Melanoma, a highly prevalent cancer worldwide, exhibits remarkable diversity and plasticity, with the adverse prognosis of advanced melanoma remaining a focal point of investigation. Despite the emergence of novel drugs and combination therapies improving patient outcomes, challenges such as drug resistance and incomplete mechanistic understanding persist. Transcriptional programs play a pivotal role in determining the characteristics of both normal and tumour cells, with their dysregulation of these programs being a hallmark of melanoma. Abnormalities in transcription regulation not only impact the characteristics of melanoma cells but also influence the tumor’s metabolism and immune microenvironment, forming a complex network in tumours. Thus, understanding these changes comprehensively is crucial for unravelling the mechanisms underlying melanoma initiation, progression, response to targeted and immune therapies, and treatment resistance. This review primarily explores the transcriptional features in normal melanocytes and melanoma cells, emphasizing their profound impact on cell metabolism and immune evasion. Furthermore, the plasticity of melanoma cells and its relationship with treatment resistance and metastasis are highlighted, emphasizing the importance of targeting dysregulated transcriptional factors and pathways. Finally, potential clinical implications in targeting transcriptional abnormalities are highlighted, particularly in metastatic or treatment-resistant melanomas. This comprehensive overview aims to contribute to the advancement of melanoma research and the development of precise and effective treatments.

Malignant melanoma remains the life-threatening form of skin cancer with high mortality and poor prognosis. Thus, an ideal melanoma therapeutic strategy is of immediate importance which can remove the primary tumor, as well as inhibit the metastasis and recurrence. Here, we report the fabrication of adjuvant monophosphoryl lipid A (MPLA) lipid bilayer-enveloped and photosensitizer indocyanine green (ICG)-loaded gold nanocages (MLI-AuNCs) for immunogenic phototherapy of aggressive melanoma. Hollow porous AuNCs are used as carriers to deliver MPLA and ICG, and protect ICG from photodegradation. Both AuNCs and ICG absorb near infrared (NIR) light and can be applied in controllable NIR-triggered photothermal and photodynamic combination therapy (PTT/PDT) of melanoma. MLI-AuNCs coated by thermosensitive lipid bilayer exhibit uniform size, good biocompatibility and bioavailability with prominent tumor accumulation, which further improve the PTT/PDT efficacy. MLI-AuNCs under NIR irradiation not only destroy the primary tumor by PTT/PDT, but also elicit robust antitumor immune response with melanoma associated antigens and MPLA released in situ. The released antigens and MPLA subsequently enhance the recruitment and maturation of dendritic cells, which further activate the effector T cells to inhibit metastases and recurrence of melanoma. This immunomodulatory-boosted PTT/PDT nanoplatform provides a new opportunity for highly aggressive melanoma treatment. STATEMENT OF SIGNIFICANCE: An ideal tumor therapeutic strategy not only can remove the primary tumor, but also inhibit metastasis and recurrence. Here, we introduced a versatile nanoplatform MLI-AuNCs for immunogenic phototherapy of aggressive melanoma. Adjuvant MPLA and photosensitizer ICG can be protected and co-delivered to the tumors by thermosensitive lipid-enveloped AuNCs. MLI-AuNCs exhibited prominent tumor accumulation ability and produced the potent PTT/PDT effect to destroy the primary tumors with a single dose of NIR irradiation, as well as elicited the strong antitumor immunity to inhibit the metastasis and relapse. This study may provide a potential therapeutic vaccination strategy against advanced melanoma and other difficult-to-treat cancers.

