Irinotecan hydrochloride (CPT-11) is an effective anticancer drug, and its metabolic pathway has been well studied. Nevertheless, in human hepatocellular carcinoma (HCC), its cytotoxicity is less well studied and the determination of its chemosensitivity is unclear. We, therefore, examined chemosensitivities of HCC cell lines for CPT-11 and SN-38, and mRNA expressions of several molecules in their metabolic pathway. Three markers were found to correlate well with chemosensitivity: breast cancer resistance protein (BCRP), cytochrome P450 (CYP) 3A4 and uridine diphosphate-glucuronosyl transferase (UGT) 1A1. Next, CYP3A4/UGT1A1/BCRP inhibitor naringenin and BCRP inhibitor elacridar were tested for enhancement of their chemosensitivity. Both of naringenin and elacridar separately enhanced the sensitivity for CPT-11 and SN-38 in KYN-2 cells abundantly expressing BCRP, CYP3A4/5 and UGT1A1, but not in KYN-1 cells expressing lower levels. However, naringenin had little effect on the sensitivity in JHH-4 and HLE cells with higher CYP3A4/5 and lower UGT1A1 and BCRP expression. On the other hand, naringenin and elacridar significantly increased the chemosensitivity for CPT-11 and SN-38 in the KYN-1-derived cells artificially overexpressing BCRP. Furthermore, flow cytometric analysis showed that naringenin raised intracellular accumulation of CPT-11 as well as elacridar. Those results suggest that BCRP is one of the chemosensitivity determinants of CPT-11 in HCC cells and its inhibition might be critical for cells expressing abundant BCRP.
Rising oncology healthcare costs have led to value-based care reimbursement models that coordinate care and improve quality while reducing overall spending. These models are increasingly important for traditional Medicare and other payers. To compare the incidence of adverse events (AEs), AE-associated excess costs, and total cost of care (TCOC) of 3 cohorts receiving first-line treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC).
Department of Colorectal Surgery, The Affiliated Xuzhou Clinical College of Xuzhou Medical University, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.
Background: The optimal second-line systemic treatment for metastatic colorectal cancer (mCRC) is inconclusive.
Methods: We searched PubMed, Web of Science, EMBASE, and Cochrane Library for RCTs comparing second-line systemic treatments for mCRC from the inception of each database up to February 3, 2024. Markov Chain Monte Carlo (MCMC) technique was used in this network meta-analysis (NMA) to generate the direct and indirect comparison results among multiple treatments in progression-free survival (PFS), overall response rate (ORR), overall survival (OS), complete response (CR), partial response (PR), grade 3 and above adverse events (Grade ≥ 3AE), and any adverse events (Any AE).
Cancer is characterized by uncontrolled cell growth and spreading throughout the body. This study employed computational approaches to investigate 18 naturally derived anticancer piscidinol A derivatives (-) as potential therapeutics. By examining their interactions with 15 essential target proteins (HIF-1α, RanGAP, FOXM1, PARP2, HER2, ERα, NGF, FAS, GRP78, PRDX2, SCF complex, EGFR, Bcl-xL, ERG, and HSP70) and comparing them with established drugs such as camptothecin, docetaxel, etoposide, irinotecan, paclitaxel, and teniposide, compound emerged as noteworthy.
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by heterogeneous molecular changes across diverse cell types, posing significant challenges for treatment development. To address this, we introduced a cell-type-specific, multi-target drug discovery strategy grounded in human data and real-world evidence. This approach integrates single-cell transcriptomics, drug perturbation databases, and clinical records.
Introduction: Nanoliposomal irinotecan (nal-IRI) + 5- fluorouracil (FU)/leucovorin (LV) is the new standard second-line therapy for advanced pancreatic cancer (PC). Tegafur, gimeracil, and oteracil potassium (S-1) have been used in advanced PC after gemcitabine (GEM) plus nab-paclitaxel treatment, but the clinical difference between nal-IRI+5-FU/LV and S-1 remains unclear.
Methods: We retrospectively compared the efficacy and safety of nal-IRI+5-FU/LV and S-1 in patients with advanced PC refractory to GEM plus nab-paclitaxel.
