Evaluation of the efficacy and safety of CalliSpheres® microsphere-transarterial chemoembolization in large hepatocellular carcinoma.

OBJECTIVE: The prognosis of large hepatocellular carcinoma (HCC) is still unfavorable due to limited and challenging treatment. CalliSpheres® microsphere-transarterial chemoembolization (CSM-TACE) is an effective therapy for general HCC but not frequently applied for large HCC. Hence, this study aimed to investigate the efficacy and safety of CSM-TACE in large HCC patients. MATERIALS AND METHODS: This prospective study analyzed 100 large HCC (tumor size >5 cm) patients receiving CSM-TACE. Treatment response, survival, change in liver function indexes, and adverse events were recorded. RESULT: The best complete response, partial response, stable disease, and progressive disease rates were 2.0%, 31.3%, 65.7%, and 1.0%, respectively, leading to the best objective response rate (ORR) of 33.3% and disease control rate of 99.9%. Multivariate analysis showed that intrahepatic metastasis was independently related to poor ORR (odd ratio = 0.366, P = 0.023). The 1- and 2-year progression-free survival (PFS) rates were 88.9% and 80.6%, with a mean [95% confidence interval (CI)] PFS of 21.6 (20.4-22.9) months. The 1- and 2-year overall survival (OS) rates were 99.0% and 99.0%, with a mean (95% CI) OS of 23.8 (23.3-24.2) months. Total bilirubin (P < 0.001), alanine transaminase (P < 0.001), aspartate transaminase (P < 0.001), and α-fetoprotein (P = 0.045) were abnormal in a short-term period then stably recovered from 1 month ± 15 days after drug-eluting bead-TACE to 24 months ± 15 days. During hospitalization and postdischarge, tolerable abdominal pain and decreased appetite were common adverse events. CONCLUSIONS: CSM-TACE shows favorable treatment response and survival with acceptable tolerance among large HCC patients, indicating that it may promote the management of these patients.

Resection of high-grade glioma involving language areas assisted by multimodal techniques under general anesthesia: a retrospective study.

BACKGROUND: Multimodal techniques-assisted resection of glioma under general anesthesia (GA) has been shown to achieve similar clinical outcomes as awake craniotomy (AC) in some studies. In this study, we aim to validate the use of multimodal techniques can achieve the maximal safe resection of high-grade glioma involving language areas (HGILAs) under GA. METHODS: HGILAs cases were reviewed and collected between January 2009 and December 2020 in our center. Patients were separated into multimodal group (using neuronavigation, intraoperative MRI combined with direct electrical stimulation [DES] and neuromonitoring [IONM]) and conventional group (neuronavigation alone) and clinical outcomes were compared between groups. Studies of HGILAs were reviewed systematically and the meta-analysis results of previous (GA or AC) studies were compared with our results. RESULTS: Finally, there were 263 patients in multimodal group and 137 patients in conventional group. Compared to the conventional group, the multimodal group achieved the higher median EOR (100% versus 94.32%, P < 0.001) and rate of gross total resection (GTR) (73.8% versus 36.5%, P < 0.001) and the lower incidence of permanent language deficit (PLD) (9.5% versus 19.7%, P = 0.004). The multimodal group achieved the longer median PFS (16.8 versus 10.3 months, P < 0.001) and OS (23.7 versus 15.7 months, P < 0.001) than the conventional group. The multimodal group achieved a higher rate of GTR than the cohorts in previous multimodal studies under GA and AC (73.8% versus 55.7% [95%CI 32.0-79.3%] versus 53.4% [35.5-71.2%]). The multimodal group had a lower incidence of PLD than the cohorts in previous multimodal studies under GA (9.5% versus 14.0% [5.8-22.1%]) and our incidence of PLD was a little higher than that of previous multimodal studies under AC (9.5% versus 7.5% [3.7-11.2%]). Our multimodal group also achieved a relative longer survival than previous studies. CONCLUSIONS: Surgery assisted by multimodal techniques can achieve maximal safe resection for HGILAs under GA. Further prospective studies are needed to compare GA with AC for HGILAs.

