A chest CT-based nomogram for predicting survival in acute myeloid leukemia.

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.

SHP-1 inhibition targets leukaemia stem cells to restore immunosurveillance and enhance chemosensitivity by metabolic reprogramming.

Leukaemia stem cells (LSCs) in acute myeloid leukaemia present a considerable treatment challenge due to their resistance to chemotherapy and immunosurveillance. The connection between these properties in LSCs remains poorly understood. Here we demonstrate that inhibition of tyrosine phosphatase SHP-1 in LSCs increases their glycolysis and oxidative phosphorylation, enhancing their sensitivity to chemotherapy and vulnerability to immunosurveillance. Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-ß-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Moreover, the upregulation of PFKP promotes MYC degradation and, consequently, reduces the immune evasion abilities of LSCs. Overall, our study demonstrates that targeting SHP-1 disrupts the metabolic balance in LSCs, thereby increasing their vulnerability to chemotherapy and immunosurveillance. This approach offers a promising strategy to overcome LSC resistance in acute myeloid leukaemia.

LncRNA ABHD11-AS1 activates EGFR signaling to promote cervical cancer progression by preventing FUS-mediated degradation of ABHD11 mRNA.

Cervical cancer is one of the most common gynecological cancers with high metastasis, poor prognosis and conventional chemotherapy. The long non-coding RNA (lncRNA) ABHD11 antisense RNA 1 (ABHD11-AS1) plays a vital role in tumorigenesis and is involved in cell proliferation, differentiation, and apoptosis. Especially for cervical cancer, the functions and mechanisms of ABHD11-AS1 are still undetermined. In this study, we explored the role and underlying mechanism of ABHD11-AS1 in cervical cancer. We found that ABHD11-AS1 is highly expressed in cervical cancer tissue. The roles of ABHD11-AS1 and EGFR have investigated the loss of function analysis and cell movability in SiHa and Hela cells. Knockdown of ABHD11-AS1 and EGFR significantly inhibited the proliferation, migration, and invasion and promoted apoptosis of SiHa and Hela cells by up-regulating p21 and Bax and down-regulating cyclin D1, Bcl2, MMP9, and Vimentin. ABHD11-AS1 knockdown could decrease the expression of EGFR. In addition, ABHD11-AS1 could regulate the EGFR signaling pathway, including p-EGFR, p-AKT, and p-ERK. Spearman's correlation analysis and cell experiments demonstrated that ABHD11 was highly expressed in tumor tissue and partially offset the effect of shABHD11-AS1 on the proliferation, migration, and invasion of SiHa and Hela cells. Then, RNA pulldown was used to ascertain the mechanisms of ABHD11-AS1 and FUS. ABHD11-AS1 inhibited ABHD11 mRNA degradation by bounding to FUS. A subcutaneous xenograft of SiHa cells was established to investigate the effect of ABHD11-AS1 in tumor tissue. Knockdown of ABDH11-AS1 inhibited tumor growth and decreased the tumor volume. ABHD11-AS1 knockdown inhibited the expression of Ki67 and Vimentin and up-regulated the expression of Tunel. Our data indicated that ABHD11-AS1 promoted cervical cancer progression by activating EGFR signaling, preventing FUS-mediated degradation of ABHD11 mRNA. Our findings provide novel insights into the potential role of lncRNA in cervical cancer therapy.

Super-enhancer-associated gene CAPG promotes AML progression.

Acute myeloid leukemia is the most common acute leukemia in adults, the barrier of refractory and drug resistance has yet to be conquered in the clinical. Abnormal gene expression and epigenetic changes play an important role in pathogenesis and treatment. A super-enhancer is an epigenetic modifier that promotes pro-tumor genes and drug resistance by activating oncogene transcription. Multi-omics integrative analysis identifies the super-enhancer-associated gene CAPG and its high expression level was correlated with poor prognosis in AML. CAPG is a cytoskeleton protein but has an unclear function in AML. Here we show the molecular function of CAPG in regulating NF-κB signaling pathway by proteomic and epigenomic analysis. Knockdown of Capg in the AML murine model resulted in exhausted AML cells and prolonged survival of AML mice. In conclusion, SEs-associated gene CAPG can contributes to AML progression through NF-κB.

A Ferroptosis-Inducing and Leukemic Cell-Targeting Drug Nanocarrier Formed by Redox-Responsive Cysteine Polymer for Acute Myeloid Leukemia Therapy.

