Radiology and Oncology最新文献

Background: Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, plays a crucial role in focal adhesion turnover by interfacing between the extracellular space, transmembrane integrins, and actin filaments. Its significance for the progression of several malignancies, including bladder cancer, has been well-documented. However, its precise role and the implications of its inhibition in bladder cancer tissues and urothelial in vitro models has not been fully explored. This study examined FAK expression and function in human bladder cancer biopsies and in vitro bladder cancer models.

Materials and methods: Ex vivo analyses were performed using reverse transcription-quantitative PCR (qRT-PCR), western blotting, and immunohistochemistry to compare FAK expression between bladder cancer tissues and adjacent normal tissues. In vitro, FAK expression was assessed in low-grade (LG) human non-invasive papilloma urothelial cell line RT4 for NMIBC (Ta), high-grade (HG) human muscle-invasive cancer urothelial cell line T24 for MIBC (T2) and normal porcine urothelial (NPU) cells using qRT-PCR and western blotting, as well as flow cytometry for the quantification of FAK-positive RT4 and T24 cells. The role of FAK in cancer cell survival was explored in vitro using microRNA (miRNA) to silence FAK expression. Additionally, we used FAK inhibitors PND-1186, PF-573228 and defactinib to investigate the effects of FAK inhibition on normal compared to cancerous bladder urothelial cells.

Results: Ex vivo analyses demonstrated significantly higher FAK expression in bladder cancer tissues compared to adjacent normal tissues. Similarly, in vitro analyses showed significantly higher FAK expression in RT4 and T24 cells than NPU cells. Silencing FAK using anti-FAK plasmids led to increased caspase-3-mediated apoptosis of RT4 and T24 cells and growth reduction of stably transfected T24 cells. Importantly, based on cell viability assays, treatment with 100 μM defactinib for 2 hours per day on 3 consecutive days was identified as a clinically relevant regimen. Under this treatment, the viability of differentiated NPU cells remained high at 108.4 ± 17.1%, while the viability of 2-day RT4 and 2-day T24 cells was drastically reduced to 4.1 ± 2.7% and 7.6 ± 2.9%, respectively.

Conclusions: To our knowledge, this is the first report demonstrating the role of FAK and its inhibition across both normal and cancerous bladder urothelial models. This study highlights the critical role of FAK in the progression of human bladder cancer and establishes a foundation for exploring FAK inhibition as a potential therapeutic approach in bladder cancer treatment.

Background: Robotic platforms are increasingly employed in the field of minimally invasive pancreatic surgery. It is essential to develop an innovative method that ensures both safety and efficacy, producing outcomes comparable to those of established treatment modalities. Implementation process should incorporate surgical science, education, local implementation, and non-technical skills. In our study, we describe the safe implementation of a robotic platform in pancreatic surgery within our medical institution.

Patients and methods: We analysed prospectively collected data from the first ten consecutive robotic-assisted distal pancreatectomies (RDP) and pancreatoduodenectomies (RPD). Due to nature of the study basic statistical analysis were performed.

Results: The mean operating time was 211minutes (±49.4) for RDP and 365 minutes (±69.6) for RPD, with blood loss 330 mL for RDP and 195 mL for RPD. Hospital stay was 8.7 days (±3.9) in RDP and 7.9 days (±3.9) in RPD. One patient (10%) in the RDP group developed clinically relevant postoperative pancreatic fistula (CR-POPF) and delayed gastric emptying (DGE). The mean tumour size was 31 mm (±9.8) in the RDP and 27 mm (±7.5) in the RPD. The mean number of lymph nodes harvested was 6 (0-24) in the RDP and 15 (6-22) in the RPD. The R0 resection rate was 60% in the RDP and 70% in the RPD.

Conclusions: Robotic surgical technology can be safely and effectively integrated into a clinical setting. This integration should be facilitated through a well-established training program and curriculum. Nonetheless, patient selection is important, especially in the early phases of robotic program development.

Background: This epidemiological study aims to assess the cancer risk potentially associated with environmental exposure resulting from cement production and waste co-incineration at the Anhovo cement plant in Western Slovenia and to develop a strong and reliable methodological framework for the long-term surveillance of environmentally related cancer risks in small geographical areas.

Materials and methods: We integrated all the available data sources: cancer cases from the population-based Slovenian Cancer Registry; background population; and available measurements on exposure to air PM₁₀ particles and chromium (Cr) in the soil in the municipality of Kanal and the wider Goriška region. Relative risks of cancer in small geographical areas were estimated using Bayesian hierarchical spatial models and the population attributable fractions of the modelled risk factors were calculated. The point source analysis compared the cancer risk near the cement plant to that in more distant areas.

Results: The analysis did not reveal any excess cancer incidence in the area of the Anhovo cement plant or an association with the PM₁₀ particles and Cr in the soil. The incidence of mesothelioma remains high in the region, but stable in the last two decades.

Conclusions: In view of the environmental pollution caused by either historical cement production or the potential impact of current waste co-incineration activities in Kanal, we strongly recommend that a follow-up epidemiological study be carried out in the next 10 to 20 years. The methodological framework established in the present study provides a foundation for the ongoing surveillance of the cancer burden in the region.

