Technology in Cancer Research & Treatment最新文献

Background: Lung cancer screening is not limited to low dose computed tomography (LDCT). Recently, molecular biomarkers have been shown to have the potential to improve the current state of early lung cancer detection. The current study determined the efficiency of seven autoantibodies against tumor-associated antigens (7-AABs) and tumor markers in patients with lung cancer. Materials and Methods: An enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 7-AABs and tumor markers in 354 patients with lung cancer and 108 patients with benign pulmonary disease under care at Ethics Committee of Tianjin Medical University General Hospital. Results: The sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic (ROC) curve of 7-AABs were 30.0%, 84.3%, 86.3%, and 0.61, respectively. When combining the 7-AABs and tumor markers, the sensitivity was 68.6%, the specificity was 52.8%, and the area under the ROC curve was 0.72. The 7-AABs positive expression rate in lung cancer patients was significantly higher than patients with benign pulmonary diseases (30.1% vs 15.7%); however, the 7-AABs positive expression rate was affected by clinical features and pathologic stages. When combining 7-AABs and tumor markers, the combined 7-AABs and tumor marker positive expression rate increased to 68.6%. Conclusion: Based on this study and previous literature, the supplemental diagnostic value of 7-AABs has been confirmed; however, due to the low sensitivity, the value of 7-AABs alone in lung cancer screening is limited. The combination of 7-AABs and tumor markers has improved sensitivity and positivity, but decreased specificity, which makes their performance in cancer screening and early detection worthy of further research.

Introduction: This study primarily aims to investigate the suitability of Halcyon in the context of cervical-thoracic esophageal cancer by exploring the dosimetric quality and delivery efficiency of Halcyon plans with different arc configurations. Additionally, it compares these findings with the dosimetric indices and delivery efficiency of TrueBeam and TomoTherapy accelerators, focusing on their capability to optimize protection for organs at risk (OARs) while maintaining efficient treatment delivery strategies.

Methods: This retrospective study involved 26 patients diagnosed with cervical-thoracic esophageal cancer, and new radiotherapy plans were created using Halcyon, TrueBeam, and TomoTherapy. Dose volume histogram (DVH) metrics and delivery efficiency for plans involving different arc numbers on Halcyon (2, 3, and 4 arcs) were compared with those from TrueBeam and TomoTherapy. T-tests were employed to evaluate differences in organ protection among the accelerators.

Results: The Halcyon plans, especially those with 4 arcs, provided superior protection for organs at risk, including the heart, lungs, and spinal cord, while maintaining excellent delivery efficiency. Compared to TrueBeam 2arc plans and TomoTherapy helical plans, Halcyon plans with 3 arcs also showed slight advantages. Although TomoTherapy offered better uniformity in dose distribution, it did not demonstrate a clear advantage over the other accelerators in terms of OAR protection or treatment efficiency. Furthermore, despite the lack of clear advantages in TrueBeam 2arc plans with flattening filter (FF), TrueBeam with flattening filter free (FFF) plans may hold potential in the treatment.

Conclusion: Halcyon, particularly with 4 arcs, offers an optimal balance between reducing toxicity to organs at risk and maintaining treatment efficiency, making it a preferred choice in cervical thoracic esophageal cancer radiotherapy. The findings highlight the need for careful selection of radiotherapy accelerators based on specific clinical goals, with Halcyon showing potential advantages in scenarios where both treatment efficiency and OAR protection are paramount.

Background: Clear cell renal cell carcinoma (ccRCC) is a widespread urogenital neoplasm. However, the therapeutic efficacy of these methods is unsatisfactory. In-depth screening of biomarkers could aid early diagnosis and therapy and predict patient prognosis.

Methods: The GEO datasets were selected with specific criteria. Differentially expressed gene (DEG), weighted gene coexpression network analysis (WGCNA), protein-protein interaction, LASSO, random forest, and Cox regression analyses were applied to identify the independent prognostic biomarkers. Survival analysis, correlation with clinical features, gene set enrichment analysis (GSEA), GO enrichment, immune infiltration analysis, and correlation with cuproptosis-related genes were carried out to determine the prognostic value and possible molecular mechanisms of the TSVR. Wound healing assays, transwell assays, cell colony formation experiments, flow cytometry, and immunohistochemistry (IHC) analysis were used to validate the functional attributes of CRYL1.

