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At least 91 records · Page 5

Clinical Utility of [{sup 18}F]FDG-PET /CT in Pericardial Disease

Identification of the etiology of pericardial disease is challenging because the accessibility to pericardial fluid and tissue is limited and there is a relatively low yield of fluid and tissue analysis. Pericardial disease is associated with various systemic diseases and is frequently a first manifestation of other systemic diseases. Detecting the cause of pericarditis and minimizing the subsequent inflammatory process can possibly prevent long-term complications. Purpose of Review: To review the clinical utility of [{sup 18}F]-2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography ([{sup 18}F]FDG-PET/CT) in the diagnosis and treatment of pericardial disease. Recent Findings: [{sup 18}F]FDG-PET/CT can visualize the hypermetabolic tissues of both malignancy and inflammation. Distribution of [{sup 18}F]FDG-PET/CT uptake can provide information for neoplastic disease. If malignancy is ruled out, high uptake of pericardium is associated with active inflammation of the pericardium, and thus response to anti-inflammatory agents can also be predicted with [{sup 18}F]FDG-PET/CT imaging. Summary: [{sup 18}F]FDG-PET/CT can be helpful for diagnosing and establishing prognosis and for planning for anti-inflammatory treatment in pericardial disease.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Programmed death-1 receptor (PD-1) and PD-ligand-1 (PD-L1) expression in non-small cell lung cancer and the immune-suppressive effect of anaerobic glycolysis

The microenvironment of a tumor may regulate the anti-tumor immune response. Intratumoral acidosis and hypoxia may suppress lymphocyte proliferation and migration, and this may have important implications in modern immunotherapy. The expression of PD-L1 by cancer cells and of PD-1 by tumor infiltrating lymphocytes (TILs) was assessed in tissue specimens from 98 operable NSCLC patients. Their prognostic role and their association with makers of glycolysis and anaerobic metabolism were assessed. Strong cytoplasmic/membrane PD-L1 expression was noted in 45/98 cases. Intense presence of TILs was noted in 42/98 cases (high TIL-score), and intense presence of PD-1 expressing TILs (high PIL-score) in 17/98 cases. PD-L1 expression was directly correlated with high PIL-score (p = 0.005). A significant inverse relationship was found between lactate dehydrogenase LDH5 expression and PIL-score (p = 0.008). Similarly, low PIL-score was significantly linked with high-hexokinase HXKII and monocarboxylate transporter MCT2 expression (p < 0.04). Cases with both intense TIL-score and PIL-score had significantly better survival (p < 0.05). For patients with high TIL-score or high PIL-score, PD-L1 overexpression defined significantly poorer survival (p = 0.01 and p = 0.03, respectively). In multivariate analysis, stage (p = 0.002, HR 3.33, 95%CI 1.4–4.5) and TIL-score (p = 0.02, HR 2.12, 95%CI 1.1–4.0) were independent predictive variables of death events. Given the low specificity of PD-L1 as a biomarker for anti-PD-1/PD-L1 immunotherapy, a combined assessment of TIL, PD-L1, PD-1, and LDH5 provides a tool for an immunological/metabolic classification of NSCLC tumors, with a different prognosis and different expected response to anti-PD-1/PD-L1 immunotherapy, which should be considered in relevant clinical trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A novel alkylating deacetylase inhibitor molecule EDO-S101 in combination with cytarabine synergistically enhances apoptosis of acute myeloid leukemia cells

Acute myeloid leukemia (AML) is a devastating disease. Hybrid agents with dual activity, which have been shown to possess anti-cancer effect, are expected to potentially improve the prognosis of AML patients. EDO-S101 is a novel alkylating deacetylase inhibitor molecule synthesized by the addition of the hydroxamic acid of histone deacetylases inhibitor vorinostat into bendamustine, a DNA-damaging agent. However, the effect of EDO-S101 in combination with traditional chemotherapy drugs has not been studied in AML. In this study, we investigated the effect of EDO-S101 in combination with cytarabine in treating AML cells. The synergic activity against AML was identified by remarkable reduction of cell viability, significant apoptosis enhancement and the upregulation of the cleaved PARP, Casepase-3 and -7 proteins compared with monotherapy. To explain the drivers, we detected the DNA damage pathway including DNA double-strand breaks marker γ-H2AX and DNA damage checkpoint proteins, which was supposed to be responsible for the enhanced apoptosis activity. In summary, our data demonstrated that EDO-S101 in combination with cytarabine could synergistically induce the apoptosis of AML cells and it might be a potential regimen for treating leukemia.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Multicenter prospective study validating the efficacy of a quantitative assessment tool for frailty in patients with urological cancers

