Wspolczesna Onkologia-Contemporary Oncology最新文献

Introduction: Previous research has shown that laminin α5 (LAMA5) is es-sential for a variety of biological processes, including cellular adhesion, cell differentiation, migration, and metastasis. However, the role of LAMA5 in bladder cancer (BC) has not been explored before. Therefore, we employed Mendelian randomization (MR) to investigate its involvement and identify underlying metabolic mechanisms.

Material and methods: Utilizing GWAS data from online databases, we employed integrated MR analyses to investigate the correlations between apoptosis-related genes, metabolites, and BC. We also confirmed the expression of LAMA5 in BC cell lines by qRT-PCR and further explored its cell proliferation, migration, and invasion abilities via the cell viability assay, wound healing, and transwell assays, respectively.

Results: Our findings suggested that LAMA5 could increase the risks of BC (OR = 1.0013, p < 0.05). Summary-data- based MR (SMR) results also confirmed the associations by cis-eQTLs (both p < 0.05). In in vitro experiments, the expression levels of LAMA5 were identified to be elevated across three different BC cell lines (p < 0.05). Knockdown of LAMA5 led to inhibition of cell proliferation, migration, and invasion, highlighting its potential as a key re-gulatory factor in BC (all p < 0.05). To further shed light on the metabolic mechanisms of LAMA5 involved in BC, MR results showed that LAMA5 was identified as a suppressor of dihydroorotate levels (OR = 0.8946, p < 0.05), which were inversely related to BC risk (OR = 0.9993, p < 0.05).

Conclusions: LAMA5 was identified as a novel eQTL-mediated oncogenic gene in BC through influencing cell proliferation, migration, and invasion, with its underlying metabolic mechanism involving inhibition of dihydroorotate levels.

Introduction: Acute myeloid leukemia (AML) is a biologically heterogeneous, malignant disease of the hema-topoietic system. In ~10% of AML cases, the full-length isoform (p42) of the transcription factor CCAAT/enhancer binding protein alpha (C/EBPα), an essential regulator of granulopoiesis, is mutated. N-terminal mutations shift expression towards the truncated C/EBPα isoform (p30), promoting proliferation of leukaemic blasts. The self-renewal ability of AML cells can be suppressed by the short isoform of the long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1.1). This study investigated whether C/EBPα-p42 or the "mutated" p30 isoforms directly regulate NEAT1.1 or the long isoform NEAT1.2 during differentiation.

Material and methods: In 184 de novo AML patients with wild-type CEBPA and 13 de novo AML patients with mutated CEBPA from the TCGA database, expression of lncRNA NEAT1 was analyzed. In vitro, a K562-based cell model for inducible granulopoietic differentia-tion of the isoforms C/EBPα-p42 and C/EBPα-p30 was used to investigate the regulation of NEAT1.1 or NEAT1.2 using qRT-PCR.

Results: NEAT1 shows significantly higher expression in wild-type CEBPA patients than in mutated CEBPA patients. In vitro, after 24 h of differentiation induced by translocation of the C/EBPα-p42 isoform from the cytoplasm into the nucleus, the expression of lncRNA NEAT1.1 is upregulated 2.15-fold. For the C/EBPα p30 isoform, NEAT1.1 expression is upregulated 1.59-fold. NEAT1.2 was not significantly regulated.

Conclusions: NEAT1.1 is regulated by C/EBPα in AML. Consequently, a mutation in the CEBPA gene not only influences direct targets in gene regulation but also affects targets regulated by NEAT1.1.

Introduction: This study investigated the impact of alterations in six key genes (HMGB1, ROS1, IL6, FGFR1, FGFR2, and TLR4) on survival outcomes in patients with esophageal squamous cell carcinoma (ESCC). These genes are implicated in signaling pathways such as RTK-Ras, PI3K-Akt, TLR, and SHP2.

Materials and methods: Genomic data from five datasets were merged to identify 437 ESCC patients, categorized into altered (n = 66, 15%) and unaltered (n = 371, 85%) groups. Gene expression was analyzed using the GSE53624 dataset, and survival outcomes were assessed with Kaplan-Meier curves and log-rank tests. Hazard ratios (HR) were derived to quantify risk.

Results: The altered group exhibited a significantly higher tumor mutational burden (TMB) and mutation count than the unaltered group (p < 1E-7). While disease-free survival analysis of 76 patients showed no significant difference, overall survival (OS) analysis of 288 patients demonstrated significantly worse survival in the altered group [median OS (95% CI): 18.63 months (18.17-28.13) vs. 40.93 months (28.42 - not reached); HR = 2.16 (1.33-3.52)]. Additionally, higher HMGB1 expression was significantly associated with poorer survival (p < 0.008). Expression-treatment response correlation using the GSE45670 dataset showed that HMGB1 expression in the pathological complete remission group was significantly higher than in the normal epithelium group, p = 0.016.

