RESUMEN
BACKGROUND: Since the 2016 WHO guidelines, glioma diagnosis has entered an era of integrated diagnosis, combining tissue pathology and molecular pathology. The WHO has focused on promoting the application of molecular diagnosis in the classification of central nervous system tumors. Genetic information such as IDH1 and 1p/19q are important molecular markers, and pathological grading is also a key clinical indicator. However, obtaining genetic pathology labels is more costly than conventional MRI images, resulting in a large number of missing labels in realistic modeling. METHOD: We propose a training strategy based on label encoding and a corresponding loss function to enable the model to effectively utilize data with missing labels. Additionally, we integrate a graph model with genes and pathology-related clinical prior knowledge into the ResNet backbone to further improve the efficacy of diagnosis. Ten-fold cross-validation experiments were conducted on a large dataset of 1072 patients. RESULTS: The classification area under the curve (AUC) values are 0.93, 0.91, and 0.90 for IDH1, 1p/19q status, and grade (LGG/HGG), respectively. When the label miss rate reached 59.3 %, the method improved the AUC by 0.09, 0.10, and 0.04 for IDH1, 1p/19q, and pathological grade, respectively, compared to the same backbone without the missing label strategy. CONCLUSIONS: Our method effectively utilizes data with missing labels and integrates clinical prior knowledge, resulting in improved diagnostic performance for glioma genetic and pathological markers, even with high rates of missing labels.
RESUMEN
BACKGROUND: Patients with breast cancer brain metastases (BCBM) experience a rapid decline in their quality of life. Recently, tertiary lymphoid structures (TLSs), analogs of secondary lymphoid organs, have attracted extensive attention. However, the potential clinical implications of TLSs in BCBMs are poorly understood. In this study, we evaluated the density and composition of TLSs in BCBMs and described their prognostic value. METHODS: Clinicopathological data were collected from 98 patients (2015-2021). TLSs were evaluated, and a TLS scoring system was constructed. Differences in progression-free survival (PFS) and overall survival (OS) between groups were calculated using the Kaplan-Meier method. Immunohistochemistry and multiplex immunofluorescence (mIF) were used to assess TLSs heterogeneity. RESULTS: TLSs were identified in 47 patients with BCBM. High TLSs density indicated favorable survival (OS, p=0.003; PFS, p<0.001). TLS was positively associated with OS (p=0.0172) and PFS (p=0.0161) in the human epidermal growth factor receptor type 2-positive subtype, and with prolonged OS (p=0.0482) in the triple-negative breast cancer subtype. The mIF results showed significant differences in the percentages of T follicular helper (Tfh) cells, M2 macrophages, cytotoxic T lymphocytes, and CD8+TIM-3+ T lymphocytes between the groups of TLS scores 0-3 (cytotoxic T lymphocytes, p=0.044; Tfh, p=0.021; M2 macrophages, p=0.033; CD8+TIM-3+ T lymphocytes, p=0.018). Furthermore, novel nomograms incorporating the TLS scores and other clinicopathological predictors demonstrated prominent predictability of the 1-year, 3-year, and 5-year outcomes of BCBMs (area under the curve >0.800). CONCLUSION: Our results highlight the impact of TLSs abundance on the OS and PFS of patients with BCBM. Additionally, we described the immune composition of TLSs and proposed novel nomograms to predict the prognosis of patients with BCBM.
Asunto(s)
Neoplasias Encefálicas , Neoplasias de la Mama , Estructuras Linfoides Terciarias , Humanos , Femenino , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Neoplasias de la Mama/patología , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/mortalidad , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/mortalidad , Persona de Mediana Edad , Pronóstico , Adulto , AncianoRESUMEN
Ternary copper (Cu) halides are promising candidates for replacing toxic lead halides in the field of perovskite light-emitting diodes (LEDs) toward practical applications. However, the electroluminescent performance of Cu halide-based LEDs remains a great challenge due to the presence of serious nonradiative recombination and inefficient charge transport in Cu halide emitters. Here, the rational design of host-guest [dppb]2Cu2I2 (dppb denotes 1,2-bis[diphenylphosphino]benzene) emitters and its utility in fabricating efficient Cu halide-based green LEDs that show a high external quantum efficiency (EQE) of 13.39% are reported. The host-guest [dppb]2Cu2I2 emitters with mCP (1,3-bis(N-carbazolyl)benzene) host demonstrate a significant improvement of carrier radiative recombination efficiency, with the photoluminescence quantum yield increased by nearly ten times, which is rooted in the efficient energy transfer and type-I energy level alignment between [dppb]2Cu2I2 and mCP. Moreover, the charge-transporting mCP host can raise the carrier mobility of [dppb]2Cu2I2 films, thereby enhancing the charge transport and recombination. More importantly, this strategy enables a large-area prototype LED with a record-breaking area up to 81 cm2, along with a decent EQE of 10.02% and uniform luminance. It is believed these results represent an encouraging stepping stone to bring Cu halide-based LEDs from the laboratory toward commercial lighting and display panels.