A Phase 1/2 Multicenter Randomized Trial of Local Ablation plus Toripalimab versus Toripalimab Alone for Previously Treated Unresectable Hepatocellular Carcinoma.

PURPOSE: To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240 mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3), or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2. RESULTS: A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate (ORR) than Schedule D14 for non-ablation lesions (37.5% vs. 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher ORR than with toripalimab alone (33.8% vs. 16.9%; P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 vs. 3.8 months; P < 0.001) and median overall survival (18.4 vs. 13.2 months; P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, eight (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis. CONCLUSIONS: In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone, with an acceptable safety profile.

miR-195-5p Targets CDK1 To Regulate New DNA Synthesis and Inhibit the Proliferation of Hepatocellular Carcinoma Cells.

In cell biological functions and viability, cyclin-dependent kinase 1 (CDK1) takes an essential part. miR-195-5p is pivotal in pathogenesis and development of hepatocellular carcinoma (HCC). But in HCC, whether there is a connection between CDK1 and miR-195-5p remains an unanswered question. In view of this, this study focuses on exploring the mechanism of miR-195-5p/CDK1 in the progression of HCC. The bioinformatics method was applied to predict target mRNA and upstream miRNAs, and further analyzes the signal enrichment pathway of target mRNA. We utilized qRT-PCR and Western blot for detecting expression of genes, as well as their corresponding protein levels. Cell cycle was assayed through flow cytometry. As for the examination of DNA replication, the EDU staining was employed. Cell proliferation was determined via plate colony formation assay. The combined application of bioinformatics analysis and dual-luciferase gene assay assisted in figuring out the binding relationship between miR-195-5p and CDK1. DNA damage was marked by immunofluorescence staining. CDK1 was overexpressed in HCC cells, and enriched in cell cycle and DNA replication pathway. Silencing CDK1 modulated cell cycle of HCC cells and inhibited DNA replication and proliferation. In HCC cells, miR-195-5p targeted and reduced CDK1 expression, inhibited the G1 phase-to-S phase transition, induced DNA damage response, and inhibited DNA replication and proliferation. miR-195-5p targeted CDK1 and repressed synthesis of new DNA in HCC cells, thus restraining HCC cell proliferation.

Metal-organic framework derived Fe3C nanoparticles coupled single-atomic iron for boosting oxygen reduction reaction.

Developing transition metal electrocatalysts, especially single-atom catalysts (SACs), is significant. However, most of the synthesis procedures of SACs involve the formation of nanoparticles (NPs), and the produced NPs always play an influential role during electrocatalytic processing, so exploring the synergistic effects between metallic and isolated metal species is of great interest. Herein, we report a Zn/Fe-metal-organic framework (MOF)-derived Fe3C coupling FeNx catalyst constructed via coordination confinement pyrolysis effect successfully. Compared with the Pt/C catalyst and most precious metal-free catalysts, the optimized catalyst Fe3C-FeNx/NC-7 demonstrates superior oxygen reduction reaction (ORR) activity in 0.1 M KOH. The half-wave potential (E1/2) reaches up to 0.93 V with the limiting current density (jL) of 5.65 mA/cm2 at 5 mV/s scanning rate and 1600 rpm. The excellent performance originates from the synergistic effect of FeNx and Fe3C active units combined with wide-distributed nitrogen atoms. The Fe3C NPs further optimize the electronic structure and adsorption/desorption free energy of the catalyst. The assembled primary Zn-air battery (ZAB) displays a satisfying open-circuit potential of 1.53 V and an excellent specific capacity of 835 mA·h·g-1. The maximum power density achieves 283 mW/cm2, outclassing the commercial Pt/C-based ZAB. This result demonstrates the promising application prospect of the catalyst-cooperated metallic NPs with isolated single metal species.

