Journal of Chemotherapy最新文献

The tumor microenvironment (TME) plays a crucial role in cancer progression and treatment response. It comprises a complex network of stromal cells, immune cells, extracellular matrix, and blood vessels, all of which interact with cancer cells and influence tumor behaviour. This review article provides an in-depth examination of the TME, focusing on stromal cells, blood vessels, signaling molecules, and ECM, along with commonly available therapeutic compounds that target these components. Moreover, we explore the TME as a novel strategy for discovering new anti-tumor drugs. The dynamic and adaptive nature of the TME offers opportunities for targeting specific cellular interactions and signaling pathways. We discuss emerging approaches, such as combination therapies that simultaneously target cancer cells and modulate the TME. Finally, we address the challenges and future prospects in targeting the TME. Overcoming drug resistance, improving drug delivery, and identifying new therapeutic targets within the TME are among the challenges discussed. We also highlight the potential of personalized medicine and the integration of emerging technologies, such as immunotherapy and nanotechnology, in TME-targeted therapies. This comprehensive review provides insights into the TME and its therapeutic implications. Understanding the TME's complexity and targeting its components offer promising avenues for the development of novel anti-tumor therapies and improved patient outcomes.

The current study was designed to assess the response to treatment, as well as clinical and survival outcomes, across different breast cancer subtypes in patients who underwent neoadjuvant chemotherapy (NAC). From 2014 to 2019, a total of 139 patients who were histologically confirmed to have breast cancer, underwent NAC, and subsequently received breast and axillary surgery, were retrospectively included in this study. The rates of pathological complete response (pCR) to NAC were significantly higher for HER2-positive and triple-negative subtypes than for luminal A and HER2-negative subtypes (p = 0.013). Multivariate analysis for disease-free survival (DFS) revealed that tumour grade and the presence of pCR were independent prognostic factors. The presence or absence of a pCR with NAC was an independent prognostic indicator in the multivariate analysis for overall survival (OS). Lastly, achieving a pCR was independently predicted by ¹⁸F-FDG PET/CT findings, the HER2-positive subtype, and the triple-negative subtype. Despite the inherent methodological limitations, our findings underscore the significance of identifying predictive markers to tailor NAC plans, with the aim of improving survival outcomes.

The main aim of this study was to compare and analyze the effectiveness of treatment regimens using ceftazidime/avibactam (CAZ/AVI) versus fosfomycin plus meropenem (FOS/MER) for managing bloodstream infections (BSI) or ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) in critically ill patients. Between 4 January 2019, and 16 July 2023, adult patients (≥18 years old) diagnosed with BSI or VAP due to culture confirmed CRKP in ICU of a tertiary care hospital were investigated retrospectively. A total of 71 patients were categorized into two groups: 30 patients in CAZ/AVI-based, and 41 patients in FOS/MER-based group. No substantial disparities were found in the total duration of ICU hospitalization, as well as the 14- and 30-day mortality rates, between patients treated with CAZ/AVI-based and FOS/MER-based therapeutic regimens. We consider that our study provides for the first time a comprehensive understanding of treatment outcomes and associated risk factors among patients with CRKP-related infections.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

Two Enterobacter hormaechei isolates harbouring three carbapenemase genes each, were isolated from two patients from different ICUs at University Hospital Centre Zagreb, Croatia, which is to our knowledge, the first report of triple carbapenemase (bla_VIM-2, bla_NDM-1, and bla_OXA-48) co-existence in E. hormachei strains and also among Enterobacterales members in Croatia. Antimicrobial susceptibility testing showed susceptibility only to colistin and amikacin. The production of carbapenemases was phenotypically tested by immunochromatographic assay and confirmed by PCR. Detailed analysis by Whole Genome Sequencing (WGS) of short reads by Illumina and long reads by Oxford Nanopore Technologies (ONT) was additionally performed and showed that both isolates belonged to ST200. They were separated by 98 Single Nucleotide Polymorphisms (SNPs) having variations in the number of bla_VIM-2 genes on the chromosome, the number of bla_NDM-1 genes on the plasmid, non-identical bla_NDM-1 plasmids, different plasmid content in general, and only one isolate carried a 94 kb prophage.

