ABSTRACT
BACKGROUND: Colorectal cancer (CRC) has been the third most prevalent cancer worldwide. Liver metastasis is the critical factor for the poor prognosis of CRC. Here, we investigated the expression and role of PLOD3 in CRC. METHODS: Different liver metastasis models were established by injecting PLOD3 stable knockdown or overexpression CT26 or MC38 mouse CRC cells into the spleen of mice to verify the tumorigenicity and metastasis ability in vivo. RESULTS: We identified PLOD3 is significantly overexpressed in liver metastasis samples of CRC. High expression of PLOD3 was significantly associated with poor survival of CRC patients. The knockdown of PLOD3 exhibited remarkable inhibition of proliferation, migration, and invasion in CRC cells, while the opposite results could be found in different PLOD3-overexpressed CRC cells. Stable knockdown of PLOD3 also significantly inhibited liver metastasis of CRC cells in different xenografts models, while stable overexpression of PLOD3 promotes liver metastasis and tumor progression. Further studies showed that PLOD3 facilitated the T cell activation in the tumor microenvironment and affected the TNF-α/ NF-κB pathway. CONCLUSIONS: This study revealed the essential biological functions of PLOD3 in colon cancer progression and metastasis, suggesting that PLOD3 is a promising translational medicine target and bioengineering targeting PLOD3 overcomes CRC liver metastasis.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Animals , Humans , Mice , Colorectal Neoplasms/genetics , Liver Neoplasms/genetics , NF-kappa B , T-Lymphocytes , Tumor Microenvironment , Tumor Necrosis Factor-alphaABSTRACT
Necroptosis has been shown to play an important role in the development of tumors. However, the characteristics of the necroptosis-related subtypes and the associated immune cell infiltration in the tumor microenvironment (TME) of breast cancer (BRCA) remain unclear. In this study, we identified three clusters related to necroptosis using the expression patterns of necroptosis-relevant genes (NRGs), and found that these three clusters had different clinicopathological features, prognosis and immune cell infiltration in the TME. Cluster 2 was characterized by less infiltration of immune cells in the TME and was associated with a worse prognosis. Then, a necroptosis risk score (NRS) composed of 14 NRGs was constructed using the least absolute shrinkage and selection operator regression (LASSO) Cox regression method. Based on NRS, all BRCA patients in the TCGA datasets were classified into a low-risk group and a high-risk group. Patients in the low-risk group were characterized by longer overall survival (OS), lower mutation burden, and higher infiltration level of immune cells in the TME. Moreover, the NRS was significantly associated with chemotherapeutic drug sensitivity. Finally, the knockdown of VDAC1 reduced the proliferation and migration of BRCA cells, and promoted cell death induced by necroptosis inducer. This study identified a novel necroptosis-related subtype of BRCA, and a comprehensive analysis of NRGs in BRCA revealed its potential roles in prognosis, clinicopathological features, TME, chemotherapy, tumor proliferation, and tumor necroptosis. These results may improve our understanding of NRGs in BRCA and provide a reference for developing individualized therapeutic strategies.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Necroptosis/genetics , Apoptosis , Risk Factors , Cell Death , Tumor Microenvironment/geneticsABSTRACT
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death due to early metastasis or recurrence. Tumor angiogenesis plays an essential role in the tumorigenesis of HCC. Accumulated studies have validated the crucial role of lncRNAs in tumor angiogenesis. Here, we established an angiogenesis-related multi-lncRNAs risk model based on the machine learning for HCC prognosis prediction. Firstly, a total of 348 differential expression angiogenesis-related lncRNAs were identified by correlation analysis. Then, 20 of these lncRNAs were selected through univariate cox analysis and used for in-depth study of machine learning. After 1,000 random sampling cycles calculating by random forest algorithm, four lncRNAs were found to be highly associated with HCC prognosis, namely LUCAT1, AC010761.1, AC006504.7 and MIR210HG. Subsequently, the results from both the training and validation sets revealed that the four lncRNAs-based risk model was suitable for predicting HCC recurrence. Moreover, the infiltration of macrophages and CD8 T cells were shown to be closely associated with risk score and promotion of immune escape. The reliability of this model was validated by exploring the biological functions of lncRNA MIR210HG in HCC cells. The results showed that MIR210HG silence inhibited HCC growth and migration through upregulating PFKFB4 and SPAG4. Taken together, this angiogenesis-related risk model could serve as a reliable and promising tool to predict the prognosis of HCC.