Aspirin inhibits the biological behavior of gallbladder carcinoma cells by modulating vascular endothelial growth factor.

OBJECTIVE: To elucidate the effect of aspirin (ASP) on the biological behavior of gallbladder carcinoma (GBC) cells and its influence on vascular endothelial growth factor (VEGF) expression. METHODS: Cell Counting Kit-8 (CCK-8) assay was performed to determine the effects of ASP on GBC-SD cell proliferation. In addition, Transwell assay and flow cytometry were carried out to observe the role of ASP in GBC-SD cell migration, invasion and apoptosis, respectively. Tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB), and VEGF concentrations in GBC-SD cells were examined by enzyme-linked immunosorbent assays (ELISAs). RESULTS: ASP suppressed GBC-SD cell proliferation in a dose-dependent manner, and a concentration ≥ 2 mmol/L could significantly inhibit the migration and invasion of GBC-SD cells and induce apoptosis. In addition, the anticancer effect of ASP in GBC-SD cells may be linked to its inhibition of TNF-α, NF-κB, and VEGF levels. CONCLUSIONS: ASP may markedly inhibit GBC-SD cell growth by significantly reducing TNF-α, NF-κB and VEGF expression.

Myosteatosis can Predict Unfavorable Outcomes in Advanced Hepatocellular Carcinoma Patients Treated With Hepatic Artery Infusion Chemotherapy and Anti-PD-1 Immunotherapy.

Aim: To evaluate the feasibility of computed tomography (CT) - derived measurements of body composition parameters to predict the risk factor of non-objective response (non-OR) in patients with hepatocellular carcinoma (HCC) undergoing anti-PD-1 immunotherapy and hepatic artery infusion chemotherapy (immune-HAIC). Methods: Patients with histologically confirmed HCC and treated with the immune-HAIC were retrospectively recruited between June 30, 2019, and July 31, 2021. CT-based estimations of body composition parameters were acquired from the baseline unenhanced abdominal CT images at the level of the third lumbar vertebra (L3) and were applied to develop models predicting the probability of OR. A myosteatosis nomogram was built using the multivariate logistic regression incorporating both myosteatosis measurements and clinical variables. Receiver operating characteristic (ROC) curves assessed the performance of prediction models, including the area under the curve (AUC). The nomogram's performance was assessed by the calibration, discrimination, and decision curve analyses. Associations among predictors and gene mutations were also examined by correlation matrix analysis. Results: Fifty-two patients were recruited to this study cohort, with 30 patients having a OR status after immune-HAIC treatment. Estimations of myosteatosis parameters, like SM-RA (skeletal muscle radiation attenuation), were significantly associated with the probability of predicting OR (P=0.007). The SM-RA combined nomogram model, including serum red blood cell, hemoglobin, creatinine, and the mean CT value of visceral fat (VFmean) improved the prediction probability for OR disease with an AUC of 0.713 (95% CI, 0.75 to 0.95) than the clinical model nomogram with AUC of 0.62 using a 5-fold cross-validation methodology. Favorable clinical potentials were observed in the decision curve analysis. Conclusions: The CT-based estimations of myosteatosis could be used as an indicator to predict a higher risk of transition to the Non-OR disease state in HCC patients treated with immune-HAIC therapy. This study demonstrated the therapeutic relevance of skeletal muscle composition assessments in the overall prediction of treatment response and prognosis in HCC patients.

Macrophage membrane coated nanoparticles: a biomimetic approach for enhanced and targeted delivery.