Results: Four GEO datasets were included to screen for hub genes. DEG combined with WGCNA showed a key module with 300 genes having the strongest correlation with "survival state" (R2 = -0.24 and P = 7e-8); six genes were identified by LASSO, random forest, and Cytoscape. Finally, CRYL1 (hazard ratio (HR) = 2.01, P < 0.001) was selected as an independent prognostic biomarker. The higher CRYL1 expression group had better DFS and overall survival (OS). GSEA demonstrated that the CRYL1-related DEGs were enriched mainly in the metabolism of sugar, fat, and amino acids. CRYL1 is positively correlated with FDX1 and the LIAS pathway, which are important molecule involved in cuproptosis. CRYL1 affects the infiltration abundance of four immune cells and can predict a positive OS. Wound healing, transwell, cell colony formation, and flow cytometry assays demonstrated that CRYL1 silencing enhances migration and proliferation and leads to a decreased apoptotic ratio. IHC analysis suggested that CRYL1 was highly expressed in adjacent tissues.

Conclusions: CRYL1 is a robust predictive marker for clinicopathological characteristics and survival status in ccRCC patients.

Objectives: The research's purpose is to develop a software that automatically integrates and overlay 3D virtual models of kidneys harboring renal masses into the Da Vinci robotic console, assisting surgeon during the intervention.

Introduction: Precision medicine, especially in the field of minimally-invasive partial nephrectomy, aims to use 3D virtual models as a guidance for augmented reality robotic procedures. However, the co-registration process of the virtual images over the real operative field is performed manually.

Methods: In this prospective study, two strategies for the automatic overlapping of the model over the real kidney were explored: the computer vision technology, leveraging the super-enhancement of the kidney allowed by the intraoperative injection of Indocyanine green for superimposition and the convolutional neural network technology, based on the processing of live images from the endoscope, after a training of the software on frames from prerecorded videos of the same surgery. The work-team, comprising a bioengineer, a software-developer and a surgeon, collaborated to create hyper-accuracy 3D models for automatic 3D-AR-guided RAPN. For each patient, demographic and clinical data were collected.

Results: Two groups (group A for the first technology with 12 patients and group B for the second technology with 8 patients) were defined. They showed comparable preoperative and post-operative characteristics. Concerning the first technology the average co-registration time was 7 (3-11) seconds while in the case of the second technology 11 (6-13) seconds. No major intraoperative or postoperative complications were recorded. There were no differences in terms of functional outcomes between the groups at every time-point considered.

Conclusion: The first technology allowed a successful anchoring of the 3D model to the kidney, despite minimal manual refinements. The second technology improved kidney automatic detection without relying on indocyanine injection, resulting in better organ boundaries identification during tests. Further studies are needed to confirm this preliminary evidence.

Background: Deficiencies in DNA damage repair responses promote chemotherapy sensitivity of tumor cells. The Nibrin homolog encoding gene Nijmegen Breakage Syndrome 1 (NBS1) is a crucial component of the MRE11-RAD50-NBN complex (MRN complex) and is involved in the response to DNA double-strand breaks (DSBs) repair that has emerged as an attractive strategy to overcome tumor drug resistance, but the functional relationship between NBS1 regulated DNA damage repair and cell cycle checkpoints has not been fully elucidated. Methods: In this study, lentivirus-mediated RNAi was used to construct NBS1-downregulated cells. Flow cytometry, qPCR, and immunohistochemistry were used to explore the regulatory relationship between NBS1 and CyclinB in vivo and in vitro. Results: Our findings suggest that NBS1 deficiency leads to defective homologous recombination repair. Inhibition of NBS1 expression activates CHK1 and CyclinB signaling pathways leading to cell cycle arrest and sensitizes ovarian cancer cells to Olaparib treatment in vitro and in vivo. NBS1-deficient ovarian cancer cells tend to maintain sensitivity to chemotherapeutic drugs through activation of cell cycle checkpoints. Conclusions: NBS1 may be a potential therapeutic target for epithelial ovarian cancer as it plays a role in the regulation of the DNA damage response and cell cycle checkpoints. Suppression of NBS1 upregulates CyclinB to induce Olaparib sensitivity in ovarian cancer.

Objectives: Circular RNAs (circRNAs) serve a crucial regulatory role in ovarian cancer (OC). Circular RNA ArfGAP with FG repeats 1 (circAGFG1) has been shown to be involved in promoting the progression of several cancers, containing triple-negative breast cancer, esophageal cancer and colorectal cancer. However, the function of circAGFG1 in OC is unclear.

Methods: Quantitative real-time reverse transcription PCR (RT-qPCR) was conducted to determine the expression levels of circAGFG1 and miR-409-3p. The proliferation and metastasis of cells were determined by colony formation assays, EdU assays, transwell assays and wound healing assays. In addition, a dual-luciferase reporter assay was performed to validate the mechanism between circAGFG1, miR-409-3p, and ZEB1.

