Reduction In Tumor Size Research Articles

Tumor-Associated Microglia Secrete Extracellular ATP to Support Glioblastoma Progression

Abstract Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and high recurrence rates. The complex immune microenvironment of GBM is highly infiltrated by tumor-associated microglia and macrophages (TAM). TAMs are known to be heterogeneous in their functional and metabolic states and can transmit either protumoral or antitumoral signals to glioma cells. Here, we performed bulk RNA sequencing and single-cell RNA sequencing on samples from patients with GBM, which revealed increased ATP synthase expression and oxidative phosphorylation activity in TAMs located in the tumor core relative to the tumor periphery. Both in vitro and in vivo models displayed similar trends of augmented TAM mitochondrial activity, along with elevated mitochondrial fission, glucose uptake, mitochondrial membrane potential, and extracellular ATP (eATP) production by TAMs in the presence of GBM cells. Tumor-secreted factors, including GM-CSF, induced the increase in TAM eATP production. Elevated eATP in the GBM microenvironment promoted glioma growth and invasion by activating the P2X purinoceptor 7 (P2X7R) on glioma cells. Inhibition of the eATP–P2X7R axis attenuated tumor cell viability in vitro and reduced tumor size and prolonged survival in glioma-bearing mouse models. Overall, this study revealed elevated TAM-derived eATP in GBM and provided the basis for targeting the eATP–P2X7R signaling axis as a therapeutic strategy in GBM. Significance: Glioblastoma-mediated metabolic reprogramming in tumor-associated microglia increases ATP secretion that supports cancer cell proliferation and invasion by activating P2X7R, which can be inhibited to attenuate tumor growth.

Photodynamic Therapy Using IR-783 Liposomes for Advanced Tongue and Breast Cancers in Humans

Photodynamic therapy (PDT) is a minimally invasive treatment that elicits tumor apoptosis using laser light exclusively applied to the tumor site. IR-783, a heptamethine cyanine (HMC) dye, impedes the proliferation of breast cancer cells, even without light. Although studies have investigated the efficacy of IR-783 in cell and animal studies, its efficacy in clinical settings remains unknown. Therefore, we aimed to determine the efficacy of PDT using IR-783 liposomes. An HMC dye, excited by long-wavelength infrared light and with high tissue permeability, was used for PDT after liposomization to enhance tumor tissue accumulation. PDT was performed using IR-783 in two patients with either tongue or breast cancer, one each. IR-783 liposomes inhibited cell proliferation in tongue cancer cells even when not excited by light. Tumor size was markedly reduced in both cases, with no significant adverse events. Furthermore, the patient with tongue cancer exhibited improved respiratory, swallowing, and speech functions, which were attributed not only to the shrinkage of the tumor but also to the improvement in airway narrowing. In conclusion, PDT using IR-783 liposomes effectively reduces tumor size in tongue and breast cancers.

Investigation of Effectiveness of Nowarta110 Against Murine Malignant Melanoma in an Implanted Animal Model.

Melanoma is a prevalent and severe disease, making the development of new treatments essential. Nowata110 has demonstrated significant therapeutic efficacy in phase II clinical study against plantar warts. It has shown promising anti-cancer effects in both in vitro and in vivo studies using HPV-16 and HPV-18-induced cervical cancer models. This study evaluated the effectiveness of Nowarta110 in murine melanoma-implanted animals. Nowata110 is a novel compound composed of colloidal silver and fig extract. Male and female immunodeficient C(Cg)-Cd 79 atm 1 (cre) and immunocompetent BALB/c mice were used. Murine melanoma cancer cells (B16-F10) were implanted subcutaneously in experimental animals. Once the top cross-sectional area of tumors reached a minimum of 5 mm2 and approximately 4 mm depth, mice were anesthetized and treated with Nowarta110 intravenously or intratumorally. Control mice received no treatment. In non-treated immunodeficient mice, tumor growth progressed over five weeks, whereas Nowarta110-treated mice drastically reduced tumor volume until five weeks after treatment was initiated. Similarly, in untreated BALB/c mice, tumor growth persisted over five weeks. However, Nowarta110-treated mice exhibited a notable reduction in tumor size. Although intravenous administration of Nowarta110 did not result in complete tumor regression in immunodeficient mice, it did lead to reduced tumor growth. In BALB/c immunocompetent mice, intravenous treatment generally stalled tumor progression. Intratumoral and intravenous administration of Nowarta110 effectively treated murine melanoma in immunodeficient and immunocompetent mice. The Nowarta110 antitumoral efficacy was more pronounced in immunocompetent mice treated intravenously than immunodeficient mice. Clinical studies to examine the efficacy of Nowarta110 in human melanoma and skin cancers are warranted.

