Technology in Cancer Research & Treatment最新文献

Background: Severe delayed diarrhea and hematological toxicity limit the use of irinotecan. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is a critical enzyme in irinotecan metabolism. The study aims to investigate the safety and efficacy of irinotecan under the guidance of the pre-treatment UGT1A1 genotype in the second-line treatment of gastric cancer. Methods: This study involved 110 patients. Irinotecan was injected intravenously every 3 weeks, and the dose of irinotecan was determined by polymorphism of the UGT1A1 gene, which was divided into three groups (125 mg/m²: GG type; 100 mg/m²: GA type; 75 mg/m²: AA type). The primary end point was overall survival (OS), the secondary end points were progression-free survival (PFS) and safety. Results: One hundred and seven patients received irinotecan treatment and three patients with AA type received paclitaxel treatment. Among 107 patients, there were no significant differences in PFS (4.8 m vs 4.9 m vs 4.4 m; p = 0.5249) and OS (9.3 m vs 9.3 m vs NA; p = 0.6821) among patients with GG/GA/AA subtypes after dose adjustment. For the patient with homozygosity mutation, treatment was switched to paclitaxel. There were no significant differences in PFS and OS among patients with different alleles or after dose adjustment (p > 0.05). There was a significant difference in the risk of delayed diarrhea (p = 0.000), leukopenia (p = 0.003) and neutropenia (p = 0.000) in patients with different UGT1A1*6 genotypes, while no difference in patients with different UGT1A1*28 genotypes. Additionally, grade 3/4 diarrhea, neutropenia, and leukopenia were significantly more common in AA genotype patients compared to GG (2%, 19%, 24%) or GA (23%, 31%, 31%) genotype patients. Conclusion: Individual irinotecan treatment shows encouraging survival and tolerability outcomes in patients with GG/GA subtype. Irinotecan may be not suitable for patients with AA subtype.

Objective: To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC).

Materials and methods: In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value < .05 was considered statistically significant. The display efficiency of the LLC between Gd-BOPTA and Gd-EOB-DTPA for HCC features was evaluated by receiver operating characteristic (ROC) curve analysis.

Results: Between Gd-BOPTA and Gd-EOB-DTPA, significant differences were observed regarding the display efficiency for capsule enhancement and the LLC in the AP/PVP/DP (P < .05), but there was no significant difference regarding the LLC in the TP/HBP. Both Gd-BOPTA and Gd-EOB-DTPA had good display efficiency in each phase (AUC_min> 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950).

Conclusion: Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation.

Background: Mitochondrial fusion is vital for cellular function and has been increasingly linked to cancer development. Kidney renal papillary cell carcinoma (KIRP), the second most common renal cell carcinoma, presents diverse prognostic outcomes. Identifying novel biomarkers is critical for improving prognosis and treatment response in KIRP.

Objective: This study aims to explore the gene expression associated with mitochondrial fusion and establish a novel gene signature model to predict KIRP prognosis and cisplatin sensitivity.

Methods: We analyzed RNA sequencing data and clinical records of 285 KIRP patients from The Cancer Genome Atlas (TCGA). LASSO regression identified four key mitochondrial fusion-related genes (BNIP3, GDAP1, MIEF2, PRKN). Multivariate Cox regression evaluated their association with overall survival. Risk stratification was developed based on gene expression. We assessed immunotherapy responses using checkpoint inhibitor scores, tumor mutation burden, TIDE scores, and tumor microenvironment characteristics. Cisplatin sensitivity was evaluated via correlation analysis of gene expression levels and half-maximal inhibitory concentration (IC50). In vitro loss- and gain-of-function experiments in KIRP cell lines (Caki-2, ACHN) assessed MIEF2's role in cisplatin sensitivity.

Results: The gene signature successfully stratified patients into high- and low-risk groups, with significant survival differences. The area under the ROC curve (AUC) for the risk model was 0.782. MIEF2 was notably associated with cisplatin sensitivity, confirmed through functional experiments. Patients in the high-risk group exhibited lower MIEF2 expression and increased cisplatin sensitivity.

Clear cell renal cell carcinoma (ccRCC) is a highly lethal urinary malignancy with poor overall survival (OS) rates. Integrating computer vision and machine learning in pathomics analysis offers potential for enhancing classification, prognosis, and treatment strategies for ccRCC. This study aims to create a pathomics model to predict OS in ccRCC patients. In this study, data from ccRCC patients in the TCGA database were used as a training set, with clinical data serving as a validation set. Pathological features were extracted from H&E-stained slides using PyRadiomics, and a pathomics model was constructed using the non-negative matrix factorization (NMF) algorithm. The model's predictive performance was assessed through Kaplan-Meier (KM) survival curves and Cox regression analysis. Additionally, differential gene expression, gene ontology (GO) enrichment analysis, immune infiltration, and mutational analysis were conducted to investigate the underlying biological mechanisms. A total of 368 pathomics features were extracted from H&E-stained slides of ccRCC patients, and a pathomics model comprising two subtypes (Cluster 1 and Cluster 2) was successfully constructed using the NMF algorithm. KM survival curves and Cox regression analysis revealed that Cluster 2 was associated with worse OS. A total of 76 differential genes were identified between the two subtypes, primarily involving extracellular matrix organization and structure. Immune-related genes, including CTLA4, CD80, and TIGIT, were highly expressed in Cluster 2, while the VHL and PBRM1 genes, along with mutations in the PI3K-Akt, HIF-1, and MAPK signaling pathways, exhibited mutation rates exceeding 40% in both subtypes. The machine learning-based pathomics model effectively predicts the OS of ccRCC patients and differentiates between subtypes. The critical roles of the immune-related gene CTLA4 and the PI3K-Akt, HIF-1, and MAPK signaling pathways offer new insights for further research on the molecular mechanisms, diagnosis, and treatment strategies for ccRCC.