Combined antitumor therapies based on nanomedicines have shown efficacy in various tumor models in recent years, overcoming the disadvantages of inefficiency and undesired toxicity of traditional therapies. Herein, we present a copper sulfide- and doxorubicin-loaded gold nanorods@mesoporous SiO2 multifunctional nanocomposite (AuNR@mSiO(2)@DOX-CuxS-PEG) to integrate chemotherapy, the photothermal properties of AuNRs, and the photodynamic properties of CuxS into a single nanoplatform based on hydrophobic interaction and electrostatic attraction. Upon near-infrared light irradiation, the AuNR@mSiO(2)@DOX-CuxS-PEG nanocomposites exhibit a synergistic therapeutic effect and inhibit the in situ tumor growth and lung metastasis in a melanoma model. This occurs because of the high photothermal conversion efficiency, boosted intracellular reactive oxygen species production, and excellent doxorubicin (DOX) release, as well as an induced tumor-specific immune response. The inspired antitumor immunity was confirmed by elevated infiltration of activated T cells in tumor tissues and improved maturation and activation of dendritic cells in tumor-draining lymph nodes. This study highlights the superior antitumor therapeutic effect elicited by a multifunctional nanoplatform for skin with in situ melanoma and lung metastasis inhibition, indicating its satisfactory clinical application prospects.

Branched polyethylenimine (BPEI) is a cationic polymer and has been applied as an antigen carrier in vaccines. However, its intrinsic adjuvanticity and underlying mechanism remain unclear. Here, we systematically explored the direct stimulation effects of a series of BPEI on bone-marrow-derived dendritic cells (BMDCs) in vitro. Only high concentrations of BPEI with molecular weight (M-W) equal to or greater than 25 kDa showed an immune-activating effect, indicating that both M-W and cationic degree contribute to this effect. In a charge neutralization experiment, the intrinsic adjuvanticity of BPEI also demonstrated a cationic degree-dependent pattern. Moreover, we identified reactive oxygen species (ROS) as the crucial messengers in BPEI-mediated BMDC activation. However, high M-W and cationic charges from the BPEI exerted a direct toxicity on dendritic cells, which would restrict its in vivo applications. Therefore, we introduced fibroblasts as bystander cells and found that BPEI-treated fibroblasts passed stimulation effects to BMDCs with undetectable cytotoxicity. During subcutaneous stimulation, which corresponded to the fibroblast-mediated coculture system, BPEI induced an inflammatory microenvironment and local immune cell infiltration without obvious cell death. To the best of our knowledge, this is the first systematic and incisive investigation of BPEI's intrinsic adjuvanticity and its functional exploration in the presence of bystander cells. This finding paves the way to advance the BPEI-based vaccines and will give insights into the use of other immunoactive biomaterials with similar properties.

Glial tumors, and in particular anaplastic astrocytomas and glioblastoma multiforme (GBM), are aggressive brain tumors with poor prognosis and high recurrence rates. Current treatment strategies are based on open surgery, chemotherapy and radiation therapy. However, not a single one of these methods of treatment, alone or in combination, is effective in combating this disease, resulting in the average life expectancy following the diagnosis of under 15 months. Treatments are inefficient mainly due to the blood-brain barrier (BBB) that makes the delivery of drugs into the tumor mass difficult. With the development of nanotechnology the effectiveness of the drugs currently in use is on an increase and the reach to glial brain tumors is expanding. Nanoparticles are a preferred carrier of medicinal agents and dyes due to their size, availability of surface modification and the flexibility enabling the integration of several functional components into a single system. This makes it possible to direct the development of nanoparticles towards applications in the treatment and diagnosis of glial tumors. This dual approach helps to understand the location of the tumor tissue, bio-distribution of nanoparticles, and treatment progress and effectiveness. In order to improve the treatment and diagnosis approaches, various strategies can be applied to modify the surface of nanoparticles, including surface markers or so-called ligands and use the characteristics of the tumor microenvironment with specific targets which respond to specific stimuli. In this paper we review various strategies for the improvement of treatment and diagnosis of glial tumors, describe some surface markers and talk about opportunities for the introduction of nanoparticles into everyday clinical practice.

