Chemotherapy最新文献

Introduction: The chemoresistance mechanism of diffuse large B-cell lymphoma (DLBCL) is still poorly understood, and patient prognosis remains unsatisfactory. This study aimed to investigate drug resistance mechanisms in non-germinal center B-cell-like (non-GCB) DLBCL.

Methods: Doxorubicin (DOX)-resistant OCI-Ly3 cells were generated through long-term incubation of cells in a medium with gradually increasing DOX concentrations. The expression levels of genes related to drug metabolism were determined using a functional gene grouping polymerase chain reaction (PCR) array. Drug-resistant proteins were identified using bioinformatics, and molecular association networks were subsequently generated. The association and mechanism of key genes were determined using a dual-luciferase reporter assay System and chromatin immunoprecipitation (ChIP). The expression of drug-resistant genes and target genes was then measured using Western blotting and immunohistochemistry. The correlation between gene expressions was analyzed using Spearman's rank correlation coefficient.

Results: Using the PCR array, MDR1 was identified as the key gene that regulates DOX resistance in OCI-Ly3/DOX-A100, a non-GCB DLBCL cell line. The dual-luciferase reporter assay system demonstrated that MDR1 transcription could be inhibited by PRDM1. ChIP results showed that PRDM1 had the ability to bind to the promoter region (-1,132 to -996) of MDR1. In OCI-Ly3/DOX cells, NF-κB activity and PRDM1 expression decreased with an increase in drug-resistant index, whereas MDR1 expression increased with enhanced drug resistance. Immunohistochemical analysis revealed that relative MDR1 expression was higher than that of PRDM1 in human DLBCL tissue samples. A negative correlation was observed between MDR1 and PRDM1.

Conclusion: In non-GCB DLBCL cells, NF-κB downregulates PRDM1 and thereby promotes MDR1 transcription by terminating PRDM1-induced transcriptional inhibition of MDR1. Such a mechanism may explain the reason for disease recurrence in non-GCB DLBCL after R-CHOP or combined CHOP with bortezomib treatment. Our findings may provide a potential therapeutic strategy for reducing drug resistance in patients with DLBCL.

Objective: In this study, we aimed to assess anxiety and sleep quality in cancer patients treated or followed up at our clinic at the time of the outbreak of the COVID-19 pandemic.

Methods: Seven hundred and sixty-one patients who were either treated or followed up at our oncology clinic between April 2020 and May 2020 were included. Patients were assessed with the State-Trait Anxiety Inventory (STAI) and the Pittsburgh Sleep Quality Index (PSQI).

Results: Mean scores of the 761 participants were STAI, 43.45 ± 9.34 (range, 23-75), and PSQI, 5.67 ± 4.24 (range, 0-19). Quality of sleep was found bad in 447 (58.7%) (global score ≥5). Univariate analyses demonstrated statistical differences by stage of cancer, status of treatment, subgroup of treatment, monthly income, and levels of education in anxiety and sleep quality levels. Multivariate analyses showed active treatment (OR: 21.4; 95% CI: 9.08-50.4; p < 0.001) as the major independent variable that affected sleep quality; the major independent variable associated with anxiety was low income (OR: 4.43; 95% CI: 1.69-11.5; p = 0.002).

Conclusion: Anxiety and sleep quality levels were found comparable to pre-pandemic reports, and the pandemic was not observed to have additional negative impact on cancer patients. Also, universal basal anxiety and sleep disorder that accompany cancer or active treatment were observed in our study. The accurate effects of the pandemic can be analyzed in further studies using repeated data obtained from the same patient group.

Background: Some chemotherapeutic agents cause carnitine deficiency, which causes general fatigue. However, there is no study on carnitine deficiency in patients with chronic myeloid leukemia (CML) during tyrosine kinase inhibitor (TKI) therapy.

Objective: In this study, we investigated carnitine concentrations in patients with CML receiving TKI therapy.

