Rapid development of multiple drug resistance against current therapies is a major barrier in the treatment of cancer. Therefore, anticancer agents that can overcome acquired drug resistance in cancer cells are of great importance. Previously, we have demonstrated that ethyl 2-amino-4-(2-ethoxy-2-oxoethyl)-6-phenyl-4H-chromene-3-carboxylate (5a, sHA 14-1), a stable analogue of ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (6, HA 14-1), mitigates drug resistance and synergizes with a variety of cancer therapies in leukemia cells. Structure-activity relationship (SAR) studies of 5a guided the development of ethyl 2-amino-6-(3',5'-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (5q, CXL017), a compound with low micromolar cytotoxicity against a wide-range of hematologic and solid tumor cells. More excitingly, our studies of 5q in camptothecin (CCRF-CEM/C2) and mitoxantrone (HL-60/MX2) resistant cancer cells highlight its ability to selectively kill drug-resistant cells over parent cancer cells. 5q inhibits tumor cell growth through the induction of apoptosis, with detailed mechanism of its selectivity toward drug-resistant cancer cells under investigation. These results suggest that 5q is a promising candidate for treatment of cancers with multiple drug resistance.
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http://dx.doi.org/10.1021/jm9005059 | DOI Listing |
Blood Rev
January 2025
Department of Hematology, First Hospital of Jilin University, Changchun, Jilin, China. Electronic address:
Multiple myeloma (MM) remains incurable and patients eventually face the relapse/refractory dilemma. B cell maturation antigen (BCMA)-targeted immunotherapeutic approaches have shown great effectiveness in patients with relapsed/refractory MM, mainly including chimeric antigen receptor T cells (CAR-T), bispecific T cell engagers (TCEs), and antibody-drug conjugates (ADCs). However, their impact on long-term survival remains to be determined.
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January 2025
Department of Breast and Thyroid Surgery, The Qinghai Provincial People's Hospital, Xining 810007, China. Electronic address:
This study utilizes single-cell RNA sequencing data to reveal the transcriptomic characteristics of breast cancer and normal epithelial cells. Nine significant cell populations were identified through stringent quality control and batch effect correction. Further classification of breast cancer epithelial cells based on the PAM50 method and clinical subtypes highlighted significant heterogeneity between triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (NTNBC).
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Dermatology, the Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin, China. Electronic address:
Many atopic dermatitis (AD) patients have suboptimal responses to Dupilumab therapy. This study identified key genes linked to this resistance using multi-omics approaches to benefit more patients. We selected a prospective cohort of 54 CE treated with Dupilumab from the GEO database.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian 223300, Jiangsu Province, PR China; Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, Jiangsu Province, PR China. Electronic address:
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, which characterized by a high degree of heterogeneity in terms of clinical presentation, molecular phenotype, and genetic features. However, approximately 30 %-40 % of patients are refractory to standard chemotherapy, and their prognosis is poor. The emergence of small-molecule inhibitors, such as Bruton's tyrosine kinase inhibitors (BTKi), has greatly improved the treatment of DLBCL; however, drug resistance associated with small-molecule inhibitors has greatly limited their clinical application.
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January 2025
Animal Science College, Tibet Agriculture & Animal Husbandry University, Linzhi, 860000, China; The Provincial and Ministerial Co-founded Collaborative Innovation Center for R & D in Tibet Characteristic Agricultural and Animal Husbandry Resources, Linzhi 860000, China. Electronic address:
Unregulated pig farming practices expose pigs to fecal sewage and antibiotic stress, which are common health risk factors. Thus, its effects on the animals' intestinal microflora were investigated herein. In total, 2,315,563 high-quality sequences were obtained via amplitude sequencing and, after OUT clustering, the fecal sewage group was identified to have the highest number and the antibiotic exposure group the lowest.
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