Cancer Biotherapy and Radiopharmaceuticals最新文献

Objective: To assess the clinical impact of docetaxel and capecitabine administered under ultrasound-mediated enhancement in patients with advanced triple-negative breast cancer (TNBC), with an emphasis on safety, quality of life, immunological modulation, and therapeutic efficacy.

Methods: A total of 80 patients with advanced TNBC who received treatment at this institution between October 2021 and October 2022 were chosen at random and placed in either the control group (CG, n = 40) or the observation group (OG, n = 40). While the OG received capecitabine and docetaxel supplemented by an ultrasound-mediated drug delivery strategy intended to enhance intratumoral absorption, the CG received cisplatin and docetaxel. The groups were compared in terms of clinical response, immunological function, quality of life (FACT-B), incidence of adverse events, and serum tumor markers.

Results: Compared with the CG, the OG showed a considerably greater response rate (RR) and disease control rate (p < 0.05). Immunoglobulin (Ig)G, IgM, and IgA levels in the CG dramatically decreased after two treatment cycles (p < 0.05), while levels in the OG were maintained and continued to be greater than those in the CG (p < 0.05). Both groups' FACT-B scores dropped (p < 0.05), but the OG's reduction was less noticeable (p < 0.05), suggesting that ultrasound-enhanced therapy improved quality-of-life preservation. The OG had decreased incidence of adverse events; however, this difference was not statistically significant (p > 0.05). Following therapy, tumor markers CA125 and CA153 reduced in both cohorts (p < 0.05), with the OG showing larger reductions (p < 0.05).

Conclusions: Capecitabine and docetaxel administered via ultrasound improve therapeutic efficacy in advanced TNBC, lessen immune suppression brought on by treatment, improve quality of life, and support a positive safety profile while encouraging higher decreases in tumor marker expression. These results demonstrate the potential therapeutic benefit of using ultrasound-based medication delivery techniques into TNBC systemic therapy.

Background: Traditional Chinese Medicine (TCM) and ultrasound-based therapy techniques have emerged as viable complementary approaches to cancer treatment, since both have modulatory effects on the tumor microenvironment (TME). TCM is distinguished by its multicomponent and multitarget processes, whereas ultrasonic treatments provide noninvasive biophysical modification to improve medication transport, immunological activation, and vascular permeability. Despite growing recognition of the synergistic potential of these modalities, no comprehensive bibliometric examination of their confluence in TME research has yet been done.

Methods: CiteSpace and VOSviewer were used to evaluate publications from the Web of Science Core Collection spanning from 2014 to 2024. A total of 771 relevant publications were used to create visual knowledge maps, highlight research hotspots, collaborative networks, and emerging trends, with a particular emphasis on studies that combined TCM and ultrasonography in cancer-related TME regulation.

Results: Over the last decade, research at the interface of TCM and ultrasonic therapy has expanded rapidly. China has dominated this sector in terms of publication volume and worldwide influence, with strong partnerships with the United States and the United Kingdom. The core institutions include the Shanghai University of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Zhejiang University, Shanghai Jiao Tong University, and the Chinese Academy of Sciences. The research field has shifted from basic studies on "cell proliferation" and "apoptosis" to more sophisticated inquiries into "immune microenvironment regulation," "ultrasound-assisted drug delivery," "nanomedicine," and "synergistic therapy."

Conclusions: The combination of TCM and ultrasonic therapy in TME research represents a new multidisciplinary frontier that combines molecular biology, materials science, and clinical oncology. This bibliometric and knowledge atlas study emphasizes the expanding body of data supporting ultrasound-enhanced TCM therapies as a promising paradigm in cancer therapy. To fully realize their combined promise in precision oncology, future initiatives should focus on mechanistic validation, standardized clinical evaluation, and worldwide collaboration.

Background: Quercetin, a naturally occurring flavonoid with recognized antitumor properties, has limited therapeutic applicability due to its low water solubility and bioavailability. To address these issues, a new quercetin derivative, ANL3, was created with superior pharmacokinetic and physicochemical characteristics.

