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1.
J Affect Disord ; 354: 752-764, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38537753

ABSTRACT

BACKGROUND: Depression affects a significant portion of the global population and has emerged as one of the most debilitating conditions worldwide. Recent studies have explored the relationship between depression and the microbiota of the intestine, revealing potential avenues for effective treatment. METHODS: To evaluate the potential alleviation of depression symptoms, we employed a depression C57BL/6 mice model induced by chronic unpredictable mild stress (CUMS). We administered Lactiplantibacillus plantarum JYLP-326 and conducted various animal behavior tests, including the open-field test (OFT), sucrose preference test (SPT), and tail-suspension test (TST). Additionally, we conducted immunohistochemistry staining and analyzed the hippocampal and colon parts of the mice. RESULTS: The results of the behavior tests indicated that L. plantarum JYLP-326 alleviated spontaneous behavior associated with depression. Moreover, the treatment led to significant improvements in GFAP and Iba1, suggesting its potential neuroprotective effects. Analysis of the hippocampal region indicated that L. plantarum JYLP-326 administration upregulated p-TPH2, TPH2, and 5-HT1AR, while downregulating the expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. In the colon, the treatment inhibited the TLR4-MyD88-NF-κB pathway and increased the levels of occludin and ZO-1, indicating improved intestinal barrier function. Additionally, the probiotic demonstrated a regulatory effect on the HMGB1-RAGE-TLR4 signaling pathway. CONCLUSIONS: Our findings demonstrate that L. plantarum JYLP-326 exhibits significant antidepressant-like effects in mice, suggesting its potential as a therapeutic approach for depression through the modulation of gut microbiota. However, further investigations and clinical trials are required to validate its safety and efficacy for human use.


Subject(s)
Depression , Gastrointestinal Microbiome , Humans , Mice , Animals , Depression/drug therapy , Depression/etiology , Toll-Like Receptor 4/metabolism , Dysbiosis/drug therapy , Dysbiosis/metabolism , Mice, Inbred C57BL , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Antidepressive Agents/metabolism , Hippocampus/metabolism , Stress, Psychological/complications , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Disease Models, Animal
2.
BMC Microbiol ; 24(1): 8, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38172689

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignant malignancy affecting the gastrointestinal tract that is usually treated clinically with chemotherapeutic agents, whereas chemotherapeutic agents can cause severe gastrointestinal toxicity, which brings great pain to patients. Therefore, finding effective adjuvant agents for chemotherapy is crucial. METHODS: In this study, a CRC mouse model was successfully constructed using AOM/DSS, and the treatment was carried out by probiotic Bifidobacterium longum SX-1326 (B. longum SX-1326) in combination with irinotecan. Combining with various techniques of modern biomedical research, such as Hematoxylin and Eosin (H&E), Immunohistochemistry (IHC), Western blotting and 16S rDNA sequencing, we intend to elucidate the effect and mechanism of B. longum SX-1326 in improving the anticancer efficacy and reducing the side effects on the different levels of molecules, animals, and bacteria. RESULTS: Our results showed that B. longum SX-1326 enhanced the expression of Cleaved Caspase-3 (M vs. U = p < 0.01) and down-regulated the expression level of B-cell lymphoma-2 (Bcl-2) through up-regulation of the p53 signaling pathway in CRC mice, which resulted in an adjuvant effect on the treatment of CRC with irinotecan. Moreover, B. longum SX-1326 was also able to regulate the gut-brain-axis (GBA) by restoring damaged enterochromaffin cells, reducing the release of 5-hydroxytryptamine (5-HT) in brain tissue (I vs. U = 89.26 vs. 75.03, p < 0.05), and further alleviating the adverse effects of nausea and vomiting. In addition, B. longum SX-1326 reversed dysbiosis in CRC model mice by increasing the levels of Dehalobacterium, Ruminnococcus, and Mucispirillum. And further alleviated colorectal inflammation by downregulating the TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: In conclusion, our work reveals that B. longum SX-1326 has a favorable effect in adjuvant irinotecan for CRC and amelioration of post-chemotherapy side effects, and also provides the theoretical basis and data for finding a safe and efficient chemotherapeutic adjuvant.