ABSTRACT
Uncontrolled cell division is a hallmark of cancer. Deregulation of Wnt components has been linked to aberrant cell division by multiple mechanisms, including Wnt-mediated stabilisation of proteins signalling, which was notably observed in mitosis. Analysis of Wnt components revealed an unexpected role of B-cell CLL/lymphoma 9 (BCL9) in maintaining mitotic Wnt signalling to promote precise cell division and growth of cancer cell. Mitotic interactome analysis revealed a mechanistic role of BCL9 in inhibiting clathrin-mediated degradation of LRP6 signalosome components by interacting with clathrin and the components in Wnt destruction complex; this function was further controlled by CDK1-driven phosphorylation of BCL9 N-terminal, especially T172. Interestingly, T172 phosphorylation was correlated with cancer patient prognosis and enriched in tumours. Thus, our results revealed a novel role of BCL9 in controlling mitotic Wnt signalling to promote cell division and growth.
Subject(s)
CDC2 Protein Kinase/metabolism , Clathrin/metabolism , Mitosis , Neoplasm Proteins/metabolism , Neoplasms/metabolism , Wnt Signaling Pathway , HCT116 Cells , HeLa Cells , Humans , Low Density Lipoprotein Receptor-Related Protein-6/metabolism , Neoplasms/pathology , Phosphorylation , Protein Domains , Transcription FactorsABSTRACT
BACKGROUND: Desmoid tumor (DT), also known as desmoid-type fibromatosis (DTF) or aggressive fibromatosis (AF) is a rare mesenchymal tumor affecting both children and adults. It is non-metastasis but infiltrative, growing with a high recurrence rate to even cause serious health problems. This study investigates the biology of desmoid tumors through integrated multi-omics studies. METHODS: We systematically investigated the clinical data of 98 extra-abdominal cases in our pediatric institute and identified some critical clinical prognostic factors. Moreover, our integrated multi-omics studies (Whole Exome Sequencing, RNA sequencing, and untargeted metabolomics profiling) in the paired PDT tumor/matched normal tissues identified more novel mutations, and potential prognostic markers and therapeutic targets for PDTs. RESULTS: The top mutation genes, such as CTNNB1 (p.T41A and p.S45F) and MUC4 (p.T3775T, p.S3450S, etc.), were observed with a mutation in more than 40% of PDT patients. We also identified a panel of genes that are classed as the FDA-approved drug targets or Wnt/ß-catenin signaling pathway-related genes. The integrated analysis identified pathways and key genes/metabolites that may be important for developing potential treatment of PDTs. We also successfully established six primary PDT cell lines for future studies. CONCLUSIONS: These studies may promote the development of novel drugs and therapeutic strategies for PDTs.
ABSTRACT
Engineering a versatile nanocomplex integrating effective penetration of the blood-brain barrier (BBB), accurate diagnosis, and boosting therapy has always been an intractable challenge in glioblastoma multiforme (GBM). Herein, biomimetic nanocomplexes (TMPsM) for single intracellular transglutaminase 2 (TG2)-triggered self-assembly imaging and RNAi therapy for GBM are subtly developed. To prove the concept, transferrin receptor (TfR) aptamer-modified brain metastatic tumor cell membrane is prepared as the shell for dual BBB targeting capability and prolonged blood retention time. Upon targeting entering into GBM, hollow MnO2 is decomposed to release KKGKGQQ-tetraphenylethene (Pep-TPE) and siRNA. Owing to TG2 dependence, the non-emissive Pep-TPE would be self-aggregated to induce the emission turn-on in GBM that contain overexpressed TG2. The resulting aggregation-induced emission fluorescence imaging with a high signal-to-noise ratio can achieve the precise localization of the tumor and dynamic detection of TG2 activity, thereby allowing the GBM accurate diagnosis. Notably, the TG2 can be silenced by the released siRNA to cause cell apoptosis and increase chemotherapeutic sensitivity, ultimately realizing excellent antitumor efficacy. In vitro and in vivo results demonstrate that the as-prepared TMPsM indeed possess superior BBB penetration, precise diagnosis, and effective therapy of GBM. The proposed strategy may pioneer a new path for the theranostics of brain tumors.
Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Biomimetics , Blood-Brain Barrier/metabolism , Brain Neoplasms/metabolism , Cell Line, Tumor , Glioblastoma/pathology , Glioma/diagnostic imaging , Glioma/metabolism , Humans , Manganese Compounds , Oxides/pharmacology , Protein Glutamine gamma Glutamyltransferase 2 , RNA, Small Interfering/metabolism , Receptors, Transferrin/metabolismABSTRACT
Metformin has potential anti-inflammatory properties and accelerates wound healing by enhancing vascular development. In this study, we aimed to investigate the effects of metformin on pulmonary vascular development and the underlying mechanism. Newborn mice were subcutaneously injected with metformin from day 2 after exposure to hyperoxia. Pulmonary vascular development, inflammation, and Shh signaling pathway-related protein expression were evaluated by western blotting and immunofluorescence staining. M2 macrophage polarization was measured by flow cytometry. The effect of metformin on macrophage polarization was determined using RAW264.7 macrophages exposed to 90% oxygen in vitro. The role of metformin and purmorphamine on M1 and M2 polarization was observed by flow cytometry. M2 polarization of pulmonary macrophages was inhibited after hyperoxic exposure, and metformin increased the number of M2 macrophages in the lung on postnatal day 14. Metformin upregulated CD31 expression and suppressed inflammation in the lung of mice exposed to hyperoxia on postnatal days 7 and 14. Metformin downregulated the Gli1 expression in macrophages in the lung after exposure to hyperoxia on postnatal day 14. In vitro studies showed that metformin inhibited the Gli1 expression in RAW264.7 macrophages exposed to 90% oxygen, which was reversed after purmorphamine pretreatment. Exposure to 90% oxygen inhibited the polarization of M2 macrophages, whereas metformin increased the number of M2 macrophages. Purmorphamine reversed the effects of metformin on M2 polarization and vascular endothelial growth factor (VEGF) upregulation in RAW264.7 macrophages exposed to hyperoxia. In conclusion, metformin regulates macrophage polarization via the Shh signaling pathway to improve pulmonary vascular development in bronchopulmonary dysplasia.