How Arterial Embolization Is Transforming Treatment of Oncologic and Degenerative Musculoskeletal Disease

Background: Arterial embolization is a minimally invasive treatment that occludes blood vessels supplying pathological tissue. Developed to control bleeding without surgery, it has evolved over decades and is now applied in musculoskeletal oncology as a preoperative treatment, palliative care, or standalone therapy for select tumors. Recently, its use has expanded globally in treating chronic pain syndromes and osteoarthritis. Materials and Methods: We reviewed the literature on arterial embolization in various musculoskeletal conditions. The focus was on established oncologic indications for primary and metastatic bone or soft tissue tumors, and emerging evidence on degenerative diseases like osteoarthritis, inflammatory musculoskeletal pathology, and intractable pain. Emphasis was placed on leading studies regarding efficacy, complications, and recurrence rates. Discussion: Arterial embolization has progressed from bleeding control to a versatile therapeutic option in musculoskeletal medicine. It offers symptom relief, reduces tumor size, and improves quality of life. Applications include oncologic interventions and management of degenerative and inflammatory conditions. Despite its benefits, variations in complications and recurrence rates highlight the need for standardized protocols and further research. Conclusions: Arterial embolization is a safe and effective minimally invasive tool in the multidisciplinary management of a wide range of musculoskeletal pathologies. Ongoing research is crucial to understand long-term efficacy, optimize protocols, and broaden its applications.

A rare case of posttraumatic subdural hematoma and intratumoral hemorrhage in a left frontotemporal meningioma: a conservative approach with longitudinal follow-up. Illustrative case.

Meningiomas are common primary intracranial tumors, with associated intratumoral hemorrhage being a rare but serious complication requiring prompt diagnosis for optimal outcomes. Although spontaneous bleeding in benign meningiomas is rare, it can lead to subarachnoid hemorrhage, subdural hematoma, or intratumoral/intracerebral hemorrhage, significantly increasing morbidity and mortality. Advanced imaging and recognition of radiographic hemorrhage patterns are crucial for accurate diagnosis. Treatment is case specific, as surgical intervention is preferred for symptomatic patients, while observation might be adequate for asymptomatic cases. When surgery is not feasible, stereotactic radiotherapy or chemotherapy, which is used only as salvage therapy, is considered. The authors present the case of a 78-year-old male with a history of recurrent falls. Imaging studies revealed a posttraumatic subdural hematoma and an intratumoral hemorrhage within a left frontotemporal meningioma. The patient was managed conservatively, showing significant improvement over 6 months. Notably, there was a marked reduction in both tumor size and intratumoral hemorrhage during follow-up. This case highlights the importance of adopting case-specific management strategies for hemorrhagic complications associated with meningiomas. While surgery is crucial for symptomatic meningiomas, this case demonstrates that conservative methods can be effective for a subset of symptomatic patients with stable clinical conditions and manageable intracranial bleeding. https://thejns.org/doi/10.3171/CASE24322.

Epigallocatechin-3-gallate inhibit the protein arginine methyltransferase 5 and enhancer of Zeste homolog 2 in breast cancer both in vitro and in vivo