RESUMEN
Lead-halide perovskite nanocrystals (NCs) are promising for fabricating deep-blue (<460 nm) light-emitting diodes (LEDs), but their development is plagued by low electroluminescent performance and lead toxicity. Herein, the synthesis of 12 kinds of highly luminescent and eco-friendly deep-blue europium (Eu2+)-doped alkali-metal halides (AX:Eu2+; A = Na+, K+, Rb+, Cs+; X = Cl-, Br-, I-) NCs is reported. Through adjustment of the coordination environment, efficient deep-blue emission from Eu-5d â Eu-4f transitions is realized. The representative CsBr:Eu2+ NCs exhibit a high photoluminescence quantum yield of 91.1% at 441 nm with a color coordinate at (0.158, 0.023) matching with the Rec. 2020 blue specification. Electrically driven deep-blue LEDs from CsBr:Eu2+ NCs are demonstrated, achieving a record external quantum efficiency of 3.15% and half-lifetime of â¼1 h, surpassing the reported metal-halide deep-blue NCs-based LEDs. Importantly, large-area LEDs with an emitting area of 12.25 cm2 are realized with uniform emission, representing a milestone toward commercial display applications.
RESUMEN
Hydrogels are well-suited for biomedical applications due to their numerous advantages, such as excellent bioactivity, versatile physical and chemical properties, and effective drug delivery capabilities. Recently, hydrogel coatings have developed to functionalize bone implants which are biologically inert and cannot withstand the complex bone tissue repair microenvironment. These coatings have shown promise in addressing unique and pressing medical needs. This review begins with the major functionalized performance and interfacial bonding strategy of hydrogel coatings, with a focus on the novel external field response properties of the hydrogel. Recent advances in the fabrication strategies of hydrogel coatings and their use in the treatment of pathologic bone regeneration are highlighted. Finally, challenges and emerging trends in the evolution and application of physiological environment-responsive and external electric field-responsive hydrogel coatings for bone implants are discussed.
RESUMEN
Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the molecular features of PCNSLs at a young age. We examined PCNSLs in 34 young patients aged between 7 and 39 years for gene rearrangements of BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, and MYC, homozygous deletions (HD) of CDKN2A, and HLA by FISH. Sequencing was performed using WES, panel target sequencing, or Sanger sequencing due to the small amount of available tissues. The median OS was 97.5 months and longer than that for older patients with PCNSLs. Overall, only 14 instances of gene rearrangement were found (5%), and patients with any gene rearrangement were significantly older (p = 0.029). CDKN2A HD was associated with a shorter OS (p < 0.001). Only 10/31 (32%) showed MYD88 mutations, which were not prognostically significant, and only three of them were L265P mutations. CARD11 mutations were found in 8/24 (33%) cases only. Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients.
RESUMEN
BACKGROUND: Glioblastoma (GBM) is the most common malignant tumour of the central nervous system. Despite recent advances in multimodal GBM therapy incorporating surgery, radiotherapy, systemic therapy (chemotherapy, targeted therapy), and supportive care, the overall survival (OS) remains poor, and long-term survival is rare. Currently, the primary obstacles hindering the effectiveness of GBM treatment are still the blood-brain barrier and tumor heterogeneity. In light of its substantial advantages over conventional therapies, such as strong penetrative ability and minimal side effects, low-frequency magnetic fields (LF-MFs) therapy has gradually caught the attention of scientists. AIM OF REVIEW: In this review, we shed the light on the current status of applying LF-MFs in the treatment of GBM. We specifically emphasize our current understanding of the mechanisms by which LF-MFs mediate anticancer effects and the challenges faced by LF-MFs in treating GBM cells. Furthermore, we discuss the prospective applications of magnetic field therapy in the future treatment of GBM. Key scientific concepts of review: The review explores the current progress on the use of LF-MFs in the treatment of GBM with a special focus on the potential underlying mechanisms of LF-MFs in anticancer effects. Additionally, we also discussed the complex magnetic field features and biological characteristics related to magnetic bioeffects. Finally, we proposed a promising magnetic field treatment strategy for future applications in GBM therapy.