Conclusions: This study highlights that genomic alterations in these six genes are associated with poorer OS in ESCC, despite higher TMB potentially increasing tumor neo-antigens. These findings underscore the need for further research to explore their prognostic and therapeutic potential.

Introduction: Perirectal spacers reduce the radiotherapy (RT) dose delivered to the rectum, but their impact on treatment toxicity remains debated. We conducted a systematic review and meta-analysis to synthesise emerging data (PROSPERO: CRD42024506380).

Material and methods: MEDLINE, Embase, Scopus, and Google Scholar were searched through 2024/08/18 for prospective randomised (RCT) and non-randomised trials evaluating the clinical outcomes of perirectal spacing in prostate cancer (PCa) patients. Random effects generalised linear mixed models were used to pool odds ratios (OR) for rectal adverse events (AEs) from RCTs. Non-randomised trials were summarised qualitatively. The risk of bias was assessed using the RoB2 and ROBINS-I tools.

Results: Three RCTs (n = 645) were identified. The rates of grade ≥ 2 (G ≥ 2) rectal AEs in control groups were low, ranging 4.2-13.8% for early AEs and 0-1.4% for late AEs. Perirectal spacers were associated with decreased incidence of early G ≥ 2 rectal AEs (OR: 0.43; 95% CI: 0.19-0.96), but not of late G ≥ 2 rectal AEs (OR: 0.26; 95% CI: 0.02-2.91). Assuming a comparator risk of 7.1% and 1%, this corresponded to a number needed to treat of 26 patients to avoid one early AE, and 135 pa- tients to avoid one late G ≥ 2 AE, respectively. Randomised clinical trial were at moderate risk of bias due to concerns regarding the concealment of allocation.

Conclusions: There is evidence that perirectal spacers result in a small decrease in acute rectal toxicity. However, modern RT for clinically localised PCa is generally well-tolerated, and severe AEs are rare. Greater scrutiny of the risks and benefits associated with perirectal spacers is necessary.

Introduction: Small cell lung cancer (SCLC) is a highly aggressive subtype of lung cancer that accounts for approximately 15% of all lung cancers. Despite advancements in treatment, real-world clinical practice in developing countries often reveals less favorable outcomes than those observed in randomized clinical trials.

Material and methods: A retrospective analysis was conducted on all patients with extensive-stage SCLC (ES-SCLC) diagnosed or treated at a single center in Bosnia and Herzego-vina. Medical and electronic health records were reviewed to collect data on patients diagnosed with ES-SCLC between 2013 and 2023. The analysis included patient demographics, clinical characteristics, treatment outcomes, and adverse events.

Results: Ninety-four patients with ES-SCLC were included in the study. Of these, 89.4% were prescribed first-line treatment, and 63.8% received first- line chemotherapy based on cisplatin and etoposide. The median progression- free survival in patients treated with first-line ES-SCLC was five months, with a response rate of 57.5%. The median overall survival of patients treated with first-line chemotherapy in our study was seven months. The most common side effect was hematologic toxicity.

Conclusions: Our results showed that the outcomes of patients with ES-SCLC in real clinical practice are poor. Further studies of real-world treatment outcomes are essential to validate the findings from randomized controlled trials. Ongoing research is needed to explore strategies for improving outcomes and addressing the unmet needs of patients with ES-SCLC.

Introduction: Globally, resistance to antimicrobial drugs is a major hazard to public health. Infections that were once easily treatable with antibiotics are becoming harder to control, leading to prolonged illnesses, increased mortality rates, and higher healthcare costs. This study aims to assess the antimicrobial and anticancer properties of different extracts obtained from Artemisia herba-alba (AHA).

Material and methods: The antibacterial tests of AHA were performed on two gram-negative bacterial (Escherichia coli and Klebsiella pneumonia), and gram-positive bacteria (Staphylococcus aureus). Initial screening for antibacterial activities was conducted using the well diffusion technique. The anticancer test was carried out in vitro on a human breast carcinoma cell line (MCF-7) using MTT assay.

Results: Among all extracts, ethanol and n-hexane extract of AHA were the most effective against Staphylococcus aureus with the highest inhibition zone, 27 ±11 mm (mean ±SD) compared to standard antibiotics (ceftriaxone, 44 mm, nitrofurantoin 34 mm). The ethanol extract of AHA showed the highest antibacterial activity against Staphylococcus aureus, demonstrating the potential of infection treatment. Ethyl acetate extract has antibacterial activity against Escherichia coli and Klebsiella pneumonia. The findings indicated that the ethanol extract of AHA exhibited the highest efficacy against MCF-7), with an IC₅₀ value of 546.75 ±16.00 µg/ml.

Conclusions: These findings suggest that the ethanol extract of AHA could be considered as a potential agent to serve as a source of antibacterial and anticancer compounds.

Introduction: Intermittent hypoxia and the inflammatory processes occur in both obstructive sleep apnea (OSA) and renal cell carcinoma (RCC). In recent years, multiple studies have shown a dose-dependent effect of OSA on the risk and prognosis of RCC. However, the pathogenesis of this process is still unknown. This study aimed to review the literature and identify the similarities in cytokine profiles of patients with OSA and RCC.