PurposeHistone methyltransferases are enzymes that selectively methylate lysine or arginine residues on both histone and non-histone proteins, categorized into lysine methyltransferases and arginine methyltransferases. Notably, EZH2 and PRMT5 are known for catalyzing trimethylation of H3 at K27 and symmetric dimethylation of H4 at R3, respectively. These methylation events are recognized as characteristic histone-repressive marks in cancer. The over expression of PRMT5 and EZH2 were reported in various cancers and recognized as a drug target. The study aims to explore the inhibitory potential of phytocompound, Epigallocatechin-3-gallate (EGCG), against PRMT5 and EZH2 in the breast cancer model. MethodsScreening of an array of phytocompounds was conducted through a combination of in-silico and in-vitro assays. Interactions between EGCG and human PRMT5: MEP50 and EZH2 were evaluated using molecular docking. Binding efficiency was validated, by Surface Plasmon Resonance studies and inhibitory potential was accessed by in vitro methylation followed by western blots, ELISA, and cell-based assays. In-vivo efficacy of EGCG was carried on cell line derived mice xenograft model. ResultsEGCG demonstrated robust interactions with PRMT5:MEP50 complex and EZH2, particularly within the SAM binding site. Surface Plasmon Resonance analysis revealed strong binding affinity in nanomolar concentrations, particularly with PRMT5-MEP50 compared to EZH2. In-vitro assays confirmed EGCG's ability to inhibit PRMT5 and EZH2, leading to a decrease in their catalytic products, namely H4R3me2s and H3K27me3, respectively. EGCG treatment induced both autophagy and apoptosis invitro. In-vivo studies demonstrated significant reductions in tumor size and the proliferation marker ki67, accompanied by a decrease in histone repressive marks. ConclusionThe findings suggest that EGCG effectively inhibits PRMT5 and EZH2, underscoring its potential for combined therapeutic strategies in cancer treatment.

Sphingosine kinase-1 regulates migration and invasion of gastric cancer cells via targeting the nuclear factor-κB signaling pathway

To investigate the role of sphingosine kinase-1 (SPHK1) in regulating migration and invasion of gastric cancer (GC) cells. TIMER2.0, GEPIA and HPA databases were used to investigate SPHK1 expression in GC, and its association with prognosis of the patients was analyzed using Kaplan-Meier Plotter database. In 40 clinical GC and adjacent tissue samples, SPHK1 and MKI67 expressions were detected with immunohistochemistry, Western blotting, and RT-qPCR. Gene enrichment pathway analysis was conducted to explore the biological functions of SPHK1. In HGC-27 and MGC-803 cells, the effects of lentivirus-mediated SPHK1 knockdown or overexpression on cell migration and invasion and expressions of key proteins in the nuclear factor-κB (NF-κB) signaling were evaluated using cell scratch test, Transwell assays and Western blotting. The changes in tumorigenic capacity of the transfected GC cells were evaluated in nude mice. SPHK1 was highly expressed in GC tissues in negative correlation with overall survival, overall survival after progression, and relapse-free survival of the patients (all P<0.001). In clinical GC samples, SPHK1 and MKI67 expressions showed a positive correlation (P= 0.00049) and were both significantly up-regulated (P<0.001). Gene enrichment pathway analysis suggested the involvement of SPHK1 in cell adhesion, migration, angiogenesis and the NF-κB pathway (P<0.05). In the cell experiment, SPHK1 knockdown significantly decreased while SPHK1 overexpression enhanced migration and invasion abilities of the GC cells. SPHK1 positively regulated the expressions of phosphorylated P65 (P-P65), VEGFA and IL-17, and blocking the NF-κB pathway by PDTC significantly lowered migration and invasion ability of the cells. In nude mice, the GC cells with SPHK1 knockdown resulted in significantly reduced tumor size and mass, while the SPHK1-overexpressing cells showed enhanced tumorigenicity. SPHK1 regulates migration and invasion of GC cells via the NF-κB signaling pathway and may serve as a potential diagnostic marker for GC progression.

Results of a Phase 2 Multicenter Study to Evaluate the Efficacy of VP-315, an Investigational Therapy for Basal Cell Carcinoma

