keyword
https://read.qxmd.com/read/38540136/analysis-of-primary-chronic-lymphocytic-leukemia-cells-signaling-pathways
#1
JOURNAL ARTICLE
Josipa Skelin, Maja Matulić, Lidija Milković, Darko Heckel, Jelena Skoko, Kristina Ana Škreb, Biljana Jelić Puškarić, Ika Kardum-Skelin, Lipa Čičin-Šain, Delfa Radić-Krišto, Mariastefania Antica
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized by a specific expansion of mature B-cell clones. We hypothesized that the disease has a heterogeneous clinical outcome that depends on the genes and signaling pathways active in the malignant clone of the individual patient. It was found that several signaling pathways are active in CLL, namely, NOTCH1, the Ikaros family genes, BCL2, and NF-κB, all of which contribute to cell survival and the proliferation of the leukemic clone...
February 26, 2024: Biomedicines
https://read.qxmd.com/read/38539460/therapeutic-potential-of-bromodomain-and-extra-terminal-domain-inhibitors-for-synovial-sarcoma-cells
#2
JOURNAL ARTICLE
Yuki Kotani, Yoshinori Imura, Sho Nakai, Ryota Chijimatsu, Haruna Takami, Akitomo Inoue, Hirokazu Mae, Satoshi Takenaka, Hidetatsu Outani, Seiji Okada
Synovial sarcoma (SS), a rare subtype of soft-tissue sarcoma distinguished by expression of the fusion gene SS18-SSX, predominantly affects the extremities of young patients. Existing anticancer drugs have limited efficacy against this malignancy, necessitating the development of innovative therapeutic approaches. Given the established role of SS18-SSX in epigenetic regulation, we focused on bromodomain and extra-terminal domain protein (BET) inhibitors and epigenetic agents. Our investigation of the BET inhibitor ABBV-075 revealed its pronounced antitumor effects, inducing G1-phase cell-cycle arrest and apoptosis, in four SS cell lines...
March 11, 2024: Cancers
https://read.qxmd.com/read/38538744/ampk-inhibition-sensitizes-acute-leukemia-cells-to-bh3-mimetic-induced-cell-death
#3
JOURNAL ARTICLE
Jia Jia, Wenbo Ji, Antoine N Saliba, Clifford M Csizmar, Kaiqin Ye, Lei Hu, Kevin L Peterson, Paula A Schneider, X Wei Meng, Annapoorna Venkatachalam, Mrinal M Patnaik, Jonathan A Webster, B Douglas Smith, Gabriel Ghiaur, Xinyan Wu, Jun Zhong, Akhilesh Pandey, Karen S Flatten, Qingmei Deng, Hongzhi Wang, Scott H Kaufmann, Haiming Dai
BH3 mimetics, including the BCL2/BCLXL /BCLw inhibitor navitoclax and MCL1 inhibitors S64315 and tapotoclax, have undergone clinical testing for a variety of neoplasms. Because of toxicities, including thrombocytopenia after BCLXL inhibition as well as hematopoietic, hepatic and possible cardiac toxicities after MCL1 inhibition, there is substantial interest in finding agents that can safely sensitize neoplastic cells to these BH3 mimetics. Building on the observation that BH3 mimetic monotherapy induces AMP kinase (AMPK) activation in multiple acute leukemia cell lines, we report that the AMPK inhibitors (AMPKis) dorsomorphin and BAY-3827 sensitize these cells to navitoclax or MCL1 inhibitors...
March 27, 2024: Cell Death and Differentiation
https://read.qxmd.com/read/38538512/therapeutic-targeting-of-apoptosis-in-chronic-lymphocytic-leukemia
#4
JOURNAL ARTICLE
Inhye E Ahn, Matthew S Davids
Therapeutic targeting of apoptosis with small molecule B-cell lymphoma 2 (BCL-2) inhibition with venetoclax is highly efficacious in CLL, leading to sustained deep responses, particularly among patients with treatment-naïve disease with favorable prognostic markers. Patients with unfavorable genetic characteristics such as TP53 aberration and unmutated IGHV may also derive durable benefits, but their remission duration after time-limited venetoclax-containing combination therapy is shorter, particularly in patients with relapsed/refractory disease...
