The Emerging Role of ADAM 12 Regulates Epithelial-mesenchymal Transition by Activating the Wnt/ß-catenin Signaling Pathway in Colorectal Cancer.

OBJECTIVE: The objective of this study is to investigate the expression and regulatory mechanisms of A disintegrin and metalloproteinase domain 12 (ADAM12) in colorectal cancer (CRC) tissues and cells. METHODS: Download and analyze the expression levels of ADAM12 in the TCGA and GSE68468 datasets. Collect paraffin-preserved specimens from the Chongqing University Jiangjin Hospital from April 2017 to December 2019 and detect the expression of ADAM12 through immunohistochemistry. Cell experiments were conducted using colorectal cancer cell lines (SW480, HCT116), and cells with high expression of ADAM12 were selected for silencing experiments, and cell proliferation ability using CCK-8, and migration ability of cells in each group using scratch assay and Transwell invasion assay. The EMT markers (E-cadherin, N-cadherin, Vimentin, Twist) and the Wnt/ß-catenin markers (ß-catenin, GSK-3ß, p-GSK-3ß, C-MYC, MMP-7) were detected using western blot. We construct a nude mouse CRC tumor model and validate the effect of ADAM12 on EMT and Wnt/ß-catenin through immunohistochemistry and Western blot. RESULTS: Bioinformatics showed that increased expression of ADAM12 was strongly correlated with patient prognosis. Immunohistochemistry showed that elevated ADAM12 was associated with vascular invasion (p < 0.05), neurological invasion (p < 0.01), lymph node metastasis (p < 0.01), and TNM staging (p < 0.001). Experiments on cell function revealed that the ADAM12 overexpression group augmented CRC cells' proliferation and migration. After overexpression of ADAM12, the expression of N-cadherin, Vimentin, and Twist increased, while the expression of E-cadherin decreased (p < 0.01). The expression of Proteins related to Wnt/ß-catenin: ß-catenin, p-GSK-3 ß, C-MYC and MMP-7 increased (p < 0.01), and Wnt/ß-catenin inhibitor MSAB can counteract the effect of ADAM12 on EMT in CRC cells. The subcutaneous tumor formation experiment results in nude mice showed that ADAM12 promoted tumor growth and induced EMT compared to the control group. CONCLUSION: ADAM12 overexpression through the Wnt/ß-catenin signal axis controls the EMT of CRC to promote invasion and metastasis.

Nrf1 is not a direct target gene of SREBP1, albeit both are integrated into the rapamycin-responsive regulatory network in human hepatoma cells.

The essential role of protein degradation by ubiquitin-proteasome system is exerted primarily for maintaining cellular protein homeostasis. The transcriptional activation of proteasomal genes by mTORC1 signaling depends on Nrf1, but whether this process is directly via SREBP1 remains elusive. In this study, our experiment evidence revealed that Nrf1 is not a direct target of SREBP1, although both are involved in the rapamycin-responsive regulatory networks. Closely scrutinizing two distinct transcriptomic datasets unraveled no significant changes in transcriptional expression of Nrf1 and almost all proteasomal subunits in either siSREBP2-silencing cells or SREBP1-∕-MEFs, when compared to equivalent controls. However, distinct upstream signaling to Nrf1 dislocation by p97 and its processing by DDI1/2, along with downstream proteasomal expression, may be monitored by mTOR signaling, to various certain extents, depending on distinct experimental settings in different types of cells. Our further evidence has been obtained from DDI1-∕-(DDI2insC) cells, demonstrating that putative effects of mTOR on the rapamycin-responsive signaling to Nrf1 and proteasomes may also be executed partially through a DDI1/2-independent mechanism, albeit the detailed regulatory events remain to be determined.

Overcoming tumor microenvironment obstacles: Current approaches for boosting nanodrug delivery.