Introduction: VP-315 is an intratumorally injected, chemotherapeutic oncolytic peptide in development as a non-surgical immunotherapeutic agent to be utilized as first line therapy in a primary or neoadjuvant setting for patients with basal cell carcinoma (BCC). Objective: In Part 2 of this study, the secondary objective was to evaluate the effect of various dosing regimens on the antitumor efficacy of VP-315 in a larger population of adult subjects with biopsy proven BCC. Methods: Eighty-two (82) subjects with up to 2 target BCC tumors (total 91 tumors) were treated intratumorally with VP-315 for up to 2 weeks. Cohort 3 was not enrolled based on results from Cohorts 1-2. Each 7-day treatment week was comprised of 2 or 3 consecutive treatment days followed by a no-treatment period of at least 4 days. Dosing scheme: Cohort 1: (n=6) Tumor injected 3 days consecutively (3X/week 4 mg loading dose Day 1 followed by 8 mg dose). Cohort 2: (n=3) Tumor injected 3 days consecutively (3X/week 8 mg dose). Cohort 4: (n=36) Each tumor was injected 2 days consecutively (2X/week 8 mg split dose*). Cohort 5: (n=37) Each tumor was injected 3 days consecutively (3X/week 8 mg split dose*). * Dose split into 2 injections, 30% injected initially; 70% injected 15-30 minutes later. Efficacy endpoints included histological clearance of target tumor(s) and estimate of remaining tumor volume (tumor size reduction) at excision (Week 12-13). Results: Eighty-two (82) subjects (n=92 lesions) completed treatment for BCC with VP-315 in Part 2. Approximately 51% of tumors achieved complete histologic clearance. All tumors treated had a reduction in tumor size. Overall tumor size reduction was 86%. Tumor size reduction in subjects who still had any residual tumor was 71%. Conclusion: Complete histological clearance in a majority of VP-315 treated tumors could eliminate the need for surgical intervention in those patients in clinical practice. In subjects with residual tumor burden, the substantial reduction in tumor size after VP-315 treatment would markedly reduce the surgical incision area and the amount of potential post-surgical scarring. Based on the favorable results, further research using VP-315 as a potential non-surgical immunotherapy for BCC as a first line therapy in a primary or neoadjuvant setting is warranted.

Ketogenic diet and its treatment for brain and other nervous system cancers

Abstract. A growing body of empirical evidence indicates the paramount importance of nutrition in cancer treatment, especially glioma. Among the various strategies proposed to enhance traditional anticancer therapy, ketogenic diets (KD) have emerged as a noteworthy approach. In this review, seven papers highly relevant to the effects of ketogenic diet on glioma are selected and the factors involved are summarized. A Google Scholar search with the subject terms ketogenic diet and brain cancer or ketone bodies and glioma results in the selection of seven papers highly relevant to the topic. Animals injected with tumor cells or patients diagnosed with glioma, which had received a ketogenic diet for at least ten days, are included in the analysis. The metabolism-related measurements are also taken. The seven papers show that the ketogenic diet can lower glucose levels, increase -OHB levels, and reduce tumor size or weight. Additionally, it can also impact brain tumor vascularity and gene expression and potentially influence survival time, making it a promising approach for managing brain cancer in humans. In conclusion, there is evidence showing that the Ketogenic diet has the potential to treat brain cancer. Due to the duration and sample volume of the previous studies, future research still needs to continue.

Targeting mitochondrial metabolism with CPI-613 in chemoresistant ovarian tumors

BackgroundThere is evidence indicating that chemoresistance in tumor cells is mediated by the reconfiguration of the tricarboxylic acid cycle, leading to heightened mitochondrial activity and oxidative phosphorylation (OXPHOS). Previously, we have shown that ovarian cancer cells that are resistant to chemotherapy display increased OXPHOS, mitochondrial function, and metabolic flexibility. To exploit this weakness in chemoresistant ovarian cancer cells, we examined the effectiveness of the mitochondrial inhibitor CPI-613 in treating preclinical ovarian cancer.MethodsChemosensitive OVCAR3, and chemoresistant CAOV3 and F2 ovarian cancer cells lines and their xenografts in nude mice were used. Functional metabolic studies were performed using Seahorse instrument. Metabolite quantification was performed using LC/MS/MS.ResultsMice treated with CPI-613 exhibited a notable increase in overall survival and a reduction in tumor development and burden in OVCAR3, F2, and CAOV3 xenografts. CPI-613 suppressed the activity of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complex, which are two of its targets. This led to a reduction in OXPHOS and tricarboxylic acid cycle activity in all 3 xenografts. The addition of CPI-613 enhanced the responsiveness of chemotherapy in the chemoresistant F2 and CAOV3 tumors, resulting in a notable improvement in survival rates and a reduction in tumor size as compared to using chemotherapy alone. CPI-613 reduced the chemotherapy-induced OXPHOS in chemoresistant tumors. The study revealed that the mechanism by which CPI-613 inhibits tumor growth is through mitochondrial collapse. This is evidenced by an increase in superoxide production within the mitochondria, a decrease in ATP generation, and the release of cytochrome C, which triggers mitochondria-induced apoptosis.ConclusionOur study demonstrates the translational potential of CPI-613 against chemoresistant ovarian tumors.

