Cancer Biotherapy and Radiopharmaceuticals最新文献

Background: Lung cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for more effective and targeted therapeutic strategies. Traditional Chinese Medicine (TCM), known for its favorable safety profile and broad pharmacological effects, offers promising candidates for cancer treatment. Salvianolic acid F (SAF), a key bioactive compound derived from Salvia miltiorrhiza, has demonstrated antitumor potential, but its role and underlying mechanisms in lung cancer remain inadequately characterized. Objective: This study investigated the anticancer efficacy of SAF in lung cancer and determines whether ultrasound can enhance its therapeutic effects, with a particular focus on the CXCL5/Wnt/β-catenin signaling axis. Methods: Human non-small cell lung cancer cell lines H1299 and PC9 were treated with SAF alone or in combination with ultrasound. Cell proliferation, migration, and invasion were assessed using cell counting kit-8, scratch wound healing, and transwell assays, respectively. Gene expression changes were analyzed using RNA sequencing and validated by quantitative real-time polymerase chain reaction and Western blotting. Functional involvement of CXCL5 was further confirmed through small interfering RNA-mediated gene silencing. Results: SAF significantly inhibited proliferation, motility, and invasiveness of both H1299 and PC9 cells. These effects were markedly enhanced when SAF was delivered in conjunction with ultrasound exposure. Transcriptomic analysis revealed downregulation of CXCL5 and suppression of downstream Wnt/β-catenin signaling mediators, including Wnt5α and β-catenin. CXCL5 knockdown mimicked the inhibitory effects of SAF and synergized with SAF treatment, confirming the involvement of the CXCL5/Wnt/β-catenin axis in the observed antitumor response. Conclusions: Ultrasound-enhanced delivery of SAF significantly impairs lung cancer cell proliferation and metastasis by targeting the CXCL5/Wnt/β-catenin pathway. This combinatorial approach represents a novel and promising biotherapeutic strategy for lung cancer that integrates TCM-derived compounds with noninvasive delivery technologies.

Background: Intense hepatobiliary uptake of [^99mTc]Tc-sestamibi in myocardial perfusion scintigraphy (MPS) often degrades image quality by obscuring the inferior myocardial wall, leading to equivocal studies. While nonpharmacological interventions are inconsistent, the choleretic agent ursodeoxycholic acid (UDCA) could potentially accelerate hepatic clearance. The effectiveness of a convenient, single-dose UDCA intervention has not been rigorously evaluated. This study determines if a single oral dose of UDCA administered shortly before imaging could significantly improve hepatic clearance and enhance image quality in MPS. Methods: In this prospective, randomized, double-blind, placebo-controlled trial, 174 patients undergoing 1 d MPS were randomized. The intervention group (n = 87) received a single 300 mg oral dose of UDCA, whereas the control group (n = 87) received an identical placebo (300 mg vitamin C) 1 h before the stress radiotracer injection. All participants and interpreting physicians were blinded. Primary end points were the semiquantitative liver-to-background (L/B) and myocardium-to-liver (M/L) ratios from SPECT images. Results: Baseline characteristics were well-matched. The primary analysis revealed no statistically significant benefit from UDCA. The mean L/B ratio was 1.82 ± 0.45 in the UDCA group versus 1.89 ± 0.52 in the placebo group (p = 0.48). The mean M/L ratio was 1.15 ± 0.31 versus 1.11 ± 0.29, respectively (p = 0.41). A post hoc power analysis revealed the study was underpowered to detect a small effect size. Conclusions: A single 300 mg oral dose of UDCA administered 1 h before stress imaging does not significantly improve hepatic clearance of [^99mTc]Tc-sestamibi or enhance M/L ratios. This is likely due to a pharmacokinetically insufficient regimen, as a single dose is unlikely to achieve the necessary biliary concentration for a significant choleretic effect. Future research should focus on alternative interventions or optimized UDCA dosing schedules, such as multiday protocols, combined with advanced imaging techniques like SPECT/CT, to conclusively determine effective strategies for improving MPS image quality.

Background: Oncologic emergencies in critically ill cancer patients frequently require rapid, real-time assessment of tumor responses to therapeutic interventions. However, conventional imaging modalities such as computed tomography and magnetic resonance imaging are often impractical in intensive care units (ICUs) due to logistical constraints and patient instability. Super-resolution ultrasound (SR-US) imaging has emerged as a promising noninvasive alternative, facilitating bedside evaluation of tumor microvascular dynamics with exceptional spatial resolution. This study assessed the clinical utility of real-time SR-US imaging in monitoring tumor perfusion changes during emergency management in oncological ICU settings. Methods: In this prospective observational study, critically ill patients with oncologic emergencies underwent bedside SR-US imaging before and after the initiation of emergency therapy (e.g., corticosteroids, decompression, or chemotherapy). SR-US was employed to quantify microvascular parameters, including perfusion density and flow heterogeneity. Data processing incorporated artificial intelligence for real-time vessel segmentation and quantitative analysis. Results: SR-US imaging successfully detected perfusion changes within hours of therapy initiation. A significant correlation was observed between reduced tumor perfusion and clinical improvement, including symptom relief and shorter ICU stay. This technology enables visualization of microvessels as small as 30 µm, surpassing conventional ultrasound limits. No adverse events were reported with the use of contrast microbubbles. In addition, SR-US imaging reduces the need for transportation to radiology departments, thereby optimizing ICU workflow. Conclusions: Real-time SR-US imaging offers a novel, bedside-compatible method for evaluating tumor vascular response during the acute phase of oncological emergencies. Its integration into ICU care pathways could enhance timely decision-making, reduce reliance on static imaging, and support personalized cancer management. Further multicenter validation is required.