In order to achieve targeted delivery of anticancer drugs, efficacy improvement, and side effect reduction, various types of nanoparticles are employed. However, their therapeutic effects are not ideal. This phenomenon is caused by tumor microenvironment abnormalities such as abnormal blood vessels, elevated interstitial fluid pressure, and dense extracellular matrix that affect nanoparticle penetration into the tumor's interstitium. Furthermore, nanoparticle properties including size, charge, and shape affect nanoparticle transport into tumors. This review comprehensively goes over the factors hindering nanoparticle penetration into tumors and describes methods for improving nanoparticle distribution by remodeling the tumor microenvironment and optimizing nanoparticle physicochemical properties. Finally, a critical analysis of future development of nanodrug delivery in oncology is further discussed. STATEMENT OF SIGNIFICANCE: This article reviews the factors that hinder the distribution of nanoparticles in tumors, and describes existing methods and approaches for improving the tumor accumulation from the aspects of remodeling the tumor microenvironment and optimizing the properties of nanoparticles. The description of the existing methods and approaches is followed by highlighting their advantages and disadvantages and put forward possible directions for the future researches. At last, the challenges of improving tumor accumulation in nanomedicines design were also discussed. This review will be of great interest to the broad readers who are committed to delivering nanomedicine for cancer treatment.

Identification of a cellular senescence-related-lncRNA (SRlncRNA) signature to predict the overall survival of glioma patients and the tumor immune microenvironment.

Background: Gliomas are brain tumors that arise from glial cells, and they are the most common primary intracranial tumors with a poor prognosis. Cellular senescence plays a critical role in cancer, especially in glioma. In this study, we constructed a senescence-related lncRNA (SRlncRNA) signature to assess the prognosis of glioma. Methods: The Cancer Genome Atlas was used to collect SRlncRNA transcriptome profiles and clinical data about glioma. Patients were randomized to training, testing, and whole cohorts. LASSO and Cox regression analyses were employed to construct the SRlncRNA signature, and Kaplan-Meier (K-M) analysis was performed to determine each cohort's survival. Receiver operating characteristic (ROC) curves were applied to verify the accuracy of this signature. Gene set enrichment analysis was used to visualize functional enrichment (GSEA). The CIBERSORT algorithm, ESTIMATE and TIMER databases were utilized to evaluate the differences in the infiltration of 22 types of immune cells and their association with the signature. RT-qPCR and IHC were used to identify the consistency of the signature in tumor tissue. Results: An SRlncRNA signature consisting of six long non-coding RNAs (lncRNAs) was constructed, and patients were divided into high-risk and low-risk groups by the median of their riskscore. The KM analysis showed that the high-risk group had worse overall survival, and the ROC curve confirmed that the riskscore had more accurate predictive power. A multivariate Cox analysis and its scatter plot with clinical characteristics confirmed the riskscore as an independent risk factor for overall survival. GSEA showed that the GO and KEGG pathways were mainly enriched in the immune response to tumor cells, p53 signaling pathway, mTOR signaling pathway, and Wnt signaling pathway. Further validation also yielded significant differences in the risk signature in terms of immune cell infiltration, which may be closely related to prognostic differences, and qRT-PCR and IHC confirmed the consistency of the expression differences in the major lncRNAs with those in the prediction model. Conclusion Our findings indicated that the SRlncRNA signature might be used as a predictive biomarker and that there is a link between it and immune infiltration. This discovery is consistent with the present categorization system and may open new avenues for research and personalized therapy.

DYRK2 downregulation in colorectal cancer leads to epithelial-mesenchymal transition induction and chemoresistance.

Colorectal cancer (CRC) is among the most prominent causes of cancer-associated mortality in the world, with chemoresistance representing one of the leading causes of treatment failure. However, the mechanisms governing such chemoresistance remain incompletely understood. In this study, the role of DYRK2 as a mediator of CRC cell drug resistance and the associated molecular mechanisms were assessed by evaluating human tumor tissue samples, CRC cell lines, and animal model systems. Initial analyses of The Cancer Genome Atlas database and clinical tissue microarrays revealed significant DYRK2 downregulation in CRC in a manner correlated with poor prognosis. We further generated LoVo CRC cells that were resistant to the chemotherapeutic drug 5-FU, and found that such chemoresistance was associated with the downregulation of DYRK2 and a more aggressive mesenchymal phenotype. When DYRK2 was overexpressed in these cells, their proliferative, migratory, and invasive activities were reduced and they were more prone to apoptotic death. DYRK2 overexpression was also associated with enhanced chemosensitivity and the inhibition of epithelial-mesenchymal transition (EMT) induction in these LoVo 5-FUR cells. Co-immunoprecipitation assays revealed that DYRK2 bound to Twist and promoted its proteasomal degradation. In vivo studies further confirmed that the overexpression of DYRK2 inhibited human CRC xenograft tumor growth with concomitant Twist downregulation. Overall, these results thus highlight DYRK2 as a promising therapeutic target in CRC worthy of further investigation.

