NEDD8 promotes radioresistance via triggering autophagy formation and serves as a novel prognostic marker in oral squamous cell carcinoma.

BACKGROUND: Radiotherapy is the first-line regimen for treating oral squamous cell carcinoma (OSCC) in current clinics. However, the development of therapeutic resistance impacts the anticancer efficacy of irradiation in a subpopulation of OSCC patients. As a result, discovering a valuable biomarker to predict radiotherapeutic effectiveness and uncovering the molecular mechanism for radioresistance are clinical issues in OSCC. METHODS: Three OSCC cohorts from The Cancer Genome Atlas (TCGA), GSE42743 dataset and Taipei Medical University Biobank were enrolled to examine the transcriptional levels and prognostic significance of neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8). Gene set enrichment analysis (GSEA) was utilized to predict the critical pathways underlying radioresistance in OSCC. The colony-forming assay was used to estimate the consequences of irradiation sensitivity after the inhibition or activation of the NEDD8-autophagy axis in OSCC cells. RESULTS: NEDD8 upregulation was extensively found in primary tumors compared to normal adjacent tissues and potentially served as a predictive marker for the therapeutic effectiveness of irradiation in OSCC patients. NEDD8 knockdown enhanced radiosensitivity but NEDD8 overexpression reduced it in OSCC cell lines. The inclusion of MLN4924, a pharmaceutical inhibitor for NEDD8-activating enzyme, dose-dependently restored the cellular sensitivity to irradiation treatment in irradiation-insensitive OSCC cells. Computational simulation by GSEA software and cell-based analyses revealed that NEDD8 upregulation suppresses Akt/mTOR activity to initiate autophagy formation and ultimately confers radioresistance to OSCC cells. CONCLUSION: These findings not only identify NEDD8 as a valuable biomarker to predict the efficacy of irradiation but also offer a novel strategy to overcome radioresistance via targeting NEDD8-mediated protein neddylation in OSCC.

Slanted recession on bilateral lateral rectus for the treatment of intermittent Exotropia with convergence insufficiency.

PURPOSE: To evaluate the efficacy and safety of slanted bilateral lateral rectus recession (S-BLRc) for the treatment of convergence insufficiency-type intermittent exotropia (CI-IXT) in children and to probe the relationship of the slanted amount and surgical outcomes. METHODS: Retrospective study. Fifty-eight patients with CI-IXT, aged 4 to 10 years old, underwent S-BLRc procedures. According to the different slanted amount between the upper and lower poles of lateral rectus, all the patients were grouped: Group A (slanting 1 mm, n = 22), Group B (slanting 1.5 mm, n = 18) and Group C (slanting 2 mm, n = 18). The successful surgical outcome was defined as deviation in the primary position ranging from exotropia< 8△ to esotropia< 5△ both at near and at distant as well as the near-distance difference (NDD) < 5△. We analyzed and compared the preoperative and postoperative data including deviations both at near and at distance, NDD, objective torsion, horizontal deviation at up and down gaze, lateral incomitance, binocular vision and surgical success rate among three groups. RESULTS: The average deviations were significantly decreased from - 37.1△ ± 4.2△ (-,exotropia) to - 1.4△ ± 4.6△ at near (P < 0.05) and from - 25.8△ ± 3.7△ to - 0.1 ± 4.1△ at distance (P < 0.05). The postoperative NDD on average was significantly reduced from 10.0△ to 1.8△ in Group A (P < 0.05), from 11.2△ to 0.8△ in Group B (P < 0.05) and from 13.3△ to 0.9△ in Group C (P < 0.05). There was a significant difference in the mean corrections of NDD among the three groups (8.2△ in group A, 10.3△ in group B and 12.4△ in group C respectively, P < 0,05). All the patients attained various improvement of stereopsis after surgery. None had torsional diplopia, A-V pattern and lateral incomitance after strabismic surgery. Totally, the surgical success rate was 89.7% in our series at the 6- to 8-month follow-up. CONCLUSIONS: Slanted bilateral lateral rectus recession is an effective and safe procedure for the treatment of CI-IXT in children. S-BLRc can successfully collapse exotropia both at distance and at near, decrease NDD and benefit to gain binocular vision. The correction of NDD was associated with the slanted amount.