Subject(s)
Bronchopulmonary Dysplasia , Hedgehog Proteins , Hyperoxia , Macrophages , Metformin , Animals , Bronchopulmonary Dysplasia/etiology , Bronchopulmonary Dysplasia/genetics , Cell Polarity , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Hyperoxia/metabolism , Inflammation/metabolism , Lung/metabolism , Macrophages/drug effects , Macrophages/metabolism , Metformin/pharmacology , Mice , Oxygen/metabolism , Signal Transduction , Vascular Endothelial Growth Factor A/metabolism , Zinc Finger Protein GLI1/metabolismABSTRACT
BACKGROUND: As the highest prevalent pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) ranks the 7th lethal malignancy worldwide. The late diagnosis, chemotherapeutic resistance, and high associated mortality make PDAC a dilemma facing the oncologists. Protein kinase C (PKC) enzymes have been shown to be important in different cancer progression. METHODS: To understand the pattern of PKC enzymes in PDAC, we examined all PKC family member genes expression in PDAC and matched normal tissues. The critical role of PKCι was further investigated in different PDAC cells using cellular and molecular technology. RESULTS: We found that PRKCI (PKCι) was the most significantly overexpressed PKCs in pancreatic cancer. However, little is known about its role and regulation of oncogenic signaling pathways in pancreatic cancer. In this study, we confirmed the overexpression of PKCι in PDAC, and this high expression was associated with poor prognosis of patients. We proved that knockdown of PKCι by small interfering RNA or shRNA significantly inhibited pancreatic cancer cell growth and migration or invasion. Conversely, PKCι overexpression promoted pancreatic cancer cell growth and migration. Moreover, bioinformatical and technical studies informed the participation of PKCι in regression of apoptosis in PDAC cells, which may be related to the regulation of both PI3K/AKT and Wnt/ß-catenin pathways. CONCLUSIONS: Therefore, our results are adding more insight into the importance of PKCι in pancreatic cancer. PKCι induces pancreatic cancer progression through activation of PI3K/AKT and Wnt/ß-catenin signaling pathways, which may provide a promising therapeutic target for pancreatic cancer.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , beta Catenin/metabolism , Biomarkers , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Cell Proliferation , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Gene Expression Regulation, Neoplastic , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Wnt Signaling Pathway , Pancreatic NeoplasmsABSTRACT
As a member of the potassium calcium-activated channel subfamily, increasing evidence suggests that KCNN4 was associated with malignancies. However, the roles and regulatory mechanisms of KCNN4 in PDAC have been little explored. In this work, we demonstrated that the level of KCNN4 in PDAC was abnormally elevated, and the overexpression of KCNN4 was induced by transcription factor AP-1. KCNN4 was closely correlated with unfavorable clinicopathologic characteristics and poor survival. Functionally, we found that overexpression of KCNN4 promoted PDAC cell proliferation, migration and invasion. Conversely, the knockdown of KCNN4 attenuated the growth and motility of PDAC cells. In addition to these, knockdown of KCNN4 promoted PDAC cell apoptosis and led to cell cycle arrest in the S phase. In mechanistic investigations, RNA-sequence revealed that the MET-mediated AKT axis was essential for KCNN4, encouraging PDAC cell proliferation and migration. Collectively, these findings reveal a function of KCNN4 in PDAC and suggest it's an attractive therapeutic target and tumor marker. Our studies underscore a better understanding of the biological mechanism of KCNN4 in PDAC and suggest novel strategies for cancer therapy.
Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism , Pancreatic Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-met/metabolism , Animals , Apoptosis/physiology , Biomarkers, Tumor , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Gene Knockdown Techniques , Humans , Mice , Transcription Factor AP-1/metabolism , Xenograft Model Antitumor Assays , Pancreatic NeoplasmsABSTRACT
Pancreatic cancer (PC) is the most severe and serious deadliest cancer type worldwide. Centromeric proteins (CENPs) family are involved in centromere formation and kinetochore organization during mitosis and play an important role in cancers. Here, we analyzed all CENPs in a panel of PC tissues and non-tumor tissues by genomics profile. We identified that CENPF is significantly upregulated in PC and correlated with poor prognosis of patients. Furthermore, silencing CENPF significantly inhibited PC cell proliferation, migration and epithelial-mesenchymal transition (EMT), and caused cell cycle arrest at the G2/M phase, meanwhile, in vivo growth of pancreatic cells. Moreover, the TNF pathway and longevity regulating pathways are two potential pathways, which were regulated by CENPF. These findings investigated the clinical and functional contribution of CENPF as a novel biomarker for PC.