Transarterial Chemoembolization in Locally Advanced Rectal Cancer: A Systematic Review

Background: Locally advanced rectal cancer (LARC) presents a significant treatment challenge. Transarterial chemoembolization (TACE) has emerged as a potential adjunctive treatment, offering targeted delivery of chemotherapeutic agents to the tumor site, minimizing systemic exposure. This systematic review aims to assess the current literature on this novel technique and evaluate the safety and efficacy profile of TACE in treating this complex cohort of patients. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, EMBASE, and Cochrane Library, to identify studies evaluating TACE in LARC. Inclusion criteria encompassed clinical trials, cohort studies, and case series reporting on outcomes such as tumor response rate, overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Results: A total of eight studies involving 543 patients met the inclusion criteria. The studies varied in design, with five prospective and three retrospective studies. A higher prevalence of male participants (68.7%) was noted, with a median age of 60.3 years. The studies primarily evaluated the efficacy and safety of TACE in LARC treatment. Pathological response rates, tumor reduction, and survival outcomes varied across studies, with TACE showing promise in reducing tumor size, improving survival, and controlling metastasis. Major complications were rare, reported in 6.0% of cases. Conclusions: TACE is a promising therapeutic option for patients with LARC, demonstrating favorable tumor response rates and manageable toxicity profiles. Further large-scale, randomized controlled trials are warranted to confirm these findings and better define the role of TACE in the multimodal treatment of LARC.

Comparison of Neoadjuvant Chemotherapy Followed by Radical Surgery with Chemoradiation in Stage IB2 to IIB of Cervical Cancer

Background: The management of locally advanced cervical cancer (stages IB2 to IIB) remains controversial, particularly in regions with limited radiotherapy (RT) resources. While chemoradiation therapy (CRT) is the standard treatment in many Western countries, neoadjuvant chemotherapy followed by radical surgery (NACT-RS) has emerged as an alternative approach. Objectives: The comparative effectiveness and safety of NACT-RS versus CRT in terms of side effects and recurrence rates remain unclear, necessitating further investigation. Methods: A cohort study was conducted from 2020 to 2023, involving 68 patients with cervical carcinoma (stages IB2 to IIB). The patients were stratified into two treatment groups: Neoadjuvant chemotherapy followed by radical surgery (N = 17) and CRT (N = 51). The study compared pathology reports, short-term treatment complications, and one-year recurrence rates between the two groups. Results: Minor complications occurred in 41.2% of the NACT-RS group and 39.2% of the CRT group (P = 0.886), while major complications were observed in 23.5% and 25.5% of the groups, respectively (P = 0.872). All NACT-RS patients responded to chemotherapy with significant tumor size reduction (47.7 ± 8.0 vs. 11.2 ± 8.6, P &lt; 0.001) and resolution of vaginal involvement. During the one-year follow-up, no recurrences were observed in the NACT-RS group, compared to eight out of 51 (16.7%) in the CRT group (P = 0.186). Conclusions: The similar short-term complication rates and potentially lower one-year recurrence rate in the NACT-RS group suggest that this approach may be a viable alternative to CRT, particularly for young patients with bulky tumors and in areas with limited RT facilities.

DNAR-03. ONCOMAGNETIC TREATMENT KILLS GLIOMA CELLS BY INHIBITING MITOCHONDRIAL ELECTRON TRANSPORT AND BY INDUCING OXIDATIVE STRESS AND DNA DAMAGE

Abstract A new noninvasive cancer therapeutic device developed in our laboratory called the Oncomagnetic device involves repeated stimulation with oscillating magnetic fields (sOMF) produced by spinning permanent magnets. It is technologically and mechanistically distinct from the Optune® device approved by the FDA and provides a novel approach for CNS tumor treatment. In 7 end-stage GBM patients, this device reversed the progression of recurrent tumors causing &amp;gt;30% reduction in their contrast-enhanced volumes within 4 – 8 weeks of treatment. Immune-competent mice with implanted mouse glioma cells in their brains also showed marked reduction in tumor size, increased survival (p&amp;lt; 0.05, n = 9) and greater DNA damage (γ-H2AX foci) in implanted tumor after sOMF treatment. Normal mice exposed to sOMF for 4 months had no adverse effects on the brain and other organs. In-vitro, sOMF inhibited mitochondrial ETC complex-I and markedly increased reactive oxygen species (ROS) levels in GBM cells. Detection of γ-H2AX and 53BP1 foci showed that sOMF caused significant DNA damage in GBM cells and diffuse intrinsic pontine glioma (DIPG) cells but not in normal astroglial SVGp12 cells. GBM cells exposed to sOMF for 4 h caused cell cycle arrest in the G1 phase and 30% - 40% loss of surviving colonies detected by clonogenic cell survival assay, while normal SVGp12 cells were not affected. This loss of survival in GBM cells was rescued by the antioxidant Trolox. These results indicate that sOMF stimulation has high anticancer potency comparable to low dose radiation therapy at the cellular level with an underlying mechanism of action that is substantially different from that proposed for Optune® TTF.