BACKGROUND AND PURPOSE:Locally advanced rectal cancer (LARC) patients showing pathological good response (pGR) of down-staging to ypT0-1N0 after neoadjuvant chemoradiotherapy (nCRT) may receive organ-preserving treatment instead of total mesorectal excision (TME). In the current study, quantitative analysis of diffusion weighted imaging (DWI) is conducted to predict pGR patients in order to provide decision support for organ-preserving strategies.MATERIALS AND METHODS:222 LARC patients receiving nCRT and TME are enrolled from Beijing Cancer Hospital and allocated into training (152) and validation (70) set. Three pGR prediction models are constructed in the training set, including DWI prediction model based on quantitative DWI features, clinical prediction model based on clinical characteristics, and combined prediction model integrating DWI and clinical predictors. Prediction performances are assessed by area under receiver operating characteristic curve (AUC), classification accuracy (ACC), positive and negative predictive values (PPV and NPV).RESULTS:The DWI (AUC = 0.866, ACC = 91.43%) and combined (AUC = 0.890, ACC = 90%) prediction model obtains good prediction performance in the independent validation set. Nevertheless, the clinical prediction model performs worse than the other two models (AUC = 0.631, ACC = 75.71% in validation set). Calibration analysis indicates that the pGR probability predicted by the combined prediction model is close to perfect prediction. Decision curve analysis reveals that the LARC patients will acquire clinical benefit if receiving organ-preserving strategy according to combined prediction model.CONCLUSION:Combination of quantitative DWI analysis and clinical characteristics holds great potential in identifying the pGR patients and providing decision support for organ-preserving strategies after nCRT treatment.

Background: Glioma represents the most common malignant brain tumor. Outcomes of surgical resection are often unsatisfactory due to low sensitivity or resolution of imaging methods. Moreover, the use of traditional chemotherapeutics, such as doxorubicin (DOX), is limited due to their low blood-brain barrier (BBB) permeability. Recently, the development of nanotechnology could overcome these obstacles. Materials and methods: Hydrophobic superparamagnetic iron oxide nanoparticles (SPIO NPs) were prepared with the use of thermal decomposition method. They were coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG 2000) and DOX using a thin-film hydration method followed by loading of indocyanine green (ICG) into the phospholipid layers. Details regarding the characteristics of NPs were determined. The in vitro biocompatibility and antitumor efficacy were established with the use of MTT assay. In vivo fluorescence and magnetic resonance (MR) imaging were used to evaluate BBB penetration and accumulation of NPs at the tumor site. Antitumor efficacy was evaluated using measures of tumor size, median survival times, body weights, and H&E staining. Results: The multifunctional NPs generated had an average diameter of 22.9 nm, a zeta potential of -38.19 mV, and were capable of providing a sustained release of DOX. In vitro experiments demonstrated that the SPIO@DSPE-PEG/DOX/ICG NPs effectively enhanced cellular uptake of DOX as compared with that of free DOX. In vivo fluorescence and MR imaging revealed that the NPs not only effectively crossed the BBB but selectively accumulated at the tumor site. Meanwhile, among all groups studied, C6 glioma-bearing rats treated with the NPs exhibited the maximal degree of therapeutic efficacy, including smallest tumor volume, lowest body weight loss, and longest survival times, with no obvious side effects. Conclusion: These results suggest that the SPIO@DSPE-PEG/DOX/ICG NPs can not only function as a nanoprobe for MR and fluorescence bimodal imaging, but also as a vehicle to deliver chemotherapeutic drugs to the tumor site, to achieve the theranostic treatment of glioma.

To assess the role of the MR radiomic signature in preoperative prediction of lymph node (LN) metastasis in patients with esophageal cancer (EC).