Free-electrodeposited anodic stripping voltammetry sensing of Cu(II) based on Ti3C2Tx MXene/carbon black.

A proof-of-principle concept for free-electrodeposited anodic stripping voltammetry (ASV) sensing of Cu2+ is proposed by using Ti3C2Tx MXene/carbon black (Ti3C2Tx@CB) nanohybrids as electrode materials. Owing to the high adsorption and reduction capability of Ti3C2Tx towards Cu2+, Ti3C2Tx MXene enables Cu2+ to be immobilized and self-reduced directly to form Cu0 on the Ti3C2Tx@CB electrode surface. As a result an oxidation peak current appears from the re-oxidation of Cu0 via differential pulse voltammetry. Carbon black (CB) was introduced to prevent Ti3C2Tx Mxene aggregation and improve the related electron transfer as well as enhance their surface area. After optimizing various conditions, a considerable low limit of detection (4.6 nM) and a wide linear range (0.01-15.0 µM) for Cu2+ were achieved at the working potential from - 0.3 V to 0.0 V (vs SCE). Relative standard deviation (RSD) of eight individual Ti3C2Tx@CB electrodes is 3.72%, and the recoveries from tap water sample and lake water sample were in the ranges of 97.0-108% and 104-107%, respectively.

High-level expression of ARID1A predicts a favourable outcome in triple-negative breast cancer patients receiving paclitaxel-based chemotherapy.

Paclitaxel-based chemotherapy is a common strategy to treat patients with triple-negative breast cancer (TNBC). As paclitaxel resistance is still a clinical issue in treating TNBCs, identifying molecular markers for predicting pathologic responses to paclitaxel treatment is thus urgently needed. Here, we report that an AT-rich interaction domain 1A (ARID1A) transcript is up-regulated in paclitaxel-sensitive TNBC cells but down-regulated in paclitaxel-resistant cells upon paclitaxel treatment. Moreover, ARID1A expression was negatively correlated with the IC50 concentration of paclitaxel in the tested TNBC cell lines. Kaplan-Meier analyses revealed that ARID1A down-regulation was related to a poorer response to paclitaxel-based chemotherapy in patients with TNBCs as measured by the recurrence-free survival probability. The pharmaceutical inhibition with p38MAPK-specific inhibitor SCIO-469 revealed that p38MAPK-related signalling axis regulates ARID1A expression and thereby modulates paclitaxel sensitivity in TNBC cells. These findings suggest that ARID1A could be used as a prognostic factor to estimate the pathological complete response for TNBC patients who decide to receive paclitaxel-based chemotherapy.

All-fiber passively Q-switched 604 nm praseodymium laser with a Bi2Se3 saturable absorber.

We experimentally demonstrated a simple passively Q-switched praseodymium (Pr3+)-doped all-fiber laser at 604 nm with a Bi2Se3 saturable absorber (SA). A Bi2Se3/polyvinyl alcohol composite film is sandwiched between two ferrules to construct a fiber-compatible Q-switcher. Two fiber end facet mirrors build a compact-linear resonator. The repetition rate of the achieved 604 nm Q-switching pulse can be widely tuned from 86.2 to 187.4 kHz, and the pulse duration can be as narrow as 494 ns. To the best of our knowledge, this is the shortest operation wavelength of a Bi2Se3-based pulsed all-fiber laser at 604 nm.

Endoscopy-assisted surgery for the management of benign breast tumors: technique, learning curve, and patient-reported outcome from preliminary 323 procedures.

