keyword
https://read.qxmd.com/read/38484153/abt199-venetoclax-synergism-with-thiotepa-enhances-the-cytotoxicity-of-fludarabine-cladribine-and-busulfan-in-aml-cells
#21
JOURNAL ARTICLE
Benigno C Valdez, Bin Yuan, David Murray, Jeremy L Ramdial, Uday Popat, Yago Nieto, Borje S Andersson
ABT199/venetoclax, an inhibitor of the pro-survival BCL-2 protein, has improved AML treatment. Its efficacy in hematopoietic stem cell transplantation (HSCT), when combined with other chemotherapeutic drugs, has not been thoroughly investigated. The present study demonstrates the synergistic cytotoxicity of ABT199/venetoclax with the DNA alkylator thiotepa (Thio) in AML cells. Cleavage of Caspase 3, PARP1 and HSP90, as well as increased Annexin V positivity, suggest potent activation of apoptosis by this two-drug combination; increased levels of γ-H2AX, P-CHK1 (S317), P-CHK2 (S19) and P-SMC1 (S957) indicate an enhanced DNA damage response...
March 14, 2024: Oncotarget
https://read.qxmd.com/read/38483263/click-capable-phenanthriplatin-derivatives-as-tools-to-study-pt-ii-induced-nucleolar-stress
#22
JOURNAL ARTICLE
Paul D O'Dowd, Andres S Guerrero, Katelyn R Alley, Hannah C Pigg, Fiona O'Neill, Justine Meiller, Chloe Hobbs, Daniel A Rodrigues, Brendan Twamley, Finbarr O'Sullivan, Victoria J DeRose, Darren M Griffith
It is well established that oxaliplatin, one of the three Pt(II) anticancer drugs approved worldwide, and phenanthriplatin, an important preclinical monofunctional Pt(II) anticancer drug, possess a different mode of action from that of cisplatin and carboplatin, namely, the induction of nucleolar stress. The exact mechanisms that lead to Pt-induced nucleolar stress are, however, still poorly understood. As such, studies aimed at better understanding the biological targets of both oxaliplatin and phenanthriplatin are urgently needed to expand our understanding of Pt-induced nucleolar stress and guide the future design of Pt chemotherapeutics...
March 14, 2024: ACS Chemical Biology
https://read.qxmd.com/read/38479571/sonic-hedgehog-restrains-the-ubiquitin-dependent-degradation-of-sp1-to-inhibit-neuronal-glial-senescence-associated-phenotypes-in-chemotherapy-induced-peripheral-neuropathy-via-the-trim25-cxcl13-axis
#23
JOURNAL ARTICLE
Ying Zou, Shu Wu, Qian Hu, Haoxian Zhou, Yuanlong Ge, Zhenyu Ju, Shengkang Luo
INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication that affects an increasing number of cancer survivors. However, the current treatment options for CIPN are limited. Paclitaxel (PTX) is a widely used chemotherapeutic drug that induces senescence in cancer cells. While previous studies have demonstrated that Sonic hedgehog (Shh) can counteract cellular dysfunction during aging, its role in CIPN remains unknown. OBJECTIVES: Herein, the aim of this study was to investigate whether Shh activation could inhibits neuronal/glial senescence and alleviates CIPN...
March 11, 2024: Journal of Advanced Research
https://read.qxmd.com/read/38473799/flash-radiotherapy-expectations-challenges-and-current-knowledge
#24
REVIEW
Andrea Borghini, Luca Labate, Simona Piccinini, Costanza Maria Vittoria Panaino, Maria Grazia Andreassi, Leonida Antonio Gizzi
Major strides have been made in the development of FLASH radiotherapy (FLASH RT) in the last ten years, but there are still many obstacles to overcome for transfer to the clinic to become a reality. Although preclinical and first-in-human clinical evidence suggests that ultra-high dose rates (UHDRs) induce a sparing effect in normal tissue without modifying the therapeutic effect on the tumor, successful clinical translation of FLASH-RT depends on a better understanding of the biological mechanisms underpinning the sparing effect...