OBJECTIVES:To assess the value of the MR-based radiomics signature in differentiating ocular adnexal lymphoma (OAL) and idiopathic orbital inflammation (IOI). METHODS:One hundred fifty-seven patients with pathology-proven OAL (84 patients) and IOI (73 patients) were divided into primary and validation cohorts. Eight hundred six radiomics features were extracted from morphological MR images. The least absolute shrinkage and selection operator (LASSO) procedure and linear combination were used to select features and build radiomics signature for discriminating OAL from IOI. Discriminating performance was assessed by the area under the receiver-operating characteristic curve (AUC). The predictive results were compared with the assessment of radiologists by chi-square test. RESULTS:Five radiomics features were included in the radiomics signature, which differentiated OAL from IOI with an AUC of 0.74 and 0.73 in the primary and validation cohorts respectively. There was a significant difference between the classification results of the radiomics signature and those of a radiology resident (p < 0.05), although there was no significant difference between the results of the radiomics signature and those of a more experienced radiologist (p > 0.05). CONCLUSIONS:Radiomics features have the potential to differentiate OAL from IOI. KEY POINTS:• Clinical and imaging findings of OAL and IOI often overlap, which makes diagnosis difficult. • Radiomics features can potentially differentiate OAL from IOI non invasively. • The radiomics signature discriminates OAL from IOI at the same level as an experienced radiologist.

Glioblastoma is the most common and aggressive primary brain tumor in adults. New drug design and development is still a major challenge for glioma treatment. Increasing evidence has shown that nitazoxanide, an antiprotozoal drug, has a novel antitumor role in various tumors and exhibits multiple molecular functions, especially autophagic regulation. However, whether nitazoxanide-associated autophagy has an antineoplastic effect in glioma remains unclear. Here, we aimed to explore the underlying molecular mechanism of nitazoxanide in glioblastoma. Our results showed that nitazoxanide suppressed cell growth and induced cell cycle arrest in glioblastoma by upregulating ING1 expression with a favorable toxicity profile. Nitazoxanide inhibited autophagy through blockage of late-stage lysosome acidification, resulting in decreased cleavage of ING1. A combination with chloroquine or Torin1 enhanced or impaired the chemotherapeutic effect of nitazoxanide in glioblastoma cells. Taken together, these findings indicate that nitazoxanide as an autophagy inhibitor induces cell cycle arrest in glioblastoma via upregulated ING1 due to increased transcription and decreased post-translational degradation by late-stage autophagic inhibition.

Background/Aims: Glioblastoma multiforme (GBM) is the most devastating and widespread primary central nervous system tumour in adults, with poor survival rate and high mortality rates. Existing treatments do not provide substantial benefits to patients; therefore, novel treatment strategies are required. Peiminine, a natural bioactive compound extracted from the traditional Chinese medicine Fritillaria thunbergii, has many pharmacological effects, especially anticancer activities. However, its anticancer effects on GBM and the underlying mechanism have not been demonstrated. This study was conducted to investigate the potential antitumour effects of peiminine in human GBM cells and to explore the related molecular signalling mechanisms in vitro and in vivo Methods: Cell viability and proliferation were detected with MTT and colony formation assays. Morphological changes associated with autophagy were assessed by transmission electron microscopy (TEM). The cell cycle rate was measured by flow cytometry. To detect changes in related genes and signalling pathways in vitro and in vivo, RNA-seq, Western blotting and immunohistochemical analyses were employed. Results: Peiminine significantly inhibited the proliferation and colony formation of GBM cells and resulted in changes in many tumour-related genes and transcriptional products. The potential anti-GBM role of peiminine might involve cell cycle arrest and autophagic flux blocking via changes in expression of the cyclin D1/CDK network, p62 and LC3. Changes in Changes in flow cytometry results and TEM findings were also observed. Molecular alterations included downregulation of the expression of not only phospho-Akt and phospho-GSK3β but also phospho-AMPK and phospho-ULK1. Furthermore, overexpression of AKT and inhibition of AKT reversed and augmented peiminine-induced cell cycle arrest in GBM cells, respectively. The cellular activation of AMPK reversed the changes in the levels of protein markers of autophagic flux. These results demonstrated that peiminine mediates cell cycle arrest by suppressing AktGSk3β signalling and blocks autophagic flux by depressing AMPK-ULK1 signalling in GBM cells. Finally, peiminine inhibited the growth of U251 gliomas in vivo. Conclusion: Peiminine inhibits glioblastoma in vitro and in vivo via arresting the cell cycle and blocking autophagic flux, suggesting new avenues for GBM therapy.