Ferroptosis is an alternative strategy to overcome chemoresistance, but effective therapeutic approaches to induce ferroptosis for acute myeloid leukemia (AML) treatment are limited. Here, we developed glutathione (GSH)-responsive cysteine polymer-based ferroptosis-inducing nanomedicine (GCFN) as an efficient ferroptosis inducer and chemotherapeutic drug nanocarrier for AML treatment. GCFN depleted intracellular GSH and inhibited glutathione peroxidase 4, a GSH-dependent hydroperoxidase, to cause lipid peroxidation and ferroptosis in AML cells. Furthermore, GCFN-loaded paclitaxel (PTX@GCFN) targeted AML cells and spared normal hematopoietic cells to limit the myeloablation side effects caused by paclitaxel. PTX@GCFN treatment extended the survival of AML mice by specifically releasing paclitaxel and simultaneously inducing ferroptosis in AML cells with restricted myeloablation and tissue damage side effects. Overall, the dual-functional GCFN acts as an effective ferroptosis inducer and a chemotherapeutic drug carrier for AML treatment.

PD-1 signalling defines and protects leukaemic stem cells from T cell receptor-induced cell death in T cell acute lymphoblastic leukaemia.

T cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy with poor prognosis, but a decisive marker and effective treatment for leukaemia stem cells (LSCs) remain unclear. Here, using lineage tracing, limiting dilution assays and in vivo live imaging approaches, we identify rare inhibitory receptor programmed cell death 1 (PD-1)-expressing cells that reside at the apex of leukaemia hierarchy for initiation and relapse in T-ALL. Ablation of PD-1-expressing cells, deletion of PD-1 in T-ALL cells or blockade of PD-1 or PD-1 ligand 1 significantly eradicated LSCs and suppressed disease progression. Combination therapy using PD-1 blockade and chemotherapy substantially extended the survival of mice engrafted with mouse or human T-ALL cells. Mechanistically, PD-1+ LSCs had high NOTCH1-MYC activity for disease initiation. Furthermore, PD-1 signalling maintained quiescence and protected LSCs against T cell receptor-signal-induced apoptosis. Overall, our data highlight the hierarchy of leukaemia by identifying PD-1+ LSCs and provide a therapeutic approach for the elimination of LSCs through PD-1 blockade in T-ALL.

FAM83A has a pro-tumor function in ovarian cancer by affecting the Akt/Wnt/ß-catenin pathway.

Family with sequence similarity 83, member A (FAM83A) is a tumor-exclusive gene that has a vital role in numerous tumors. However, its role in tumorigenesis remains controversial. This work is dedicated to the study of the role of FAM83A in ovarian cancer. We observed elevated levels of FAM83A in ovarian cancer specimens and cells. Kaplan-Meier survival curves revealed that elevated FAM83A levels predicted a worse overall survival in ovarian cancer patients. The inhibition of FAM83A caused remarkable suppressive effects on the proliferation and invasion of ovarian cancer cells, and enhanced their chemosensitivity. On the contrary, the upregulation of FAM83A had opposite effects. Mechanistically, FAM83A had an effect on the Akt and Wnt/ß-catenin pathways in ovarian cancer cells. The repression of Akt could cancel the regulatory effect of FAM83A overexpression on the Wnt/ß-catenin pathway. Moreover, reactivation of the Wnt/ß-catenin pathway abolished FAM83A-inhibition-evoked antitumor effects. Additionally, FAM83A inhibition weakened the tumorigenic potential of ovarian cancer in vivo. Taken together, this work shows that FAM83A exerts a pro-tumor function in ovarian cancer by affecting the Akt/Wnt/ß-catenin pathway and proposes FAM83A as an effective and possible treatment target for ovarian cancer.

Runt-Related Transcription Factor 3 Promotes Acute Myeloid Leukemia Progression.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with high relapse/refractory rate. Genetic and epigenetic abnormalities are driving factors for leukemogenesis. RUNX1 and RUNX2 from the Runt-related transcription factor (RUNX) family played important roles in AML pathogenesis. However, the relationship between RUNX3 and AML remains unclear. Here, we found that RUNX3 was a super-enhancer-associated gene and highly expressed in AML cells. The Cancer Genome Atlas (TCGA) database showed high expression of RUNX3 correlated with poor prognosis of AML patients. We observed that Runx3 knockdown significantly inhibited leukemia progression by inducing DNA damage to enhance apoptosis in murine AML cells. By chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we discovered that RUNX3 in AML cells mainly bound more genes involved in DNA-damage repair and antiapoptosis pathways compared to that in normal bone marrow cells. Runx3 knockdown obviously inhibited the expression of these genes in AML cells. Overall, we identified RUNX3 as an oncogene overexpressed in AML cells, and Runx3 knockdown suppressed AML progression by inducing DNA damage and apoptosis.