Subject(s)
Biomarkers, Tumor/genetics , Chromosomal Proteins, Non-Histone/genetics , Microfilament Proteins/genetics , Pancreatic Neoplasms/genetics , Animals , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Chromosomal Proteins, Non-Histone/metabolism , Epithelial-Mesenchymal Transition , Humans , Mice , Mice, Nude , Microfilament Proteins/metabolism , Network Pharmacology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Tumor Necrosis Factor-alpha/metabolism , Up-RegulationABSTRACT
We reported unique molecular features of cerebrospinal fluid (CSF) of NSCLC patients with leptomeningeal metastasis (LM), suggesting to establish CSF as a better liquid biopsy in clinical practices. We performed next-generation panel sequencing of primary tumor tissue, plasma and CSF from 131 NSCLC patients with LM, and observed high somatic copy number variations (CNV) in CSF of NSCLC patients with LM. The status of EGFR-activating mutations was highly concordant between CSF, plasma, and primary tumors. ALK translocation was detected in 8.3% of tumor tissues, but only 2.4% in CSF and 2.7% in plasma. Others such as ROS1 rearrangement, RET fusion, HER2 mutation, NTRK1 fusion, and BRAF V600E mutation were detected in 7.9% of CSF and 11.1% of tumor tissues, but only 4% in plasma. Our study has shed light on the unique genomic variations of CSF and demonstrated that CSF may represent better liquid biopsy for NSCLC patients with LM.
ABSTRACT
The S100 protein family genes play a crucial role in multiple stages of tumorigenesis and progression. Most of S100 genes are located at chromosome locus 1q21, which is a region frequently rearranged in cancers. Here, we examined the expression of the S100 family genes in paired pancreatic ductal adenocarcinoma (PDAC) samples and further validated the expression of S100A16 by immunohistochemistry staining. We found that S100A16 is significantly upregulated in clinical PDAC samples. However, its roles in PDAC are still unclear. We next demonstrated that S100A16 promotes PDAC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Knockdown of S100A16 induces PDAC cell cycle arrest in the G2/M phase and apoptosis. Furthermore, we also demonstrated that S100A16 promotes PDAC cell proliferation, migration, and invasion via AKT and ERK1/2 signaling in a fibroblast growth factor 19 (FGF19)-dependent manner. Taken together, our results reveal that S100A16 is overexpressed in PDAC and promotes PDAC progression through FGF19-mediated AKT and ERK1/2 signaling, suggesting that S100A16 may be a promising therapeutic target for PDAC. S100A16 was upregulated in PDAC and associated with prognosis of PDAC patients. S100A16 regulates apoptosis and the cell cycle of pancreatic cancer cells. S100A16 promotes the progression of pancreatic cancer by AKT-ERK1/2 signaling. S100A16 may be a promising therapeutic target for PDAC.
Subject(s)
Pancreatic Neoplasms , Proto-Oncogene Proteins c-akt , Cell Line, Tumor , Cell Movement , Cell Proliferation/genetics , Fibroblast Growth Factors , Gene Expression Regulation, Neoplastic , Humans , MAP Kinase Signaling System , Pancreatic Neoplasms/genetics , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , S100 Proteins/genetics , S100 Proteins/metabolismABSTRACT
To understand the androgen receptor (AR) in different human malignancies, we conducted a pan-cancer analysis of AR in different tumor tissues and association with patient survival and obtained AR expression data from The Cancer Genome Atlas. Pan-Cancer Analysis of AR indicated that 12 tumor types had decreased AR expression in the tumor, while glioblastoma multiforme has overexpressed AR. The survival analysis showed that high AR mRNA is associated with poor survival of stomach adenocarcinoma and low-grade glioma, but better survival of adrenocortical carcinoma, kidney renal clear cell carcinoma, acute myeloid leukemia, liver hepatocellular carcinoma, ovarian serous cystadenocarcinoma, and skin cutaneous melanoma based on AR mRNA, protein or AR-score. AR was associated with different clinical characteristics and AR correlated genes enriched in cancer-related pathways. These data indicate that AR signaling may be strongly associated with some cancer development and patients' survival, which is promising for potential treatment using antiandrogen therapies.