Methods and results: In vitro investigations showed that ANL3 effectively inhibited the proliferation, invasion, and migration of human osteosarcoma cells (MG-63 and SaOS-2) with lower IC₅₀ values than quercetin. Transcriptomic analysis and molecular testing revealed the FOXO1A-NDRG2-superoxide dismutase 2 (SOD2) axis as a critical mechanistic route. ANL3 directly interacted with FOXO1A, increasing its phosphorylation without decreasing total protein expression, upregulating NDRG2, and downregulating SOD2, resulting in increased reactive oxygen species (ROS) buildup and endoplasmic reticulum (ER) stress. This cascade reduced the epithelial-mesenchymal transition and slowed osteosarcoma growth. In vivo, ANL3 therapy decreased tumor volume, increased survival in naked mice, and had little systemic toxicity.Ultrasound Augmentation:Based on these findings, low-intensity focused ultrasound was used to increase ANL3 delivery and intracellular activation. Ultrasound exposure increased cellular uptake, boosted local ROS production, and amplified ER stress signaling via the FOXO1A-NDRG2-SOD2 pathway.

Conclusions: These findings show that ultrasound-augmented ANL3 treatment is a viable biotherapeutic method for osteosarcoma because it improves ER stress-mediated tumor suppression while reducing systemic adverse effects. This article proposes a mechanistic framework for incorporating ultrasound-mediated medication activation into precision cancer biotherapy.

Sonodynamic treatment (SDT) is also beginning to be of interest as an effective noninvasive approach to treat glioblastoma multiforme, in which ultrasonically triggered sensitizers generate an effector of cytotoxic reactive oxygen species (ROS). The current research determined the competence of three structurally novel porphyrin-based sensitizers (named as P1, P2, and P3) under the arm of low-intensity pulsed ultrasound (LIPUS) as an agent that enhances ROS-mediated apoptosis in the cells of the glioma. The authors tested the model of U87-MG human glioblastoma cell cultures under the treatment with porphyrins at the concentration of 27 M down to 10.7 M with and without LIPUS treatment (1 MHz, 1.0W/cm², 50% duty cycle, 5 min). The effects of the combined porphyrin and LIPUS treatment were also more likely to show effects of increased production of ROS in all of its concentrations compared with monotherapies or control, which was not treated. P3 + LIPUS yielded the highest amount of ROS, with the number increasing 3.2 0.4 times more than control (p < 0.001). To compare, the percentage of apoptosis increased to 46.7% relative to the 8.6% of the untreated cells using the combined SDT (adjusted odds ratio [aOR] = 6.9; 95% confidence interval [CI]: 3.21-5.0). Porphyrin and ultrasound also had a synergistic effect with all the sensitizers and P3 represented the highest synergy index. The multivariate regression analysis showed that interaction between light concentration of sensitizer and the parameters of ultrasound exposure had a statistical significance (p < 0.01) such that it was possible to state that there was upregulated oxidative stress with dual-modality treatment. The findings clearly confirm that a mixture of LIPUS and newly identified porphyrin-based sensitizers is more effective in promoting the intracellular concentration of ROS and triggering an apoptosis in glioma cells than either of the two groups. This synergy has been observed in preclinical studies that are underway on the further development of such a process in the treatment of gliomas. The results are already included in a growing collection of literature on the potential SDT overcoming the disadvantages that are associated with the traditional photodynamic therapy to chemoresistance in gliomas. Besides determining the efficacy of P3, this study provides the requisite quantitative biomarkers and synergy models, which may be implemented to construct intelligent and closed-loop SDT systems. The results form the basis of the quantitative development of adaptive, closed-loop SDT systems in the future.

Purpose: To explore the efficacy and safety of ¹²⁵I source implantation via a coaxial puncture in treating locally advanced pancreatic cancer (LAPC).

Methods: A retrospective analysis was used to investigate the efficacy and safety of 40 patients with LAPC treated with radioactive ¹²⁵I particles under CT guidance in the hospital. A treatment planning system was used to develop the preoperative plan, and the radioactive ¹²⁵I particles were implanted using a coaxial puncture technique in the same plane to simulate a sector distribution system. CT scans were performed at postoperative months 2, 4, and 6 for follow-up treatment outcome assessment. Overall survival (OS) time and progression-free survival (PFS) were calculated, and factors affecting prognosis were assessed.

Results: All patients completed the operation successfully. The overall response rate of treatment at 2, 4, and 6 months was 37.5%, 47.5%, and 50.0%. The median OS and PFS were 11.0 months (95% confidence interval [CI]: 9.14-12.86) and 9.0 months (95% CI: 7.45-10.55), respectively. The 6- and 12-month PFS rates were 85.0% (95% CI: 69.6%-93.0%) and 35.0% (95% CI: 20.8%-49.5%), respectively. The 12-month OS rates were 47.5% (95% CI: 20.2%-49.8%). The intraoperative complications related to the operation were local abdominal hemorrhage in 2 cases, subcutaneous soft tissue hematoma in 2 cases, and wrong puncture of the pancreatic duct in 1 case. The main side-effects were fever in 10 cases and decreased appetite in 3 cases in the recent postoperative period. Eighteen grade 0 cases and 3 cases of grade I acute radiation enteritis occurred. No acute radiation damage above grade II and late radiation damage was observed.