ECM1 regulates the resistance of colorectal cancer to 5-FU treatment by modulating apoptotic cell death and epithelial-mesenchymal transition induction.

5-Fluorouracil (5-FU) chemoresistance is a persistent impediment to the efficient treatment of many types of cancer, yet the molecular mechanisms underlying such resistance remain incompletely understood. Here we found CRC patients resistant to 5-FU treatment exhibited increased extracellular matrix protein 1 (ECM1) expression compared to CRC patients sensitive to this chemotherapeutic agent, and higher levels of ECM1 expression were correlated significantly with shorter overall survival and disease-free survival. 5-FU resistant HCT15 (HCT15/FU) cells expressed significantly higher levels of ECM1 relative to parental HCT15 cells. Changes in ECM1 expression altered the ability of both parental and HCT15/FU cells to tolerate the medication in vitro and in vivo via processes associated with apoptosis and EMT induction. From a mechanistic perspective, knocking down and overexpressing ECM1 in HCT15/FU and HCT15 cell lines inhibited and activated PI3K/AKT/GSK3ß signaling, respectively. Accordingly, 5-FU-induced apoptotic activity and EMT phenotype changes were affected by treatment with PI3K/AKT agonists and inhibitors. Together, these data support a model wherein ECM1 regulates CRC resistance to 5-FU via PI3K/AKT/GSK3ß pathway-mediated modulation of apoptotic resistance and EMT induction, highlighting ECM1 as a promising target for therapeutic intervention for efforts aimed at overcoming chemoresistance in CRC patients.

The evolving epidemiology of monkeypox virus.

Monkeypox, caused by the monkeypox virus (MPXV), is a zoonotic disease endemic mainly in West and Central Africa. As of 27 September 2022, human monkeypox has occurred in more than 100 countries (mostly in non-endemic regions) and caused over 66,000 confirmed cases, which differs from previous epidemics that mainly affected African countries. Due to the increasing number of confirmed cases worldwide, the World Health Organization (WHO) has declared the monkeypox outbreak as a Public Health Emergency of International Concern on July 23, 2022. The international outbreak of human monkeypox represents a novel route of transmission for MPXV, with genital lesions as the primary infection, and the emergence of monkeypox in the current outbreak is also new, as novel variants emerge. Clinical physicians and scientists should be aware of this emerging situation, which presents a different scenario from previous outbreaks. In this review, we will discuss the molecular virology, evasion of antiviral immunity, epidemiology, evolution, and detection of MPXV, as well as prophylaxis and treatment strategies for monkeypox. This review also emphasizes the integration of relevant epidemiological data with genomic surveillance data to obtain real-time data, which could formulate prevention and control measures to curb this outbreak.

Corrigendum: Developing an immune-related signature for predicting survival rate and the response to immune checkpoint inhibitors in patients with glioma.

[This corrects the article DOI: 10.3389/fgene.2022.899125.].

Distinct Roles of Nrf1 and Nrf2 in Monitoring the Reductive Stress Response to Dithiothreitol (DTT).