We prospectively validate the efficacy of the frailty discriminant score (FDS) in individuals with urological cancers, as there has been growing importance in evaluating frailty in clinical practice. A prospective, multicenter study was conducted from February 2017 to April 2019. We enrolled 258 patients with urological cancers and 301 community-dwelling participants who were assessed for frailty. Frailty was assessed using FDS that includes ten items, such as physical, mental, and blood biochemical tests. The primary outcome was the non-inferiority (margin 5%) of FDS in discriminating patients with urological cancers from controls (Ctrl). The sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve for each predictive test were calculated. The secondary endpoints included the prediction of overall survival between patients with urological cancer who have high and low FDS. FDS was significantly higher in patients with urological cancers than that in the Ctrl. The AUROC curves for individuals with non-prostate cancers (such as bladder cancer, upper tract urothelial carcinoma, and renal cell carcinoma; 0.942) and those with prostate cancer (0.943) were within the non-inferior margin. The overall survival values were significantly lower in patients with higher FDS score than in those with lower FDS score. The study met its primary and secondary endpoints. The FDS is a reliable and valid tool for assessing frailty and prognosis in patients with urological cancers.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Caffeine enhances the anti-tumor effect of 5-fluorouracil via increasing the production of reactive oxygen species in hepatocellular carcinoma

The development of drug resistance affecting the prognosis of patients with hepatocellular carcinoma (HCC) leads to low survival rate of HCC patients. Caffeine is reported to have a function of protecting the liver and anti-tumor activity. Therefore, caffeine may be an ideal enhancer for HCC chemotherapy regimens. Our study showed that the combination of caffeine and 5-FU significantly inhibited the proliferation of HCC cells in vivo and in vitro comparing with caffeine or 5-FU monotherapy. The CI values of caffeine (0.5 mM) combined with 5-FU (25, 50 μM) were all less than 1, confirming that the utilization of drug combination has a synergistic inhibitory effect on the proliferation of HCC cells. Meanwhile, results of Western blot and TUNEL assays demonstrated that the apoptotic level of HCC cells in the combined group was significantly increased. The protein expression level of cleaved PARP was up-regulated, while the protein level of Bcl-2 and Bcl-xL was down-regulated. In addition, we found that ROS levels were increased in the 1 mM caffeine and 25 μM 5-FU combination group comparing with the control or single drug group. Taken together, this is the first study to demonstrate that the combination of caffeine and 5-FU inhibits HCC cells proliferation and promotes cellular apoptosis by regulating intracellular ROS production. The present data provides a basis for the application of caffeine combined with 5-FU as a novel chemotherapy regimen for HCC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Multiplexed Quantitative Proteomics in Prostate Cancer Biomarker Development

Prostate cancer (PCa) is the most common non-skin cancer among men in the United States. However, the widely used protein biomarker in PCa, prostate-specific antigen (PSA), while useful for initial detection, its use alone cannot detect aggressive PCa and can lead to overtreatment. This chapter provides an overview of PCa protein biomarker development. It reviews the state-of-the-art liquid chromatography-mass spectrometry-based proteomics technologies for PCa biomarker development, such as enhancing the detection sensitivity of low-abundance proteins through antibody-based or antibody-independent protein/peptide enrichment, enriching post-translational modifications such as glycosylation as well as information-rich extracellular vesicles, and increasing accuracy and throughput using advanced data acquisition methodologies. This chapter also summarizes recent PCa biomarker validation studies that applied those techniques in diverse specimen types, including cell lines, tissues, proximal fluids, urine, and blood, developing novel protein biomarkers for various clinical applications, including early detection and diagnosis, prognosis, and therapeutic intervention of PCa.

Prostate cancer, SRM, PRM, DIA, protein biomarker↗

Analysis of degradation in residential battery energy storage systems for rate-based use-cases

This article examines the impact of residential battery energy storage (BES) systems' operational modes on the life (i.e. usable energy capacity) of the battery under several climatic conditions and battery chemistries. The sharp increase in residential BES installations has been a result of decreasing costs of batteries, increase in rate structures motivated applications such as solar self-consumption and time-of-use energy management, and customers purchasing these systems for backup power. While these different modes of operations provide a combination of increased bill savings, reliability of supply, and energy sustainability to the customer, their operational characteristics vary significantly between use-cases. Functional life of BES systems is known to be strongly dependent on their operating conditions. In this article, we analyze the operation of residential BES systems under different rate-based use-cases, for different battery chemistries and cell designs, and under different environmental conditions. This is conducted by simulating the control of BES operations using rate-based cycling algorithms and analyzing the prognosis of multiple battery lifetime models that consider complex nonlinear dependencies of operational stress factors such as state-of-charge, depth-of-discharge, and temperature on degradation. Significant variations in battery life are observed owing to the differences in characteristics of the uses-cases coupled with environmental conditions and battery chemistries. Such differences lead to the conclusion that choice of residential BES technologies and chemistries should account for their intended use-cases.