Method: This study included patients with well-controlled CML. Total carnitine and free carnitine concentrations were evaluated using the enzyme cycling method. The brief fatigue inventory (BFI) and cancer fatigue scale (CFS) were used to assess general fatigue developed during TKI therapy.

Results: Fifty-five patients on TKI therapy were included. Of these, 12 (21.8%) patients had low free carnitine concentrations. Free carnitine concentrations were higher in men than in women. Younger age was closely associated with lower free carnitine concentrations. TKI type, TKI dose, treatment response, or therapy duration were not associated with free carnitine concentrations. None of the scores (the global fatigue score with the BFI and CFS score) correlated with carnitine concentrations. Concentrations of free carnitine in patients in the treatment-free remission group were slightly higher than those in the TKI group, with only 9.1% having a low concentration of free carnitine.

Conclusion: Carnitine deficiency is probably not a major cause of general fatigue but may occur in patients with CML receiving TKI therapy.

Acute myeloid leukemia (AML) is the most common leukemia in adults. In spite of the most recent discoveries about the molecular landscape of this disease, the treatment of elderly and unfit young patients continues to be a great challenge. The hypomethylating agents (HMA) still represent an effective therapeutic option for these categories, especially for the low-risk subgroups. We report the case of a young patient with NPM1mut-AML who underwent a first cycle of intensive induction treatment, achieving a complete remission, but suffered from a serious life-threatening neurologic toxicity. Due to the ineligibility to further lines of intensive chemotherapy, we decided to consolidate the response with azacitidine, administered according to the regular schedule. The minimal residual disease (MRD), monitored through the NPM1 mutation at diagnosis, progressively decreased and became undetectable after 36 cycles of hypomethylating therapy. After 1 year from discontinuation of azacitidine, MRD remains undetectable. Therefore, HMA might still represent a feasible and effective option for patients with low-risk AML, especially when the standard chemotherapy is not indicated, or as maintenance therapy in nontransplantable patients.

Objectives: Emergence and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) have become a major universal health concern, limiting therapeutic options.

Methods: A total number of 37 MRSA isolates, including 19 clinical isolates from hospitalized patients and 18 colonizing isolates from health care workers were identified from 3 hospitals, in Gorgan, North of Iran. Antimicrobial susceptibility test was performed using the disk diffusion method and E-test. The presence of virulence and antibiotic resistance determinants were evaluated by PCR. The genotypical characterization was further analyzed using multi-locus sequence, spa, staphylococcal cassette chromosome, mec (SCCmec), and agr typing.

Results: The frequency of MRSA among S. aureus isolates was 38.14% (37/97). The most frequent S. aureus resistant isolates were found to be obstinate against penicillin (98%) and gentamicin (82.5%). Additionally, the lowest resistance rates were found against daptomycin (0%), vancomycin (2.7%), and quinupristin-dalfopristin (5.4%). All MRSA isolates were susceptible to daptomycin with minimum inhibitory concentration (MIC)50/MIC90 of 0.25/0.5 μg/mL. One isolate belonging to sequence type 239 (ST239)-SCCmecIII/t037 clone (MIC ≥16 μg/mL) was resistant to vancomycin. All but 1 isolate that shares ST22-SCCmec IV/t790 strain were positive for both tsst and pvl genes. The most predominant MRSA isolates (27%) were associated with ST239-SCCmec III/t037, and ST239-SCCmec III/t924 (16.2%) clones, subsequently. In our study, circulating MRSA strains were genetically diverse with a high prevalence of ST239-SCCmec III/t037 clone.

Conclusion: These findings emphasize the need for future and continuous surveillance studies on MRSA to prevent the dissemination of existing multidrug resistance MRSA clones in an effective manner.

Introduction: Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have limited oral therapeutic options and pose significant clinical challenges. The goal of this study was to evaluate the in vitro synergy between CFM and AMC against ESBL E. coli with aims to identify an oral treatment option for UTIs.