The enhanced and targeted drug delivery with low systemic toxicity and subsequent release of drugs is a major concern among researchers and pharmaceutics. In spite of greater advancement and discoveries in nanotherapeutics, the application of synthetic nanomaterials in clinics is still a challenging task due to immune barriers, limited blood circulation time, biodistribution and toxicity. In order to overcome these issues, cell membrane coated nanoparticles are widely employed for effective and targeted delivery. The macrophages have the ability to cross the physiological barriers and escape immune recognition and intracellular trafficking and have the ability to release potent pro-inflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin 6 (IL-6), and therefore macrophage membrane coated nanoparticles have been exploited in the development of various therapeutics. In the present review, we have summarized the role of macrophage membranes as a coating material for the delivery of drugs to the targeted tissue in order to cure different diseases such as cancers, microbial infections, atherosclerosis and various inflammations. The review has critically analysed the latest approaches, and how to develop the macrophage membrane coated nanocarriers and their role in the improvement of the therapeutic index.

LncRNA ADAMTS9-AS1 knockdown suppresses cell proliferation and migration in glioma through downregulating Wnt/ß-catenin signaling pathway.

The long non-coding RNA antisense 1 ADAMTS9-AS1 has been reported to serve as an oncogene or tumor suppressor in several tumors, including colorectal cancer and hepatocellular carcinoma. Nevertheless, the clinical significance and biological behaviors of ADAMTS9-AS1 in glioma still remain unclear. Therefore, the goal of this study was to evaluate the functional roles and potential mechanisms of ADAMTS9-AS1 in glioma cells. Using quantitative real-time PCR analysis, we found that ADAMTS9-AS1 was upregulated in glioma tissues and cells in comparison to corresponding controls. ADAMTS9-AS1 expression level was correlated to tumor size (p=0.005) and WHO grade (p=0.002). Kaplan-Meier analysis and Cox multivariate analysis showed that ADAMTS9-AS1 could serve as an independent prognostic factor affecting the overall survival of glioma patients. Functionally, depletion of ADAMTS9-AS1 significantly suppressed the proliferation, migration and invasion in glioma cell lines (U251 and U87), as shown via CCK-8 assay, Edu corporation assay, wound healing assay and transwell assay. Furthermore, we demonstrated that knockdown of ADAMTS9-AS1 suppressed Wnt1, ß-catenin, c-myc and PCNA, while upregulating E-cadherin expression. In conclusion, our data revealed that ADAMTS9-AS1 confers oncogenic function in the progression of glioma, thus targeting ADAMTS9-AS1 might be a promising therapeutic strategy for this disease.

GOLPH3/CKAP4 promotes metastasis and tumorigenicity by enhancing the secretion of exosomal WNT3A in non-small-cell lung cancer.

Cancer metastasis is the main cause of mortality associated with non-small-cell lung cancer (NSCLC), accounting for up to 70% of deaths among patients. The mechanisms underlying distal metastasis remain largely unknown. Golgi phosphoprotein 3 (GOLPH3) correlates negatively with overall survival in multiple tumors. In this study, we evaluated the function of GOLPH3 in NSCLC distal metastasis. GOLPH3 was expressed at high levels in samples from patients with NSCLC and was positively associated with clinicopathologic characteristics including clinical stage (P < 0.001), T (P = 0.001), N (P = 0.007), and M (P = 0.001) classification. Functionally, Transwell and wound-healing assays suggested that GOLPH3 overexpression enhances NSCLC cell migration and invasion abilities. Tumor-sphere formation and flow cytometry assays demonstrated that GOLPH3 overexpression enhances a stem cell-like phenotype of NSCLC cells. Metastasis models established by tail vein and intracardiac injection confirmed the pro-metastatic function of GOLPH3 in vivo. A subcutaneous tumor formation model confirmed that GOLPH3 overexpression increased the tumorigenicity of NSCLC cells. Mechanistically, gene set enrichment analysis revealed a positive association of GOLPH3 mRNA expression with WNT-activated gene signatures. Luciferase-reporter and nuclear extract assays showed that GOLPH3 overexpression enhances metastasis and tumorigenicity through activation of the WNT/ß-catenin pathway. Immunoprecipitation-mass spectrometry and gene ontology analysis demonstrated that GOLPH3 interacts with cytoskeleton-associated protein 4 (CKAP4) in exosome-mediated distal metastasis. We found that GOLPH3 decreased the amount of plasma membrane-localized CKAP4 and increased the amount of exosome-localized CKAP4 to promote the formation of CKAP4-containing exosomes. Furthermore, we demonstrated that CKAP4 binds exosomal WNT3A to enhance its secretion. Therefore, the GOLPH3/CKAP4 axis plays a crucial role in promoting exosomal-WNT3A secretion to enhance and maintain the stem-like phenotype and metastasis in NSCLC, thus indicating the therapeutic potential of GOLPH3 in patients with NSCLC metastasis.