Transcription factor Nrf2 (nuclear factor, erythroid 2-like 2, encoded by Nfe2l2) has been accepted as a key player in redox regulatory responses to oxidative or reductive stresses. However, relatively little is known about the potential role of Nrf1 (nuclear factor, erythroid 2-like 1, encoded by Nfe2l1) in the redox responses, particularly to reductive stress, although this 'fossil-like' factor is indispensable for cell homeostasis and organ integrity during the life process. Herein, we examine distinct roles of Nrf1 and Nrf2 in monitoring the defense response to 1,4-dithiothreitol (DTT, serving as a reductive stressor), concomitantly with unfolded protein response being induced by this chemical (also defined as an endoplasmic reticulum stressor). The results revealed that intracellular reactive oxygen species (ROS) were modestly increased in DTT-treated wild-type (WT) and Nrf1α-/- cell lines, but almost unaltered in Nrf2-/-ΔTA or caNrf2ΔN cell lines (with a genetic loss of transactivation or N-terminal Keap1-binding domains, respectively). This chemical treatment also enabled the rate of oxidized to reduced glutathione (i.e., GSSG to GSH) to be amplified in WT and Nrf2-/-ΔTA cells, but diminished in Nrf1α-/- cells, along with no changes in caNrf2ΔN cells. Consequently, Nrf1α-/-, but not Nrf2-/-ΔTA or caNrf2ΔN, cell viability was reinforced by DTT against its cytotoxicity, as accompanied by decreased apoptosis. Further experiments unraveled that Nrf1 and Nrf2 differentially, and also synergistically, regulated DTT-inducible expression of critical genes for defending against redox stress and endoplasmic reticulum stress. In addition, we also identified that Cys342 and Cys640 of Nrf1 (as redox-sensing sites within its N-glycodomain and DNA-binding domain, respectively) are required for its protein stability and transcription activity.

miR-596-3p suppresses brain metastasis of non-small cell lung cancer by modulating YAP1 and IL-8.

Brain metastasis (BM) frequently occurs in advanced non-small cell lung cancer (NSCLC) and is associated with poor clinical prognosis. Due to the location of metastatic lesions, the surgical resection is limited and the chemotherapy is ineffective because of the existence of the blood brain barrier (BBB). Therefore, it is essential to enhance our understanding about the underlying mechanisms associated with brain metastasis in NSCLC. In the present study, we explored the RNA-Seq data of brain metastasis cells from the GEO database, and extracted RNA collected from primary NSCLC tumors as well as paired brain metastatic lesions followed by microRNA PCR array. Meanwhile, we improved the in vivo model and constructed a cancer stem cell-derived transplantation model of brain metastasis in mice. Our data indicated that the level of miR-596-3p is high in primary NSCLC tumors, but significantly downregulated in the brain metastatic lesion. The prediction target of microRNA suggested that miR-596-3p was considered to modulate two genes essential in the brain invasion process, YAP1 and IL-8 that restrain the invasion of cancer cells and permeability of BBB, respectively. Moreover, in vivo experiments suggested that our model mimics the clinical aspect of NSCLC and improves the success ratio of brain metastasis model. The results demonstrated that miR-596-3p significantly inhibited the capacity of NSCLC cells to metastasize to the brain. Furthermore, these finding elucidated that miR-596-3p exerts a critical role in brain metastasis of NSCLC by modulating the YAP1-IL8 network, and this miRNA axis may provide a potential therapeutic strategy for brain metastasis.

The Role of MicroRNA in the Regulation of Tumor Epithelial-Mesenchymal Transition.

Consistently, the high metastasis of cancer cells is the bottleneck in the process of tumor treatment. In this process of metastasis, a pivotal role is executed by epithelial-mesenchymal transition (EMT). The epithelial-to-mesenchymal transformation was first proposed to occur during embryonic development. Later, its important role in explaining embryonic developmental processes was widely reported. Recently, EMT and its intermediate state were also identified as crucial drivers in tumor progression with the gradual deepening of research. To gain insights into the potential mechanism, increasing attention has been focused on the EMT-related transcription factors. Correspondingly, miRNAs target transcription factors to control the EMT process of tumor cells in different types of cancers, while there are still many exciting and challenging questions about the phenomenon of microRNA regulation of cancer EMT. We describe the relevant mechanisms of miRNAs regulating EMT, and trace the regulatory roles and functions of major EMT-related transcription factors, including Snail, Twist, zinc finger E-box-binding homeobox (ZEB), and other families. In addition, on the basis of the complex regulatory network, we hope that the exploration of the regulatory relationship of non-transcription factors will provide a better understanding of EMT and cancer metastasis. The identification of the mechanism leading to the activation of EMT programs during diverse disease processes also provides a new protocol for the plasticity of distinct cellular phenotypes and possible therapeutic interventions. Here, we summarize the recent progress in this direction, with a promising path for further insight into this fast-moving field.

Developing an Immune-Related Signature for Predicting Survival Rate and the Response to Immune Checkpoint Inhibitors in Patients With Glioma.