With the development of newer biomarkers in the diagnosis of gastric cancer (GC), therapeutic targets are emerging and molecular-targeted therapy is in progress RNA interference has emerged as a promising method of gene targeting therapy. However, naked small interfering RNA (siRNA) is unstable and susceptible to degradation, so employing vectors for siRNA delivery is the focus of our research. Therefore, we developed LMWP modified PEG-SS-PEI to deliver siRNA targeting BRD4 (L-NPs/siBRD4) for GC therapy. L-NPs/siBRD4 were prepared by electrostatic interaction and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The release characteristics, cellular uptake and intracellular localization were also investigated. The in vitro anticancer activity of the prepared nanoparticles was analysed by MTT, Transwell invasion and wound healing assay. Quantitative real time-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of gene silencing. The results showed that the optimal N/P was 30 and the prepared L-NPs/siBRD4 uniformly distributed in the system with a spherical and regular shape. L-NPs/siBRD4 exhibited an accelerated release in GSH-containing media from 12h to 24h. The uptake of L-NPs/siBRD4 was enhanced and mainly co-localized in the lysosomes. After 6h incubation, LMWP modified PEG-SS-PEI helped siRNA escape from the lysosomes and diffused into the cytoplasm. L-NPs/siBRD4 significantly inhibited the proliferation, migration and invasion of cells. This might be related with the silence of BRD4, then inhibition of PI3K/Akt and c-Myc. Our results demonstrate that L-NPs/siBRD4 are a novel delivery system with anticancer, which may provide a more effective strategy for GC treatment.

Few studies have been conducted to evaluate the efficacy of HAIC using circulating tumour cells (CTCs). In this study, a total of 100 patients who received HAIC treatment and CTC detection were selected. The results showed that after HAIC treatment, the levels of CTC, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) decreased. Postoperative progression-free survival (PFS) rates between patients with positive and negative preoperative CTC results, and for CA19-9, CEA were significantly different. The positive rate of CTCs was 61% before chemotherapy and 23% after chemotherapy, and the correlation coefficient between the two was 0.385. Those whose CTC values increased after chemotherapy had shorter PFS rates. CTCs are an independent predictor of recurrence. Patients with CTC-positive results are more susceptible to recurrence. The CTC count in peripheral blood has a close bearing on the postoperative chemotherapy efficacy of patients with CRC and affects patients' PFS.

This retrospective study investigated whether piperacillin/tazobactam (PIPC/TAZ) monotherapy affects renal function compared to cefepime (CFPM) or meropenem (MEPM) monotherapy. Hospitalized patients who received PIPC/TAZ, CFPM, or MEPM monotherapy between April 2021 and December 2022 were enrolled in this study. We used inverse probability of treatment weighting (IPTW) to balance baseline characteristics and compare the incidence of acute kidney injury (AKI). Overall, 259, 104, and 98 patients were enrolled in the PIPC/TAZ, CFPM, and MEPM groups, respectively. After applying IPTW, PIPC/TAZ administration was found to be significantly associated with an increased risk of AKI (odds ratio [OR]: 6.75, 95% confidence interval [CI]: 1.30-34.8, p = 0.023 compared to CFPM; and OR: 7.71, 95% CI: 1.00-59.2, p = 0.049 compared to MEPM). PIPC/TAZ monotherapy may be associated with a higher risk of AKI than CFPM or MEPM monotherapy.

We review the case of a 58-year-old female on extracorporeal membrane oxygenation (ECMO) support diagnosed with invasive pulmonary aspergillosis (IPA). Intravenous isavuconazole was started, requiring dose escalation to achieve isavuconazole trough concentration (ISA-Cmin) within the therapeutic range (2.5-5.0 μg/mL). For more than 4 months, she maintained a dose of 200 mg q12h, with a median ISA-Cmin of 3.4 (interquartile range [IQR]: 3.1-4.9) µg/mL. Throughout this interval, 17 assessments of ISA-Cmin were performed (weekly). Of these, 82% (14/17) were within the therapeutic range, with an intra-individual variability of 36.8%. Although no signs of hepatotoxicity were observed, she experienced short-term gastrointestinal adverse events related to potential isavuconazole over-exposure (ISA-Cmin > 5.0 μg/mL). ECMO circuit changes did not appear to affect ISA-Cmin. She was not obese (IMC ≈ 25 kg/m²) and did not require other extracorporeal therapy, but hypoalbuminemia may have contributed to an increase in unbound isavuconazole fraction and consequently its clearance.