SRPK1/AKT axis promotes oxaliplatin-induced anti-apoptosis via NF-κB activation in colon cancer.

BACKGROUND: Colorectal cancer is the third most common diagnosis. Oxaliplatin is used as first-line treatment of colon cancer. However, oxaliplatin resistance greatly reduces its therapeutic effect. SRPK1 involves in pre-mRNA splicing and tumorigenesis. How SRPK1 mediates drug resistance in colon cancer is unknown. METHODS: The expression of SRPK1 was analyzed in the TCGA and the CPTAC pan-cancer samples and detected in colon cancer cell lines and tissues by IHC and western blot. The MTT and TUNEL assay were used to verify the anti-apoptosis ability of colon cancer cell. The activation of NF-κB was determined by luciferase assay and qRT-PCR. AKT, IKK, IκB and their phosphorylation level were verified by western blot. RESULTS: We found that SRPK1 expression was the second highest in TCGA and the CPTAC pan-cancer samples. The mRNA and protein levels of SRPK1 were increased in tissues from patients with colon cancer. SRPK1 was associated with clinical stage and TNM classifications in 148 cases of colon cancer patients. High SRPK1 levels correlated with poor prognosis (p < 0.001). SRPK1 overexpression enhanced the anti-apoptosis ability of colon cancer cells, whereas SRPK1 silencing had the opposite effect under oxaliplatin treatment. Mechanistically, SRPK1 enhances IKK kinase and IκB phosphorylation to promote NF-κB nuclear translocation to confer oxaliplatin resistance. CONCLUSIONS: Our findings suggest that SRPK1 participates in colon cancer progression and enhances the anti-apoptosis capacity to induce drug resistance in colon cancer cells via NF-κB pathway activation, and thus might be a potential pharmaceutically target for colon cancer treatment.

Hepatic Artery Infusion of Floxuridine in Combination With Systemic Chemotherapy for Pancreatic Cancer Liver Metastasis: A Propensity Score-Matched Analysis in Two Centers.

AIM: To evaluate the efficacy of hepatic artery infusion (HAI) of floxuridine (FUDR) in combination with systemic chemotherapy in patients with pancreatic cancer liver metastases (PCLM). PATIENTS AND METHODS: We retrospectively collected clinical data of 347 patients with PCLM who underwent first-line chemotherapy at two Chinese centers between 2012 and 2019. Propensity score matching between patients with and without HAI was performed to compensate for differences in baseline characteristics. Objective response rate (ORR) and overall survival (OS) between groups were compared. HAI pump functionality was recorded. RESULTS: Data of 258 patients (62 patients with HAI and 196 patients without HAI) were used for matching. After 1:1 ratio matching, 62 patients per group were included. The intrahepatic ORR was 66.1% in the HAI group and 22.6% in the non-HAI group (P < 0.001), and the extrahepatic ORR was 25.0 versus 28.9% (P = 0.679). The median OS was significantly longer in HAI group (14.0 versus 10.8 months, P = 0.001). Multivariance COX regression showed HAI led to a decrease in hazard ratio for death by 61.8% (HR = 0.382; 95% CI: 0.252-0.578; P< 0.001). Subgroup analysis revealed that patients without EHM, with higher intrahepatic tumor burden and with synchronous liver metastasis benefited more from HAI. Dysfunction of HAI pump occurred in 5.7% of patients during the period of follow-up. CONCLUSIONS: In patients with PCLM, first-line treatment with HAI FUDR plus SCT resulted in higher intrahepatic response and better OS.