EXTH-80. A NOVEL BISAMINOQUINOLINE DERIVATIVE NANOPARTICLE (BAQ13-NP) FOR THE TREATMENT OF GLIOBLASTOMA

Abstract Aminoquinolines, such as hydroxycholoquine, are known to inhibit autophagy and slow cancer cell growth, improving survival in preclinical models of glioblastoma. Unfortunately, they failed to demonstrate benefit in clinical trials due to a lack of sufficient potency and BBB penetration. We have developed a novel bisaminoquinoline derivative packaged in a nanoparticle (BAQ13-NP) with improved potency and intratumoral accumulation after systemic administration, confirmed by distribution and toxicity studies in animals. In this study, we evaluated the impact of BAQ13-NP on tumor cell autophagy and survival using patient-derived glioma cell lines and murine models. GBM patient-derived cell lines (n=4) and murine glioma cells (GL261, CT-2A) were treated with BAQ13-NP (1-4 µM) in culture, demonstrating growth restriction to less than 50% of control at 5-7 days (p&amp;lt;0.01) by MTT assay. Cells treated with BAQ13-NP also demonstrated reduced autophagy with significant increases in accumulation of LC3B and p62 (p&amp;lt;0.01) and reduced IL-6 dependent STAT3 phosphorylation in tumor cells, T cells, and myeloid cells (p&amp;lt;0.01). In addition, treatment of tumor cells with BAQ13-NP reduced IL-6 production over 50% (p&amp;lt;0.01). Mice with orthotopic GL261 or CT2A tumors were treated with BAQ13-NP by tail vein injection (25 mg/kg q2 days) starting 7 days post implantation. Significantly increased survival was observed in BAQ13-NP treated GL261 (HR 0.75, p=0.030) and CT2A (HR 0.78, p=0.033) bearing mice compared to vehicle control treated animals. Reduced tumor size at specific intervals was also observed with BAQ13-NP treatment, corelating with improved survival. BAQ13-NP can inhibit autophagy and slow glioma tumor growth, improving survival in preclinical models. Given the excellent distribution and low toxicity of this novel agent when delivered intravenously, we believe it has great potential to improve outcomes for GBM patients. Our drug has recently received IND approval and will soon be tested in a phase I clinical trial.

Ki-67 With MRI in Predicting the Complete Pathological Response Post-neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) is increasingly used for high-risk breast cancer to achieve pathologic complete response (pCR), an indicator of event-free survival and favorable survival outcomes. Integrating MRI and Ki-67 biomarker analysis into predictive models offers a promising approach to optimize NAC response assessment and guide personalized treatment strategies. This study evaluates the validity of combined MRI and Ki-67 metrics for predicting pCR. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including studies on NAC-treated breast cancer patients assessed by MRI and Ki-67. The predictive models were evaluated based on key parameters, including MRI-based tumor size reduction and Ki-67 levels, with outcomes measured by area under the receiver operating characteristic curve (AUC) and calibration metrics. Findings across ten studies consistently show that high Ki-67 levels and significant tumor size reduction on MRI are predictive of pCR, achieving AUCs near 0.90. The analysis highlighted that models integrating MRI with Ki-67 metrics outperformed single-modality approaches, showing enhanced predictive accuracy and calibration. However, high heterogeneity (I² = 77%) was noted, suggesting variability in imaging and Ki-67 assessment protocols across studies. Thisstudy underscores the combined utility of MRI and Ki-67 for the non-invasive prediction of pCR, offering both structural and biological insights into tumor responsiveness. The results align with prior research, affirming the role of Radiomic-clinicopathological models in providing a more comprehensive assessment compared to individual markers. Further refinement of imaging and biomarker protocols could improve model reproducibility and applicability. Our findings highlight the robust predictive accuracy of MRI-Ki-67 integrated models for assessing pCR, marking a significant step toward personalized cancer care. Future studies should focus on refining these models with additional biomarkers and standardized protocols, facilitating their integration into routine clinical oncology to enhance treatment decision-making and patient outcomes.