25 ENERGY STORAGE↗

Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors

Comparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer. We analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases. From multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH 1Gy ) for death from the first primary cancer was not significantly different from zero – p = 0.23, EH 1Gy = 0.038 (95 % CI: –0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH 1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH 1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001. There is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors. A direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.

60 APPLIED LIFE SCIENCES↗

Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies.

CPTAC↗

Bayesian model updating with finite element vs surrogate models: Application to a miter gate structural system

Bayesian finite element (FE) model updating using direct model evaluations of large-scale high-fidelity FE models is extremely computationally expensive. Surrogate models can be used as fast emulators of FE models to accelerate the model calibration process. The physics/mechanics-based FE models are still the underpinning behind the surrogate models. Here, this paper evaluates the loss in accuracy and the gain in computational time while performing Bayesian model updating by using surrogate model evaluations compared to using direct FE model evaluations. This evaluation is crucial before entirely relying on surrogate models in model updating for structural health monitoring (SHM) and damage prognosis (DP) purposes. This paper also demonstrates Bayesian updating and surrogate model construction of large-scale high-fidelity FE models of infrastructure systems. In this regard, the miter gate structural system is considered as the testbed structure. Three predominant damage modes (loss of contact between gate and wall, loss of thickness due to corrosion, and loss of tension in the diagonal rods) are considered for model updating purposes. Bayesian model updating is performed using direct FE evaluations by leveraging parallel computing. Two types of surrogates, namely polynomial chaos expansion (PCE) and Gaussian process regression (GPR), are developed for the miter gate. Model updating is performed again using the trained surrogate models, and the updating results are compared with their counterparts obtained using the direct FE evaluation results. The posterior distribution of the FE model parameters obtained using the trained surrogates are sufficiently accurate with respect to the posterior obtained utilizing the direct FE evaluations. In addition, an approximate 4-fold decrease in the computational time was observed when using surrogate model evaluations instead of direct FE evaluations for model updating.

42 ENGINEERING↗

Modern Radiation Therapy for Extranodal Nasal-Type NK/T-cell Lymphoma: Risk-Adapted Therapy, Target Volume, and Dose Guidelines from the International Lymphoma Radiation Oncology Group

In the multidisciplinary management of early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL), with curative intent, radiation therapy is the most efficacious modality and is an essential component of a combined-modality regimen. In the past decade, utilization of upfront radiation therapy and non–anthracycline-based chemotherapy has improved treatment and prognosis. This guideline mainly addresses the heterogeneity of clinical features, principles of risk-adapted therapy, and the role and appropriate design of radiation therapy. Radiation therapy methods (including target volume definition, dose and delivery methods) are crucial for optimizing cure for patients with early-stage ENKTCL. The application of the principles of involved site radiation therapy in this lymphoma entity often leads to a more extended clinical target volume (CTV) than in other lymphoma types because it usually presents with primary tumor invasion, multifocal lesions, or extensive submucosal infiltration beyond the macroscopic disease. The CTV varies across different primary sites and is classified mainly into nasal, nonnasal upper aerodigestive tract (UADT), and extra-UADT entities. This review is a consensus of the International Lymphoma Radiation Oncology Group regarding the approach to radiation therapy, target-volume definition, optimal dose, and dose constraints in ENKTCL treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Randomized Trial of Radiation Therapy With Weekly Cisplatin or Cetuximab in Low-Risk HPV-Associated Oropharyngeal Cancer (TROG 12.01) – A Trans-Tasman Radiation Oncology Group Study

The excellent prognosis of patients with low-risk human papillomavirus (HPV)- associated oropharyngeal squamous cell carcinoma has led to concerns about overtreatment and excessive toxicity with radiation therapy and cisplatin, leading to interest in de-intensification trials. We investigated whether cetuximab, an epidermal growth factor receptor targeting antibody, when combined with radiation therapy would result in a decrease in symptom burden and toxicity with similar efficacy compared with weekly cisplatin.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A prognostic risk model for glioma patients by systematic evaluation of genomic variations

The overall survival rate of gliomas has not significantly improved despite new effective treatments, mainly due to tumor heterogeneity and drug delivery. Here, we perform an integrated clinic-genomic analysis of 1, 477 glioma patients from a Chinese cohort and a TCGA cohort and propose a potential prognostic model for gliomas. We identify that SBS11 and SBS23 mutational signatures are associated with glioma recurrence and indicate worse prognosis only in low-grade type of gliomas and IDH-Mut subtype. We also identify 42 genomic features associated with distinct clinical outcome and successfully used ten of these to develop a prognostic risk model of gliomas. The high-risk glioma patients with shortened survival were characterized by high level of frequent copy number alterations including PTEN, CDKN2A/B deletion, EGFR amplification, less IDH1 or CIC gene mutations, high infiltration levels of immunosuppressive cells and activation of G2M checkpoint and Oxidative phosphorylation oncogenic pathway.