BACKGROUND: Endoscopy-assisted breast surgery (EABS), a technique that optimizes cosmetic outcome because it is performed through small wounds hidden in inconspicuous areas, could be an alternative surgical technique for benign breast tumors. In this study, we report the preliminary results of 323 EABS procedures performed at our institution for the management of benign breast tumors. METHODS: The medical records of patients who underwent EABS for benign breast lesions during the periods August 2010 to December 2015 were collected from the Changhua Christian Hospital EABS database. Data on clinicopathologic characteristics, type of surgery, hospital stay, and complications were analyzed to determine the effectiveness of the procedure for benign breast tumors. The operating time with the number of procedure performed was analyzed for learning curve evaluation. Patient satisfaction with cosmetic outcome was evaluated with a self-report questionnaire. RESULTS: A total of 323 EABS procedures were performed in 286 patients with benign breast lesions, including 249 (90.5%) patients with unilateral lesions. The mean age was 36 years, the mean tumor size was 2.2 cm, and the mean distance from the nipple to the tumor was 5.2 cm. Most (93.8%, 303/323) of these tumors were excised through a transareolar wound, 2.4% (8/323) through an axillary wound, and 0.3% (1/323) through the infra-mammary fold. Histopathologic analysis revealed that 63.5% (202/318) of the tumors were fibroadenoma-related lesions. The mean operative time was 81.4 min (59~89 min), which was decreased with experience increased. The overall rate of complications was 6.5%, and all were minor and wound-related. Among the 110 patients who participated in the self-report cosmetic outcome evaluation, 85.4% reported being satisfied with the cosmetic result, and almost all were satisfied with breast symmetry. Of the patients interviewed, 92.7% reported that they would choose the same procedure if they had to undergo the operation again. CONCLUSIONS: Our preliminary results show that transareolar video-assisted breast surgery is a safe and effective procedure with good cosmetic outcome and that it could be appropriate for patients with moderate to large peripherally located breast tumors. TRIAL REGISTRATION: CCH-IRB No.15115. Registered 14 December 2015 (retrospectively registered).

The Utility of Magnetic Resonance Enterography and Double Balloon Enteroscopy-Assisted Endoscopic Balloon Dilatation for Small Bowel Strictures in Crohn's Disease: A Retrospective Observational Study.

Introduction: Crohn's disease (CD) of the small bowel is associated with a severe course and increased risk of complications. Strictures at this location are challenging to diagnose and out-of-reach of colonoscopy. We aimed to evaluate the detection rate of small bowel strictures with magnetic resonance enterography (MRE) and assess the efficacy of double balloon enteroscopy-assisted endoscopic balloon dilatation (DBE-assisted EBD) in managing these strictures. Methods: A retrospective study included all patients with DBE-assisted EBD of small bowel strictures in CD in our facility. All patients had MRE to detect strictures prior to the dilatation. Sequential dilatation protocol was performed using through-the-scope (TTS) working channel balloons. The outcomes included technical success defined by the passage of the enteroscope post-dilatation, resolution of symptoms, and the requirement of repeated procedures or surgery during 12 months of follow-up. Results: Twenty DBE-assisted EBDs of small bowel strictures were attempted during 13 DBE procedures in 10 patients (6 males, median age 42). MRE identified 75% of the strictures with 100% accuracy in localisation. Retrograde DBE was the approach in 16/20 (80%) strictures. Anaesthetic intubation was used in 8/20 (40%). DBE reached 19/20 strictures. All the reached strictures were dilated successfully; the technical success following dilatation was 72.2%. The median DBE insertion time with TTS balloon dilatation was 66 min. Three patients required follow-up dilatations within 2-3 months. Surgery was not needed during the follow-up period. Conclusions: MRE is essential in diagnosing and localising small bowel strictures in CD. DBE reached 95% of strictures with successful dilatation. Immediate technical success was high, and safety was demonstrated. Planned repeat procedures for sequential dilatation were performed in a few patients. Surgical resection was avoided in all patients.

Nurses' perspectives on child-friendly care needs in emergency departments: A qualitative study.

