efficacy, and combination therapy.Strategies to combat drug resistance and minimize toxicities areexplored, along with future research directions...
March 12, 2024: Expert Opinion on Therapeutic Patents
https://read.qxmd.com/read/38443470/strain-release-alkylation-of-asp12-enables-mutant-selective-targeting-of-k-ras-g12d
#12
JOURNAL ARTICLE
Qinheng Zheng, Ziyang Zhang, Keelan Z Guiley, Kevan M Shokat
K-Ras is the most commonly mutated oncogene in human cancer. The recently approved non-small cell lung cancer drugs sotorasib and adagrasib covalently capture an acquired cysteine in K-Ras-G12C mutation and lock it in a signaling-incompetent state. However, covalent inhibition of G12D, the most frequent K-Ras mutation particularly prevalent in pancreatic ductal adenocarcinoma, has remained elusive due to the lack of aspartate-targeting chemistry. Here we present a set of malolactone-based electrophiles that exploit ring strain to crosslink K-Ras-G12D at the mutant aspartate to form stable covalent complexes...
March 5, 2024: Nature Chemical Biology
https://read.qxmd.com/read/38442565/multiplexed-electrochemical-nucleic-acid-sensor-based-on-visible-light-mediated-metal-free-thiol-yne-click-reaction-for-simultaneous-detection-of-different-nucleic-acid-targets
#13
JOURNAL ARTICLE
Jinlong Fan, Hanlin Gong, Fan Wang, Li Wang, Yongsheng Yu, Danqing Liu, Weiwei Yang
Simultaneous detection of multiple tumor biomarkers with a simple and low-cost assay is crucial for early cancer detection and diagnosis. Herein, we presented a low-cost and simple assay for multiplexed detection of tumor biomarkers using a spatially separated electrodes strategy. The sensor is fabricated based on a metal-free thiol-yne click reaction, which is mediated by visible light, on commercially available indium tin oxide (ITO) electrodes. Four biomarkers, including p53 DNA, Brca2 DNA, K-ras DNA, and MicroRNA-204 RNA, were used as model analytes, and the corresponding oligonucleotide probes were modified on the desired electrode units sequentially with 530 nm irradiation light in the presence of photosensitizer Eosin Y...
March 1, 2024: Talanta
https://read.qxmd.com/read/38440831/shp2-inhibition-displays-efficacy-as-a-monotherapy-and-in-combination-with-jak2-inhibition-in-preclinical-models-of-myeloproliferative-neoplasms
#14
JOURNAL ARTICLE
Garima Pandey, Lucia Mazzacurati, Tegan M Rowsell, Nathan P Horvat, Narmin E Amin, Guolin Zhang, Afua A Akuffo, Christelle M Colin-Leitzinger, Eric B Haura, Andrew T Kuykendall, Ling Zhang, Pearlie K Epling-Burnette, Gary W Reuther
Myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocytosis, and primary myelofibrosis, are clonal hematopoietic neoplasms driven by mutationally activated signaling by the JAK2 tyrosine kinase. Although JAK2 inhibitors can improve MPN patients' quality of life, they do not induce complete remission as disease-driving cells persistently survive therapy. ERK activation has been highlighted as contributing to JAK2 inhibitor persistent cell survival. As ERK is a component of signaling by activated RAS proteins and by JAK2 activation, we sought to inhibit RAS activation to enhance responses to JAK2 inhibition in preclinical MPN models...
March 5, 2024: American Journal of Hematology
https://read.qxmd.com/read/38436766/revolutionizing-urology-the-advancements-and-applications-of-robotic-platforms
#15
REVIEW
Kinju Adhikari, Gowtham Krishna Penmetsa, Deepak Krishnappa, Ravi Taori, S K Raghunath
Robot-assisted surgery is developing as an acme of minimally invasive surgery, given its utmost dominance over laparoscopic surgery. The objective was to review the status of robotic surgery in urological practice with its advantages and disadvantages in current scenario. We conducted a literature search using MEDLINE and identified 72 articles which were relevant to urology. Single-port and various multiport robotic platforms like Da Vinci, Versius, Hugo RAS, Revo-I, Senhance, Mantra, Avatera, Hinotori, and MicroSurge are described with pros and cons...