PURPOSE: To build and validate a radiomics-based nomogram for the prediction of pre-operation lymph node (LN) metastasis in esophageal cancer. PATIENTS AND METHODS: A total of 197 esophageal cancer patients were enrolled in this study, and their LN metastases have been pathologically confirmed. The data were collected from January 2016 to May 2016; patients in the first three months were set in the training cohort, and patients in April 2016 were set in the validation cohort. About 788 radiomics features were extracted from computed tomography (CT) images of the patients. The elastic-net approach was exploited for dimension reduction and selection of the feature space. The multivariable logistic regression analysis was adopted to build the radiomics signature and another predictive nomogram model. The predictive nomogram model was composed of three factors with the radiomics signature, where CT reported the LN number and position risk level. The performance and usefulness of the built model were assessed by the calibration and decision curve analysis. RESULTS: Thirteen radiomics features were selected to build the radiomics signature. The radiomics signature was significantly associated with the LN metastasis (P<0.001). The area under the curve (AUC) of the radiomics signature performance in the training cohort was 0.806 (95% CI: 0.732-0.881), and in the validation cohort it was 0.771 (95% CI: 0.632-0.910). The model showed good discrimination, with a Harrell’s Concordance Index of 0.768 (0.672 to 0.864, 95% CI) in the training cohort and 0.754 (0.603 to 0.895, 95% CI) in the validation cohort. Decision curve analysis showed our model will receive benefit when the threshold probability was larger than 0.15. CONCLUSION: The present study proposed a radiomics-based nomogram involving the radiomics signature, so the CT reported the status of the suspected LN and the dummy variable of the tumor position. It can be potentially applied in the individual preoperative prediction of the LN metastasis status in esophageal cancer patients.

Background/Aims: Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms. Methods: Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining. Autophagy was detected by transmission electron microscopy and western blotting. A U251 glioma xenograft model was established to evaluate the effect of RA in vivo. Results: The data demonstrated that RA inhibited viability, and abrogated the invasive/migratory abilities of glioblastoma cells. In addition, RA induced apoptosis by reactive oxygen species (ROS)/ Jun N-terminal kinase (JNK) signaling in glioblastoma. Conversely, the antioxidant N-Acetyl-L-cysteine (NAC) and pan-caspase inhibitor z-VAD-fmk attenuated RA-induced apoptosis by scavenging ROS and inactivating caspase-3. Furthermore, the inhibition of autophagy by 3-MA exacerbated apoptosis through ROS generation and JNK phosphorylation. In vivo, RA exhibited a curative effect on U251-derived xenografts in nude mice. Conclusions: The results of this study suggest that RA suppressed the growth of glioblastoma, thus serving as a promising and potential strategy for glioblastoma chemotherapy.

For superficial skin tumors (SST) with high incidence, surgery and systemic therapy are relatively invasive and possible to cause severe side effect, respectively. Yet, topical therapy is confronted with the limited transdermal capacity because of the stratum corneum barrier layer of skin. Therefore, it is crucial to develop a highly effective and minimally invasive alternative transdermal approach for treating SST. Here, we developed gold nanocage (AuNC)- and chemotherapeutic drug doxorubicin (DOX)-loaded hyaluronic acid dissolving microneedle (MN) arrays. The loaded AuNCs are not only reinforcers to enhance the mechanical strength of the MNs, but also effective agents for photothermal therapy to obtain effective transdermal therapy for SST. The resultant MNs can effectively penetrate the skin, dissolve in the skin and release cargoes within the tumor site. Photothermal effect of AuNCs initiated by near-infrared laser irradiation combined with the chemotherapy effect of DOX destroyed tumors synergistically. Moreover, we verified the potent antitumor effects of the DOX/AuNC-loaded MNs after four administrations to SST-bearing mice without obvious side effects. Therefore, the drug/AuNC-loaded dissolving MN system provides a promising platform for effective, safe, minimally invasive combined treatment of SST.