RESUMEN
Chronic diabetic wounds pose significant challenges due to uncontrolled bacterial infections, prolonged inflammation, and impaired angiogenesis. The rapid advancement of photo-responsive antibacterial therapy showed promise in addressing these complex issues, particularly utilizing 2D heterojunction materials, which offer unique properties. Herein, we designed an in situ sprayed Bi/BiOCl 0D/2D heterojunction composite fibrin gel with the characteristics of rapid formation and effective near-infrared activation for the treatment of non-healing diabetes-infected wounds. The sprayed composite gel can provide protective shielding for skin tissues and promote endothelial cell proliferation, vascularization, and angiogenesis. The Bi/BiOCl 0D/2D heterojunction, with its localized surface plasmon resonance (LSPR), can overcome the wide bandgap limitation of BiOCl, enhancing the generation of local heat and reactive oxygen species under near-infrared irradiation. This facilitated bacterial elimination and reduced inflammation, supporting the accelerated healing of diabetes-infected wounds. Our study underscores the potential of LSPR-enhanced heterojunctions as advanced wound therapies for chronic diabetic wounds. This article is protected by copyright. All rights reserved.
RESUMEN
Cell membrane is crucial for the cellular activities, and any disruption to it may affect the cells. It is demonstrated that cell membrane perforation is associated with some biological processes like programmed cell death (PCD) and infection of pathogens. Specific developments make it a promising technique to perforate the cell membrane controllably and precisely. The pores on the cell membrane provide direct pathways for the entry and exit of substances, and can also cause cell death, which means reasonable utilization of cell membrane perforation is able to assist intracellular delivery, eliminate diseased or cancerous cells, and bring about other benefits. This review classifies the patterns of cell membrane perforation based on the mechanisms into 1) physical patterns, 2) biological patterns, and 3) chemical patterns, introduces the characterization methods and then summarizes the functions according to the characteristics of reversible and irreversible pores, with the aim of providing a comprehensive summary of the knowledge related to cell membrane perforation and enlightening broad applications in biomedical science.
Asunto(s)
Membrana Celular , Membrana Celular/metabolismo , Humanos , Animales , Permeabilidad de la Membrana Celular , ApoptosisRESUMEN
Near-Infrared (NIR) light emitting metal halides are emerging as a new generation of optical materials owing to their appealing features, which include low-cost synthesis, solution processability, and adjustable optical properties. NIR-emitting perovskite-based light-emitting diodes (LEDs) have reached an external quantum efficiency (EQE) of over 20% and a device stability of over 10,000 h. Such results have sparked an interest in exploring new NIR metal halide emitters. In this review, several different types of NIR-emitting metal halides, including lead/tin bromide/iodide perovskites, lanthanide ions doped/based metal halides, double perovskites, low dimensional hybrid and Bi3+/Sb3+/Cr3+ doped metal halides, are summarized, and their recent advancement is assessed. The characteristics and mechanisms of narrow-band or broadband NIR luminescence in all these materials are discussed in detail. Also, the various applications of NIR-emitting metal halides are highlighted and an outlook for the field is provided.
RESUMEN
The long-term durability of the implant is influenced by two significant clinical challenges, namely bacterial infection and fixation loosening. Conventional implant materials have failed to meet the demands of the dynamic process of infectious bone repair, which necessitates early-stage bacterial sterilization and a conducive environment for late-stage osteogenesis. Consequently, there is an urgent requirement for an implant material that can sequentially regulate antibacterial properties and promote osteogenesis. The study aimed to develop a micropatterned graphene oxide nanocomposite on titanium implant (M-NTO/GO) for the sequential management of bacterial infection and osteogenic promotion. M-NTO/GO exhibited a micropattern nanostructure surface and demonstrated responsiveness to near-infrared (NIR) light. Upon NIR light irradiation, M-NTO/GO exhibited effective antibacterial properties, achieving antibacterial rates of 96.9% and 98.6% against E. coli and S. aureus, respectively. Under no-light condition, the micropatterned topography of M-NTO/GO exhibited the ability to induce directed cell growth, enhance cell adhesion and spreading, and facilitate osteogenic differentiation. These findings suggest the successful development of a functionalized micropatterned nanocomposite implant capable of sequentially regulating antibacterial and osteogenesis activity. Consequently, this highly effective strategy holds promise for expanding the potential applications of orthopedic implants.