Clinical and Genetic Features of Brainstem Glioma in Adults: A Report of 50 Cases in a Single Center.

BACKGROUND AND PURPOSE: Brainstem gliomas (BSGs) in adults are rare brain tumors with dismal outcomes. The aim of this study was to determine the clinical and genetic features in a series of BSGs and their association with the prognosis. METHODS: Fifty patients who underwent a stereotactic biopsy between January 2016 and April 2018 at a single institution were collected. Data on clinicopathological characteristics were analyzed and factors associated with patient survival were identified using a Cox regression model. RESULTS: The median age at diagnosis was 55.5 years, and 62% of the patients were male. Glioblastoma (44%) accounted for the largest proportion of BSGs, and oligodendroglioma (2 of 50) was rarely encountered. The IDH mutation (6 of 44) occurred infrequently in astrocytomas, and IDH-mutant tumors harbored both ATRX loss and MGMT promoter methylation at a relatively low level. Wild-type IDH astrocytomas were identified as having high rates of 1p/19q codeletion (5 of 38) and loss of heterozygosity 1p (8 of 38) or 19q (8 of 38) only. In diffuse midline glioma H3K27M mutant, MGMT promoter methylation occurred in three of four cases. Patients were offered radiotherapy and/or concurrent/adjuvant temozolomide chemotherapy, and their median survival time was 13 months. Multivariate analysis revealed that a low tumor grade, absence of tumor enhancement, duration of symptoms ≥3 months, Karnofsky performance status ≥70, and ATRX loss conferred a survival advantage. CONCLUSIONS: Adult BSGs showed different molecular genetic characteristics, but also resembled supratentorial gliomas in their clinical features associated with oncological outcomes.

Identification of key mutations in central nervous diffuse large B-cell lymphoma (DLBCL) by comprehensive analysis between sequencing and TCGA database.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma, and hence, a comprehensive understanding based on the gene expression profile is imperative. Although several studies have identified some critical mutant genes of DLBCL, the disease in the central nervous system has not been investigated clearly. This study is aimed to identify some novel and important mutant genes of DLBCL in central nervous system. METHODS: A total of 156 cases of central nervous tumors were collected from 2016 to 2018, in which the DLBCL cases were confirmed by H&E staining and immunohistochemistry. With the whole-genome high-throughput sequencing, the mutations of samples were identified. By matching with TCGA database, the common mutations of DLBCL were further confirmed. RESULTS: Twelve cases were designated as DLBCL, of which 1 case was classified into germinal center B cell (GCB) subtype, and 11 cases were non-GCB subtypes. The gene mutation spectrum demonstrated that the most common substitutions of six single bases were C>T/G>A, wherein the mutation frequency of C(C>T) G was the highest. The most common type of mutation is missense, and the most frequently mutated genes included MYD88, LRP1B, CD79B, GNA13 and PIM1. Based on the TCGA database, finally, the 4 significantly mutated genes (SMG), including MYD88, PIM1, CD79B, and BTG1 common in the above groups, were identified. CONCLUSIONS: Taken together, the analysis of the TCGA database and the results of the sequencing experiment displayed four mutations that might provide novel targets for the treatment of DLBCL.

Long Noncoding RNA TRIM52-AS1 Sponges miR-514a-5p to Facilitate Hepatocellular Carcinoma Progression Through Increasing MRPS18A.