February 7, 2024: Seminars in Hematology
https://read.qxmd.com/read/38532054/atp-releasing-channels-and-the-ameliorative-effects-of-high-intensity-interval-training-on-diabetic-heart-a-multifaceted-analysis
#5
JOURNAL ARTICLE
Siyavash Joukar, Mohammad Amin Rajizadeh, Mohammad Abbas Bejeshk, Samaneh Sadat Alavi, Fatemeh Bagheri, Mohammad Rami, Kayvan Khoramipour
Type 2 diabetes (T2D) can cause severe cardiac complications at functional, histologic and molecular levels. These pathological complications could be mediated by ATP-releasing channels such as Panx1 and ATP receptors, in particular P2X7. The aim of our study was to investigate the effect of high-intensity interval training (HIIT) on T2D-induced cardiac complications at the functional, histopathological and molecular levels, with a particular focus on ATP-releasing channels. 48 male Wistar rats at the age of 8 weeks were randomly allocated into four groups: control (Con), Diabetes (T2D), Training (TR), and Diabetes + Training (T2D + TR)...
March 26, 2024: Scientific Reports
https://read.qxmd.com/read/38460306/generation-of-two-human-induced-pluripotent-stem-cell-lines-with-bax-and-bak1-double-knock-out-using-crispr-cas9
#6
JOURNAL ARTICLE
Katarzyna Anna Ludwik, Lina Hellwig, Tanja Fisch, Jörg Contzen, Claudia Schaar, Philipp Mergenthaler, Harald Stachelscheid
Bcl-2-associated X protein (BAX) and Blc-2 homologous antagonist killer 1 (BAK) are two pro-apoptotic members of BCL2 family. Here, two BAX/BAK double knock-out human induced pluripotent stem cell lines (iPSC) we generated using CRISPR-Cas9 to generate apoptosis incompetent cell lines. The resulting cell lines were karyotypically normal, had typical morphology and expressed typical markers for the undifferentiated state.
March 5, 2024: Stem Cell Research
https://read.qxmd.com/read/38459020/mcl1-inhibition-targets-myeloid-derived-suppressors-cells-promotes-antitumor-immunity-and-enhances-the-efficacy-of-immune-checkpoint-blockade
#7
JOURNAL ARTICLE
Nabanita Mukherjee, Elizabeth Katsnelson, Tonya M Brunetti, Kylie Michel, Kasey L Couts, Karoline A Lambert, William A Robinson, Martin D McCarter, David A Norris, Richard P Tobin, Yiqun G Shellman
Immune checkpoint inhibitors (ICIs) are now the first-line treatment for patients with advanced melanoma. Despite promising clinical results, many patients fail to respond to these therapies. BH3 mimetics, a novel class of small molecule inhibitors that bind and inhibit anti-apoptotic members of the BCL2 family proteins such as BCL2 or MCL1, have been very successful in treating hematologic malignancies. However, there are limited studies on the immunomodulatory role of the BH3 mimetics. Several factors contribute to ICI resistance including myeloid-derived suppressor cells (MDSCs) that exert immunosuppressive effects through direct and indirect inhibition of antitumor immunity...
March 8, 2024: Cell Death & Disease
https://read.qxmd.com/read/38447451/changes-in-chromatin-accessibility-and-transcriptional-landscape-induced-by-hdac-inhibitors-in-tp53-mutated-patient-derived-colon-cancer-organoids
#8
JOURNAL ARTICLE
Teresa Gagliano, Emanuela Kerschbamer, Umberto Baccarani, Martina Minisini, Eros Di Giorgio, Emiliano Dalla, Christian X Weichenberger, Vittorio Cherichi, Giovanni Terrosu, Claudio Brancolini
Here we present the generation and characterization of patient-derived organoids (PDOs) from colorectal cancer patients. PDOs derived from two patients with TP53 mutations were tested with two different HDAC inhibitors (SAHA and NKL54). Cell death induction, transcriptome, and chromatin accessibility changes were analyzed. HDACIs promote the upregulation of low expressed genes and the downregulation of highly expressed genes. A similar differential effect is observed at the level of chromatin accessibility...