February 22, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38473708/%C3%AE-h2a-%C3%AE-h2ax-mediates-dna-damage-specific-control-of-checkpoint-signaling-in-saccharomyces-cerevisiae
#25
JOURNAL ARTICLE
Jasmine Siler, Na Guo, Zhengfeng Liu, Yuhua Qin, Xin Bi
DNA lesions trigger DNA damage checkpoint (DDC) signaling which arrests cell cycle progression and promotes DNA damage repair. In Saccharomyces cerevisiae , phosphorylation of histone H2A (γH2A, equivalent to γH2AX in mammals) is an early chromatin mark induced by DNA damage that is recognized by a group of DDC and DNA repair factors. We find that γH2A negatively regulates the G2/M checkpoint in response to the genotoxin camptothecin, which is a DNA topoisomerase I poison. γH2A also suppresses DDC signaling induced by the DNA alkylating agent methyl methanesulfonate...
February 20, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38473234/proguanil-suppresses-breast-tumor-growth-in-vitro-and-in-vivo-by-inducing-apoptosis-via-mitochondrial-dysfunction
#26
JOURNAL ARTICLE
Nehal Gupta, Marina Curcic, Sanjay K Srivastava
Breast cancer, ranking as the second leading cause of female cancer-related deaths in the U.S., demands the exploration of innovative treatments. Repurposing FDA-approved drugs emerges as an expedited and cost-effective strategy. Our study centered on proguanil, an antimalarial drug, reveals notable anti-proliferative effects on diverse breast cancer cell lines, including those derived from patients. Proguanil-induced apoptosis was associated with a substantial increase in reactive oxygen species (ROS) production, leading to reduced mitochondrial membrane potential, respiration, and ATP production...
February 22, 2024: Cancers
https://read.qxmd.com/read/38473215/statin-sensitive-akt1-src-caveolin-1-signaling-enhances-oxidative-stress-resistance-in-rhabdomyosarcoma
#27
JOURNAL ARTICLE
Silvia Codenotti, Leonardo Sandrini, Delia Mandracchia, Luisa Lorenzi, Giovanni Corsetti, Maura Poli, Michela Asperti, Valentina Salvi, Daniela Bosisio, Eugenio Monti, Stefania Mitola, Luca Triggiani, Michele Guescini, Enrico Pozzo, Maurilio Sampaolesi, Stefano Gastaldello, Matteo Cassandri, Francesco Marampon, Alessandro Fanzani
Identifying the molecular mechanisms underlying radioresistance is a priority for the treatment of RMS, a myogenic tumor accounting for approximately 50% of all pediatric soft tissue sarcomas. We found that irradiation (IR) transiently increased phosphorylation of Akt1, Src, and Cav1 in human RD and RH30 lines. Synthetic inhibition of Akt1 and Src phosphorylation increased ROS levels in all RMS lines, promoting cellular radiosensitization. Accordingly, the elevated activation of the Akt1/Src/Cav1 pathway, as detected in two RD lines characterized by overexpression of a myristoylated Akt1 form (myrAkt1) or Cav1 (RDCav1), was correlated with reduced levels of ROS, higher expression of catalase, and increased radioresistance...
February 20, 2024: Cancers
https://read.qxmd.com/read/38467768/stat3-protects-hematopoietic-stem-cells-by-preventing-activation-of-a-deleterious-autocrine-type-i-interferon-response
#28
JOURNAL ARTICLE
Bhakti Patel, Yifan Zhou, Rachel L Babcock, Feiyang Ma, M Anna Zal, Dhiraj Kumar, Yusra B Medik, Laura M Kahn, Josué E Pineda, Elizabeth M Park, Sarah M Schneider, Ximing Tang, Maria Gabriela Raso, Collene R Jeter, Tomasz Zal, Karen Clise-Dwyer, Khandan Keyomarsi, Filippo G Giancotti, Simona Colla, Stephanie S Watowich
Hematopoietic stem and progenitor cells (HSPCs) maintain blood-forming and immune activity, yet intrinsic regulators of HSPCs remain elusive. STAT3 function in HSPCs has been difficult to dissect as Stat3-deficiency in the hematopoietic compartment induces systemic inflammation, which can impact HSPC activity. Here, we developed mixed bone marrow (BM) chimeric mice with inducible Stat3 deletion in 20% of the hematopoietic compartment to avoid systemic inflammation. Stat3-deficient HSPCs were significantly impaired in reconstitution ability following primary or secondary bone marrow transplantation, indicating hematopoietic stem cell (HSC) defects...