March 4, 2024: Journal of Robotic Surgery
https://read.qxmd.com/read/38427166/yap-tead-involvement-in-resistance-to-paclitaxel-chemotherapy-in-lung-cancer
#16
JOURNAL ARTICLE
S Brosseau, P Abreu, C Bouchez, L Charon, Y Kieffer, G Gentric, V Picant, I Veith, J Camonis, S Descroix, F Mechta-Grigoriou, M C Parrini, G Zalcman
The Yes-associated protein (YAP) oncoprotein has been linked to both metastases and resistance to targeted therapy of lung cancer cells. We aimed to investigate the effect of YAP pharmacological inhibition, using YAP/TEA domain (TEAD) transcription factor interaction inhibitors in chemo-resistant lung cancer cells. YAP subcellular localization, as a readout for YAP activation, cell migration, and TEAD transcription factor functional transcriptional activity were investigated in cancer cell lines with up-regulated YAP, with and without YAP/TEAD interaction inhibitors...
March 1, 2024: Molecular and Cellular Biochemistry
https://read.qxmd.com/read/38423665/renin-angiotensin-system-inhibitors-suppress-the-growth-of-leukemia-cells
#17
JOURNAL ARTICLE
Mai Itoh, Shun Sasaki, Shuji Tohda
BACKGROUND/AIM: The renin-angiotensin system (RAS) regulates blood pressure. The RAS is also related to cell growth, and its activation has been reported in various cancer cells. Therefore, we investigated the effects of RAS inhibitors on the in vitro growth of leukemia cell lines. MATERIALS AND METHODS: THP-1, MV4-11, and TMD7 cells derived from acute myeloid leukemia, K-562 cells from chronic myeloid leukemia, and Jurkat and KOPT-K1 cells from T-lymphoblastic leukemia (T-ALL) with NOTCH1 mutations were used...
March 2024: Anticancer Research
https://read.qxmd.com/read/38418613/membrane-lipids-drive-formation-of-kras4b-raf1-rbdcrd-nanoclusters-on-the-membrane
#18
JOURNAL ARTICLE
Rebika Shrestha, Timothy S Carpenter, Que N Van, Constance Agamasu, Marco Tonelli, Fikret Aydin, De Chen, Gulcin Gulten, James N Glosli, Cesar A López, Tomas Oppelstrup, Chris Neale, Sandrasegaram Gnanakaran, William K Gillette, Helgi I Ingólfsson, Felice C Lightstone, Andrew G Stephen, Frederick H Streitz, Dwight V Nissley, Thomas J Turbyville
The oncogene RAS, extensively studied for decades, presents persistent gaps in understanding, hindering the development of effective therapeutic strategies due to a lack of precise details on how RAS initiates MAPK signaling with RAF effector proteins at the plasma membrane. Recent advances in X-ray crystallography, cryo-EM, and super-resolution fluorescence microscopy offer structural and spatial insights, yet the molecular mechanisms involving protein-protein and protein-lipid interactions in RAS-mediated signaling require further characterization...
February 28, 2024: Communications Biology
https://read.qxmd.com/read/38410222/the-safety-and-efficacy-of-anti-pd-1-inhibitor-based-combinational-therapy-in-non-small-cell-lung-cancer-patients-with-oncogenic-alterations
#19
JOURNAL ARTICLE
Lu Chen, Jingyuan Xie, Meiying Zhu, Dong Wang, Hongbin Liu, Ping Zhan, Jie Yin, Mingxiang Ye, Yong Song, Tangfeng Lv
BACKGROUND: The anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunotherapy has been extensively used in patients with non-small cell lung cancer (NSCLC) in which the tumors are negative for oncogenic alterations. However, whether PD-1/PD-L1 blockade therapy could be applicable in patients harboring oncogenic mutations is largely unknown. METHODS: In this retrospective study, we analyzed the safety and efficacy of anti-PD-1 inhibitor-based combinational therapy in a NSCLC cohort of 84 patients who harbored oncogenic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), k-Ras, RET, HER2 and BRAF...
January 31, 2024: Translational Cancer Research
https://read.qxmd.com/read/38406594/pathological-features-of-gastric%C3%A2-type-endocervical-adenocarcinoma-a-report-of-two-cases
#20
Jiahui Zhou, Xiangning Zhang, Weibo Mao, Yiling Zhu, Liping Yan, Jiangle Jiang, Min Zhang
Gastric-type endocervical adenocarcinoma (GEA) is an uncommon form of uterine cervical adenocarcinoma with an unfavorable prognosis. The tumor consists of glands exhibiting a morphological resemblance to gastric cells and occasionally manifests features akin to pancreaticobiliary mucinous adenocarcinoma. GEA differs from the typical cervical cancer, particularly in its lack of association with the human papillomavirus. Immunophenotypic analysis suggests intestinal differentiation. The present study reports two cases of GEA occurring in postmenopausal individuals who were diagnosed in Lishui Central Hospital (Lishui, China) between January 2015 and January 2023...
April 2024: Oncology Letters
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