Cancer Biotherapy and Radiopharmaceuticals最新文献

Background: Colorectal cancer (CRC) development and therapy resistance are heavily controlled by the tumor microenvironment (TME). Although anti-PD-1 immunotherapy has significant therapeutic advantages, resistance remains a key challenge. Recent research has identified the gut microbiota as a key regulator of host immunity and checkpoint inhibitor effectiveness. Ultrasound (US) has emerged as a viable biophysical technique for improving medication and microbial delivery and controlling immune activation within tumors.

Objectives: The purpose of this work was to assess the synergistic effects of US-assisted fecal microbiota transplantation (US-FMT) on TME remodeling and anti-PD-1 resistance in a CRC cell line-derived xenograft mouse model.

Materials and methods: Tumor-bearing mice were randomized into four treatment groups: vehicle control, anti-PD-1 alone, fecal microbiota transplantation (FMT) alone, and US-FMT plus anti-PD-1 therapy. Low-intensity focused US was utilized to promote microbial engraftment and intestinal permeability. Flow cytometry, ELISA, and transcriptome profiling were used to investigate tumor growth kinetics, immune cell infiltration, cytokine profiles, and TME-related gene expression.

Results: In comparison with the other groups, US-FMT reduced tumor development and restored sensitivity to anti-PD-1 treatment. US facilitated beneficial microbial colonization, boosted CD8 T cell infiltration, and decreased immunosuppressive cell populations. Furthermore, US-FMT modified cytokine release and reduced pro-tumorigenic inflammatory mediators, reprogramming the TME to be immune-active.

Conclusions: US-assisted microbiota manipulation is a unique and synergistic biotherapeutic method for reversing immunological resistance in CRC. The combination of US and FMT has translational promise for enhancing immunotherapy response and developing noninvasive cancer treatment techniques.

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.

Background: Cyclooxygenase-2 (COX-2) serves as a pivotal molecule bridging inflammation and tumor development, playing a central role in the initiation, progression, and malignant transformation of colorectal adenomas.

Methods: This review systematically examines COX-2 expression patterns, molecular regulatory networks, and its potential applications in clinical diagnosis, prognosis assessment, and chemoprevention.

Results: Evidence indicates that COX-2 exhibits significantly elevated expression in adenoma tissues (e.g., 54.8% positive rate in polyps vs. 18.5% in adjacent tissue), driving pathological progression through multiple mechanisms including cell proliferation induction, apoptosis inhibition, angiogenesis promotion, and tumor immune microenvironment remodeling. Nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors have demonstrated clear promise in adenoma chemoprevention (with agents such as celecoxib reducing advanced adenoma recurrence risk by 33%-45%).

Conclusions: COX-2 is a critical early-event biomarker and therapeutic target in colorectal adenomas. Targeting the COX-2 pathway represents a viable strategy for prevention, although challenges regarding safety and personalized application remain.

Background: Lung cancer is the biggest reason of cancer-correlated death worldwide, owing primarily to immune evasion and poor response to current immunotherapies. Objective: The aim of this work was focused on the immunomodulatory effect of histone deacetylase 4 (HDAC4) in tumor immunological milieu, specifically CD8⁺ T cell trafficking. Methods: Quantitative RT-PCR, immunofluorescence labeling, and FISH tests were used to determine HDAC4 and CXCR3 expression and location in lung cancer tissues. Flow cytometry assessed CD8⁺ T cell function, and histological analysis revealed tumor development. Results: Our results showed that HDAC4 was highly overexpressed in lung tumor samples, and it was associated with advanced clinical stage, lymph node metastases, and a worse overall survival rate. HDAC4 decreased CXCR3 expression, affecting CD8⁺ T cell infiltration and effector function. HDAC4 knockdown increased CD8⁺ T cell cytotoxicity, whereas CXCR3 inhibition reversed this effect. HDAC4 expression predicted poor survival with a ROC AUC of 0.78. SB939 treatment raised CXCR3 expression by 2.4 times and CD8⁺ infiltration by 39%. Conclusion: These findings point to HDAC4 as a crucial epigenetic regulator of immune cell trafficking in lung cancer. Given the growing interest in ultrasound-assisted medication delivery and immunological priming, our findings point to HDAC4 as a viable therapeutic target in ultrasound-guided immunomodulatory methods for lung cancer.