March 11, 2024: Leukemia
https://read.qxmd.com/read/38467631/gins2-regulates-temozolomide-chemosensitivity-via-the-egr1-ect2-axis-in-gliomas
#29
JOURNAL ARTICLE
Hua He, Lu Liang, Shiyao Jiang, Yueying Liu, Jingjing Huang, Xiaoyan Sun, Yi Li, Yiqun Jiang, Li Cong
Temozolomide (TMZ), a DNA alkylating agent, has become the primary treatment for glioma, the most common malignancy of the central nervous system. Although TMZ-containing regimens produce significant clinical response rates, some patients inevitably suffer from inferior treatment outcomes or disease relapse, likely because of poor chemosensitivity of glioma cells due to a robust DNA damage response (DDR). GINS2, a subunit of DNA helicase, contributes to maintaining genomic stability and is highly expressed in various cancers, promoting their development...
March 11, 2024: Cell Death & Disease
https://read.qxmd.com/read/38466467/nicaraven-attenuates-the-acquired-radioresistance-of-established-tumors-in-mouse-models-via-parp-inhibition
#30
JOURNAL ARTICLE
Kai Huang, Chen Yan, Lina Abdelghany, Xu Zhang, Keiichi Jingu, Tao-Sheng Li
Nicaraven has been reported to inhibit the activity of poly (ADP-ribose) polymerase (PARP). In this study, we investigated the probable ability of nicaraven to attenuate cancer radioresistance during fractionated radiotherapy. Tumor models were established in C57BL/6 mice and BALB/c nude mice by subcutaneous injection of Lewis mouse lung carcinoma cancer cells and A549 human lung cancer cells, respectively. When the tumors had grown to approximately 100 mm3 , we initiated fractionated radiotherapy. Nicaraven or saline was administered immediately after each irradiation exposure...
March 11, 2024: Molecular and Cellular Biochemistry
https://read.qxmd.com/read/38466010/heat-stroke-induces-pyroptosis-in-spermatogonia-via-the-cgas-sting-signaling-pathway
#31
JOURNAL ARTICLE
Q-F Deng, Y Liu, H Chu, B Peng, X Li, Y-S Cao
To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating cryptorchidism-induced infertility. Spermatogonial GC-1 cells were heat stimulated to simulate the heat hurt microenvironment of cryptorchidism. The cell viability was assayed by CCK-8, and cellular DNA damage was detected by gamma-H2AX immunofluo-rescence assay. Flow cytometry was employed to assess pyroptosis index, while western blot, ELISA and PCR were used to examine the expressions of pyroptosis-related proteins (Caspase-1, IL-1beta, NLRP3) and cGAS-STING pathway proteins (cGAS, STING)...
March 11, 2024: Physiological Research
https://read.qxmd.com/read/38464175/subcellular-functions-of-tau-mediates-repair-response-and-synaptic-homeostasis-in-injury
#32
David Grosshans, Riya Thomas, Die Zhang, Christopher Cronkite, Rintu Thomas, Sanjay Singh, Lawrence Bronk, Rodrigo Morales, Joseph Duman
Injury responses in terminally differentiated cells such as neurons is tightly regulated by pathways aiding homeostatic maintenance. Cancer patients subjected to neuronal injury in brain radiation experience cognitive declines similar to those seen in primary neurodegenerative diseases. Numerous studies have investigated the effect of radiation in proliferating cells of the brain, yet the impact in differentiated, post-mitotic neurons, especially the structural and functional alterations remain largely elusive...