Expression and prognosis analyses of CASP1 in acute myeloid leukemia.

Caspase1 (CASP1) is a gene that encodes multiple proteins related to cell death. Nevertheless, the function of CASP1 in the pathogenesis of AML is still unclear. In the present study, a detailed analysis of cancer versus normal samples was performed to explore the relationship between CASP1 and leukemia. We used sequencing data from multiple cancer gene databases to analyze the gene expression and regulatory network of CASP1 in leukemia. We discovered that mRNA expression levels of CASP1 are increased in leukemia cell lines, especially in acute myelocytic leukemia (AML). Then, we verified the mRNA expression of CASP1 in AML clinical samples and observed significantly higher expression of CASP1 in relapsed AML patients. High CASP1 expression was associated with poor prognosis and CASP1 inhibition could impair the proliferation of AML cells. Related functional network identification suggests that CASP1 regulates apoptosis, immune and inflammatory response via pathways involving LYN, LCK, and the E2F family. These findings suggest that CASP1 probably contributes to the pathogenesis, and identify CASP1 as a factor for predicting the prognosis and as a therapeutic target of AML patients.

Retinoic Acid Inhibits Tumor-Associated Mesenchymal Stromal Cell Transformation in Melanoma.

Bone marrow mesenchymal stem/stromal cells (BMSCs) can be transformed into tumor-associated MSCs (TA-MSCs) within the tumor microenvironment to facilitate tumor progression. However, the underline mechanism and potential therapeutic strategy remain unclear. Here, we explored that interleukin 17 (IL-17) cooperating with IFNγ transforms BMSCs into TA-MSCs, which promotes tumor progression by recruiting macrophages/monocytes and myeloid-derived suppressor cells (MDSCs) in murine melanoma. IL-17 and IFNγ transformed TA-MSCs have high expression levels of myelocyte-recruiting chemokines (CCL2, CCL5, CCL7, and CCL20) mediated by activated NF-κB signaling pathway. Furthermore, retinoic acid inhibits NF-κB signaling, decreases chemokine expression, and suppresses the tumor-promoting function of transformed TA-MSCs by prohibiting the recruitment of macrophages/monocytes and MDSCs in the tumor microenvironment. Overall, our findings demonstrate that IL-17 collaborating with IFNγ to induce TA-MSC transformation, which can be targeted by RA for melanoma treatment.

SUV39H1-Mediated DNMT1 is Involved in the Epigenetic Regulation of Smad3 in Cervical Cancer.

BACKGROUND: SMAD3 is a pivotal intracellular mediator for participating in the activation of multiple immune signal pathways. OBJECTIVE: The epigenetic regulation mechanism of the positive immune factor SMAD3 in cervical cancer remains unknown. Therefore, the epigenetic regulation on SMAD3 is investigated in this study. METHODS: The methylation status of SMAD3 was detected by Methylation-Specific PCR (MS-PCR) and Quantitative Methylation-Specific PCR (MS-qPCR) in cervical cancer tissues and cell lines. The underlying molecular mechanisms of SUV39H1-DNMT1-SMAD3 regulation were elucidated using cervical cancer cell lines containing siRNA or/and over-expression systems. The regulation of DNMT1 by SUV39H1 was confirmed using Chromatin Immunoprecipitation-qPCR (ChIP-qPCR). The statistical methods used for comparing samples between groups were paired t-tests and one-way ANOVAs. RESULTS: H3K9me3 protein regulated by SUV39H1 directly interacts with the DNMT1 promoter region to regulate its expression in cervical cancer cells, resulting in the reduced expression of the downstream target gene DNMT1. In addition, DNMT1 mediates the epigenetic modulation of the SMAD3 gene by directly binding to its promoter region. The depletion of DNMT1 effectively restores the expression of SMAD3 in vitro. Moreover, in an in vivo assay, the expression profile of SUV39H1-DNMT1 was found to correlate with SMAD3 expression in accordance with the expression at the cellular level. Notably, the promoter region of SMAD3 was hypermethylated in cervical cancer tissues, and this hypermethylation inhibited the subsequent gene expression. CONCLUSION: These results indicate that SUV39H1-DNMT1 is a crucial SMAD3 regulatory axis in cervical cancer. SUV39H1-DNMT1 axis may provide a potential therapeutic target for the treatment of cervical cancer.