Vaccines have shown great success in treating and preventing tumors and infections, while adjuvants are always demanded to ensure potent immune responses.Polyethylenimine (PEI), as one of the well-studied cationic polymers, has been used as a transfection reagent for decades.However, increasing evidence has shown that PEI-based particles are also capable of acting as adjuvants.In this paper, we briefly review the physicochemical properties and the broad applications of PEI in different fields, and elaborate on the intracellular processes of PEI-based vaccines.In addition, we sum up the proof of their in vivo and clinical applications.We also highlight some mechanisms proposed for the intrinsic immunoactivation function of PEI, followed by the challenges and future perspectives of the applications of PEI in the vaccines, as well as some strategies to elicit the desirable immune responses.

Glioma is among the most common types of cancer of the central nervous system and is difficult to cure. Due to the lack of glioma-specific treatments, patients with glioma exhibit high mortality rates. MicroRNAs (miRNAs) participate in the pathogenesis of glioma, and upregulation of specific miRNAs promotes cell proliferation, whereas apoptosis-inducing miRNAs are markedly downregulated in the context of glioma. Therefore, miRNAs may be important contributors to the pathogenesis of glioma. In the present study, nine miRNAs were investigated as miRNA-miRNA pairs, and the measured cell viabilities were consistent with the results of synergy predictions. Extensive synergy occurred among upregulated miRNAs in U87 cells, whereas downregulated miRNAs rarely exhibited synergism. Treatment with an miRNA-miRNA pair exhibiting strong synergy increased the inhibitory effects of these miRNAs on tumor cells, and the combined inhibitory effects were increased compared with the sum of the individual inhibitory effects of each miRNA. Using cell viability assays, TUNEL staining, and flow cytometry, the present study demonstrates that cotransfection with miR-20a and miR-21inhibitors resulted in the highest synergistic effect on the promotion of apoptosis in U87 cells. The results of the present study provide important insights into the potential use of miRNAs in the treatment of glioma.

OBJECTIVE: To compare 2D and 3D radiomics features prognostic performance differences in CT images of non-small cell lung cancer (NSCLC). METHOD: We enrolled 588 NSCLC patients from three independent cohorts. Two sets of 463 patients from two different institutes were used as the training cohort. The remaining cohort with 125 patients was set as the validation cohort. A total of 1014 radiomics features (507 2D features and 507 3D features correspondingly) were assessed. Based on the dichotomized survival data, 2D and 3D radiomics indicators were calculated for each patient by trained classifiers. We used the area under the receiver operating characteristic curve (AUC) to assess the prediction performance of trained classifiers (the support vector machine and logistic regression). Kaplan–Meier and Cox hazard survival analyses were also employed. Harrell's concordance index (C-Index) and Akaike's information criteria (AIC) were applied to assess the trained models. RESULTS: Radiomics indicators were built and compared by AUCs. In the training cohort, 2D_AUC = 0.653, 3D_AUC = 0.671. In the validation cohort, 2D_AUC = 0.755, 3D_AUC = 0.663. Both 2D and 3D trained indicators achieved significant results (P < .05) in the Kaplan-Meier analysis and Cox regression. In the validation cohort, 2D Cox model had a C-Index = 0.683 and AIC = 789.047; 3D Cox model obtained a C-Index = 0.632 and AIC = 799.409. CONCLUSION: Both 2D and 3D CT radiomics features have a certain prognostic ability in NSCLC, but 2D features showed better performance in our tests. Considering the cost of the radiomics features calculation, 2D features are more recommended for use in the current study.

