Cancer Biotherapy and Radiopharmaceuticals最新文献

Malignant brain tumors remain a major therapeutic challenge due to poor intracellular delivery of therapeutics. Radiopharmaceuticals such as Technetium-99m (^^99mTc) are valuable for imaging and therapy but suffer from limited tumor uptake caused by cellular and membrane barriers. Focused ultrasound (FUS) offers a noninvasive strategy to transiently enhance membrane permeability through sonoporation. Unlike prior studies largely focused on blood-brain barrier disruption, this work specifically investigates direct tumor cell sonoporation as an independent uptake mechanism. This study evaluates FUS-mediated enhancement of ^^99mTc radiopharmaceutical uptake in brain tumor cells and determines optimal acoustic parameters balancing efficacy and safety. Human glioblastoma (U87-MG) and astrocytoma (A172) cells were cultured and exposed to FUS at intensities of 0.3, 0.5, and 0.7 W/cm² for 30-120 s. Radiopharmaceutical uptake was quantified using γ-scintillation counting. Membrane integrity was assessed by live/dead fluorescence microscopy and lactate dehydrogenase release, while cell viability was evaluated via medical training therapy (MTT) assays. U87-MG cells exhibited up to a 3.1-fold increase at 0.7 W/cm² for 120 s, with a 2.3-fold enhancement at the clinically relevant 0.5 W/cm² for 60 s while maintaining >92% viability. A172 cells showed similar trends with slightly lower magnitudes. Safety assays confirmed reversible membrane permeabilization at ≤0.5 W/cm². The temporal uptake kinetics aligned with established membrane pore resealing dynamics, supporting reversible sonoporation as the uptake mechanism. Importantly, while ^^99mTc complexes are primarily diagnostic, enhanced intracellular delivery achieved by optimized FUS may also support future theranostic strategies, including radionuclide therapy. These findings underscore the translational potential of FUS in neuro-oncology, where tumor heterogeneity necessitates parameter optimization to maximize radiopharmaceutical delivery, improve imaging contrast, and overcome therapeutic resistance.

Background: Response to neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer varies. This study compares tumor response to NACT across anatomical locations, considering clinicopathological differences. Materials and Methods: This retrospective study included 212 patients with gastric adenocarcinoma who received NACT followed by surgery. Tumors were classified by location (antrum-pylorus, corpus-fundus, cardia). Treatment response was assessed using the Modified Ryan Scoring System (0 = complete, 1 = near complete, 2 = partial, 3 = minimal/none). Results: Tumor locations were antrum-pylorus (30.2%), corpus-fundus (28.3%), and cardia (41.5%). Localization showed no statistically significant differences in response (p = 0.337). However, cardia tumors were more frequent in Groups 3 (40.9%) and 4 (48.1%), which showed poorer pathological responses, whereas antrum (34.6%) and corpus (38.5%) tumors were more common in Group 1, representing patients with a pathological complete response. These findings suggest that cardia tumors may have a lower response to NACT, although definitive conclusions cannot be drawn. In multivariate analysis, only advanced T stage (T3-4) was independently associated with poor tumor regression grade response (odds ratio 14.3, 95% confidence interval 5.4-37.5, p < 0.001). Conclusions: Tumor response to NACT varied by anatomical location, although differences were not statistically significant. Cardia tumors showed a trend toward lower response rates. To the authors' knowledge, this is the first study evaluating gastric anatomical subgroups in this context. While not conclusive, the findings suggest that tumor location may influence treatment strategies, warranting validation in larger studies.

Ocular malignancies provide a unique therapeutic challenge because of their anatomical intricacy, limited accessibility, and vision-critical nature. Recent developments in radiopharmaceutical design have been paired with ultrasound-mediated medicine administration to create highly targeted, less invasive therapies for intraocular cancers. This research looks at the emerging topic of ultrasound-responsive radiopharmaceutical devices built specifically for ocular oncology. These methods enhance tumor selectivity, decrease off-target effects, and enable real-time imaging-guided therapy by utilizing targeted ultrasound to induce localized medication release or radiotherapeutic agent activation. Microbubble-assisted delivery, thermosensitive liposomes, and phase-transition nanodroplets carrying radionuclides have all been designed to optimize ocular pharmacokinetics and tissue penetration. Preclinical studies reveal promising results in increasing radiotherapeutic efficacy against retinoblastoma and uveal melanoma while sparing healthy ocular tissues.