Introduction: α-emitting radiopharmaceuticals are increasingly being evaluated as potential cancer therapeutics. In this study, the authors evaluated the distribution of thorium-227 (²²⁷Th) and its first daughter nuclide, radium-223 (²²³Ra), by analyzing tissue activity data from monkey studies from different antibody-based targeted thorium conjugates (hereafter called "conjugates"). This study clarified the extent of elimination by physical decay and redistribution from tissues for both radionuclides. Methods: In monkey biodistribution studies for four different conjugates, animals were sacrificed at multiple time points, and organ activities of ²²⁷Th and ²²³Ra were measured by direct γ counting. These values were compared to the maximally expected organ activities based on physical decay as the sole elimination path to evaluate the impact of redistribution from tissues. Whole-body activities in cancer patients, measured with high-purity germanium detectors during a first-in-human study of a CD22-targeting conjugate, were evaluated similarly to determine whether they aligned with the overall patterns seen in tissue data. Results: The integrated analysis demonstrated that for all conjugates, the physical decay appeared to be the main elimination path for ²²⁷Th without a strong redistribution from organs, whereas ²²³Ra shows a fast and strong redistribution (≥90%) from most of the tissues except for bone (∼0%) and (large) intestine. The lack of redistribution from bone as well as the high radioactivity in the intestine is consistent with data obtained with ²²³Ra chloride in monkeys and humans. These findings were independent of the assessed compound, target, dose, and administered activity. The observation in monkeys that physical decay is the main elimination path for ²²⁷Th and that ²²³Ra undergoes a fast additional elimination in a typical tissue was consistent with clinical whole-body radioactivity data. Conclusions: The overarching consistency of the findings regarding tissue redistribution of ²²⁷Th and ²²³Ra across different conjugates and the consistency with clinical observations of whole body radioactivity in patients emphasize the importance of considering the potential redistribution of long-lived daughter nuclides of radionuclides used in therapeutic applications in humans.

Background: Graphene oxide (GO), a multifunctional two-dimensional nanomaterial, has gained significant attention in oncology due to its large surface area, tunable surface chemistry, and excellent biocompatibility. These properties enable innovative strategies for cancer treatment and detection. Objective: This review aims to summarize the diverse biomedical applications of GO, focusing on its role in targeted drug and gene delivery, immunomodulation, photothermal and photodynamic therapy, and theranostic approaches. Methods: Recent preclinical studies and reports on GO-based nanostructures were critically analyzed to explore their physicochemical characteristics, functionalization strategies, and therapeutic performance. The review also evaluates translational aspects by assessing pharmacokinetics, toxicity, and regulatory considerations related to GO systems. Results: GO exhibits abundant oxygen-rich functional groups such as hydroxyl and carboxyl, facilitating high drug-loading efficiency and controlled release through pH- and redox-sensitive mechanisms. These properties enhance tumor-targeted drug delivery and minimize systemic toxicity. GO's photothermal conversion ability supports near-infrared-triggered therapy, achieving tumor size reductions up to 80% in preclinical models using photosensitizers like chlorin e6. Moreover, GO-based nanoplatforms augment cancer immunotherapy by modulating immune signaling, promoting antigen presentation, and stimulating cytokine secretion. Despite these advantages, clinical translation is limited by challenges such as dose-dependent cytotoxicity, hemocompatibility, uncertain biodegradation, and lack of standardized synthesis. Variations in particle size, oxidation level, and surface functionalization lead to inconsistent biological outcomes, impeding regulatory approval and clinical progress. Conclusion: Theranostic platforms combining GO with agents such as doxorubicin and indocyanine green enable integrated chemotherapy, phototherapy, and imaging functionalities. Optimization of GO synthesis, surface modification, and large-scale production could enhance its safety and clinical viability. This review presents a multidisciplinary framework connecting GO nanomaterial design with translational oncology and categorizes GO-based hybrids such as GO polymer conjugates and metal nanocomposites to guide future design, mechanism elucidation, and clinical translation.