Asunto(s)
Infecciones Bacterianas , Nanocompuestos , Humanos , Osteogénesis , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Nanocompuestos/química , Titanio/farmacología , Titanio/química , Propiedades de SuperficieRESUMEN
Lead halide perovskite nanocrystals (NCs) are highly promising for backlighting display applications due to their high photoluminescence quantum yields (PLQYs) and wide color gamut values. However, the practical applications of blue emitters are limited due to the toxicity of lead, unstable structure, and unsatisfactory PLQY. Herein, we report the successful synthesis of divalent europium-based perovskite CsEuBr3 NCs using a modified hot injection method. By optimizing the reaction conditions, the CsEuBr3 NCs display a deep-blue emission at 443 nm with a full width at half maximum (FWHM) of 28.5 nm, a color purity of 99.61%, and a record high PLQY of 93.51% for deep-blue narrow-band emissive lead-free perovskite NCs as far as we know. The emission mechanism of CsEuBr3 NCs is proved through first-principles calculations and spectral analysis. Notably, the CsEuBr3 NCs exhibit remarkable stability when exposed to high temperature, UV irradiation, and long-term sealed storage. The incorporation of CsEuBr3 NCs into polydimethylsiloxane (PDMS) serving as a converter is utilized for white light-emitting devices (WLEDs). WLEDs for backlight displays achieves a wide color gamut of 127.1% of the National Television System Committee standard (NTSC), 94.9% coverage of the ITU-R Recommendation BT.2020 (Rec.2020), and their half-lifetime is up to 1677 h, providing a promising pathway for highly efficient, environment-friendly and practical liquid crystal display backlights.
RESUMEN
Pediatric high-grade gliomas (HGG) of the cerebellum are rare, and only a few cases have been documented in detail in the literature. A major differential diagnosis for poorly differentiated tumors in the cerebellum in children is medulloblastoma. In this study, we described the histological and molecular features of a series of five pediatric high-grade gliomas of the cerebellum. They actually showed histological and immunohistochemical features that overlapped with those of medulloblastomas and achieved high scores in NanoString-based medulloblastoma diagnostic assay. Methylation profiling demonstrated these tumors were heterogeneous epigenetically, clustering to GBM_MID, DMG_K27, and GBM_RTKIII methylation classes. MYCN amplification was present in one case, and PDGFRA amplification in another two cases. Interestingly, target sequencing showed that all tumors carried TP53 mutations. Our results highlight that pediatric high-grade gliomas of the cerebellum can mimic medulloblastomas at histological and transcriptomic levels. Our report adds to the rare number of cases in the literature of cerebellar HGGs in children. We recommend the use of both methylation array and TP53 screening in the differential diagnoses of poorly differentiated embryonal-like tumors of the cerebellum.