BACKGROUND: Children can become anxious when undergoing emergency medical treatment. Therefore, emergency departments should be child friendly. This study explored emergency nurses' perspectives on children's needs during emergency care. METHOD: This qualitative study employed purposive sampling to recruit 17 emergency nurses from 3 medical centers in northern and central Taiwan. Individual interviews were conducted between January and August 2021. Data were analyzed through qualitative content analysis. RESULTS: The participants had 2-23 years of experience in caring for children in emergency departments. We identified 208 unique meaning units in the interview data, 79 of which were related to child-friendly emergency care. These were classified into 42 codes across 6 categories and 27 subcategories. The six categories were timely comfort, emotional care, frontline safety, emergency response, human resources support, and treatment efficiency. CONCLUSION: Emergency nurses have professional competencies, play a crucial role as care providers for children in the emergency department, and ensure the comfort and safety of children seeking treatment. The categories related to child-friendly emergency care identified in this study can serve as a basis for developing child-friendly care emergency guidelines.

Cervical Tuberculosis Combined With Papillary Thyroid Carcinoma With Lateral Neck Metastasis.

Extrapulmonary tuberculosis in the head and neck region accounts for 10% of all tuberculosis cases. Cervical lymph nodes are the most common sites of head and neck tuberculosis and often mimics neck metastasis leading to overstaging and overtreatment. Fine needle aspiration has proven effective in diagnosing cervical tuberculosis. If a diagnosis of tuberculosis is confirmed, then the first-line treatment is oral antituberculosis medication.

Adalimumab originator versus adalimumab biosimilars in inflammatory bowel disease in Australia.

BACKGROUND: Biosimilar adalimumabs have improved treatment access, but without any clinical advantage, distributors rely on delivery device design-enhancements, support services, and removal of painful excipients to capture market share. Prescribers, however, are often unaware of these differences. This article compares and contrasts originator versus biosimilar adalimumab agents to identify key differences that might influence adalimumab selection. RESEARCH DESIGN AND METHODS: We reviewed listed adalimumab biosimilars in Australia and compared them to the originator adalimumab. Similarities and differences identified were confirmed with the manufacturers via two rounds of interviews: the first to collate a list of features and benefits of their product, and the second to consolidate and confirm the data. RESULTS: The originator adalimumab Humira [by AbbVie, U.S.A] and four adalimumab biosimilars (Amgevita [by Amgen, U.S.A], Hadlima [by Organon, U.S.A], Hyrimoz [by Sandoz, Switzerland], and Idacio [by Fresenius Kabi, Germany]) are included in this review. Key differences identified include product formulation, dosages available, delivery devices, physician support, patient support, and the supply of other biosimilar products by the company. CONCLUSION: Adalimumab biosimilars are different from each other with unique advantages and disadvantages likely to influence prescriber and patients. Therefore, the choice of agent should be individualized to the needs of the patient and the healthcare service.

Next-generation materials for RNA-lipid nanoparticles: lyophilization and targeted transfection.

RNA, including mRNA, siRNA and miRNA, is part of a new class of patient treatments that prevent and treat several diseases. As an alternative to DNA therapy using plasmid DNA, RNA functions in the cellular cytosol, avoiding the potential risks of insertion into patient genomes. RNA drugs, including mRNA vaccines, need carrier materials for delivery into the patient's body. Several delivery carriers of mRNA, such as cationic polymers, lipoplexes, lipid-polymer nanoparticles and lipid nanoparticles (LNPs), have been investigated. For clinical applications, one of the most commonly selected types of RNA delivery carrier is LNPs, which are typically formed with (a) ionizable lipids, which bind to RNA; (b) cholesterol for stabilization; (c) phospholipids to form the LNPs; and (d) polyethylene glycol-conjugated lipids to prevent aggregation and provide stealth characteristics. Most RNA-LNP research has been devoted to achieving highly efficient RNA expression in vitro and in vivo. It is also necessary to study the extended storage of RNA-LNPs under mild conditions. One of the most efficient methods to store RNA-LNPs for a long time is to prepare freeze-dried (lyophilized) RNA-LNPs. Future research should include investigating LNP materials for the development of freeze-dried RNA-LNPs using optimal lipid components and compositions with optimal cryoprotectants. Furthermore, the development of sophisticated RNA-LNP materials for targeted transfection into specific tissues, organs or cells will be a future direction in the development RNA therapeutics. We will discuss the prospects for the development of next-generation RNA-LNP materials.