Material and methods: We included articles in English assessing cytokine levels in pediatric and adult patients with OSA and in patients with RCC. The exclusion criteria were animal and in vitro studies. The PubMed database was searched for articles.

Results: After analyzing the search results, 66 articles were selected. Twenty different interleukins were studied in OSA research. Most RCC pro-cancerogenic cytokines (IL-1, IL-4, IL-6, IL-8, IL-17, IL-18, IL-23, IL-33) had higher levels in OSA patients than in controls.

Conclusions: This review emphasizes similarities in a spectrum of cytokines in OSA and RCC patients, with significantly elevated levels of RCC pro-cancerogenic interleukins in OSA patients. This may suggest a possible link between untreated OSA and the prognosis of RCC. Also, the treatment of OSA with continuous positive airway pressure led to a decrease in pro-cancerogenic cytokines, which could have important therapeutic implications in OSA-positive patients treated for RCC.

Introduction: Non-muscle invasive bladder cancer (NMIBC) is one of the most commonly diagnosed urogenital types of cancer with a relatively favourable prognosis. Cystoscopy stands as the most significant diagnostic and monitoring procedure, however more accessible methods are needed for diagnosis and follow-up.

Material and methods: A total of 285 pa-- tients with NMIBC were enrolled in this prospective study. Complete blood count (CBC) biomarkers and nutritional risk scores were evaluated for predicting cancer recurrence or progression after radical transurethral resection of bladder tumour (TURB). Additionally, the correlation between CBC biomarkers and European Organisation for Research and Treatment of Cancer (EORTC) risk scores was performed. A final study group with complete follow-up and dataset, comprised of 183.

Results: After a 3-month follow-up period, 104 subjects experienced cancer recurrence or progression. A group of 79 patients were tumour free. The neutrophil-to-lymphocyte ratio (NLR) showed the highest area under the curve of 0.618 (95% CI: 0.536-0.699) with p = 0.0047, for discrimination of the study outcomes. None of nutritional risk scores has predicted disease progression or recurrence. Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio and derived NLR enhanced the diagnostic performance for EORTC recurrence and progression points.

Conclusions: Complete blood count biomarkers can predict recurrence or progression of NMIBC after TURB, yet nutritional risk scores have demonstrated inadequate predictive value. Complete blood count biomarkers increase prognostic properties of EORTC risk score.

Introduction: Lung cancer is one of the most common malignancies in the world. Many attempts have been made to increase survival of this devastating disease, including the addition of local therapies in oligometastatic non-small cell lung cancer (OMD NSCLC). Oligometastatic disease is an intermediate state between a local and widely disseminated disease. The aim of the study was to assess the efficacy of stereotactic radiation therapy (SRT) in treatment of OMD NSCLC and to evaluate prognostic factors for survival.

Material and methods: Medical records of 127 consecutive patients with OMD NSCLC who underwent SRT in University Clinical Centre in Gdańsk, Poland between 2016 and 2022 were obtained and clinical data were analysed for toxicity and efficacy.

Results: There were 64.6% of patients with adenocarcinoma, 25.2% with squamous-cell carcinoma and 10.2% with other histological subtypes. Mean age was 66.9 years. Treatment was well tolerated in the majority of patients. Median progression-free survival (PFS) for synchronous OMD (sOMD) and metachronous OMD (mOMD) was 11.1 months and 14.4 months, respectively (p = 0.61). Median PFS for oligoprogression was 5.43 months. Median overall survival for sOMD and mOMD was 24.5 months and 36.8 months, respectively (p = 0.11). The most important prognostic factors were the number of metastases and performance status.

Conclusions: Radical treatment in OMD NSCLC should be judicious and reserved for selected patients. Stereotactic radiation therapy is an important tool in the management of OMD NSCLC.

Introduction: This study aimed to investigate the cytotoxicity and apoptotic effects of the ethyl acetate fraction of Zanthoxylum acanthopodium DC (ZA) fruit on B16F10 melanoma cell cultures.

Material and methods: The ethyl acetate fraction was obtained through maceration followed by fractionation with n-hexane and ethyl acetate. Cytotoxicity was assessed using the MTT assay to determine the IC₅₀ value. B16F10 melanoma cells were then grouped into control, IC₅₀, ¾ IC₅₀, ½ IC₅₀, and doxorubicin groups. Apoptosis induction was analysed using Annexin V and caspase-3 expression assays.

Results: The ethyl acetate fraction of ZA fruit exhibited cytotoxic activity on B16F10 melanoma cells, with an IC₅₀ value of 249.3 µg/ml. Apoptosis induction was confirmed by a significant increase in caspase-3 expression compared to the control group (p < 0.05).

Conclusions: The ethyl acetate fraction of ZA fruit demonstrated cytotoxic effects and induced apoptosis in B16F10 melanoma cells, potentially through caspase-3 activation.