60 APPLIED LIFE SCIENCES↗

NIRDye 812: A molecular platform tailored for multimodal bioimaging applications of targeted fluorescence- and photoacoustic-guided surgery

The primary treatment for malignant tumors remains to be surgical removal of the diseased tissue. The presence or absence of residual diseased tissue at the tumor margin is the strongest predictor of postoperative prognosis and recurrence. Accordingly, reliance on the ability of surgeons to visually distinguish diseased tissue from healthy tissue unambiguously in real time is crucial. Near infrared-I (NIRsingle bondI) fluorescence-emitting targeting biomolecular constructs such as anticancer antibody-fluorophore conjugates, namely cetuximab-IRDye® 800CW (CTB-IRDye® 800CW), are FDA-approved for clinical trial usage in the fluorescence-guided resection of diseased tissue due to affording improved direct visualization of tumor tissue when compared to the use of either the unaided eye under standard white light illumination (WLI) surgical techniques or non-targeting fluorophores. Unfortunately, though helpful, CTB-IRDye® 800CW affords limited (i) identification of diseased tissue and (ii) tumor margin delineation, because the immunoconjugate generates suboptimal tumor-to-background ratios (TBRs) as a result of its spectral/photophysical profiles poorly aligning with the fixed optical windows of pre-/clinical setups. As such, CTB-IRDye® 800CW is more prone to affording incomplete resection compared to if TBRs were higher due to otherwise. Here, to aid in accurately identifying deep-seated diseased tissue, photoacoustic (PA) tomography has been implemented alongside CTB-IRDye® 800CW to achieve PA signals that could result in higher TBRs. However, in clinical trial practice, using IRDye® 800CW for PA imaging also yields subpar TBRs due to it affording low PA signals. To overcome such limitations, we developed NIRDye 812, a structurally-modified topological equivalent of IRDye® 800CW, to confer it the capability to yield both higher TBRs and superior PA signal than that of the equivalent CTB-conjugate and fluorophore IRDye® 800CW itself, respectively. To do so, we substituted the oxygen atom at its meso-position with a sulfur atom. CTB-NIRDye 812 demonstrated a red-shifted absorption wavelength at 796 nm and a peak NIR-I fluorescence emission wavelength at 820 nm, which better dovetails with the fixed windows of preinstalled fixed emission filters within commercial pre-/clinical NIR-I fluorescence imaging instruments. Overall, CTB-NIRDye 812 provided a ~ 2-fold increase in TBRs compared to those of CTB-IRDye® 800CW in vivo. Also, NIRDye 812 displayed an ~60% higher PA signal than that of IRDye® 800CW. Collectively, we achieved our goal of improving upon the spectral/photophysical and PA properties of IRDye® 800CW via introducing a subtle modification to its electronic core such that its CTB immunoconjugate could potentially allow for fast track or breakthrough designation by the FDA due to its near-identical structure displaying considerably improved efficacy.

59 BASIC BIOLOGICAL SCIENCES↗

NaroNet: Discovery of tumor microenvironment elements from highly multiplexed images

Understanding the spatial interactions between the elements of the tumor microenvironment -i.e. tumor cells. fibroblasts, immune cells- and how these interactions relate to the diagnosis or prognosis of a tumor is one of the goals of computational pathology. We present NaroNet, a deep learning framework that models the multi-scale tumor microenvironment from multiplex-stained cancer tissue images and provides patient-level interpretable predictions using a seamless end-to-end learning pipeline. Trained only with multiplex-stained tissue images and their corresponding patient-level clinical labels, NaroNet unsupervisedly learns which cell phenotypes, cell neighborhoods, and neighborhood interactions have the highest influence to predict the correct label. To this end, NaroNet incorporates several novel and state-of-the-art deep learning techniques, such as patch-level contrastive learning, multi-level graph embeddings, a novel max-sum pooling operation, or a metric that quantifies the relevance that each microenvironment element has in the individual predictions. We validate NaroNet using synthetic data simulating multiplex-immunostained images where a patient label is artificially associated to the -adjustable- probabilistic incidence of different microenvironment elements. We then apply our model to two sets of images of human cancer tissues: 336 seven-color multiplex-immunostained images from 12 high-grade endometrial cancer patients; and 382 35-plex mass cytometry images from 215 breast cancer patients. In both synthetic and real datasets, NaroNet provides outstanding predictions of relevant clinical information while associating those predictions to the presence of specific microenvironment elements.