Methods: Minimum inhibitory concentrations (MICs) of CFM in the presence of AMC were determined for 46 clinical isolates by placing a CFM Etest on a plate with AMC impregnated in the agar. Isolates with CFM MIC ≤1 μg/mL in the presence of AMC were considered susceptible to the CFM and AMC combination. Five isolates were then selected for further testing using time-kill analysis in the presence of CFM, AMC, and CFM with AMC. Time-kill curves were plotted to determine synergy over 24 h.

Results: AMC improved the activity of CFM against ESBL E. coli isolates by 128-fold in the Etest analysis with 85% of tested isolates being susceptible to the combination. A fourfold or greater reduction in CFM MIC was exhibited in 44 of 46 (96%) isolates when in the presence of AMC. Synergy and bactericidal activity between CFM and AMC were exhibited in each of the five isolates tested by time-kill analysis.

Discussion/conclusion: This study found that AMC improves the activity of CFM against ESBL E. coli and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL E. coli UTIs.

Objective: The objective was to study the effectiveness and safety of super-selective bronchial arterial infusion (SBAI) chemotherapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).

Methods: The clinical data of 120 advanced NSCLC patients were retrospectively analyzed. Among them, 60 NSCLC patients were treated with SBAI method, another 60 NSCLC patients received systemic intravenous chemotherapy as the control group. The efficacy and safety between two groups of patients were compared.

Results: The objective response rate and disease control rate of NSCLC patients treated with SBAI were significantly higher than those of the control group (p < 0.05). The 3-month progression-free survival (PFS) rate (96.67%) and 6-month PFS rate (86.67%) of the SBAI group were significantly higher than those of the control group (73.33% and 56.67%) (p < 0.01). After treatment, the FACT-L scores of patients in the SBAI group were significantly higher than those of the control group (p < 0.05). The scores of all the 13 core symptom items and six symptom interference items of NSCLC patients in the SBAI group were lower than those of the control group (p < 0.05). The adverse reactions rate in the SBAI group were significantly lower than those in the control group (p < 0.05).

Conclusion: The short-term efficacy of SBAI chemotherapy for advanced NSCLC is significantly higher than that of traditional peripheral intravenous chemotherapy, and it can significantly improve patients' quality of life and reduce the incidence of adverse reactions.

Introduction: We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC).

Methods: CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry.

Results: Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time.

Conclusion: CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

Aim: The optimal number of neoadjuvant chemotherapy (NACT) cycles is unclear in epithelial ovarian cancer. Our study aimed to evaluate the effect of the number of NACT cycles before interval debulking surgery on survival.

Methods: Data of 221 patients with advanced-stage serous epithelial ovarian cancer (EOC) were retrospectively evaluated. The patients were divided into groups as who received 3 cycles of NACT (group A), 4-5 cycles of NACT (group B), and 6 cycles of NACT (group C).

Results: There were 67 (30%) patients in group A, 70 (32%) in group B, and 84 (38%) in group C. Median overall survival (OS) was 61 (range 43-79) months for group A, 44 (range 36-52) months for group B, and 39 (range 27-50) months for group C. In addition, median disease-free survival (DFS) was 23.1 (range 8.5-32.1) months for group A, 19.2 (range 10.1-28.4) months for group B, and 21.5 (range 16-27) months for group C. Patients receiving >3 NACT cycles had worse OS than patients who received 3 NACT cycles (for group A vs. B, p = 0.018; for group A vs. C, p = 0.049). However, in terms of DFS, patients receiving 3 NACT cycles had no statistically significant difference compared to patients who received >3 NACT cycles.

Conclusions: Patients with advanced-stage serous EOC who received more than 3 cycles of NACT had poor OS. However, there was no statistical difference in terms of DFS. In addition, >3 cycles of NACT did not increase the probability of achieving complete cytoreduction at the time of surgery.