Background: Glioma is one of the most aggressive cancer types affecting the central nerve system, with poor overall survival (OS) rates. The present study aimed to construct a novel immune-related signature to predict prognosis and the efficiency of immunotherapy in patients with glioma. Methods: The mRNA expression data and other clinical information of patients with glioblastoma multiforme (GBM) and low grade glioma (LGG) were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. The immune-related genes were obtained from the Immunology Database and Analysis Portal database. Subsequently, an immune-related signature was created following the results obtained from the Least Absolute Shrinkage and Selection Operator regression model. To validate the predictability of the signature, Kaplan-Meier survival curves and time-dependent receiver operating characteristic curves were created. Moreover, both univariate and multivariate analyses were carried out using the OS between this signature and other clinicopathologic factors, and a nomogram was constructed. In addition, the association between signature, immune cell infiltration, tumor mutation burden and immunophenoscore were determined. Results: Results of the present study using 118 GBM and LGG samples uncovered 15 immune-related genes that were also differently expressed in glioma samples. These were subsequently used to construct the immune-related signature. This signature exhibits the ability to predict prognosis, the infiltration of immune cells in the tumor microenvironment and the response of patients with glioma to immunotherapy. Conclusion: Results of the present study demonstrated that the aforementioned novel immune-related signature may accurately predict prognosis and the response of patients with glioma to immunotherapy.

Extracellular Matrix Protein 1 Regulates Colorectal Cancer Cell Proliferative, Migratory, Invasive and Epithelial-Mesenchymal Transition Activities Through the PI3K/AKT/GSK3ß/Snail Signaling Axis.

In prior reports, extracellular matrix protein 1 (ECM1) upregulation has been reported in colorectal cancer (CRC) patient tumor tissues, and has been suggested to be related to the metastatic progression of CRC, although the underlying mechanisms have yet to be clarified. In this study, we found that ECM1 was overexpressed in both CRC tissues and cell lines. Upregulation of ECM1 was correlated with tumor size, lymph node status and TNM stage in CRC patients. Knocking down ECM1 suppressed CRC cell growth, migration and invasion, in addition to reducing the expression of Vimentin and increasing E-cadherin expression. The overexpression of ECM1, in contrast, yielded the opposite phenotypic outcomes while also promoting the expression of p-AKT, p-GSK3ß, and Snail, which were downregulated when ECM1 was knocked down. Treatment with LY294002 and 740 Y-P reversed the impact upregulation and downregulation of ECM1 on CRC cell metastasis and associated EMT induction. In vivo analyses confirmed that ECM1 overexpression was able to enhance EMT induction and CRC tumor progression. In conclusion, ECM1 influences CRC development and progression in an oncogenic manner, and regulates CRC metastasis and EMT processes via the PI3K/AKT/GSK3ß/Snail signaling axis.

Poricoic acid A (PAA) inhibits T-cell acute lymphoblastic leukemia through inducing autophagic cell death and ferroptosis.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer with poor clinical outcome. Poricoic acid A (PAA) is the main chemical constituent on the surface layer of the mushroom Poria cocos, and exerts protective effects against various diseases. In the study, its effects on T-ALL progression were investigated both in vitro and in vivo. Our results showed that PAA strongly reduced the cell viability of T-ALL cell lines, and induced cell G2 cycle arrest and apoptosis in vitro. Mitochondrial dysfunction was also elevated by PAA, along with enhanced cellular reactive oxygen species (ROS) production. Importantly, PAA-suppressed cell viability and -triggered apoptosis were ROS-dependent. Additionally, autophagy was significantly induced by PAA in T-ALL cells through regulating AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and LC3 signaling pathways. PAA treatments also provoked ferroptosis in T-ALL cells with reduced glutathione (GSH) levels and elevated malonaldehyde (MDA) contents. Suppressing autophagy and ferroptosis almost abrogated the capacity of PAA to restrain T-ALL proliferation and growth. The effects of PAA to suppress T-ALL tumor growth were also confirmed in vivo with undetectable toxicity. Therefore, the present study highlighted the potential of PAA for T-ALL treatment mainly through inducing autophagic cell death and ferroptosis.

Circular RNA circBFAR promotes glioblastoma progression by regulating a miR-548b/FoxM1 axis.