Recent research has significantly altered the understanding of the immunogenic profile of certain processes of cancer cell death, leading to the recognition of a new subclass of apoptosis called "immunogenic apoptosis." This form of cell death, induced by specific chemotherapeutic agents, has been shown to elicit a "chemotherapy vaccine effect" in vivo, effectively stimulating an antitumor immune response. At the molecular level, "a collection of molecules" known as "damage-associated molecular patterns (DAMPs)" have been identified as key contributors to the immunogenicity of various cell death pathways. Intracellular molecules, such as heat-shock proteins, high-mobility group box 1 protein, and calreticulin, act as DAMPs when exposed or secreted in response to specific certain stressors, stimuli, and modes of cell death. These discoveries have fueled ongoing research focused on the identification of novel DAMPs, uncovering new mechanisms of their exposure or secretion and developing therapeutic agents capable of inducing immunogenic cell death (ICD). In addition, there is growing interest in addressing the current challenges and limitations within this emerging paradigm. The authors believe that this integrated strategy-combining DAMPs, ICD, and anticancer therapies-may hold the key to significantly reducing cancer-related mortality in the near future.

To properly target tumors during preoperative chemoradiotherapy, differentiated thyroid carcinoma (DTC) must be careful. This method increases treatment success and decreases recurrence. Ultrasound coupled with SPECT/CT may provide novel localization and dose planning possibilities. Many systems solely use anatomical or functional imaging. This may result in insufficient dosage delivery and wasted radiation exposure to healthy tissues. These issues are addressed by Dual-Modality Imaging-Guided Adaptive Chemoradiotherapy Planning (DMI-ACP). This innovative approach combines real-time ultrasound imaging with 6 Å SPECT/CT imaging for precise tumor delineation and tailored dosimetry. This system enables clinicians to adjust chemoradiotherapy regimens by seamlessly integrating functional iodine absorption data with anatomical characteristics, thereby targeting therapy to cancerous areas. The outcomes of this method for patients with DTC were promising, including better lesion targeting, reduced radiation exposure to healthy tissues, and improved chemotherapeutic dose distribution. In clinical evaluations, the DMI-ACP framework demonstrated a sensitivity of 94% and a specificity of 89% in identifying malignant lesions compared with traditional imaging techniques. Furthermore, the integration of adaptive planning resulted in a 20% improvement in tumor control probability and a 15% reduction in exposure to surrounding healthy tissue, as assessed through dosimetric analysis. 2023075 Nanjing Drum Tower Hospital Group Suqian Hospital/The Affiliated Suqian Hospital of Xuzhou Medical University.

Colorectal cancer (CRC) remains a significant factor contributing to the morbidity and mortality rates linked with cancer throughout the world, especially in its stages of progression. Increasingly attractive therapeutic options include immune modulation combined with preoperative chemotherapy and radiation therapy (CRT). Recent studies have revealed that the protein serine peptidase inhibitor Kazal type 4 (SPINK4), which is abundantly expressed in gastrointestinal tract tissues, plays a role in immune evasion and treatment resistance in cancers. This meta-analysis aims to assess the relationship between SPINK4 expression levels and the therapeutic effectiveness of radiolabeled immune modulators in patients with advanced CRC who are undergoing preoperative chemotherapy and radiation treatment. The degree of SPINK4 expression and a lower objective response to radiolabeled immune modulators showed a statistically significant link. Conversely, patients with low SPINK4 expression have more favorable treatment responses and ongoing clinical improvement following CRT. High SpINK4 expression can act as a negative prognostic biomarker for radiolabeled immune control in advanced CRC.

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.

Background: Chemotherapy sensitivity in renal carcinoma may be influenced by renal ischemia-reperfusion injury (RIRI). This study elucidates the underlying mechanism by investigating the regulatory role of MYDGF. Methods: The public dataset was downloaded, and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to analyze functional and pathway enrichment of genes in the most significant modules. MitoTracker Green and MitoSOX were used to assess mitochondrial activity and superoxide production in oxygen-glucose deprivation/reoxygenation (OGD/R)-treated renal proximal tubular epithelial cells (RPTECs), with or without MYDGF treatment. Reactive oxygen species production and apoptosis were further analyzed through flow cytometry. A mouse model of RIRI was established and treated with MYDGF, followed by kidney evaluation after 24 h. Histological damage was assessed using hematoxylin-eosin and Masson staining in both RIRI mice and IR-induced patients with AKI. Immunohistochemistry and quantitative real-time polymerase chain reaction were performed to evaluate MYDGF, BCL2, and BAX expression levels in renal tissues. Results: A total of 557 differentially expressed genes were identified. GO and KEGG analyses revealed significant enrichment in oxidative phosphorylation and apoptosis pathways, both of which are relevant to chemosensitivity. MYDGF treatment significantly inhibited apoptosis, enhanced mitochondrial function, and reduced superoxide production in OGD/R-treated RPTECs. In vivo, MYDGF reduced tubular apoptosis and protected against kidney injury, as shown by TUNEL and Masson staining. Notably, MYDGF increased BCL2 and decreased BAX expression both in vitro and in vivo, suggesting an antiapoptotic shift. These changes may contribute not only to protection from RIRI but also to increased susceptibility of damaged renal cells to chemotherapy-induced apoptosis by maintaining mitochondrial integrity. Conclusions: Regulation of apoptotic signaling by MYDGF attenuates ischemia-reperfusion injury and improves chemotherapy outcomes in advanced renal carcinoma.