60 APPLIED LIFE SCIENCES↗

Mapping the proteogenomic landscape enables prediction of drug response in acute myeloid leukemia

Acute myeloid leukemia is a poor prognosis cancer commonly stratified by genetic aberrations, but these mutations are often heterogeneous and don’t always predict therapeutic response. Here we combine transcriptomic, proteomic, and phosphoproteomic datasets with ex vivo drug sensitivity data to help understand the underlying pathophysiology of AML beyond mutations. We measured the proteome and phosphoproteome of 210 patients and combined them with genomics and transcriptomic measurements to identify four proteogenomic subtypes that complemented existing genetic subtypes. We then built a predictor to classify samples into subtypes based on 147 molecular features and mapped them to a ‘landscape’. Each region of this landscape corresponded to specific drug response patterns. We then built a drug response prediction model to identify drugs that target distinct subtypes. We can ultimately use these models to predict drug treatment response and prioritize treatments. Finally, we extended our models and mapped a series of cell lines representing various stages of quizartinib resistance into our subtype landscape, predicting and experimentally validating a switch in sensitivity to venetoclax to panobinostat, two drugs with very different mechanisms than quizartinib. Our results show how multi-omics data together with drug sensitivity data can inform therapy stratification and drug combinations in AML.

59 BASIC BIOLOGICAL SCIENCES↗

Cancer/testis antigen LDHC promotes proliferation and metastasis by activating the PI3K/Akt/GSK-3β-signaling pathway and the in lung adenocarcinoma

The cancer/testis antigen lactate dehydrogenase-C4 (LDHC) is a specific isoenzyme of the LDH family that regulates invasion and metastasis in some malignancies; however, little is known regarding its role in progression of lung adenocarcinoma (LUAD). Thus, we investigated LDHC expression by immunohistochemistry, and analyzed its clinical significance in 88 LUAD specimens. The role and molecular mechanisms subserving LDHC in cellular proliferation, migration, and invasion were explored both in vitro and in vivo. As a result, we found that high LDHC expression was significantly correlated with clinicopathological features of aggressive LUAD and a poor prognosis. Overexpression of LDHC induced LUAD cells to produce lactate and ATP, increased their metastatic and invasive potential—, and accelerated xenograft tumor growth. We further demonstrated that overexpression of LDHC affected the expression of cell proliferation-related proteins (cyclin D1 and c-Myc) and epithelial-mesenchymal transition (EMT)-related proteins (MMP-2, MMP-9, E-cadherin, Vimentin, Twist, Slug, and Snail) both in vitro and in vivo. Finally, excessive activation of LDHC enhanced the phosphorylation levels of AKT and GSK-3β, revealing activation of the PI3K/Akt/GSK-3β oncogenic-signaling pathways. Treatment with a PI3K inhibitor reversed the effects of LDHC overexpression by inhibiting cellular proliferation, migration, and invasion, with diminished levels of p-Akt and p-GSK3β. PI3K inhibition also reversed cell proliferation-related and EMT-related proteins in LDHC-overexpressing A549 cells. In conclusion, LDHC promotes proliferation, migration, invasion, and EMT in LUAD cells via activation of the PI3K/Akt/GSK-3β pathway.

60 APPLIED LIFE SCIENCES↗

Long non-coding RNA GClnc1 knockdown suppresses progression of epithelial ovarian cancer by recruiting FOXC2 to disrupt the NOTCH1/NF-κB/Snail pathway

Highlights: • GClnc1 is highly expressed in EOC patients and is associated with poor prognosis. • shGClnc1 inhibits the growth and metastasis of EOC cells and promotes apoptosis. • GClnc1 transcriptionally activates NOTCH1 by recruiting FOXC2 in the nucleus. • NOTCH1 promotes the activation of the NF-κB/Snail signaling. • GClnc1 may be one of the possible targets for the treatment of EOC. Epithelial ovarian cancer (EOC) is a highly fatal gynecological cancer. A long noncoding RNA (lncRNA) gastric cancer-associated lncRNA1 (GClnc1) has been revealed to play critical roles in metastasis. Therefore, the present study aims to explore the correlation between GClnc1 and the metastasis and progression of EOC.

60 APPLIED LIFE SCIENCES↗