RESUMEN
The blood-brain barrier (BBB) and drug resistance present challenges for chemotherapy of glioblastoma (GBM). A microneedle (MN) patch with excellent biocompatibility and biodegradability was designed to bypass the BBB and release temozolomide (TMZ) and PLCG1-siRNA directly into the tumor site for synergistic treatment of GBM. The codelivery of TMZ and PLCG1-siRNA enhanced DNA damage and apoptosis. The potential mechanism behind this enhancement is to knockdown of PLCG1 expression, which positively regulates the expression of signal transducer and activator of transcription 3 genes, thereby preventing DNA repair and enhancing the sensitivity of GBM to TMZ. The MN patch enables long-term sustainable drug release through in situ implantation and increases local drug concentrations in diseased areas, significantly extending mouse survival time compared to other drug treatment groups. MN drug delivery provides a platform for the combination treatment of GBM and other central nervous system diseases.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Animales , Ratones , Temozolomida/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , ARN Interferente Pequeño/genética , Resistencia a Antineoplásicos/genética , Terapia Combinada , Línea Celular Tumoral , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The time-varying brain activity may parallel the disease progression of cerebral glioma. Assessment of brain dynamics would better characterize the pathological profile of glioma and the relevant functional remodeling. This study aims to investigate the dynamic properties of functional networks based on sliding-window approach for patients with left frontal glioma. The generalized functional plasticity due to glioma was characterized by reduced dynamic amplitude of low-frequency fluctuation of somatosensory networks, reduced dynamic functional connectivity between homotopic regions mainly involving dorsal attention network and subcortical nuclei, and enhanced subcortical dynamic functional connectivity. Malignancy-specific functional remodeling featured a chaotic modification of dynamic amplitude of low-frequency fluctuation and dynamic functional connectivity for low-grade gliomas, and attenuated dynamic functional connectivity of the intrahemispheric cortico-subcortical connections and reduced dynamic amplitude of low-frequency fluctuation of the bilateral caudate for high-grade gliomas. Network dynamic activity was clustered into four distinct configuration states. The occurrence and dwell time of the weakly connected state were reduced in patients' brains. Support vector machine model combined with predictive dynamic features achieved an averaged accuracy of 87.9% in distinguishing low- and high-grade gliomas. In conclusion, dynamic network properties are highly predictive of the malignant grade of gliomas, thus could serve as new biomarkers for disease characterization.
Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Imagen por Resonancia Magnética , Encéfalo , Glioma/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico por imagen , Mapeo EncefálicoRESUMEN
BACKGROUND: Molecular diagnosis is crucial for biomarker-assisted glioma resection and management. However, some limitations of current molecular diagnostic techniques prevent their widespread use intraoperatively. With the unique advantages of ultrasound, this study developed a rapid intraoperative molecular diagnostic method based on ultrasound radio-frequency signals. METHODS: We built a brain tumor ultrasound bank with 169 cases enrolled since July 2020, of which 43483 RF signal patches from 67 cases with a pathological diagnosis of glioma were a retrospective cohort for model training and validation. IDH1 and TERT promoter (TERTp) mutations and 1p/19q co-deletion were detected by next-generation sequencing. We designed a spatial-temporal integration model (STIM) to diagnose the three molecular biomarkers, thus establishing a rapid intraoperative molecular diagnostic system for glioma, and further analysed its consistency with the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5). We tested STIM in 16-case prospective cohorts, which contained a total of 10384 RF signal patches. Two other RF-based classical models were used for comparison. Further, we included 20 cases additional prospective data for robustness test (ClinicalTrials.govNCT05656053). FINDINGS: In the retrospective cohort, STIM achieved a mean accuracy and AUC of 0.9190 and 0.9650 (95% CI, 0.94-0.99) respectively for the three molecular biomarkers, with a total time of 3 s and a 96% match to WHO CNS5. In the prospective cohort, the diagnostic accuracy of STIM is 0.85 ± 0.04 (mean ± SD) for IDH1, 0.84 ± 0.05 for TERTp, and 0.88 ± 0.04 for 1p/19q. The AUC is 0.89 ± 0.02 (95% CI, 0.84-0.94) for IDH1, 0.80 ± 0.04 (95% CI, 0.71-0.89) for TERTp, and 0.85 ± 0.06 (95% CI, 0.73-0.98) for 1p/19q. Compared to the second best available method based on RF signal, the diagnostic accuracy of STIM is improved by 16.70% and the AUC is improved by 19.23% on average. INTERPRETATION: STIM is a rapid, cost-effective, and easy-to-manipulate AI method to perform real-time intraoperative molecular diagnosis. In the future, it may help neurosurgeons designate personalized surgical plans and predict survival outcomes. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
Asunto(s)
Neoplasias Encefálicas , Aprendizaje Profundo , Glioma , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Mutación , Glioma/diagnóstico por imagen , Glioma/genética , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Biomarcadores de Tumor/genética , Isocitrato Deshidrogenasa/genética , Cromosomas Humanos Par 1RESUMEN
The harmonic mode-locking (HML) "invisible" pulsation (IP) is reported, here, in a bidirectional passively mode-locked fiber laser (BPMLFL). With the help of dispersive Fourier transform (DFT) technology, it is found that due to the alike nonlinear effects experienced by two pulse trains in HML, their evolution is consistent during the IP. Further, as the increase of pump power, period-doubling bifurcations (PDBs) can be observed based on the IP phenomenon in the HML regime, the PDB path experienced by the HML from steady to chaotic is statistically obtained. Finally, the IP and PDB in the bidirectional laser are reproduced and studied through numerical simulations. The effect of IP on the coherence of solitons is further analyzed. We believe our research results will provide new insights into the study of soliton dynamics in fiber lasers.