SUV39H1-DNMT3A-mediated epigenetic regulation of Tim-3 and galectin-9 in the cervical cancer.

BACKGROUND: Methylation of histone 3 at lysine 9 (H3K9) and DNA methylation are epigenetic marks correlated with genes silencing. The tumor microenvironment significantly influences therapeutic responses and clinical outcomes. The epigenetic-regulation mechanism of the costimulatory factors Tim-3 and galectin-9 in cervical cancer remains unknown. METHODS: The methylation status of HAVCR2 and LGALS9 were detected by MS-PCR in cervical cancer tissues and cell lines. The underlying molecular mechanism of SUV39H1-DNMT3A-Tim-3/galectin-9 regulation was elucidated using cervical cancer cell lines containing siRNA or/and over-expression system. Confirmation of the regulation of DNMT3A by SUV39H1 used ChIP-qPCR. RESULTS: SUV39H1 up-regulates H3K9me3 expression at the DNMT3A promoter region, which in turn induced expression of DNMT3A in cervical cancer. In addition, the mechanistic studies indicate that DNMT3A mediates the epigenetic modulation of the HAVCR2 and LGALS9 genes by directly binding to their promoter regions in vitro. Moreover, in an in vivo assay, the expression profile of SUV39H1 up-regulates the level of H3K9me3 at the DNMT3A promoter region was found to correlate with Tim-3 and galectin-9 cellular expression level. CONCLUSION: These results indicate that SUV39H1-DNMT3A is a crucial Tim-3 and galectin-9 regulatory axis in cervical cancer.

Evaluation of the Efficacy and Safety of PARP Inhibitors in Advanced-Stage Epithelial Ovarian Cancer.

Purpose: PARP inhibitors are a novel targeted anti-cancer drug and a large number of clinical studies on PARP inhibitors have been accomplished. This updated meta-analysis was conducted to evaluate the efficacy and safety of PARP inhibitors in advanced-stage epithelial ovarian cancer. Methods: Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched to identify the eligible trials up to April 2020. ClinicalTrials.gov was also screened for additional unpublished trials. Data extraction and risk of bias assessment were performed by two independent investigators, respectively. The hazard ratios (HRs) and its 95% confidence intervals (CI) for time-to-event data of progression-free survival (PFS) and overall survival (OS), and the risk ratios (RRs) with 95% CI for dichotomous data of overall response rate (ORR) and occurrence of adverse events (AEs) were calculated by Review Manager 5.3 and Stata 12.0 software. Results: A total of 12 trials with 5,347 patients were included in this meta-analysis. Compared with the control group, PARP inhibitors significantly improved PFS (HR, 0.51; 95% CI, 0.40-0.65; P < 0.00001) and ORR (RR, 1.26; 95% CI, 1.11-1.43; P = 0.0003). Specifically, PFS was improved regardless of BRCA genes mutations and homologous-recombination status. However, no difference was observed in OS between the PARP inhibitors group and the control group (95% CI, 0.73-1.01; P = 0.06). PARP inhibitors were associated with a statistically significant higher risk of hematologic events and different PARP inhibitors had different toxicities profiles. Conclusion: PARP inhibitors are an effective and well-tolerated treatment for patients with advanced-stage epithelial ovarian cancer.

Construction of a tumor microenvironment pH-responsive cleavable PEGylated hyaluronic acid nano-drug delivery system for colorectal cancer treatment.

