Journal of Chemotherapy最新文献

A two-compartmental mathematical pharmacokinetic model with first-order elimination of patients receiving CAPD of 4 exchanges for 6 h with 2 L of dialysate used in each cycle was developed to predict daptomycin disposition in 120 h of therapy. The pharmacodynamic target was plasma AUC/MIC equal to or greater than 666. The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. Administering intraperitoneal 300 mg daily for 1 exchange daily regimen would be sufficient to treat peritonitis with S. aureus infection with MICs of 0.25 mg/L in patients undergoing CAPD. A higher dosage may be required for infections with a higher minimum inhibitory concentration. Pharmacodynamic targets and MICs significantly contributed to daptomycin doses in this setting. Clinical validation of our recommendations is recommended.

This cross-sectional study aimed to analyze the associated factors of poor nutrition in non-small cell lung cancer (NSCLC) patients after chemotherapy. Concretely, 176 NSCLC patients who attended our hospital from June 2020 to December 2022 were enrolled. Standard-compliant patients were categorized into nutrition group (n = 38) and malnutrition group (n = 70) according to different nutrition statuses. Baseline characteristics and nutrition level were assessed. Associated factors of poor nutrition were analyzed by logistic regression analysis. There were obvious differences between nutrition group and malnutrition group in terms of age (P = 0.041), body mass index (BMI, p = 0.021), residence (P  = 0.023), per capita monthly income of family (P  = 0.023), tumor staging (P  = 0.017), Karnofsky (KPS) score (P  < 0.001), effect of chemotherapy (P  = 0.045), and nutrition support before chemotherapy only (P  = 0.023) and perichemotherapy (P = 0.011). The higher proportion of NSCLC patients was found in malnutrition group relative to nutrition group in terms of having poor nutritional cognition (67.14% vs. 47.37%, P  = 0.045), and lacking access to vitamins (65.71% vs. 44.74%, P  = 0.047) and trace elements (57.14% vs. 36.84%, P  = 0.044). BMI <18.5 (OR = 3.707, P = 0.007, 95%CI (1.434-9.586)), residence in village (OR = 3.426, P = 0.013, 95%CI (1.291-9.092)), and KPS score ≤70 (OR = 7.608, P < 0.001, 95%CI (2.842-20.367)) were associated factors for poor nutrition. Collectively, BMI, residence, and KPS score were associated factors of poor nutrition in NSCLC patients after chemotherapy.

The rapid rise of nosocomial infections and the growing ineffectiveness of frontline antibiotics against Gram-negative bacteria (GNB) have put the healthcare sector under unprecedented stress. In this scenario, colistin, an antibiotic of the polymyxin class, has become the last resort treatment option. However, the unrestricted use of colistin in the preceding decades has led to the emergence of colistin-resistant (Col^R) bacterial strains. Unfortunately, comprehensive data on the prevalence of Col^R nosocomial pathogens in India are scarce. This study was conducted to address this information gap. A systematic review and meta-analysis were conducted to determine the prevalence of Col^R among the nosocomial GNB species in India and their geographical distribution. A systematic search of the online databases was performed and eligible studies meeting the inclusion criteria were used for qualitative synthesis. The combined event rate and 95% confidence interval were estimated using a forest plot with a random-effect model. Cochrane Q statistics and I² statistics were used to detect possible heterogeneity. From a total of 1865 retrieved records from 4 databases, 33 studies were included in the study. Among the most common nosocomial pathogens, Klebsiella pneumoniae showed a rate of Col^R at 16.1% (95% CI: 10.1 to 24.6), followed by Pseudomonas aeruginosa (13.3%) (95% CI: 9.1 to 19.2), Acinetobacter baumannii (10%) (95% CI: 7.5 to 13.2), and Escherichia coli (7.8%) (95% CI: 5.3 to 11.2). Interestingly, our analysis revealed that Enterobacter cloacae have the highest rate of Col^R at 27.9% (95% CI: 12.7 to 50.9). The results indicate that the prevalence of Col^R nosocomial pathogens vary among regions and over time; however, continuous monitoring, and sustained efforts are crucial to ensure the effectiveness of colistin antibiotic.