Subject(s)
Biomarkers, Tumor/genetics , Neoplasms/genetics , Receptors, Androgen/genetics , Biomarkers, Tumor/metabolism , Humans , Neoplasms/classification , Neoplasms/pathology , Receptors, Androgen/metabolism , Survival AnalysisABSTRACT
BACKGROUND: There is an urgent need to improve the clinical and basic research of esophageal cancer. The purpose of this study was to explore the prognostic value of tumor-infiltrating plasma cells (TIP) on overall survival (OS) of patients with esophageal squamous cell carcinoma (ESCC). METHODS: Three independent cohorts, which include 116 consecutive cases who received radical resection of ESCC in our institution (set to be discovery set), 179 cases from public GEO database (validation GEO set) and 95 cases from TCGA (validation TCGA set), with a total of 390 cases were retrospectively enrolled in this study. RESULTS: TIP was detected by immunohistochemical staining of CD138 in the paraffin-embedded specimen after surgery in the discovery set and was validated by using an established computational algorithm in the GEO and TCGA sets. Kaplan-Meier survival analysis showed high TIP was coincidently and significantly associated with favorable OS of ESCC in discovery set (p = 0.004) and validation GEO set (p = 0.002), showed a trend of better survival in validation TCGA set (p = 0.256 for 5-year OS, p = 0.034 for 15-month OS). Univariate and multivariate Cox regression analysis, together with survival analysis of the interaction between TIP and other variables, confirmed TIP to be a significant and independent prognostic factor for OS of ESCC. The incorporation of TIP into the TNM staging system could improve the accuracy of prognosis prediction for ESCC. CONCLUSION: This study revealed that high TIP in ESCC was associated with positive regulation of adaptive immunity and anti-tumor activity.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Biomarkers, Tumor/genetics , Esophageal Neoplasms/pathology , Humans , Plasma Cells/pathology , Prognosis , Retrospective StudiesABSTRACT
PURPOSE: To investigate the molecular mechanisms underlying the variable standard uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging in hepatocellular carcinoma (HCC) and whether hypoxia-induced glucose transporter expression contributes to the progression of HCC and the rate of glycolysis in HCC cells. MATERIALS AND METHODS: Sixteen HCC specimens obtained from patients who underwent pre-treatment staging with 18F-FDG PET-CT imaging were divided into high maximum SUV (SUVmax > 8) and low SUVmax (SUVmax < 5) groups and employed for whole-genome gene expression profiling using GeneChip Human Genome U133 Plus 2.0 Arrays. The relationship between SUVmax and the expression of glucose transporters 1 and 3 (GLUT1 and GLUT3) was further validated using immunohistochemical analysis. The expression of GLUT1 and GLUT3 in different HCC cells under hypoxia and normoxia conditions were monitored by quantitative reverse transcription PCR (RT-qPCR). Glycolysis and FDG uptake by HCC cells were measured using the Seahorse XF glycolysis stress test and 18F-FDG PET-CT imaging. The effect of GLUT1 and GLUT3 on glucose uptake in HCC cells was examined using the fluorescent D-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) followed by detection of fluorescence produced by the cells using flow cytometry. RESULTS: Glucose transporters are differentially expressed between samples from HCC patients with high and low SUVmax. In particular, over-expression of GLUT1 and GLUT3 in high SUVmax patients was correlated with high glucose uptake and overall survival. The expression of GLUT1 and GLUT3 was significantly induced by hypoxia in different HCC cells. High expression of GLUT1 and GLUT3 in HCC cells were correlated with high rates of glycolysis and 18F-FDG uptake. Therefore, our data suggested that hypoxia-induced glucose transporters expression could result in the variations of 18F-FDG PET-CT imaging and progression of HCC, contributing to more aggressive disease phenotypes like large tumor size, recurrence, and poor survival. CONCLUSION: Over-expression of GLUT1 and GLUT3 significantly increase glucose uptake in HCC cells. Hypoxia-induced glucose transporters expression may therefore be a contributing variable in 18F-FDG PET-CT imaging and progression in HCC.