Objective: This study explored the role of monocarboxylate transporter 1 (MCT1) in nasopharyngeal carcinoma (NPC) metastasis and its regulation via DNA methyltransferase 3B (DNMT3B)-mediated methylation, to identify therapeutic targets for NPC. Methods: MCT1/DNMT3B expression was analyzed in NPC (n = 30) and normal tissues (n = 30) using quantitative polymerase chain reaction (qPCR) and immunohistochemistry. DNMT3B overexpression plasmids were transfected into NPC cells to assess MCT1 expression and promoter methylation via bisulfite sequencing PCR. Luciferase and chromatin immunoprecipitation (ChIP) assays identified DNMT3B-MCT1 promoter interactions. Migration/invasion assays and Western blot evaluated functional impacts of MCT1 silencing on metastasis-related pathways. Bioinformatic validation utilized GEO datasets. Results: MCT1 mRNA/protein levels were significantly elevated in NPC versus normal tissues (***p < 0.001), whereas DNMT3B was downregulated. DNMT3B overexpression reduced MCT1 expression (*p < 0.05) and increased MCT1 promoter methylation (**p < 0.01). Luciferase assays revealed that DNMT3B suppressed wild-type MCT1 promoter activity, dependent on an 80 bp CpG island (**p < 0.01). ChIP confirmed DNMT3B enrichment at hypermethylated MCT1 promoter regions (**p < 0.01). MCT1 silencing inhibited NPC cell migration/invasion (*p < 0.05) and downregulated p-AKT, p-mTOR, and p-NFκB (*p < 0.05). High MCT1 correlated with Epstein-Barr virus (EBV)-associated EBNA1BP2 (**p < 0.01), but not PD-L1 markers. DNMT3B inversely correlated with MCT1 (*p < 0.05) and was upregulated in advanced-stage NPC (Stage III + IV vs. I + II, ***p < 0.001), indicating stage-specific epigenetic dysregulation. Conclusion: MCT1 promotes NPC metastasis via NF-κB and PI3K/AKT/mTOR pathways, regulated by DNMT3B-driven promoter methylation. The MCT1-DNMT3B axis, linked to EBV-associated metabolic reprogramming, represents a prognostic biomarker and therapeutic target for advanced NPC.

Objective: This study elucidated the role of the forkhead box E1 (FOXE1)-laminin γ2 (LAMC2) signaling axis in promoting brain metastasis (BM) of lung cancer and evaluated its potential as a therapeutic target to enhance the efficacy of preoperative chemoradiotherapy (CRT). Methods: Bioinformatics analysis of the GSE126548 dataset revealed a significant association between elevated FOXE1 expression and BM in lung cancer patients. Functional in vitro assays-including real-time polymerase chain reaction, Western blotting, migration, invasion, and endothelial permeability assays-were conducted in lung cancer cells and human umbilical vein endothelial cells exposed to tumor-conditioned media. In addition, in vivo xenograft and BM mouse models were established to assess the impact of FOXE1 on tumor growth, metastatic potential, and treatment responsiveness. Results: FOXE1 knockdown significantly inhibited lung cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Mechanistically, LAMC2 was identified as a downstream effector of FOXE1, with rescue experiments confirming that the FOXE1-LAMC2 axis plays a central role in driving tumor progression and brain metastatic potential. Notably, FOXE1 silencing enhanced sensitivity to CRT in preclinical models. Conclusions: FOXE1 promotes lung cancer progression and BM by upregulating LAMC2. Targeting the FOXE1-LAMC2 pathway may improve the efficacy of preoperative CRT and offers a promising strategy for therapeutic intervention in lung cancer patients at high risk of BM.