RESUMEN
OBJECTIVES: As a few types of glioma, young high-risk low-grade gliomas (HRLGGs) have higher requirements for postoperative quality of life. Although adjuvant chemotherapy with delayed radiotherapy is the first treatment strategy for HRLGGs, not all HRLGGs benefit from it. Accurate assessment of chemosensitivity in HRLGGs is vital for making treatment choices. This study developed a multimodal fusion radiomics (MFR) model to support radiochemotherapy decision-making for HRLGGs. METHODS: A MFR model combining macroscopic MRI and microscopic pathological images was proposed. Multiscale features including macroscopic tumor structure and microscopic histological layer and nuclear information were grabbed by unique paradigm, respectively. Then, these features were adaptively incorporated into the MFR model through attention mechanism to predict the chemosensitivity of temozolomide (TMZ) by means of objective response rate and progression free survival (PFS). RESULTS: Macroscopic tumor texture complexity and microscopic nuclear size showed significant statistical differences (p < 0.001) between sensitivity and insensitivity groups. The MFR model achieved stable prediction results, with an area under the curve of 0.950 (95% CI: 0.942-0.958), sensitivity of 0.833 (95% CI: 0.780-0.848), specificity of 0.929 (95% CI: 0.914-0.936), positive predictive value of 0.833 (95% CI: 0.811-0.860), and negative predictive value of 0.929 (95% CI: 0.914-0.934). The predictive efficacy of MFR was significantly higher than that of the reported molecular markers (p < 0.001). MFR was also demonstrated to be a predictor of PFS. CONCLUSIONS: A MFR model including radiomics and pathological features predicts accurately the response postoperative TMZ treatment. CLINICAL RELEVANCE STATEMENT: Our MFR model could identify young high-risk low-grade glioma patients who can have the most benefit from postoperative upfront temozolomide (TMZ) treatment. KEY POINTS: ⢠Multimodal radiomics is proposed to support the radiochemotherapy of glioma. ⢠Some macro and micro image markers related to tumor chemotherapy sensitivity are revealed. ⢠The proposed model surpasses reported molecular markers, with a promising area under the curve (AUC) of 0.95.
RESUMEN
Background: The development of new therapies for malignant gliomas has been stagnant for decades. Through the promising outcomes in clinical trials of oncolytic virotherapy, there is now a glimmer of hope in addressing this situation. To further enhance the antitumor immune response of oncolytic viruses, we have equipped a modified oncolytic adenovirus (oAds) with a recombinant interferon-like gene (YSCH-01) and conducted a comprehensive evaluation of the safety and efficacy of this modification compared to existing treatments. Methods: To assess the safety of YSCH-01, we administered the oAds intracranially to Syrian hamsters, which are susceptible to adenovirus. The efficacy of YSCH-01 in targeting glioma was evaluated through in vitro and in vivo experiments utilizing various human glioma cell lines. Furthermore, we employed a patient-derived xenograft model of recurrent glioblastoma to test the effectiveness of YSCH-01 against temozolomide. Results: By modifying the E1A and adding survivin promoter, the oAds have demonstrated remarkable safety and an impressive ability to selectively target tumor cells. In animal models, YSCH-01 exhibited potent therapeutic efficacy, particularly in terms of its distant effects. Additionally, YSCH-01 remains effective in inhibiting the recurrent GBM patient-derived xenograft model. Conclusions: Our initial findings confirm that a double-modified oncolytic adenovirus armed with a recombinant interferon-like gene is both safe and effective in the treatment of malignant glioma. Furthermore, when utilized in combination with a targeted therapy gene strategy, these oAds exhibit a more profound effect in tumor therapy and an enhanced ability to inhibit tumor growth at remote sites.