Background: Radiotherapy is a cornerstone of treatment for various cancers, but often causes collateral damage to surrounding healthy tissue, including skeletal muscle. Ionizing radiation leads to oxidative stress and inflammation, which impairs the regenerative capacity of muscle tissue. Irradiation reduces the number and functionality of satellite cells and disrupts the tightly regulated processes of myogenesis and tissue remodelling. In addition, irradiation alters the muscle microenvironment by promoting fibrosis and vascular damage, which further impedes effective regeneration. Cytokine signalling pathways are also dysregulated following irradiation, contributing to impaired activation and differentiation of satellite cells.

Conclusions: There is evidence that factors such as melatonin and growth factors can improve muscle regeneration. Understanding the molecular and cellular mechanisms underlying the impairment of muscle regeneration after radiotherapy is crucial for the development of targeted strategies to mitigate side effects and improve patients' quality of life. Overall, the preservation and restoration of muscle function in irradiated tissue remains a critical challenge that requires multidisciplinary approaches.

Background: Treatment of malignant mesothelioma (MM) still relies on chemotherapy with cisplatin in combination with pemetrexed or other drugs. Studies indicate that hypoxic conditions within tumour tissue may reduce responsiveness to cisplatin-based chemotherapy. Hypoxia-inducible factors (HIF) play an important role in regulation of cellular adaptation to hypoxia. The aim of our study was to investigate single nucleotide polymorphisms (SNPs) in the HIF1A gene coding for the regulatory alpha subunit (HIF-1A) and their role in the response to chemotherapy in patients with MM.

Patients and methods: Our retrospective genetic association study included 234 patients with MM, who were treated with a combination of cisplatin/pemetrexed or cisplatin/gemcitabine at the Institute of Oncology Ljubljana between January 2001 and September 2018. Selected HIF1A SNPs (rs1154965, rs11549467, and rs2057482) were genotyped using the competitive allele-specific polymerase chain reaction (KASP). Additionally, we used a TaqMan assay for independent confirmation of rs11549465 genotyping results. The impact of the SNPs on response to chemotherapy was analysed using logistic regression. For survival analysis, we used the Kaplan-Meier method and Cox regression.

Results: In heterozygotes with the HIF1A rs11549465 CT genotype, response to chemotherapy was significantly worse compared to homozygotes with the CC genotype, but only after adjustment for weight loss and CRP (RO_adj = 0.37; 95% CI = 0.14-0.97; P_adj = 0.044). HIF1A rs11549467 and rs2057482 were not associated with response to chemotherapy (all P > 0.05). None of the investigated SNPs were associated with progression-free survival or overall survival (all P > 0.05).

Conclusions: Among the investigated HIF1A SNPs, only rs11549465 has showed association with a worse response to chemotherapy after the adjustment for clinical parameters. The findings of this study have improved our understanding of the role of HIF1A polymorphisms in MM and may offer valuable insights into their impact on other cancers as well.

Background: Uveal melanoma (UM) patients with liver metastases often undergo hepatic artery infusion therapy (HAIC). Due to diffuse metastatic spread in the liver, patients often develop hepatomegaly and secondary, portal hypertension which may lead to splenomegaly. This study aimed to compare spleen volumetry and the change of spleen volume (SV) for the evaluation of HAIC treatment response.

Patients and methods: In this study, 179 UM patients (mean age 64.8 ± 11.0y, 53% female) with liver metastases undergoing HAIC were included. Treatment response was analyzed by RECIST 1.1 and SV on CT imaging before and after first HAIC. The correlation of change in spleen and liver volume was analyzed with Spearman test. Overall survival (OS) was calculated as the time from the first HAIC to patient death using Kaplan-Meier test and multivariate analysis was performed for RECIST 1.1 and SV.

Results: In the study population, OS was 13.8 months (95% CI 10.6-14.7 months). Change in SV before and after first HAIC was +4% (interquartile range [IQR] -4.0%-12.0%, p = 0.49) and showed a weak correlation with OS (r = -0.11, p = 0.18). UM patients with progressive disease (PD) according to RECIST 1.1 showed an increase in SV compared to patients with stable disease (SD) (p = 0.04). Compared to RECIST 1.1, SV was not significant prognostic factor that can identify a change in OS.

Conclusions: In uveal melanoma patients with liver metastases undergoing HAIC, neither the change of SV nor splenomegaly could be identified as prognostic factors for OS.

Background: First evaluation of the performance of MR cytometry incorporating transcytolemmal water exchange in predicting immunohistochemical factor status and molecular subtypes of breast cancer.

Patients and methods: We prospectively enrolled 90 breast cancer patients in the study. For each participant, pulsed gradient spin-echo (PGSE) with diffusion time of 70 ms and oscillating gradient spin-echo (OGSE) diffusion-weighted imaging of 25 Hz and 50 Hz were performed on a 3T MRI scanner. Time-dependent apparent diffusion coefficients (ADC) and microstructural parameters including cell diameter d , intracellular volume fraction v_in , water exchange rate constant k_in , and apparent extracellular diffusivity D_ex were calculated. Single- and multi-variable logistic regression analyses were performed to evaluate their performance in identifying immunohistochemistry (IHC) factor status and molecular subtypes. The area under the receiver operating characteristic curve (AUC) was computed.