In order to improve active tumor targeting, tumor cell uptake efficiency and circulation time of doxorubicin (DOX) in vivo, we constructed a cleavable PEGylated hyaluronic acid nano-drug delivery system (HA-mPEG2k-DOX) based on a tumor microenvironment pH-responsive imine bond. In this study, HA-mPEG2k-DOX can self-assemble into stable nanoparticles (HA-mPEG2k-DOX NPs) with a particle size of 50 nm. And the NPs can efficiently target CD44 positive CT26 cells and the pH-responsive cleavable PEG shell can be detached under weakly acidic environments and effectively promote the cellular uptake of HA-DOX NPs. Compared with DOX·HCl, the HA-mPEG2k-DOX NPs can significantly increase the DOX circulation time by 12.5 times, efficiently target the tumor tissues of CT26 tumor-bearing mice and remain for 72 hours. Therefore, the antitumor results in vivo indicated that the HA-mPEG2k-DOX NPs have the best anti-tumor effect while reducing the toxicity of the DOX. Overall, the cleavable PEGylated HA-mPEG2k-DOX NPs responding to pH-sensitive imine bonds, while actively targeting CD44-positive tumor cells, improve the dilemma of cellular uptake and delivery by the PEGylated nano delivery system.

Evaluation of Risk Factors for Venous Thromboembolism in Patients Who Underwent Gynecological Surgery and Validation of a Fast-Rating Assessment Table.

BACKGROUND The aim of this study was to retrospectively analyze the risk factors for venous thromboembolism (VTE) in gynecological patients and verify the validity of a fast-rating assessment table. MATERIAL AND METHODS From October 2015 to October 2017, 53 patients complicated with VTE after gynecological operations were analyzed, and a total of 106 patients with 2 adjacent operations were selected as the control group. Factors such as age, body mass index (BMI), and tumor type were analyzed by univariate and multivariate analysis. A fast-rating assessment table of VTE risk factors was constructed. This fast-rating assessment table and the Caprini score table were used to compare the scores of all patients. RESULTS In the univariate analysis, there were significant differences in BMI, tumor type, operation duration, blood loss, blood transfusion, bed rest time, and thrombus-related history between the 2 groups. In the multiple factor analysis, age >60 years old, BMI >28 kg/m², malignant tumors, operation duration ≥3 hours, laparoscopic surgery and thrombus-related history were independent risk factors for VTE in patients. Both the fast-rating assessment table and the Caprini score table identified 90% of VTE patients as high-risk and very high-risk, and there was no significant difference between the tables. CONCLUSIONS Patients with older age, high BMI, malignant tumors, longer operation duration, laparoscopic surgery, or history of thrombosis may be more prone to VTE after gynecologic surgery. The fast-rating assessment table is easy to operate and has a high recognition level for VTE. It can be applied widely.

Crosstalk between histone modification and DNA methylation orchestrates the epigenetic regulation of the costimulatory factors, Tim­3 and galectin­9, in cervical cancer.

Persistent infection with high­risk human papillomavirus is known to cause cervical cancer. The binding of the costimulatory factors, Tim­3 and galectin­9, can cause immune tolerance and lead to immune escape during carcinogenesis. Epigenetic regulation is essential for Tim­3/galectin­9 expression, which affects the outcome of local cervical cancer infection. Hence, exploring the epigenetic regulatory mechanisms of costimulatory signaling by Tim­3/galectin­9 is of great interest for investigating the mechanisms through which these proteins are regulated in cervical cancer tumorigenesis. In this study, we report that E2F­1 and FOXM1 mediated by HPV18 E6 and E7 can enhance the transcriptional activity of Enhancer of zeste homolog 2 (EZH2) by binding to its promoter region, resulting in the induced expression of the EZH2­specific target protein, H3K27me3, which consequently reduces the expression of the downstream target gene, DNA (cytosine­5)­methyltransferase 3A (DNMT3A). EZH2 and H3K27me3 directly interact with the DNMT3A promoter region to negatively regulate its expression in HeLa cells. Moreover, the downregulated DNMT3A and the decreased methylation levels in HAVCR2/LGALS9 promoter regions in HeLa cells promoted the expression of Tim­3/galectin­9. Furthermore, the high expression of Tim­3/galectin­9 was associated with HPV positivity among patients with cervical cancer. Moreover, HAVCR2/LGALS9 promoter regions were hypermethylated in normal cervical tissues, and this hypermethylated status inhibited gene expression. On the whole, these findings suggest that EZH2, H3K27me3 and DNMT3A mediate the epigenetic regulation of the negative stimulatory molecules, Tim­3 and galectin­9 in cervical cancer which is associated with HPV18 infection.

Cysteine-based redox-responsive nanoparticles for small-molecule agent delivery.