March 4, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38437959/ursolic-acid-alleviates-paclitaxel-induced-peripheral-neuropathy-through-ppar%C3%AE-activation
#9
JOURNAL ARTICLE
Yulian Yang, Zhongzheng He, Shuangchan Wu
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) reduces the overall quality of life and leads to interruption of chemotherapy. Ursolic acid, a triterpenoid naturally which presents in fruit peels and in many herbs and spices, can function as a peroxisome proliferator-activated receptor γ (PPARγ) agonist, and has been widely used as an herbal medicine with a wide spectrum of pharmacological activities, including anti-cancer, anti-inflammatory and neuroprotective effect...
March 2, 2024: Toxicology and Applied Pharmacology
https://read.qxmd.com/read/38423670/apoptotic-potential-and-molecular-docking-of-3-4-dihydro-lactucin-a-compound-with-anticancer-properties-derived-from-microbispora-rosea-al22
#10
JOURNAL ARTICLE
Thongchai Taechowisan, Thanaporn Chuen-Im, Waya S Phutdhawong
BACKGROUND/AIM: Tetrazolium-based cell proliferation assays using MDA-MB-231 and HeLa cells revealed that 3,4-dihydro-lactucin (3,4-DHL), a compound isolated from Microbispora rosea AL22, possesses anticancer properties. Apoptotic cell death was observed in 3,4-DHL-treated cells. Lactucopicrin, a related compound, reportedly exerts anticancer activity against different cancer types. However, data on the anticancer mechanism of lactucins are limited. This study aimed to investigate apoptosis induction in MDA-MB-231 cells treated with 3,4-DHL...
March 2024: Anticancer Research
https://read.qxmd.com/read/38397018/synergistic-anticancer-activity-of-plumbagin-and-xanthohumol-combination-on-pancreatic-cancer-models
#11
JOURNAL ARTICLE
Ranjith Palanisamy, Nimnaka Indrajith Kahingalage, David Archibald, Ilaria Casari, Marco Falasca
Among diverse cancers, pancreatic cancer is one of the most aggressive types due to inadequate diagnostic options and treatments available. Therefore, there is a necessity to use combination chemotherapy options to overcome the chemoresistance of pancreatic cancer cells. Plumbagin and xanthohumol, natural compounds isolated from the Plumbaginaceae family and Humulus lupulus, respectively, have been used to treat various cancers. In this study, we investigated the anticancer effects of a combination of plumbagin and xanthohumol on pancreatic cancer models, as well as the underlying mechanism...
February 16, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38392190/molecular-characterization-and-expression-changes-of-the-bcl2l13-gene-in-response-to-hypoxia-in-megalobrama-amblycephala
#12
JOURNAL ARTICLE
Axin Zhang, Xuefei Guo, Kaikai Bao, Danyang Wu, Hong Liu, Zexia Gao, Huanling Wang
Hypoxia is a unique environmental stress, which not only reflects the insufficient oxygen supply of cells and tissues, but also occurs in various physiological and pathological environments. Mitophagy as a selective autophagy can recover and utilize damaged organelles and misfolded proteins to ensure normal cell functions and promote cell survival. Bcl2l13 (B-cell lymphoma-2 like 13) is reported to induce mitophagy as a functional mammalian homolog of Atg32. However, the function of the bcl2l13 gene is still unclear in fish...