This review article aims to synthesize existing data on radiation-induced heart diseases in patients undergoing chest radiation therapy and also explores cardiac-sparing techniques to mitigate cardiotoxic effects. We conducted a comprehensive database search to review and consolidate data regarding chest radiotherapy and effects on the heart as well as techniques to minimize exposure to the heart. The research findings demonstrate associations between radiation exposure to cardiac substructures and subsequent cardiotoxicity. This review also stresses the importance of identifying patients at high-risk for cardiotoxicity as well as advocates for the adoption of stringent cardiac dose constraints in these patients. Advanced cardiac-sparing techniques, notably respiratory motion management, have emerged as pivotal strategies to minimize the likelihood of cardiac events. This narrative review emphasizes the critical role of these innovations in optimizing cardiac health during radiation treatment.

Background: Immune checkpoint inhibitor (ICI) plus chemotherapy is effective in advanced gastric or gastroesophageal junction (G/GEJ) cancer. This study aims to evaluate the clinical effect of first-line immunotherapy in combination with chemotherapy for advanced G/GEJ cancer. Methods: PubMed, Web of Science, Embase and Cochrane databases were systematically searched from the inception of the databases to December 2021. Randomized trials comparing ICI plus chemotherapy with chemotherapy in first-line treatment for advanced G/GEJ cancer were included. The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Analyses were performed in Stata 14.0 software. The study protocol was registered with PROSPERO, number CRD42022300907. Results: Five trials were included for analysis, involving 2, 814 patients. ICI plus chemotherapy can significantly improve OS (hazards ratio [HR], 0.86; 95% CI 0.78-0.94; P = .002), PFS (HR, 0.79; 95% CI 0.63-0.99; P ＜ .001) and ORR (relative ratio [RR], 1.20; 95% CI 1.11-1.30; P < .001). In safety analyses, there were no significant differences in incidence of all AEs, treatment-related adverse event (TRAE), TRAE of grade 3 or higher, serious TRAE and TRAE leading to death between two arms (P > .05). Conclusions: ICI plus chemotherapy is more effective first-line treatment for advanced G/GEJ cancer in contrast to chemotherapy regrading to improving OS, PFS and ORR, without increasing TRAE risk. This study will redefine the role of ICI in combination with chemotherapy in the first-line setting for G/GEJ cancer, and provide reference for clinical treatment.

Purpose: Radiotherapy (RT) is commonly used in the treatment of breast cancer and often, despite advances in fractionated dosing schedules, produces undesirable skin toxicity. The purpose of this study was to evaluate the feasibility of using a keratin-based topical cream, KeraStat® Cream (KC; KeraNetics, Inc., Winston Salem, NC, USA) to manage the symptoms of radiation dermatitis (RD) in breast cancer patients undergoing RT. Materials and Methods: A total of 24 subjects were enrolled on this single-center, randomized, open-label study. Participants were randomly assigned to KC or standard of care (SOC, patient's choice of a variety of readily available creams or moisturizers). Patients were asked to apply the assigned treatment to the irradiated area twice daily, beginning with day 1 of RT, through 30 days post-RT. The primary outcome was compliance of use. Secondary outcomes included safety and tolerability of KC, as well as RD severity assessed using the Radiation Therapy Oncology Group (RTOG) scale and the patient-reported Dermatology Life Quality Index (DLQI). Results: All subjects in the KC group were assessed as compliant with no adverse events. The rate of RTOG Grade 2 RD was lower in the KC group (30.8%) compared to the SOC group (54.5%, P = .408). At the final RT visit, the mean RTOG RD score was lower in the KC group (1.0) versus the SOC group (1.4). Similarly, patient-reported quality of life measured by the DLQI at the end of RT was improved in the KC group (mean 4.25, small effect) versus the SOC group (mean 6.18, moderate effect, P = .412). Conclusions: KC was safe and well tolerated with no adverse events. Though efficacy measures were not powered to draw definitive conclusions, trends and clinical assessments suggest that there is a benefit of using KC compared to SOC for breast cancer patients treated with RT, and a larger powered study for efficacy is warranted. Trial Registry: This clinical trial is registered as NCT03374995 titled KeraStat(R) Cream for Radiation Dermatitis.