February 29, 2024: Research Square
https://read.qxmd.com/read/38461549/inhibition-of-intracellular-atp-synthesis-impairs-the-recruitment-of-homologous-recombination-factors-after-ionizing-radiation
#33
JOURNAL ARTICLE
Ryota Hayashi, Hikaru Okumura, Mayu Isono, Motohiro Yamauchi, Daiki Unami, Rahmartani Tania Lusi, Masamichi Yamamoto, Yu Kato, Yuki Uchihara, Atsushi Shibata
Ionizing radiation (IR)-induced double-strand breaks (DSBs) are primarily repaired by non-homologous end joining or homologous recombination (HR) in human cells. DSB repair requires adenosine-5'-triphosphate (ATP) for protein kinase activities in the multiple steps of DSB repair, such as DNA ligation, chromatin remodeling, and DNA damage signaling via protein kinase and ATPase activities. To investigate whether low ATP culture conditions affect the recruitment of repair proteins at DSB sites, IR-induced foci were examined in the presence of ATP synthesis inhibitors...
March 8, 2024: Journal of Radiation Research
https://read.qxmd.com/read/38456590/cdk1-promotes-the-phosphorylation-of-kifc1-to-regulate-the-tumorgenicity-of-endometrial-carcinoma
#34
JOURNAL ARTICLE
Xi Lin, Yingying He, Yiming Liu, Huihao Zhou, Xiaomin Xu, Jingui Xu, Kening Zhou
OBJECTIVE: This study aims to clarify the mechanical action of cyclin-dependent protein kinase 1 (CDK1) in the development of endometrial carcinoma (EMCA), which may be associated with the phosphorylation of kinesin family member C1 (KIFC1) and further activate the PI3K/AKT pathway. METHODS: The protein and gene expression of CDK1 in EMCA tissues and tumor cell lines were evaluated by western blot, quantitative polymerase chain reaction, and immunohistochemistry staining...
February 26, 2024: Journal of Gynecologic Oncology
https://read.qxmd.com/read/38447826/fibronectin-1-supports-oocyte-in-vitro-maturation-in-pigs
#35
JOURNAL ARTICLE
Mingju Sun, Xiangyu Wang, Fanglong Bi, Hongxiao Xiang, Ning Wang, Wenju Gao, Yixuan Liu, Zizhen Lv, Youwei Li, Yanjun Huan
Oocyte in vitro maturation (IVM) based on the follicular fluid (FF) environment can exploit untapped resources, however, what FF factors regulate oocyte maturation remains unclear. This work demonstrated that serum and FF significantly promoted oocyte polar body extrusion (PBE) and subsequent embryo development, and FF was especially effective. Fibronectin 1 (FN1) was predicted as one potential candidate to regulate oocyte maturation by proteomics. FN1 transcription obviously decreased, and the protein expression significantly increased and migrated to plasma membrane or even outside during oocyte IVM...
March 4, 2024: International Journal of Biological Macromolecules
https://read.qxmd.com/read/38445232/assessing-longitudinal-treatment-efficacies-and-alterations-in-molecular-markers-associated-with-glutamatergic-signaling-and-immune-checkpoint-inhibitors-in-a-spontaneous-melanoma-mouse-model
#36
JOURNAL ARTICLE
Kevinn Eddy, Kajal Gupta, Mohamad Naser Eddin, Christina Marinaro, Sanjana Putta, John Michael Sauer, Anna Chaly, Katie B Freeman, Jeffrey C Pelletier, Anna Fateeva, Philip Furmanski, Ann W Silk, Allen B Reitz, Andrew Zloza, Suzie Chen
Previous work done by our laboratory described the use of an immunocompetent spontaneous melanoma-prone mouse model, TGS (TG-3/SKH-1), to evaluate treatment outcomes using inhibitors of glutamatergic signaling and immune checkpoint for 18 weeks. We showed a significant therapeutic efficacy with a notable sex-biased response in male mice. In this follow-up 18-week study, the dose of the glutamatergic signaling inhibitor was increased (from 1.7 mg/kg to 25 mg/kg), which resulted in improved responses in female mice but not male mice...