EXTH-61. TOWARDS A QUANTUM THERAPY FOR GLIOBLASTOMA: A NEW THERAPEUTIC PARADIGM IN MEDICINE

Abstract BACKGROUND A cell operates as an interconnected bioelectrical circuit, utilising electron transfer processes for intracellular communication, with cytochrome c (Cyt c) playing a pivotal role. The redox processes of Cyt c, occurring via electron tunnelling, are essential for its translocation into the cytosol and modulation of its conformation to bind apoptotic protease activating factor 1. This highlights the need for novel technologies capable of interacting with these processes at the atomic scale to control downstream effects and induce apoptosis in cancer cells. METHODS We demonstrate that ‘bio-nanoantennae’, when supplied with an electrical current, enable quantum biological tunnelling for electron transfer (QBET) and facilitate cellular apoptosis in patient-derived IDH wild-type glioblastoma from both the infiltrative tumour margin and proliferative core. The bio-nanoantennae were constructed from gold nanoparticles functionalised with reduced Cyt c and zinc porphyrin as a redox couple. RESULTS Electrical polarisation of these bio-nanoantennae via resonant alternating currents in preclinical glioblastoma cells led to decreased metabolic activity and reduced cell viability by oxidizing Cyt c, thus inducing cellular stress. No significant effect was observed in healthy human astrocyte counterparts. The cytosol localised bio-nanoantennae induced differential gene expression related to ion channels, apoptosis, cancer proliferation and tumour suppression upon activation, in tumour relative to astrocyte cell populations. The bio-nanoantennae were also tested in 3D glioblastoma spheroid models, showing similar effects, and in vivo studies demonstrated a significant reduction in glioblastoma xenograft tumour size. CONCLUSION We propose that bio-nanoantennae modulate the redox state of Cyt c under an electrical field through QBET. To validate this, we investigated the tunnel junction energy and plasmon resonance scattering, and developed a mathematical model to explain the system’s behaviour. This innovative wireless electrical–molecular nanodevice, capable of inducing cancer cell apoptosis, paves the way for further applications of quantum signalling as a new (non-pharmacological) therapeutic paradigm.

STEM-07. UNVEILING THE ROLE OF HYPOXIA AND TAM-SECRETED TGF-Β1 IN PROMOTING GLIOMA STEM CELL MAINTENANCE VIA YAP/TAZ ACTIVATION IN GLIOBLASTOMA PERI-NECROTIC NICHE

Abstract Glioblastoma (GBM) is a highly malignant brain tumor with rapid growth and poor outcomes. In the tumor microenvironment (TME), necrosis triggers significant reshaping and rapid progression, marked by tumor-associated macrophages (TAMs) and glioma stem cells (GSCs) accumulation in peri-necrotic zones. Analysis of Ivy-GAP and single-cell RNA-Seq data revealed consistent Hippo pathway activation in the hypoxic peri-necrotic zone, despite canonical stem-cell transcription factors such as SOX2, OLIG2, and FOXM1 not being upregulated. We hypothesize that Hippo transcription activation may promote GSC stemness via direct effects of hypoxia and/or TAM-secreted cytokines. Exposing patient-derived GBM neurospheres to 1% hypoxia increased nuclear YAP1 and TAZ expression, along with CYR61, a Hippo pathway readout, compared to normoxia at 48 hours. Single-cell RNA-Seq identified potential hypoxia-regulated genes upstream of YAP/TAZ, including Zyxin, upregulated in 1% hypoxia-treated cultures, possibly facilitating nuclear YAP/TAZ transport. Culturing GBM cells with primary macrophage-conditioned media activated Hippo transcription, with TGF-β1 identified as a hypoxia-specific driver of malignant cell gene expression with single-cell RNA-Seq analysis using NichenetR. Treating GBM cells with TGF-β1 increased CYR61 expression, signifying Hippo transcription activation. Furthermore, we showed that hypoxia and TGF-β1 synergistically maintained GSCs with extreme limiting dilution assays. In the immunocompetent RCAS/tv-a mouse model, Verteporfin, a YAP/TAZ inhibitor, significantly reduced tumor size and prolonged mouse lifespan. TAZ knockdown similarly extended lifespan and reduced tumor growth, with flow cytometry showing a decrease in CD133/CD44 positive GSC populations in knockdown mice. These findings suggest the conclusion that hypoxia and TAM-secreted TGF-β1 directly stimulate YAP/TAZ activation and potentially promote GSC stemness in the GBM peri-necrotic niche.