Clinical Predictors for Abnormal ALT in Patients Infected with COVID-19-A Retrospective Single Centre Study.

OBJECTIVE: Abnormal liver tests have been associated with worse clinical outcomes in patients infected with COVID-19. This retrospective observational study from Singapore aims to elucidate simple clinical predictors of abnormal alanine aminotransferase (ALT) in COVID-19 infections. DESIGN: 717 patients hospitalised with COVID-19 at the National Centre for Infectious Diseases (NCID), Singapore, from 23 January-15 April 2020 were screened, of which 163 patients with baseline normal alanine transferase (ALT) and at least two subsequent ALTs performed were included in the final analysis. Information on baseline demographics, clinical characteristics and biochemical laboratory tests were collected. RESULTS: 30.7% of patients developed abnormal ALT. They were more likely to be older (60 vs. 55, p = 0.022) and have comorbidities of hyperlipidaemia and hypertension. The multivariate logistic regression showed that R-factor ≥1 on admission (adjusted odds ratio (aOR) 3.13, 95% Confidence Interval (CI) 1.41-6.95) and hypoxia (aOR 3.54, 95% CI 1.29-9.69) were independent risk factors for developing abnormal ALT. The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58% vs. 18.6%, p < 0.0005), admission to the Intensive Care Unit (ICU)/High Dependency Unit (HDU) (32% vs. 11.5%, p = 0.003) and intubation (20% vs. 2.7%, p < 0.0005). There was no difference in death rate between the two groups. CONCLUSIONS: Liver injury is associated with poor clinical outcomes in patients with COVID-19. R-factor ≥1 on admission and hypoxia are independent simple clinical predictors for developing abnormal ALT in COVID-19.

N and P co-doped MXenes nanoribbons for electrodeposition-free stripping analysis of Cu(II) and Hg(II).

The present electrochemical stripping analysis (ESA) for multiple heavy metal ions (HMI) generally requires an electrodeposition process at a very low potential below -1.0 V, which inevitably makes the sensing procedures more complex, inefficient and power-wasting. Meanwhile, the emerging MXenes rising-star materials have been studied in various fields recently. While there are only few reports focusing on the heteroatom doping of MXenes, especially no doping-MXenes for electroanalysis. Based on these issues, a novel multifunctional heteroatoms-doped MXenes nanomaterial, N and P co-doped Ti3C2Tx MXenes nanoribbons (N,P-Ti3C2TxR), was prepared herein for the first time, and then N,P-Ti3C2TxR was used as electrode material to propose an electrodeposition-free ESA strategy for multiple HMI (Cu2+, Hg2+). Owing to the unique spontaneous adsorption and reducing capacities of N,P-Ti3C2TxR towards Cu2+ and Hg2+ coupled with the excellent sensing performances, Cu2+ and Hg2+ can undergo self-reduction to be preconcentrated on N,P-Ti3C2TxR surface with the form of Cu0 and Hg0, thus a simple and ultrasensitive electrodeposition-free ESA platform was developed successfully for the simultaneous detection of Cu2+and Hg2+. This work opened a new pathway for the detection for multiple HMI and the preparation/application of heteroatoms doping MXenes.

Multifactorial Analysis of Clinical Prognosis of Liver Metastasis and Vascular Intervention Combined with Ablation in Colorectal Cancer.