Better in vitro models are needed to identify active drugs to treat pancreatic adenocarcinoma (PAC) patients. We used 3D hanging drop cultures to produce spheroids from five PAC cell lines and tested nine FDA-approved drugs in clinical use. All PAC cell lines in 2D culture were sensitive to three drugs (gemcitabine, docetaxel and nab-paclitaxel), however most PAC (4/5) 3D spheroids acquired profound chemoresistance even at 10 µM. In contrast, spheroids retained sensitivity to the investigational drug triptolide, which induced apoptosis. The acquired chemoresistance was also transiently retained when cells were placed back into 2D culture and six genes potentially associated with chemoresistance were identified by microarray and confirmed using quantitative RT-PCR. We demonstrate the additive effect of gemcitabine and erlotinib, from the 12 different combinations of nine drugs tested. This comprehensive study shows spheroids as a useful multicellular model of PAC for drug screening and elucidating the mechanism of chemoresistance.

Colorectal cancer (CRC) is the second leading cause of cancer death, and about 10% of all malignancies are CRC. Cancer stem cells are considered main culprits in CRC treatment resistance and disease recurrence. This study explored the effects of tripartite motif containing 24 (TRIM24) and zinc finger protein, X-linked (ZFX) on CRC cell stemness and 5-FU resistance. A 5-FU-resistant cell line (HT29-5-FU) was constructed for functional analysis of CRC 5-FU-resistant cells. qRT-PCR and western blot (WB) were employed to analyze mRNA and protein levels of ZFX in 5-FU resistant cells and sensitive cells. WB was also utilized to analyze the surface markers of stem cells in each group. CCK-8 assay determined the IC₅₀ values of different cell groups treated with 5-FU. The sphere-forming ability of cells in each group was determined using tumor sphere assay. Dual-luciferase reporter gene assay validated binding of ZFX to TRIM24. ZFX was highly expressed in HT29-5-FU cells. Silencing ZFX significantly reduced the 5-FU resistance and IC₅₀ value of HT29-5-FU cells, and the surface markers and cell sphere-forming ability of stem cells were also significantly reduced. The function of HT29 cells was opposite when ZFX was overexpressed. In CRC cells, TRIM24 was an upstream transcription factor of ZFX, and they interacted with each other. TRIM24 activated the expression of ZFX to influence the stemness and 5-FU resistance of cells. The TRIM24/ZFX regulatory axis affected the stemness of CRC cells and their sensitivity to 5-FU, providing potential drug targets for novel therapeutic avenues for CRC.

Caspases (cysteinyl aspartate-specific proteinases) are a group of structurally similar proteases in the cytoplasm that can be involved in cell differentiation, programmed death, proliferation, and inflammatory generation. Experts have found that caspase-3 can serve as a terminal splicing enzyme in apoptosis and participate in the mechanism by which cytotoxic drugs kill cancer cells. Breast cancer (BC) has become the most common cancer among women worldwide, posing a severe threat to their lives. Finding new therapeutic targets for BC is the primary task of contemporary physicians. Numerous studies have revealed the close association between caspase-3 expression and BC. Caspase-3 is essential in BC's occurrence, invasion, and metastasis. In addition, Caspase-3 exerts anticancer effects by regulating cell death mechanisms. Traditional Chinese medicine acting through caspase-3 expression is increasingly used in clinical treatment. This review summarizes the biological mechanism of caspase-3 and research progress on BC. It introduces a variety of traditional Chinese medicine related to caspase-3 to provide new ideas for the clinical treatment of BC.

Resveratrol (RSV) has been found to have a cancer-suppressing effect in a variety of cancers, including non-small cell lung cancer (NSCLC). Studies have shown that sine oculis homeobox 4 (SIX4) and sphingosine kinase 2 (SPHK2) are tumour promoters of NSCLC. However, whether RSV regulates SIX4 and SPHK2 to mediate NSCLC cell functions remains unclear. NSCLC cell functions were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, transwell assay and wound healing assay. Protein expression levels were detected by western blot. SIX4 and SPHK2 mRNA levels in NSCLC tumour tissues were examined using quantitative real-time PCR. In addition, mice xenograft models were built to explore the impact of RSV on NSCLC tumour growth. RSV inhibited NSCLC cell proliferation, invasion and migration, while facilitated apoptosis. SIX4 and SPHK2 were up-regulated in NSCLC tissues and cells, and their expression was reduced by RSV. Knockdown of SIX4 and SPHK2 suppressed NSCLC cell growth, invasion and migration, and the regulation of RSV on NSCLC cell functions could be reversed by SIX4 and SPHK2 overexpression. RSV inactivated Wnt/β-catenin pathway via decreasing SIX4 and SPHK2 levels. In animal experiments, RSV reduced NSCLC tumour growth in vivo. RSV repressed NSCLC malignant process by decreasing SIX4 and SPHK2 levels to restrain the activity of Wnt/β-catenin pathway.