January 25, 2024: Current Issues in Molecular Biology
https://read.qxmd.com/read/38371625/pbrm1-loss-is-associated-with-increased-sensitivity-to-mcl1-and-cdk9-inhibition-in-clear-cell-renal-cancer
#13
JOURNAL ARTICLE
Norman Fultang, Ashley M Schwab, Sophia McAneny-Droz, Alexander Grego, Stephanie Rodgers, Brian Vidal Torres, Diane Heiser, Peggy Scherle, Neha Bhagwat
MCL1 is a member of the BCL2 family of apoptosis regulators, which play a critical role in promoting cancer survival and drug resistance. We previously described PRT1419, a potent, MCL1 inhibitor with anti-tumor efficacy in various solid and hematologic malignancies. To identify novel biomarkers that predict sensitivity to MCL1 inhibition, we conducted a gene essentiality analysis using gene dependency data generated from CRISPR/Cas9 cell viability screens. We observed that clear cell renal cancer (ccRCC) cell lines with damaging PBRM1 mutations displayed a strong dependency on MCL1...
2024: Frontiers in Oncology
https://read.qxmd.com/read/38338698/biomarkers-of-response-to-venetoclax-therapy-in-acute-myeloid-leukemia
#14
REVIEW
Carlos Rodríguez-Medina, Ruth Stuckey, Cristina Bilbao-Sieyro, María Teresa Gómez-Casares
Recent progress in the use of massive sequencing technologies has greatly enhanced our understanding of acute myeloid leukemia (AML) pathology. This knowledge has in turn driven the development of targeted therapies, such as venetoclax, a BCL-2 inhibitor approved for use in combination with azacitidine, decitabine, or low-dose cytarabine for the treatment of newly diagnosed adult patients with AML who are not eligible for intensive chemotherapy. However, a significant number of AML patients still face the challenge of disease relapse...
January 24, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38316746/efficacy-of-novel-agents-against-cellular-models-of-familial-platelet-disorder-with-myeloid-malignancy-fpd-mm
#15
JOURNAL ARTICLE
Christopher P Mill, Warren C Fiskus, Courtney D DiNardo, Patrick Reville, John A Davis, Christine E Birdwell, Kaberi Das, Hanxi Hou, Koichi Takahashi, Lauren Flores, Xinjia Ruan, Xiaoping Su, Sanam Loghavi, Joseph D Khoury, Kapil N Bhalla
Germline, mono-allelic mutations in RUNX1 cause familial platelet disorder (RUNX1-FPD) that evolves into myeloid malignancy (FPD-MM): MDS or AML. FPD-MM commonly harbors co-mutations in the second RUNX1 allele and/or other epigenetic regulators. Here we utilized patient-derived (PD) FPD-MM cells and established the first FPD-MM AML cell line (GMR-AML1). GMR-AML1 cells exhibited active super-enhancers of MYB, MYC, BCL2 and CDK6, augmented expressions of c-Myc, c-Myb, EVI1 and PLK1 and surface markers of AML stem cells...
February 5, 2024: Blood Cancer Journal
https://read.qxmd.com/read/38311257/wp1066-a-small-molecule-inhibitor-of-stat3-chemosensitizes-paclitaxel-resistant-ovarian-cancer-cells-to-paclitaxel-by-simultaneously-inhibiting-the-activity-of-stat3-and-the-interaction-of-stat3-with-stathmin
#16
JOURNAL ARTICLE
Jun Yang, Nanjing Li, Xinyu Zhao, Wenhao Guo, Yang Wu, Chunlai Nie, Zhu Yuan
Paclitaxel is widely used to treat cancer, however, drug resistance limits its clinical utility. STAT3 is constitutively activated in some cancers, and contributes to chemotherapy resistance. Currently, several STAT3 inhibitors including WP1066 are used in cancer clinical trials. However, whether WP1066 reverses paclitaxel resistance and the mechanismremains unknown. Here, we report that in contrast to paclitaxel-sensitive parental cells, the expressions of several pro-survival BCL2 family members such as BCL-2, BCL-XL and MCL-1 are higher in paclitaxel-resistant ovarian cancer cells...