Results: The multi-variable regression models generated from MR cytometry-derived metrics provided higher AUC compared to those from time-dependent ADC metrics, i.e. 0.744 vs. 0.645 for estrogen receptor (ER), 0.727 vs. 0.688 for progesterone receptor (PR), 0.734 vs.0.623 for HER2, and 0.679 vs. 0.633 for Ki67, 0.751 vs. 0.644 for Triple-Negative Breast Cancer (TNBC), 0.819 vs. 0.765 for HER2-enriched, 0.730 vs. 0.659 for Luminal A, 0.633 vs. 0.633 for Luminal B. MR cytometry with transcytolemmal water exchange (JOINT and EXCHANGE) outperformed the original one with the impermeable model (IMPULSED) in predicting PR (0.727 vs. 0.705), HER2 (0.734 vs. 0.689), Ki67 (0.679 vs. 0.646), TNBC (0.751 vs. 0.748) and HER2-enriched (0.819 vs. 0.739), Luminal A (0.730 vs. 0.666), Luminal B (0.633 vs. 0.630).

Conclusions: MR cytometry outperformed conventional ADC measurements in clinical breast cancer subtyping. Incorporating transcytolemmal water exchange further enhanced classification accuracy.

Background: Preoperative neoadjuvant chemoradiation (NACR) benefits disease control in most locally advanced rectal cancer (LARC) patients. However, effective biomarkers predicting response to NACR are still not accessible. This study aimed to find potential biomarkers to assess therapy response and susceptibility to LARC.

Materials and methods: Differentially expressed genes (DEGs) between NACR-sensitive and resistant patients were screened using GEO database. STRING and Cytoscape were utilized to construct PPI networks and identify hub genes. Based on CIBERSORT, TCGA, GTEx, GSEA and ROC curves, the connections between hub genes and specific signaling pathways, immune cell infiltration, prognosis value and miRNA-transcription factor (TF)-target network were investigated. Human Protein Atlas (HPA) database was used to visualize hub gene expression in clinical samples.

Results: We identified 2619 up- and 2466 down-regulated genes between NACR-sensitive and resistant patients. The up-regulated DEGs were searched for highly expressed genes in the NACR-resistant, TCGA and GTEx-related datasets compared to the NACR-sensitive group, yielding six hub genes (RRM2, HNRNPL, EZH2, METTL1, NHP2L1 and ASF1B). ROC curves demonstrated the predictive utility of the six genes in NACR sensitivity. Immune infiltration research revealed no significant relationship between NACR sensitivity and immune cell infiltration extent. The miRNA-TF-target network of hub genes was established. Finally, HPA database results showed that six genes were expressed at variable levels in rectal cancer patients.

Conclusions: This study identified six hub genes (RRM2, HNRNPL, EZH2, METTL1, NHP2L1 and ASF1B) up-regulated in LARC and valuable for predicting patient susceptibility and response to NACR.

Background: Background. Pancreatic adenocarcinoma (PAAD) is a malignancy with a very poor prognosis. The clinical significance of cuproptosis in PAAD combining single cell data with The Cancer Genome Atlas (TCGA) data is unclear.

Materials and methods: In this study, we first identified gene modules associated with cuproptosis by performing single-cell analysis and weighted co-expression network analysis (WCGNA). According to TCGA data, Cox regression and LASSO regression analysis were used to establish prognostic models, and PAAD patients were divided into high-risk and low-risk groups according to cuproptosis-related risk score. Then 7 algorithms were used to evaluate cancer immune microenvironment, followed by the mutation analysis. The expression levels and prognostic significance of the 8 model genes were analysed using single-gene analysis, Kaplan-Meier survival plots, and quantitative PCR (qPCR) validation. Finally, the biological function of CEP55 in PAAD was verified by in vitro experiments.

Results: We identified cuproptosis-related genes (CRG) in PAAD by performing single-cell analysis and WCGNA, and constructed a cuproptosis-related prognostic model of PAAD by comprehensive bioinformatics analyses. Based on cuproptosis-related risk score, there were significant differences in survival time between two groups. We further constructed a cuproptosis-related risk score-based nomogram to accurately assess PAAD patient prognosis. Immune infiltration analysis revealed that PAAD samples with higher cuproptosis-related scores exhibited significantly lower immune infiltration levels, which may mechanistically underlie their poorer clinical outcomes. Furthermore, the high-risk group had a higher mutation rate of the same mutated gene, which means that they are more likely to benefit from immunotherapy. Finally, we identified that CEP55 was significantly overexpressed in PAAD and correlated with poor patient prognosis. In vitro knockdown of CEP55 effectively suppressed proliferation and invasion capabilities in pancreatic cancer cell lines.

Conclusions: In this study, a novel prognostic model of PAAD was constructed to evaluate the prognosis and immune microenvironment of PAAD patients, and CEP55 was identified as a central gene of PAAD. In vitro studies verified the biological function of CEP55, providing a new potential target for the treatment of PAAD.