Glioblastoma multiforme (GBM) is the most common and aggressive type of tumor of the primary nervous system. Treatment options for GBM include surgery, chemotherapy, and radiation therapy; however, the clinical outcomes are poor, with a high rate of recurrence. An increasing number of studies have shown that circular RNAs (circRNAs) serve important roles in several types of cancer. Gene Expression Omnibus (GEO) database was utilized to identify the differentially expressed circRNAs and their biological functions. Then, we detected the circular RNA bifunctional apoptosis regulator (circBFAR) was significantly increased in three GEO datasets. However, the role of circBFAR has not been reported in GBM. In this study, the expression of circBFAR was significantly increased both in GBM tissues or cell lines and was negatively correlated with overall survival in patients with GBM. Knockdown of circBFAR inhibited proliferation and invasion both in vitro and in vivo. Increased expression of circBFAR resulted in a reduction of miR-548b expression in glioma cells. A luciferase reporter and RIP assay indicated that miR-548b was a direct target of circBFAR, and miR-548b may negatively regulate the expression of FoxM1. Rescue experiments showed that overexpression of FoxM1 could counter the effect of circBFAR silencing on the proliferation and invasion of glioma cell lines. Moreover, we identified that circBFAR regulates FoxM1 by interacting with miR-548b in glioma cells. In conclusion, the present study demonstrated that a circBFAR/miR-548b/FoxM1 axis regulates the development of GBM and highlights potentially novel therapeutic targets for the treatment of GBM.

ZEB1 promotes colorectal cancer cell invasion and disease progression by enhanced LOXL2 transcription.

Disease progression after curative surgery is still the main challenge for colorectal cancer (CRC). Identifying biomarkers and precise mechanisms in CRC disease progression is necessary for therapeutic improvement. As a transcription factor, ZEB1 promotes malignancy, but the precise mechanism by which ZEB1-dependent transcriptional regulation remains largely undefined. In this study, the transcriptional regulation of lysyl oxidase-like 2 (LOXL2) by ZEB1 in CRC was investigated. Our data show that ZEB1 enhanced LOXL2 transcription through direct binding to its promoter. The gain of function assays of ZEB1 showed increased cell proliferation, migration, and invasion. The inhibition of LOXL2 impaired the invasion and migratory ability of CRC cells, but had no effect on cell proliferation in vitro and in vivo. Immunohistochemical staining of tumor tissues indicated that elevated ZEB1/LOXL2 expression was significantly associated with lymph node metastasis and TNM stage. More importantly, elevated ZEB1/LOXL2 expression was an independent prognostic factor in CRC patients. These findings provide a molecular basis for the promotion of an invasive cancer phenotype by ZEB1-LOXL2 overexpression. Our results identify ZEB1/LOXL2 as a prognostic biomarker and potential therapeutic target against progression of CRC.

Peg-Enhanced Behavioral Recovery After Sciatic Nerve Transection and Either Suturing Or Sleeve Conduit Deployment in Rats.

Polyethylene glycol (PEG) has previously been reported to improve outcomes of peripheral nerve microsuturing. However, recent studies have challenged this finding. Given its clinical importance, we investigated the potential of PEG as a facilitator of peripheral nerve restoration. The sciatic nerve of 144 rats was transected and submitted either to simple suturing (Group A), PEG-enhanced suturing (Group B), and insertion in an arterial sleeve conduit without PEG (Group C), or with PEG (Group D) in equal numbers. Behavioral recovery was assessed with the sciatic function index (SFI). Nerve impulse conduction was assessed with compound muscle action potentials (CMAPs). Histology comprised standard hematoxylin/eosin staining, electron microscopy and glial cell line-derived neurotrophic factor (GDNF) immunohistochemistry. Expression of GDNF was also assessed with western blotting. Results were evaluated at weeks 1, 4, and 8. PEG treatment significantly improved behavioral recovery and morphology of nerve restoration, particularly in the sleeve conduit group, relative to that of controls. In conclusion, PEG may improve outcomes of peripheral nerve reconstruction.