Silver nanoparticle induced immunogenic cell death can improve immunotherapy

Cancer immunotherapy is often hindered by an immunosuppressive tumor microenvironment (TME). Various strategies are being evaluated to shift the TME from an immunologically ‘cold’ to ‘hot’ tumor and hereby improve current immune checkpoint blockades (ICB). One particular hot topic is the use of combination therapies. Here, we set out to screen a variety of metallic nanoparticles and explored their in vitro toxicity against a series of tumor and non-tumor cell lines. For silver nanoparticles, we also explored the effects of core size and surface chemistry on cytotoxicity. Ag-citrate-5 nm nanoparticles were found to induce high cytotoxicity in Renca cells through excessive generation of reactive oxygen species (ROS) and significantly increased cytokine production. The induced toxicity resulted in a shift of the immunogenic cell death (ICD) marker calreticulin to the cell surface in vitro and in vivo. Subcutaneous Renca tumors were treated with anti-PD1 or in combination with Ag-citrate-5 nm. The combination group resulted in significant reduction in tumor size, increased necrosis, and immune cell infiltration at the tumor site. Inhibition of cytotoxic CD8 + T cells confirmed the involvement of these cells in the observed therapeutic effects. Our results suggest that Ag-citrate-5 nm is able to promote immune cell influx and increase tumor responsiveness to ICB therapies.

A collagenase-decorated Cu-based nanotheranostics: remodeling extracellular matrix for optimizing cuproptosis and MRI in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC), characterized by a dense extracellular matrix (ECM), presents significant therapeutic challenges due to its poor prognosis and high resistance to chemotherapy. Current chemodrugs and diagnostic agents largely fail to cross the barrier posed by the ECM, which severely limits the PDAC theranostics. This study introduces a novel theranostic strategy using thioether-hybridized hollow mesoporous organosilica nanoparticles (dsMNs) for the co-delivery of copper (Cu) and disulfiram (DSF), aiming to induce cuproptosis in PDAC cells. Our approach leverages the ECM-degrading enzyme collagenase, integrated with dsMNs, to enhance drug penetration by reducing matrix stiffness. Furthermore, the innovative use of a pancreatic cancer cell membrane coating on the nanoparticles enhances tumor targeting and stability (dsMCu-D@M-Co). The multifunctional platform not only facilitates deep drug penetration and triggers cuproptosis effectively but also utilizes the inherent properties of Cu to serve as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vitro and in vivo assessments demonstrate significant tumor size reduction in PDAC-bearing mice, highlighting the dual functionality of our platform in improving therapeutic efficacy and diagnostic precision. This integrated strategy represents a significant advancement in the management of PDAC, offering a promising new direction for overcoming one of the most lethal cancers.Graphical

081. Radiofrequency Ablation for Retrosternal Thyroid Tumour: A Rare Case Report

Background: Retrosternal thyroid tumours, though uncommon, present complex diagnostic and therapeutic challenges due to their location behind the sternum. These tumours can cause significant symptoms, such as difficulty breathing and chest pressure, which can impact patient quality of life. Radiofrequency ablation (RFA) has emerged as a minimally invasive treatment option, offering potential benefits over conventional surgical methods for retrosternal thyroid tumor. Case: A 54-year-old male with a history of right thyroid isthmolobectomy presented with a rapidly growing left-sided neck mass, causing increasing chest pressure and shortness of breath. Imaging studies, including ultrasound and CT scans, revealed a large tumour extending retrosternally and compressing the trachea. The patient opted for RFA over surgery. A core biopsy confirmed a benign struma adenomatosa. RFA was performed using the moving shoot technique, resulting in effective tumor ablation. Follow-up imaging showed a significant reduction in tumor size and symptom relief. Conclusion: This case demonstrates that RFA is a safe and effective alternative to conventional surgery for retrosternal thyroid tumours. It provides substantial symptom relief and tumour reduction with fewer complications. RFA should be considered a valuable treatment option for patients who are not ideal candidates for surgery or who prefer less invasive approaches. Continued research and long-term studies are needed to confirm its broader efficacy.