Dacarbazine (DTIC) is one of the most important chemotherapeutic agents for the treatment of melanoma; however, its poor solubility, photosensitivity, instability, and serious toxicity to normal cells limit its clinical applications. In this article, we present a rationally designed nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for the encapsulation and targeted release of DTIC for eradicating melanoma. The nanocarrier (DTIC@HMLBFs) is prepared by modifying HMSNs with carboxyl groups to enhance the loading of DTIC, followed by further enveloping of folic acid-grafted liposomes, which act as a melanoma active target for controlled and targeted drug release. In vitro, DTIC@HMLBFs exhibited the strongest cytotoxicity to melanoma cells compared with DTIC@HMSNs and free DTIC. The in vivo investigations demonstrate that the rationally designed nanocarrier loaded with DTIC achieves significant improvement against lung metastasis of melanoma via targeting melanoma cells and tumor-associated macrophages. This study provides a promising platform for the design and fabrication of multifunctional nanomedicines, which are potentially useful for the treatment of melanoma.

Codelivery of combinational antigenic peptides and adjuvant to antigen presenting cells is expected to amplify tumor specific T lymphocytes immune responses while minimizing the possibility of tumor escaping and reducing immune tolerance to single antigenic peptide. However, the varied hydrophobicities of these multivariant derived short antigenic peptides limit their codelivery efficiency in conventional delivery systems. Here, a facile yet effective route is presented to generate monodisperse and stable hollow mesoporous silica nanoparticles (HMSNs) for codelivering of HGP10025-33 and TRP2180-188 , two melanoma-derived peptides with varied hydrophobicities. The HMSNs with large pore size can improve the encapsulation efficiency of both HGP100 and TRP2 after NH2 modification on the inner hollow core and COOH modification in the porous channels. HGP100 and TRP2 loaded HMSNs (HT@HMSNs) are further enveloped within monophosphoryl lipid A adjuvant entrapped lipid bilayer (HTM@HMLBs), for improved stability/biocompatibility and codelivery efficiency of multiple peptides, adjuvant, and enhanced antitumor immune responses. HTM@HMLBs increase uptake by dendritic cells (DCs) and stimulate DCs maturation efficiently, which further induce the activation of both tumor specific CD8+ and CD4+ T lymphocytes. Moreover, HTM@HMLBs can significantly inhibit tumor growth and lung metastasis in murine melanoma models with good safety profiles. HMSNs enveloped with lipid bilayers (HMLBs) are believed to be a promising platform for codelivery of multiple peptides, adjuvant, and enhancement of antitumor efficacy of conventional vaccinations.

BACKGROUND Gliomas are the most common primary brain neoplasms. Misdiagnosis occurs in glioma grading due to an overlap in conventional MRI manifestations. The aim of the present study was to evaluate the power of radiomic features based on multiple MRI sequences - T2-Weighted-Imaging-FLAIR (FLAIR), T1-Weighted-Imaging-Contrast-Enhanced (T1-CE), and Apparent Diffusion Coefficient (ADC) map - in glioma grading, and to improve the power of glioma grading by combining features. MATERIAL AND METHODS Sixty-six patients with histopathologically proven gliomas underwent T2-FLAIR and T1WI-CE sequence scanning with some patients (n=63) also undergoing DWI scanning. A total of 114 radiomic features were derived with radiomic methods by using in-house software. All radiomic features were compared between high-grade gliomas (HGGs) and low-grade gliomas (LGGs). Features with significant statistical differences were selected for receiver operating characteristic (ROC) curve analysis. The relationships between significantly different radiomic features and glial fibrillary acidic protein (GFAP) expression were evaluated. RESULTS A total of 8 radiomic features from 3 MRI sequences displayed significant differences between LGGs and HGGs. FLAIR GLCM Cluster Shade, T1-CE GLCM Entropy, and ADC GLCM Homogeneity were the best features to use in differentiating LGGs and HGGs in each MRI sequence. The combined feature was best able to differentiate LGGs and HGGs, which improved the accuracy of glioma grading compared to the above features in each MRI sequence. A significant correlation was found between GFAP and T1-CE GLCM Entropy, as well as between GFAP and ADC GLCM Homogeneity. CONCLUSIONS The combined radiomic feature had the highest efficacy in distinguishing LGGs from HGGs.