Results: Our data suggested that circAGFG1 was significantly overexpressed in OC tissues compared to normal ovarian epithelial tissues. Overexpression of circAGFG1 was correlated with intraperitoneal metastasis, tumor recurrence and advanced stage. Additionally, circAGFG1 overexpression revealed a poor prognosis in OC patients. Knockdown of circAGFG1 suppressed the proliferation, invasion and migration of OC cells. Mechanistically, circAGFG1 acted as a sponge of miR-409-3p to enhance the expression level of zinc finger E-box binding homeobox 1 (ZEB1), thereby conferring OC cell proliferation, invasion and migration. Importantly, re-expression of ZEB1 effectively reversed the effects of circAGFG1 knockdown on OC cells.

Conclusions: In summary, our study indicated that circAGFG1 may act as a prognostic biomarker and potential therapeutic target for patients with OC.

Introduction: Breast cancer (BC) is a common cancer characterized by a high molecular heterogeneity. Therefore, understanding its biological properties and developing effective treatments for patients with different molecular features is imperative. Calcium-sensing receptor (CaSR) has been implicated in several regulatory functions in various types of human cancers. However, its underlying pathological mechanism in BC progression remains elusive.

Methods: We utilized The Cancer Genome Atlas and Gene Expression Omnibus databases to explore the function of CaSR in the metastasis of BC. Gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis of biological processes and cell signaling pathways revealed that CaSR could be activated or inhibited. Importantly, quantitative reverse transcriptase-polymerase chain reaction and western blotting were used to verify the gene expression of the CaSR. Wound healing and transwell assays were conducted to assess the effect of CaSR on the migration of BC cells.

Results: We demonstrated that CaSR expression in metastatic BC was higher than that in non-metastatic BC. It is the first time that database information has been used to reveal the biological process and molecular mechanism of CaSR in BC. Moreover, the CaSR expression in normal breast epithelial cells was notably less compared to that in BC cells. The activation of CaSR by Cinacalcet (a CaSR agonist) significantly enhanced the migration of BC cells, whereas NPS-2143 (a CaSR antagonist) treatment dramatically inhibited these effects.

Conclusion and future perspective: Bioinformatics techniques and experiments demonstrated the involvement of CaSR in BC metastasis. Our findings shed new light on the receptor therapy and molecular pathogenesis of BC, and emphasize the crucial function of CaSR, facilitating the metastasis of BC.

Epigenetic machinery is a cornerstone in normal cell development, orchestrating tissue-specific gene expression in mammalian cells. Aberrations in this intricate landscape drive substantial changes in gene function, emerging as a linchpin in cancer etiology and progression. While cancer was conventionally perceived as solely a genetic disorder, its contemporary definition encompasses genetic alterations intertwined with disruptive epigenetic abnormalities. This review explores the profound impact of DNA methylation, histone modifications, and noncoding RNAs on fundamental cellular processes. When these pivotal epigenetic mechanisms undergo disruption, they intricately guide the acquisition of the 6 hallmark characteristics of cancer within seemingly normal cells. Leveraging the latest advancements in decoding these epigenetic intricacies holds immense promise, heralding a new era in developing targeted and more efficacious treatment modalities against cancers driven by aberrant epigenetic modifications.

Objective: In external radiotherapy, dose boluses and compensators are used for treatment of irregular facial topography surfaces. In such cases, skewed isodose curves need to be addressed using a bolus that gives the deep dose distribution a shape adapted to the anatomical structures to be protected or irradiated. The combination of 3D modeling and printing technologies is a promising alternative to the conventional inaccurate and uncomfortable bolus fabrication technique. In this work, the proposed technologies will be used in the design and fabrication of high-performance and high-accuracy boluses that respond to the main constraints on metrology, adhesion to the patient's surface, comfort, and dose delivery. Methods: As a first phase in the implementation of the proposed solution, 3D printing materials, to be used in the fabrication of radiotherapy boluses, were selected and characterized to check how they respond to the required criteria on functionality, safety, and quality. Results: The obtained results show that among the studied materials, thermoplastic polyurethane (TPU) was found to be slightly more suitable than polylactic acid (PLA) for the fabrication of 3D printing boluses but for some kinds of treatments, PLA may be preferred despite its relative rigidity. Conclusion: In this work, procedures for dose bolus fabrication were proposed, and necessary data were obtained for some available 3D printing materials (TPU and PLA) that can be used for targeted applications. This achievement is a major step toward the final implementation of 3D modeling and printing technologies for the efficient fabrication of radiotherapy dose boluses.