Efficacy and Safety of Iodine-125 Brachytherapy in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is a difficult challenge for physicians, especially when patients have been treated with external beam radiotherapy. The purpose of this study was to assess the clinical efficacy and safety of computed tomography (CT)-guided iodine-125 brachytherapy as a palliative treatment for R/M HNSCC. METHODS: From May 2011 to July 2018, we enrolled 87 patients with R/M HNSCC who had previously received external beam radiotherapy. Among these patients, 43 successfully underwent CT-guided iodine-125 brachytherapy and chemotherapy (group A); 44 patients who only received chemotherapy (group B) were matched with patients in group A. Patients' pain score, Eastern Cooperative Oncology Group (ECOG) score, tumor compression symptoms, and side effects of iodine-125 implantation were recorded. Clinical follow-up was performed to assess progression-free survival (PFS) and overall survival (OS). RESULTS: Both groups of patients completed the treatment and were followed up for 9-66 months, with a median follow-up time of 44 months. The OS was 51 months (95% CI: 42.93-59.06 months) versus 28 months (95% CI: 23.79-32.21 months) (p < 0.05), the PFS was 10 months (95% CI: 6.15-13.84 months) versus 6 months (95% CI: 4.40-7.59 months) (p < 0.05) in groups A and B, respectively. The RR in group A was 25/43 (58.14%) versus 15/44 (34.10%) in group B (p < 0.05). Compared with group B, patients in group A had lower pain scores, better physical performance, and better improvement of compression symptoms. No serious treatment-related complications were observed in either group of patients. CONCLUSION: Compared with chemotherapy alone, iodine-125 seed implantation combined with chemotherapy was a more effective and safer strategy for R/M HNSCC.

DDX49 is a novel biomarker and therapeutic target for lung cancer metastases.

The identification of lymph node metastases is important for the diagnosis, treatment and prognosis of patients with lung cancer. We found DDX49 was associated with the lymph node metastases in lung cancer by the Akt/ß-catenin pathway. Transcriptome sequencing, bioinformatics analysis, quantitative RT-PCR, cell transfection and the Cancer Genome Atlas (TCGA) data set were used to identify DDX49 responsible for lymph node metastases. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to explore the possible molecular mechanism in experimental cell. The DDX49 gene was correlated significantly with lymph node metastases of lung cancer. The knockdown of DDX49 inhibited the cell proliferation and migration in PC-9 and H460 cells. The mechanism research found downexpression of DDX49 decreased the Akt/ß-catenin pathway in lung cancer cell. In vivo experiments showed that DDX49 promoted the proliferation and metastases of lung cancer cells by increasing the Akt/ß-catenin pathway. These findings suggested that DDX49 may be useful as a novel biomarker of lymph node metastases and therapeutic target for lung cancer metastasis.

Efficacy and safety of iodine-125 brachytherapy combined with chemotherapy in the treatment of advanced NSCLC in the elderly.

BACKGROUND: Advanced non-small-cell lung cancer (NSCLC) is a huge challenge for physicians. Traditional chemoradiotherapy is associated with high rates of toxicities, especially when treating gerontal patients. Our study was focused on investigating the safety and efficacy of permanent iodine-125 seed implantation and chemotherapy for the treatment of advanced NSCLC in the elderly. METHODS: Fifty elderly patients with stage III or IV NSCLC at our hospital from January 2011 to June 2017 were treated with the chemotherapy regimens (paclitaxel/cisplatin) and computed tomography (CT)-guided iodine-125 brachytherapy (group A), 50 patients who received chemotherapy consisting of paclitaxel and cisplatin only (group B) were matched-up with the patients in group A. The local response rate was evaluated by CT. Progression-free survival (PFS) and overall survival (OS) data were obtained through clinical follow-up. RESULTS: The patients were followed-up for 3-46 months. With a median follow-up time of 20 months, the OS and PFS were 20 months (95% CI: 19.09-20.90 months) vs 15 months (95% CI: 14.48-15.51 months) (P<0.05) and 13 months (95% CI: 11.96-14.04 months) vs 8 months (95% CI: 7.63-8.37 months) (P<0.05) in group A and group B, respectively. The symptoms of patients in group A were significantly relieved when compared with group B. Severe complications were not observed in either of the groups. CONCLUSION: The combination of iodine-125 seed brachytherapy and chemotherapy is an effective and safe therapy and is superior to chemotherapy alone for advanced NSCLC in the elderly.