Background: Neoadjuvant chemotherapy for breast cancer (BC) improves patient prognosis, but its efficacy is hindered by the disease's high heterogeneity. This study enhances effectiveness of targeted therapy to improve clinical outcomes. Methods: This study enrolled 335 patients from three centers. Differentially expressed genes were identified using DESeq2, and Venn analysis was applied to identify hub Complement genes. Hub gene expression was validated through public databases and IHC in real-world samples. In addition, associations between these genes and clinical factors were evaluated. Survival analysis, using the log-rank test, assessed overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) as end points. The authors also locate hub Complement 3 gene position by immunofluorescence. Results: The study identified C3 as a hub Complement gene associated with trastuzumab sensitivity. C3 shows higher expression in normal than tumor tissues. C3 was highly expressed in HER2-negative and early-stage BC, but showed no differences in lymph node or metastasis subgroups. High C3 expression correlated with better OS, DSS, and PFI, particularly in HER2+ patients. IHC analysis confirmed higher C3 expression in normal tissues with the lowest in triple-negative BC. Immunofluorescence findings suggest that C3 recruits complement receptor 2 to enhance trastuzumab efficacy in HER2+ patients. Conclusions: This finding highlights the potential of complement 3 to improve therapeutic outcomes and pave the way for more personalized treatment strategies in BC.

Introduction: Cancer remains a major global health burden, with treatment outcomes often impacted by tumor heterogeneity and individual patient factors. Personalized cancer therapies are increasingly essential to improve prognosis and response. Methods: This study explores the integration of epigenomics and radiopharmaceuticals into preoperative chemoradiotherapy as a strategy to personalize cancer treatment. Epigenomic profiling identifies reversible heritable changes in gene expression, revealing tumor biology and therapy resistance mechanisms. Radiopharmaceuticals, which combine radioactive isotopes with tumor-specific ligands, enable targeted radiation delivery. Results: The combined use of epigenetic markers and radiopharmaceuticals allows for tailoring chemoradiotherapy regimens, enhancing tumor selectivity, and minimizing off-target effects. Early clinical data show improved therapeutic efficacy, tumor downstaging, higher survival rates, and reduced recurrence. Epigenetic therapies, including DNA methylation and histone deacetylase inhibitors, further sensitize tumors to radiopharmaceuticals, enhancing treatment synergy. Conclusions: Integrating epigenomics and radiopharmaceuticals into preoperative chemoradiotherapy represents a significant advancement toward personalized oncology. This approach enhances treatment precision and effectiveness while reducing toxicity. Continued research and clinical validation are critical to transitioning this dual strategy into routine practice.

Objective: To find out the effects of laparoscopic myomectomy on myoglobin (MYO), ischemic modified albumin (IMA), total antioxidant capacity (TAC), serum malondialdehyde (MDA), and reactive oxygen species (ROS) in patients with uterine myoma. Methods: According to different surgical treatment methods, 116 patients with uterine fibroids included from February 2022 to February 2023 were divided into two groups, including a laparotomy group and a laparoscope group. The former (n = 58) underwent open myomectomy, while the latter (n = 58) underwent laparoscopic myomectomy. The indexes of oxidative stress were compared before surgery and on the 1st and 3rd days after surgery. Intraoperative and postoperative recovery indicators and the incidence of postoperative complications were also compared. Results: Before surgery, there was no significant difference in oxidative stress level between the two groups (p > 0.05). The levels of MYO, IMA, MDA, and ROS decreased in the laparoscope group on the 1st and 3rd days after surgery. The data in the laparotomy group were lower than that in the laparoscope group, so the statistical difference appeared significantly (p < 0.05). The index of TAC in laparoscope group was higher than that in laparotomy group, so the statistical difference was significant (p < 0.05). Data such as the intraoperative time, intraoperative blood loss, the first time to get out of bed, the first time to exhaust, and the first time to eat in laparoscope group were lower than those in laparotomy group, suggesting that the statistical differences were significant (p < 0.05). Three months after surgery, the incidence of incision bleeding, emphysema, nerve damage, intestinal obstruction, and back pain in the laparoscopic group was lower than that in the cesarean section group. The incidence of incision bleeding and nerve damage in this group was 0, while the incidence of incision bleeding in the cesarean section group was as high as 8.62%, significantly higher than that in the laparoscope group (p < 0.05). Conclusions: It can reduce the oxidative stress of patients and shorten the recovery time of postoperative symptoms, so as to reduce the incidence of complications by means of laparoscopic myomectomy.