March 2024: JID innovations
https://read.qxmd.com/read/38442236/atr-signaling-controls-the-bystander-responses-of-human-chondrosarcoma-cells-by-promoting-rad51-dependent-dna-repair
#37
JOURNAL ARTICLE
Nho Cong Luong, Hidemasa Kawamura, Hiroko Ikeda, Reiko T Roppongi, Atsushi Shibata, Jiaxuan Hu, Jinmeng G Jiang, David S Yu, Kathryn D Held
PURPOSE: Radiation-induced bystander effect (RIBE) frequently is seen as DNA damage in unirradiated bystander cells, but the repair processes initiated in response to that DNA damage are not well understood. RIBE-mediated formation of micronuclei (MN), a biomarker of persistent DNA damage, was previously observed in bystander normal fibroblast (AG01522) cells, but not in bystander human chondrosarcoma (HTB94) cells. The molecular mechanisms causing this disparity are not clear. Herein, we investigate the role of DNA repair in the bystander responses of the two cell lines...
March 5, 2024: International Journal of Radiation Biology
https://read.qxmd.com/read/38439918/acute-genetic-damage-induced-by-ethanol-and-corticosterone-seems-to-modulate-hippocampal-astrocyte-signaling
#38
JOURNAL ARTICLE
Ana Laura Reyes-Ábalos, Magdalena Álvarez-Zabaleta, Silvia Olivera-Bravo, María Vittoria Di Tomaso
Astrocytes maintain CNS homeostasis but also critically contribute to neurological and psychiatric disorders. Such functional diversity implies an extensive signaling repertoire including extracellular vesicles (EVs) and nanotubes (NTs) that could be involved in protection or damage, as widely shown in various experimental paradigms. However, there is no information associating primary damage to the astrocyte genome, the DNA damage response (DDR), and the EV and NT repertoire. Furthermore, similar studies were not performed on hippocampal astrocytes despite their involvement in memory and learning processes, as well as in the development and maintenance of alcohol addiction...
2024: International Journal of Cell Biology
https://read.qxmd.com/read/38439738/relevance-of-comet-assay-and-phosphorylated-hsp90%C3%AE-in-cancer-patients-peripheral-blood-leukocytes-as-tools-to-assess-cisplatin-based-chemotherapy-clinical-response-and-disease-outcome
#39
JOURNAL ARTICLE
Mayra L Sottile, Laura C Gómez, Analía Redondo, Jorge Ibarra, María B García, Lucía Gonzalez, Laura M Vargas-Roig, Silvina B Nadin
Cisplatin (cPt) is a commonly used treatment for solid tumors. The main target of its cytotoxicity is the DNA molecule, which makes the DNA damage response (DDR) crucial for cPt-based chemotherapy. Therefore, it is essential to identify biomarkers that can accurately predict the individual clinical response and prognosis. Our goal was to assess the usefulness of alkaline comet assay and immunocytochemical staining of phosphorylated Hsp90α (p-Hsp90α), γH2AX, and 53BP1 as predictive/prognostic markers...
March 5, 2024: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://read.qxmd.com/read/38438958/nuclear-respiratory-factor-1-regulates-super-enhancer-controlled-spidr-to-protect-hepatocellular-carcinoma-cells-from-oxidative-stress
#40
JOURNAL ARTICLE
Baowang Liu, Jian Dou, Jinglin Cao
BACKGROUND: Cellular response to oxidative stress plays significant roles in hepatocellular carcinoma (HCC) development, yet the exact mechanism by which HCC cells respond to oxidative stress remains poorly understood. This study aimed to investigate the role and mechanism of super enhancer (SE)-controlled genes in oxidative stress response of HCC cells. METHODS: The GSE112221 dataset was used to identify SEs by HOMER. Functional enrichment of SE-controlled genes was performed by Metascape...
March 4, 2024: BMC Gastroenterology
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