February 2, 2024: Biochemical Pharmacology
https://read.qxmd.com/read/38311091/characterization-and-functional-analysis-of-socs9-from-orange-spotted-grouper-epinephelus-coioides-during-virus-infection
#17
JOURNAL ARTICLE
Junxi Chen, Zhaofeng Chen, Yi Li, Bei Wang, Yishan Lu, Jichang Jian, Jufen Tang, Jia Cai
The suppressor of cytokine signaling (SOCS) proteins family have twelve members including eight known mammalian SOCS members (CISH, SOCS1-7) and four new discovery members (SOCS3b, SOCS5b, SOCS8 and SOCS9) that is regarded as a classic feedback inhibitor of cytokine signaling. Although the function of the mammalian SOCS proteins have been well studied, little is known about the roles of SOCS in fish during viral infection. In this study, the molecular characteristics of SOCS9 from orange-spotted grouper (Epinephelus coioides, EcSOCS9) is investigated...
February 2, 2024: Fish & Shellfish Immunology
https://read.qxmd.com/read/38278978/albendazole-inhibits-colon-cancer-progression-and-therapy-resistance-by-targeting-ubiquitin-ligase-rnf20
#18
JOURNAL ARTICLE
Iram Fatima, Rizwan Ahmad, Susmita Barman, Saiprasad Gowrikumar, Kristina Pravoverov, Mark Primeaux, Kurt W Fisher, Amar B Singh, Punita Dhawan
BACKGROUND: The repurposing of FDA-approved drugs for anti-cancer therapies is appealing due to their established safety profiles and pharmacokinetic properties and can be quickly moved into clinical trials. Cancer progression and resistance to conventional chemotherapy remain the key hurdles in improving the clinical management of colon cancer patients and associated mortality. METHODS: High-throughput screening (HTS) was performed using an annotated library of 1,600 FDA-approved drugs to identify drugs with strong anti-CRC properties...
January 26, 2024: British Journal of Cancer
https://read.qxmd.com/read/38273334/characterization-modeling-and-anticancer-activity-of-l-arginase-production-from-marine-bacillus-licheniformis-of2
#19
JOURNAL ARTICLE
Manal S Selim, Marwa M Mounier, Sayeda A Abdelhamid, Ahmed Abdelghani Hamed, Mostafa M Abo Elsoud, Sahar S Mohamed
BACKGROUND: L-arginase, is a powerful anticancer that hydrolyzes L-arginine to L-ornithine and urea. This enzyme is widely distributed and expressed in organisms like plants, fungi, however very scarce from bacteria. Our study is based on isolating, purifying, and screening the marine bacteria that can produce arginase. RESULTS: The highest arginase producing bacteria will be identified by using microbiological and molecular biology methods as Bacillus licheniformis OF2...
January 25, 2024: BMC Biotechnology
https://read.qxmd.com/read/38203479/andrographolide-alleviates-oxidative-damage-and-inhibits-apoptosis-induced-by-ihnv-infection-via-ctsk-bcl2-cytc-axis
#20
JOURNAL ARTICLE
Qi Liu, Linfang Li, Jingzhuang Zhao, Guangming Ren, Tongyan Lu, Yizhi Shao, Liming Xu
Infectious hematopoietic necrosis virus (IHNV) is an important pathogen that causes significant economic losses to salmon trout farming. Although vaccines have been invented for the treatment of IHNV, findings from our previous survey show that breeding enterprises and farmers require effective oral drugs or immune enhancers. However, studies on the development of oral drugs are limited. In the present study, we used bioinformatics methods to predict the protein targets of andrographolide (Andro) in IHNV. Cells were infected with IHNV, and the effect of andrographolide was explored by evaluating the expression levels of genes implicated in oxidative stress, activities of antioxidant enzymes, and the expression of genes implicated in apoptosis and necrosis...
December 25, 2023: International Journal of Molecular Sciences
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