Subject(s)
Carcinoma, Hepatocellular , Glucose Transporter Type 1/genetics , Glucose Transporter Type 3/genetics , Hypoxia , Liver Neoplasms , Carcinoma, Hepatocellular/diagnostic imaging , Fluorodeoxyglucose F18 , Humans , Liver Neoplasms/diagnostic imaging , Neoplasm Recurrence, Local , Positron Emission Tomography Computed Tomography , Positron-Emission TomographyABSTRACT
OBJECTIVE: The aim is to explore the prediction effect of 5 machine learning algorithms on peritoneal metastasis of gastric cancer. METHODS: 1080 patients with postoperative gastric cancer were divided into a training group and test group according to the ratio of 7:3. The model of peritoneal metastasis was established by using 5 machine learning (gbm(Light Gradient Boosting Machine), GradientBoosting, forest, Logistic and DecisionTree). Python pair was used to analyze the machine learning algorithm. Gbm algorithm is used to show the weight proportion of each variable to the result. RESULT: Correlation analysis showed that tumor size and depth of invasion were positively correlated with the recurrence of patients after gastric cancer surgery. The results of the gbm algorithm showed that the top 5 important factors were albumin, platelet count, depth of infiltration, preoperative hemoglobin and weight, respectively. In training group: Among the 5 algorithm models, the accuracy of GradientBoosting and gbm was the highest (0.909); the AUC values of the 5 algorithms are gbm (0.938), GradientBoosting (0.861), forest (0.796), Logistic(0.741) and DecisionTree(0.712) from high to low. In the test group: among the 5 algorithm models, the accuracy of forest, DecisionTree and gbm was the highest (0.907); AUC values ranged from high to low to gbm (0.745), GradientBoosting (0.725), forest (0.696), Logistic (0.680) and DecisionTree (0.657). CONCLUSION: Machine learning can predict the peritoneal metastasis in patients with gastric cancer.
Subject(s)
Machine Learning , Neoplasm Recurrence, Local/epidemiology , Peritoneal Neoplasms/epidemiology , Stomach Neoplasms/pathology , Aged , Female , Gastrectomy , Humans , Incidence , Logistic Models , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Peritoneal Neoplasms/secondary , ROC Curve , Retrospective Studies , Risk Assessment/methods , Stomach/pathology , Stomach/surgery , Stomach Neoplasms/surgery , Treatment OutcomeABSTRACT
OBJECTIVE: To study the safety and efficacy of magnetic resonance imaging (MRI)-compatible incubator in cranial MRI examination for neonates. METHODS: A total of 120 neonates who were hospitalized in three hospitals and needed to undergo MRI examination were randomly divided into a control group and an experimental group, with 60 neonates in each group. The neonates in the experimental group were transferred with MRI-compatible incubator and underwent cranial MRI examination inside the MRI-compatible incubator, and those in the control group were transferred using a conventional neonatal transfer incubator and then underwent MRI examination outside the incubator. The two groups were compared in terms of the primary efficacy index (total examination time), secondary efficacy indices (times of examination, MRI completion rate on the first day of use), and safety indices (incidence rate of adverse events and vital signs). RESULTS: There were no significant differences in total examination time, times of examination, and MRI completion rate on the first day of use between the two groups (P > 0.05). There were also no significant differences between the two groups in the incidence rate of adverse events and vital signs such as respiratory rate, heart rate, blood pressure, and blood oxygen saturation rate at different time points before and after examination (P > 0.05). CONCLUSIONS: The use of MRI-compatible incubator does not significantly shorten the examination time of cranial MRI, but it does provide a relatively stable environment for examination with acceptable safety. There is a need for further studies with a larger population.
Subject(s)
Incubators, Infant , Magnetic Resonance Imaging/instrumentation , Skull/diagnostic imaging , Humans , Infant, Newborn , Prospective StudiesABSTRACT
Digestive malignancies are the leading cause of mortality among all neoplasms, contributing to estimated 3 million deaths in 2012 worldwide. The mortality rate hassurpassed lung cancer and prostate cancer in recent years. The transcription factor Forkhead Box O1 (FOXO1) is a key member of Forkhead Box family, regulating diverse cellular functions during tumor initiation, progression and metastasis. In this review, we focus on recent studies investigating the antineoplastic role of FOXO1 in digestive malignancy. This review aims to serve as a guide for further research and implicate FOXO1 as a potent therapeutic target in digestive malignancy.