Background: Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality and has become the most frequently diagnosed liver cancer globally. Long noncoding RNAs have been widely studied because they exert essential functions in human diseases. Aim of the Study: The aim of the study is to explore the role and molecular regulatory mechanism of TRIM52-AS1 in HCC. Materials and Methods: Real-time quantitative polymerase chain reaction examined TRIM52-AS1, miR-514a-5p, and mitochondrial ribosomal protein S18a (MRPS18A) expression in HCC cells. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, JC-1, transwell, and Western blot assays uncovered the function of TRIM52-AS1 in HCC. RNA immunoprecipitation (RIP), RNA pull down, and luciferase reporter assays validated the association among TRIM52-AS1, miR-514a-5p, and MRPS18A. Nuclear-cytoplasmic fractionation assay revealed the subcellular location of TRIM52-AS1 in HCC cells. Results: TRIM52-AS1 was revealed to be upregulated in HCC tissue samples according to GEPIA database. Consistent results were recognized in HCC cell lines. Subsequently, loss-of-function assays confirmed that TRIM52-AS1 ablation depressed cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition process in vitro and inhibited tumor growth in vivo. Furthermore, the authors validated TRIM52-AS1 bound with miR-514a-5p in HCC. TRIM52-AS1 inversely regulated miR-514a-5p expression. Afterward, MRPS18A was identified to be a downstream target of miR-514a-5p. Ultimately, rescue assays manifested that MRPS18A upregulation could neutralize the attenuated effects resulting from TRIM52-AS1 deficiency. Conclusions: All in all, TRIM52-AS1 sponged miR-514a-5p to facilitate HCC progression through increasing MRPS18A expression. The findings highlight TRIM52-AS1 as a novel therapeutic target for HCC.

Clinicopathological characteristics of multiple intracranial Rosai-Dorfman disease with increased IgG4-positive plasma cells: a report of two cases.

Rosai-Dorfman disease (RDD) is an uncommon condition characterized by the proliferation of histiocytes and multiple intracranial involvements and it is extremely rare. Here, we present two cases of multiple intracranial RDD mimicking meningioma. These patients underwent surgery for tumour resection and pathological findings revealed an increased number of IgG4-positive plasma cells in RDD. The radiographic appearance and histology may contribute to a diagnostic dilemma, and immunohistochemical and serological examinations are a necessary complement for definitive diagnosis. Treatment protocols pertaining to such types of RDD cases are reviewed. Currently, surgical resection is the most effective therapy, and steroid therapy, radiotherapy, or chemotherapy may be provided as adjuvant treatments in some selected patients.

Hepatic artery infusion pump for nasopharyngeal carcinoma with liver metastasis.

To evaluate the benefits and risks of hepatic artery infusion (HAI) gemcitabine and floxuridine (FUDR) in patients with nasopharyngeal carcinoma liver metastases. HAI catheter systems were implanted under the guide of digital subtract angiography (DSA) in 16 patients with unresectable nasopharyngeal carcinoma liver metastases. HAI gemcitabine and FUDR in combination with radiotherapy and systemic chemotherapy were delivered. Disease control rate (DCR) of intrahepatic lesions is 100%, objective response rate (ORR) of intrahepatic lesions is 87.5%, including 4 patients (25%) with complete response (CR), 10 patients (62.5%) with partial response (PR) and 2 patients (12.5%) with stable disease (SD). The median overall survival (mOS) was 30 months. There was no significant difference between patients with < 9 intrahepatic lesions and patients with ≥ 9 intrahepatic lesions (31 months vs. 24 months, P = 0.562). Patients without extrahepatic metastases has longer survival than patients with extrahepatic metastases (31 months vs. 17 months, P = 0.005). In all 72 cycles of HAI, the main grade 3/4 toxicities related to HAI include: leukopenia occur in 8 cycles (11.1%), thrombocytopenia in 5 cycles (6.9%), AST/ALT elevation in 12 cycles (16.7). Catheter related complications occurred in 2 patients (12.5%). HAI gemcitabine and FUDR is effective to improve DCR of intrahepatic lesions and prolong mOS for patients with nasopharyngeal carcinoma liver metastases, and is associated with a relative low rate of toxicity.

Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy.

Radiofrequency ablation (RFA) promotes tumor antigen-specific T cell responses and enhances the effect of immunotherapy in preclinical settings. Here we report that the existence of remnant tumor masses due to incomplete RFA (iRFA) is associated with earlier new metastases and poor survival in patients with colorectal cancer liver metastases (CRCLM). Using mouse models, we demonstrate that iRFA promotes tumor progression and hinders the efficacy of anti-PD-1 therapy. Immune analysis reveals that iRFA induces sustained local inflammation with predominant myeloid suppressor cells, which inhibit T cell function in tumors. Mechanistically, tumor cell-derived CCL2 is critical for the accumulation of monocytes and tumor-associated macrophages (TAMs). The crosstalk between TAMs and tumor cells enhances the CCL2 production by tumor cells. Furthermore, we find that administration of a CCR2 antagonist or the loss of CCL2 expression in tumor cells enhances the antitumor activity of PD-1 blockade, providing a salvage alternative for residual tumors after iRFA.

Medium-chain triglyceride/water Pickering emulsion stabilized by phosphatidylcholine-kaolinite for encapsulation and controlled release of curcumin.

Pickering emulsions have received widespread attention for encapsulating lipophilic guests in the biomedical and food fields. However, control of the stabilities and demulsification of Pickering emulsions to allow the release of encapsulated species remains a challenge in gastrointestinal conditions. In this work, phosphatidylcholine-kaolinite was prepared by modification of natural kaolinite with phosphatidylcholine and was used as an emulsifier to stabilize medium-chain triglyceride (MCT)/water Pickering emulsions for encapsulating curcumin, a natural antioxidant drug. Simulated gastric and intestinal digestion and a cell uptake assay were implemented for the curcumin-loaded MCT/water Pickering emulsion to study its demulsification and the bioavailability of curcumin. The results revealed that the wettability of phosphatidylcholine-kaolinite could be tailored by controlling the modification temperature so that it could control the emulsion stability. The prepared phosphatidylcholine-kaolinite, with a three-phase contact angle of 123°, was an optimal emulsifier for the enhanced stabilization of the MCT/water Pickering emulsion, especially in the presence of gastric acid. The phosphatidylcholine-kaolinite distributed at the water-oil interface and formed a dense shell structure on the surfaces of the emulsion droplets, controlling the demulsification efficiency to release the encapsulated curcumin. Only 18.9% of the curcumin was released in the simulated gastric conditions after 120 min of digestion due to the demulsification of the MCT/water Pickering emulsion, while it was completely released after 150 min of digestion in simulated intestinal conditions, as expected. This Pickering emulsion stabilized by phosphatidylcholine-kaolinite is a promising delivery system for lipophilic foods or drugs to enhance their bioavailability.

Neutrophil-Derived MRP14 Supports Plasma Cell Commitment and Protects Myeloma Cells from Apoptosis.

Neutrophils have recently been proposed as cells with high functional plasticity and are involved in the pathogenesis of infections, malignancy, and autoimmune diseases. However, less is known about the role of neutrophil in humoral response. In this study, we examined the importance of neutrophils and the neutrophil-derived DAMP protein, MRP14, in antibody production. Splenic neutrophils and MRP14 that are present in the splenic peri-MZ region have a close contact with MZ B cells and promote their differentiation into plasma cells. Using neutrophil-depleting mice and an MRP14-blocking compound, we showed that the presence of neutrophil and MRP14 is required for class switch, plasma cell maintenance, and antibody production in the spleen. We found that MRP14 could also be produced by neutrophils in the bone marrow and support the maintenance of bone marrow plasma cells. MRP14 binding could enhance the effect of the BAFF signal and protect primary multiple myeloma cells from doxorubicin-induced apoptosis. Our data demonstrate the effects of neutrophils on neighboring B cells and plasma cells, which provides new insights into the connection between neutrophil and humoral responses.