Conclusions: Coaxial puncture ¹²⁵I source implantation is a promising percutaneous minimally invasive technology that is safe and effective in treating LAPC.

Background: Boron neutron capture therapy (BNCT) is a precision binary radiotherapy. In this modality, thermal neutrons combine with 10B to induce a nuclear reaction that kills tumor cells. Its therapeutic efficacy depends on the targeted accumulation of boron delivery agents. BNCT has demonstrated clinical efficacy in treating head and neck cancers and recurrent gliomas. However, there is limited evidence regarding its application in hepatocellular carcinoma (HCC). This review systematically examines recent advances in novel boron carriers. It also assesses the potential of BNCT for treating HCC and aims to provide a new therapeutic option for HCC.

Methods: We used a systematic research approach to investigate the latest advances in novel boron carrier development. We also analyzed existing clinical data related to BNCT treatment for HCC. We aimed to systematically assess the feasibility and potential of applying BNCT to HCC.

Results: Newly designed boron carriers show significantly enhanced targeted aggregation within tumor cells and reduced systemic toxicity compared to traditional carriers. Preliminary clinical studies have confirmed the potential efficacy of BNCT in inhibiting HCC growth. Notably, BNCT possesses the unique advantage of precise tumor targeting, which shows promising potential in minimizing damage to surrounding normal liver tissue.

Conclusion: The progress made in the development of boron carriers has built a solid foundation for improving the efficacy and safety of BNCT treatment for HCC. By addressing current limitations in boron delivery and clinical evidence, BNCT has the potential to complement existing treatment modalities, improve outcomes for HCC patients, and provide new directions for the clinical treatment of HCC.

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.

Chemotherapy, radiation, and targeted biological treatments are examples of cancer therapies that have a significant effect on the immune system. They frequently interfere with the manufacture of immunoglobulins (Igs), which results in immunodeficiency. The processes via which these medications affect B cell activity and antibody production are examined in this review, with an emphasis on cytokine regulation, bone marrow suppression, and therapy-induced lymphopenia. Reduced Ig levels can have clinical repercussions such as increased vulnerability to infections, decreased effectiveness of vaccinations, and compromised immune monitoring. This study also looks at new and existing methods to lessen these consequences, including immunomodulatory techniques, prophylactic antibiotics, and Ig replacement treatment. Optimizing patient outcomes, striking a balance between immunological protection and oncologic efficacy, and directing future research in supportive cancer care all depend on an understanding of how humoral immunity and cancer treatment interact.

Purpose: This study evaluated the correlations between findings from ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET), contrast-enhanced magnetic resonance imaging (MRI), and diffusion-weighted imaging (DWI) for hepatocellular carcinoma (HCC) lesions, and differences in imaging features between the infiltrative and noninfiltrative morphological subtypes of HCC were investigated.

Methods: In this retrospective study, 79 patients with HCC imaged with hepato-specific contrast-enhanced dedicated liver PET/MRI were included. Patients were grouped as positive or negative based on MRI, and the sensitivity and specificity of PET imaging were calculated. In addition, patients were classified as infiltrative and noninfiltrative, and tumor SUV, metabolic tumor volume, total lesion glycolysis (TLG), and apparent diffusion coefficient (ADC) variables were compared. Correlations between SUV, tumor size, and ADC values were investigated through regression analyses. Linear regression analyses were used to investigate the relationships between DWI-/PET-derived variables and serum alfa-feto protein (AFP) levels.

Results: A total of 79 patients were included in the study. PET imaging demonstrated 77% sensitivity and 88% specificity, and 19 (27%) patients had infiltrative morphology. The infiltrative subgroup showed a higher rate of portal venous tumor thrombosis (79%), and most tumor thrombi (79%) were ¹⁸F-FDG-avid. A significant relationship was observed between tumor SUV values, ADCmin, and tumor size. Serum AFP levels correlated with SUV_peak (R² = 0.223) and TLG (R² = 0.283; both p < 0.001) values.

Conclusions: Higher ¹⁸F-FDG uptake was observed in infiltrative lesions compared with noninfiltrative ones. The majority of malignant tumor thrombi exhibited increased ¹⁸F-FDG uptake. Although the ability of ¹⁸F-FDG PET to detect HCC lesions is limited by the variable uptake in HCC tumors, it proves valuable in assessing tumor aggressiveness.