Subject(s)
Carcinogenesis/genetics , Forkhead Box Protein O1/genetics , Gastrointestinal Neoplasms/genetics , Liver Neoplasms/genetics , Disease Progression , Gastrointestinal Neoplasms/pathology , Humans , Liver Neoplasms/pathology , Neoplasm MetastasisABSTRACT
Multidrug resistance is a major cause of failure in the clinical cancer therapy, in which the overexpression of P-glycoprotein (P-gp) plays a crucial role. Herein, we fabricate a theranostic nanoprobe with the function of simultaneous detection and inhibition of P-gp to diagnose and combat multidrug-resistant cancer in vitro and in vivo. For constructing the nanoprobe, elacridar modified quantum dots (QDs-Ela), acting as a gatekeeper, are grafted onto the doxorubicin (DOX) loaded, folic acid (FA) decorated mesoporous silica nanoparticles (MSNs). Upon targeted uptake by multidrug-resistant cancer cells, Bel-7402/ADR are used as a model, the acidic environment results in QDs-Ela removal from the nanoprobe, and subsequent DOX release. The removed QDs-Ela could specifically combine with P-gp in the cancer cell membrane and inhibit their active sites, which prevents the efflux of intracellular DOX and increases the retention of DOX. Another way, the fluorescence intensity of the binding QDs-Ela quantifies the P-gp expression level. Subsequently, in vitro and in vivo experiments both demonstrate the enhanced multidrug-resistant cancer therapy efficacy, i.e., nanoprobe has 10 times better curative effect than free DOX. In addition, due to the conjugation of FA, the nanoprobe exhibits a selective cell targeting ability to Bel-7402/ADR cells. This nanoplatform paves a new avenue for the accurate treatment of multidrug-resistant cancers.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , Antibiotics, Antineoplastic/pharmacology , Doxorubicin/pharmacology , Liver Neoplasms/drug therapy , Nanoparticles/chemistry , Theranostic Nanomedicine , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Animals , Antibiotics, Antineoplastic/chemistry , Cell Line, Tumor , Doxorubicin/chemistry , Drug Carriers/chemistry , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms, Experimental/diagnosis , Liver Neoplasms, Experimental/drug therapy , Mice , Mice, Nude , Particle Size , Quantum Dots/chemistry , Surface PropertiesABSTRACT
INTRODUCTION: Diabetes and cancer are among the most frequent causes of death worldwide. Recent epidemiological findings have indicated a link between diabetes and cancer in several organs, particularly the liver. A number of epidemiological studies have demonstrated that diabetes is an established independent risk factor for hepatocellular carcinoma (HCC). However, the metabolites connecting diabetes and HCC remains less well understood. OBJECTIVES: The study aimed to identify clinical and metabolomics differences of HCC from patients with/without diabetes using comprehensive global metabolomics analysis. METHODS: Metabolite profiling was conducted with the Metabolon platform for 120 human diabetes/non-diabetes HCC tumor/normal tissues. Standard statistical analyses were performed using the Partek Genomics Suite on log-transformed data. Principal component analysis (PCA) was conducted using all and dysregulated metabolites. RESULTS: We identified a group of metabolites that are differentially expressed in the tumor tissues of diabetes HCC compared to non-diabetes HCC patients. Meanwhile, we also identified a group of metabolites that are differentially expressed in the matched normal liver tissues of diabetes HCC compared to non-diabetes HCC patients. Some metabolites are consistently dysregulated in the tumor or matched normal tissues of HCC with or without diabetes. However, some metabolites, including 2-hydroxystearate, were only overexpressed in the tumor tissues of HCC with diabetes and associated with the glucose level. CONCLUSION: Metabolic profiling identifies distinct dysregulated metabolites in HCC patients with/without diabetes.