As a significant part of molecular-targeted therapies, small-molecule agents (SMAs) have been increasingly used for cancer treatment. Nevertheless, most SMAs are currently administered orally due to their poor solubility, resulting in a low bioavailability and unavoidable side effects. Herein, we proposed a promising SMA delivery strategy using a biocompatible and redox-responsive nanoparticle (NP) delivery system to improve their bioavailability, alleviate side effects and enhance therapeutic performance. To demonstrate the feasibility of this strategy, a type of cysteine-based hydrophobic polymer was employed to construct a redox-sensitive nanoplatform for the delivery of various hydrophobic oral SMAs. These SMA-loaded nanoparticles (SMA-NPs) all have a small particle size and good drug-loading capacity. Particularly, lapatinib-loaded nanoparticles (LAP-NPs) with a minimal particle size (79.71 nm) and an optimal drug-loading capacity (12.5%) were utilized as a model to systemically explore the in vitro and in vivo anticancer potential of SMA-NPs. As expected, the LAP-NPs exhibited rapid redox-responsive drug release, enhanced in vitro cytotoxicity and cell apoptosis, and demonstrated notable anti-metastasis ability and desirable intracellular localization. Additionally, the in vivo results demonstrated the preferential accumulation of LAP-NPs in tumor tissues and the significant suppression of tumor growth. Therefore, the generated SMA-NP delivery system shows great SMA delivery potential for advanced molecular-targeted therapies.

Targeted Nanoparticle Drug Delivery System for the Enhancement of Cancer Immunotherapy.

Immunotherapy is one of the most potent options for cancer treatment, with numerous breakthroughs in this field, bringing us closer to the realization of cancer eradication. However, the intrinsic limits of immunotherapy, such as its low responsive rate, narrow therapeutic window and systemic toxicity, have hindered its clinical application and thus prompted the development of nanotechnology-assisted modality for more effective and safer cancer immunotherapy. By locally increasing the drug concentration and limiting drug exposure to normal tissues, nanocarriers significantly potentiate the effects of immunotherapy while reducing side effects. Additionally, nanoparticle-based drug delivery systems allow different therapeutic strategies as a complement to conventional immunotherapeutic modalities, providing numerous novel and effective approaches for combinational cancer therapy. In this review, we first briefly introduce the five main classes of immunotherapy, and then we extensively covered some advanced biomaterials and novel strategies of nanotechnology intervention and detailed how these approaches function to enhance immunotherapeutic and combinational combination therapeutic efficacy.

Magnetic Resonance Imaging (MRI) and Three-Dimensional Transvaginal Ultrasonography Scanning for Preoperative Assessment of High Risk in Women with Endometrial Cancer.

BACKGROUND To evaluate the diagnostic performance of MRI and 3D-TVS for assessment of deep myometrial invasion (MI), cervical involvement (CI), and Lymph node metastases (LNM) in endometrial cancer staging before surgery. MATERIAL AND METHODS From January 2016 to December 2017, we reviewed data from 314 women with endometrial cancer who underwent preoperative MRI and 3D-TVS before surgery. The diagnostic sensitivity, specificity, PPV, NPV, and accuracy in detecting MI, CI, and LNM were estimated based on ultimate pathology results. RESULTS The sensitivity, specificity, PPV, NPV, and accuracy of MRI in the diagnosis of MI were 89.19%, 88.97%, 67.35%, 97.99%, and 89.01%, respectively, and the indexes of 3D-TVS for MI were 86.36%, 91.07%, 79.17%, 94.44%, and 89.74%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of MRI for CI were 75% and 92.35%, 40.9%, 98.13%, and 91.2%, respectively. The indicators of 3D-TVS were 77.78%, 94.29%, 63.63%, 97.06%, and 92.4%, respectively. There were no significant differences in sensitivity, specificity, NPV, and accuracy between MRI and 3D-TVS in the diagnosis of MI and CI. For MI and CI, the sensitivity of combined MRI and 3D-TVS was higher than any other single method (P<0.05). For LNM, the sensitivity, specificity, PPV, NPV, and accuracy of MRI were 58.33%, 96.26%, 63.63%, 95.37%, and 92.43%, respectively. CONCLUSIONS 3D-TVS is equivalent to MRI in predicting MI and CI. Combined MRI and 3D-TVS can improve the assessment sensitivity, and they are useful in optimizing individualized surgical procedures. The sensitivity of MRI for LNM prediction needs to be improved.