Colorectal cancer is one of the leading causes of deaths in China. The initial stages of colorectal cancer can be treated by surgery, radiation, and chemotherapy. However, in the advanced stages, it warrants an application of multimodality treatment. With advances in the medical field, there are applications of new modality of treatment that could possibly provide the appropriate treatment for the advanced stage tumours. The first site of metastasis after colorectal cancer is the liver and the conventional treatment to cure the metastatic lesion involves the administration of chemotherapy. With further advancement, chemotherapy has been directly administered at the thorough transarterial chemoembolization (TACE) which is a vascular intervention. With further advancement, the nonvascular intervention, such as radiofrequency ablations (RFAs), has been administered to the patients. A large amount of data support the use of vascular intervention (TACE) with ablation for hepatic carcinoma; there is no sufficient literature to support the application of the modality in the metastatic liver lesion. In this prospective observational study, we have enrolled 80 patients with metastatic liver lesion from the adenocarcinoma of colon or rectum, treated the patients with a combination of the TACE and ablation therapy, and followed up the patients for a period of 3 years. A multivariate analysis of the various factors that influence the prognosis and outcome has been studied and it has been concluded that the combination therapy is medically beneficial for individuals with aggressive liver lesions, improving overall as well as progression-free life span.

Novel methodology for anodic stripping voltammetric sensing of heavy-metal ions using Ti3C2Tx nanoribbons.

Conventional anodic stripping voltammetry (ASV) sensing of heavy-metal ions (HMIs) generally includes a two-step approach: (a) preconcentration via electrodeposition and (b) re-oxidation, while the requirement of the electrodeposition step makes the detection processes more complex. Herein, a novel methodology using self-reduction instead of electrodeposition was developed for the ASV sensing of HMIs (selecting Cd2+ as a representative analyte) by introducing Ti3C2Tx MXene nanoribbons (Ti3C2Tx NR) as a sensing element that can exhibit direct adsorption and reduction capabilities towards HMIs. Compared with conventional ASV technology, the proposed methodology is simpler and power-saving, and has a significant low detection limit (0.94 nM) and wide linear range (0.005-3.0 µM).

RGL2 Drives the Metastatic Progression of Colorectal Cancer via Preventing the Protein Degradation of ß-Catenin and KRAS.

Colorectal cancer (CRC) is one of the most common cancers and results in high mortality worldwide, owing to cancer progression, i.e., metastasis. However, the molecular mechanism underlying the metastatic evolution of CRC remains largely unknown. Here, we find that the upregulation of Ral Guanine Nucleotide Dissociation Stimulator Like 2 (RGL2) is commonly detected in primary tumors compared normal tissues and is significantly associated with a poorer prognosis in CRC patients. Moreover, RGL2 expression appeared to positively correlate with the metastatic potentials of CRC cells. Whereas RGL2 knockdown dramatically suppresses the metastatic potentials of CRC cells in vitro and in vivo, RGL2 overexpression in the poorly metastatic CRC cells and reconstitution in the RGL2-silenced CRC cells enhanced and rescued the cellular metastatic ability, respectively. Computational simulation using Gene Set Enrichment Analysis program and cell-based assays demonstrated that RGL2 expression causally associated with the activity of Wnt/ß-catenin signaling axis and Kirsten ras (KRAS)S, as well as the progression of epithelial-mesenchymal transition (EMT) in the detected CRC cells. Importantly, RGL2 upregulation was capable of preventing the protein degradation of ß-catenin and KRAS in CRC cells. These findings suggest that RGL2 acts as a driver to promote the metastatic progression of CRC and also serves as a poor prognostic biomarker in CRC patients.

Purification of Colon Carcinoma Cells from Primary Colon Tumor Using a Filtration Method via Porous Polymeric Filters.

Cancer stem cells (CSCs) or cancer-initiating cells (CICs) are key factors for tumor generation and metastasis. We investigated a filtration method to enhance CSCs (CICs) from colon carcinoma HT-29 cells and primary colon carcinoma cells derived from patient colon tumors using poly(lactide-co-glycolic acid)/silk screen (PLGA/SK) filters. The colon carcinoma cell solutions were permeated via porous filters to obtain a permeation solution. Then, the cell cultivation media were permeated via the filters to obtain the recovered solution, where the colon carcinoma cells that adhered to the filters were washed off into the recovered solution. Subsequently, the filters were incubated in the culture media to obtain the migrated cells via the filters. Colon carcinoma HT-29 cells with high tumorigenicity, which might be CSCs (CICs), were enhanced in the cells in the recovered solution and in the migrated cells based on the CSC (CIC) marker expression, colony-forming unit assay, and carcinoembryonic antigen (CEA) production. Although primary colon carcinoma cells isolated from colon tumor tissues contained fibroblast-like cells, the primary colon carcinoma cells were purified from fibroblast-like cells by filtration through PLGA/SK filters, indicating that the filtration method is effective in purifying primary colon carcinoma cells.

IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma.

Although mTOR inhibitors have been approved as first-line therapy for treating metastatic clear cell renal cell carcinoma (ccRCC), the lack of useful markers reduces their therapeutic effectiveness. The objective of this study was to estimate if inositol monophosphatase 2 (IMPA2) downregulation refers to a favorable outcome in metastatic ccRCC receiving mTOR inhibitor treatment. Gene set enrichment analysis predicted a significant activation of mTORC1 in the metastatic ccRCC with IMPA2 downregulation. Transcriptional profiling of IMPA2 and mTORC1-related gene set revealed significantly inverse correlation in ccRCC tissues. Whereas the enforced expression of exogenous IMPA2 inhibited the phosphorylation of Akt/mTORC1, artificially silencing IMPA2 led to increased phosphorylation of Akt/mTORC1 in ccRCC cells. The pharmaceutical inhibition of mTORC1 activity by rapamycin reinforced autophagy initiation but suppressed the cellular migration and lung metastatic abilities of IMPA2-silenced ccRCC cells. In contrast, blocking autophagosome formation with 3-methyladenine rescued the mitigated metastatic potential in vitro and in vivo in IMPA2-overexpressing ccRCC cells. Our findings indicated that IMPA2 downregulation negatively activates mTORC1 activity and could be a biomarker for guiding the use of mTOR inhibitors or autophagy inducers to combat metastatic ccRCC in the clinic.

TNFSF13 upregulation confers chemotherapeutic resistance via triggering autophagy initiation in triple-negative breast cancer.

Since chemotherapy is a main strategy to treat triple-negative breast cancer (TNBC) patients currently, identifying a biomarker to predict chemotherapeutic responses is urgently needed for patients to avoid suffering through unnecessary chemotherapeutic treatments. Here, we found that the endogenous expression of TNFSF13 in a panel of TNBC cell lines highly correlates with paclitaxel (PTX) and doxorubicin IC50 concentrations. Whereas knocking down TNFSF13 enhances PTX effectiveness in PTX-insensitive MDA-MB231 cells, recombinant TNFSF13 (recTNFSF13) desensitizes PTX-sensitive HCC1806 cells to PTX treatment. Moreover, Kaplan-Meier analysis revealed that higher TNFSF13 mRNA expression significantly predicts an increased risk for cancer recurrence in estrogen receptor (ER)-negative breast cancer patients receiving an anthracycline-based treatment. Accordingly, immunohistochemistry experiments indicated that higher levels of TNFSF13 protein are detected in TNBC patients who do not respond to an anthracycline-based treatment. The in silico analysis and Western blotting demonstrated that TNFSF13 expression inversely associates with the activity of the Akt-mTOR pathway, which acts as a negative regulator of autophagy activity. Significantly, the pharmaceutical inhibition of autophagy activity restores the therapeutic effectiveness of PTX in TNFSF13-treated HCC1806 cells. These findings suggest that TNFSF13 can serve as a predictive biomarker for TNBC patients, who can use it to decide whether to receive chemotherapy. KEY MESSAGES: TNFSF13 upregulation correlates with a poor response to chemotherapy in TNBCs. TNFSF13 promotes autophagy initiation in chemotherapeutic resistant TNBCs. Therapeutic targeting of autophagy initiation overcomes the TNFSF13-related chemoresistance. TNFSF13 could be a predictive biomarker for TNBC patients receiving chemotherapy.

Erratum: Lee, H.H., et al. Histone 2A Family Member J Drives Mesenchymal Transition and Temozolomide Resistance in Glioblastoma Multiforme. Cancers 2020, 12, 98.

The authors wish to make the following changes to this paper [...].