Introduction: Integrating radiopharmaceuticals in anesthesia and orthopedic oncology has revolutionized cancer biotherapy and targeted therapy. This multidisciplinary approach leverages molecular imaging, radioisotopes, and precision medicine to enhance perioperative pain management and improve therapeutic efficacy. Methods: Radiopharmaceutical-based anesthetic techniques (R-ATs) have emerged to facilitate intraoperative monitoring and postsurgical pain control, ensuring better patient outcomes in orthopedic oncology procedures. This article explores combining radiopharmaceuticals with orthopedic cancer management, emphasizing novel theranostic agents, α- and β^--emitting radionuclides, in treating metastatic bone disease. Innovations in peptide receptor radionuclide therapy (PRRT) and radiolabeled bisphosphonates have provided a significant leap forward in mitigating skeletal-related events and improving survival rates. Results: This article discusses radiopharmaceutical-guided anesthesia's role in enhancing intraoperative imaging precision and personalizing analgesic regimens for patients with cancer undergoing orthopedic interventions. The article aligns with recent developments in molecular medicine by addressing the translational impact of radiopharmaceuticals on cancer treatment paradigms. In targeted therapy, R-AT attained an effectiveness of up to 96.25%, while PRRT reached 97.45%. Conclusions: It highlights integrating artificial intelligence and molecular imaging in real-time surgical decision-making, redefining personalized oncology care. The synergistic use of radiopharmaceuticals in anesthesia and orthopedic oncology holds immense promise in precision-driven therapeutic strategies for cancer biotherapy.

Introduction: Pancreatic cancer remains one of the most challenging malignancies to treat, characterized by limited therapeutic options and persistently poor survival rates. Conventional radiotherapy presents several limitations, including nonspecific tumor targeting, elevated toxicity to adjacent healthy tissues, and intrinsic radioresistant pancreatic tumors, necessitating innovative treatment strategies. In comparison to previous studies, which reported a median survival rate of 12 months for patients undergoing conventional radiotherapy, the results of this study demonstrate a significant improvement, with a median survival increase to 18 months using a novel targeted approach. Additionally, our findings show a 30% reduction in off-target tissue toxicity, compared with the 45% toxicity seen with traditional methods. Methods: Nanoparticle-enhanced radiotherapy (NERT) introduces a novel therapeutic approach using biocompatible nanoparticles functionalized with tumor-specific ligands. These nanoparticles serve as radiosensitizers, selectively increasing the local radiation dose within the tumor microenvironment while minimizing exposure normal tissues. This targeted delivery mechanism leverages precision nanotechnology to enhance the therapeutic index. Results: Preclinical studies have shown NERT significantly improves treatment outcomes in pancreatic cancer. The method achieves 97.4% increase in treatment efficiency, 45.2% reduction in toxicity, 96.3% enhancement in patient outcomes, 40.3% decrease in systemic side-effects, and 98.6% improvement in tumor targeting when compared with conventional radiotherapy. Conclusions: These findings underscore the transformative potential of NERT in addressing key limitations of traditional pancreatic cancer treatments. By integrating precision targeting with advanced nanotechnology, NERT enhances the efficacy radiotherapy while mitigating adverse effects, thereby improving patient outcomes. This innovative modality holds promise for redefining clinical protocols and elevating standards of care in oncology. The proposed method achieves the treatment efficiency by 97.4%, toxicity by 45.2%, patient outcome by 96.3%, systematic side-effect by 40.3%, and tumor targeting by 98.6%.

Objective: This study identifies shared genetic factors linking Hashimoto's thyroiditis (HT) and thyroid cancer (TC) using an integrated multiomics approach. Methods: We combined Mendelian randomization (MR) analysis using FinnGen genome-wide association study data, single-cell RNA sequencing of 76,243 thyroid cells, and machine learning classification models to identify causal genes and their expression patterns across disease states. Results: MR analysis identified 10 genes with consistent directional effects across both diseases. Peroxiredoxin 2 (PRDX2) emerged as the strongest protective factor (HT: odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.31-0.94; TC: OR = 0.68, 95% CI: 0.50-0.91). Single-cell analysis revealed progressively decreased PRDX2 expression from normal thyroid to papillary to anaplastic TC. Machine learning confirmed PRDX2 as the most discriminative gene for disease classification. PRDX2 expression negatively correlated with inflammatory TNF-TNFRSF1A signaling and was associated with improved survival in patients with TC (hazard ratios = 0.33, 95% CI: 0.11-0.96, p = 0.043). Conclusions: PRDX2 functions as a key protective factor in both HT and TC pathogenesis, likely through modulation of oxidative stress and inflammatory signaling. These findings provide mechanistic insights into the HT-TC relationship and highlight PRDX2 as a promising therapeutic target for thyroid diseases.