Subject(s)
Bifidobacterium longum , Gastrointestinal Microbiome , Animals , Humans , Mice , Brain-Gut Axis , Irinotecan/metabolism , Signal Transduction , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/pharmacology
3.
Front Immunol ; 14: 1220165, 2023.
Article in English | MEDLINE | ID: mdl-37426650

ABSTRACT

Nausea and vomiting (CINV) are distressful and widespread side effects of chemotherapy, and additional efficient regimens to alleviate CINV are urgently needed. In the present study, colorectal cancer (CRC) mice model induced by Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) was employed to evaluate the cancer suppression and CINV amelioration effect of the combination of thalidomide (THD) and Clostridium butyricum. Our results suggested that the combination of THD and C. butyricum abundantly enhanced the anticancer effect of cisplatin via activating the caspase-3 apoptosis pathway, and also ameliorated CINV via inhibiting the neurotransmitter (e.g., 5-HT and tachykinin 1) and its receptor (e.g., 5-HT3R and NK-1R) in brain and colon. Additionally, the combination of THD and C. butyricum reversed the gut dysbacteriosis in CRC mice by increasing the abundance of Clostridium, Lactobacillus, Bifidobacterium, and Ruminococcus at the genus level, and also led to increased expression of occludin and Trek1 in the colon, while decreased expression of TLR4, MyD88, NF-κB, and HDAC1, as well as the mRNA level of IL-6, IL-1ß, and TNF-α. In all, these results suggest that the combination of THD and C. butyricum had good efficacy in enhancing cancer treatments and ameliorating CINV, which thus provides a more effective strategy for the treatment of CRC.


Subject(s)
Antineoplastic Agents , Clostridium butyricum , Gastrointestinal Microbiome , Mice , Animals , Clostridium butyricum/physiology , Thalidomide/pharmacology , Thalidomide/therapeutic use , Serotonin , Nausea , Vomiting , Antineoplastic Agents/pharmacology
4.
Int J Surg ; 109(9): 2624-2630, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37288562

ABSTRACT

BACKGROUND: Postoperative intra-abdominal infection (PIAI) is one of the most serious complications of abdominal surgery, increasing the risk of postoperative morbidity and mortality and prolonging hospital stay. Rapid diagnosis of PIAI is of great clinical value. Unfortunately, the current diagnostic methods of PIAI are not fast and accurate enough. METHODS: The authors performed an exploratory study to establish a rapid and accurate diagnostic method of PIAI. The authors explored the turnaround time and accuracy of metagenomic next-generation sequencing (mNGS) in diagnosing PIAI. Patients who underwent elective abdominal surgery and routine abdominal drainage with suspected PIAI were enroled in the study. The fresh midstream abdominal drainage fluid was collected for mNGS and culturing. RESULTS: The authors found that the median sample-to-answer turnaround time of mNGS was dramatically decreased than that of culture-based methods (<24 h vs. 59.5-111 h). The detection coverage of mNGS was much broader than culture-based methods. The authors found 26 species from 15 genera could only be detected by mNGS. The accuracy of mNGS was not inferior to culture-based methods in the 8 most common pathogens detected from abdominal drainage fluid (sensitivity ranged from 75 to 100%, specificity ranged from 83.3 to 100%, and kappa values were higher than 0.5). Moreover, the composition of the microbial spectrum established by mNGS varied between upper and lower gastrointestinal surgery, enhancing the understanding of PIAI pathogenesis. CONCLUSION: This study preliminarily revealed the clinical value of mNGS in the rapid diagnosis of PIAI and provided a rationale for further research.


Subject(s)
Abdominal Cavity , Intraabdominal Infections , Humans , Intraabdominal Infections/diagnosis , Drainage , Postoperative Complications/diagnosis , Elective Surgical Procedures , Sensitivity and Specificity
5.
Healthcare (Basel) ; 11(9)2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37174758

ABSTRACT

Topspin is one of the most attacking strokes in table tennis, and topspin forehand loop is an effective way to score. The aim of this study was to investigate the kinematics of the lower extremities in topspin forehand loop between different levels via OpenSim Musculoskeletal Modelling. Ten elite athletes (NL1) and ten medium athletes (NL2) performed the topspin forehand loop without muscle and joint injuries. An eight-camera Vicon motion capture system was used to measure the kinematics data. During the topspin forehand loop, the forward phase (FP) and the entire phase (EP) of the NL1 were significantly shorter than that of the NL2. In the sagittal plane, NL1 significantly had greater hip and ankle flexion and extension at range of motion (ROM) but less hip flexion and knee flexion at FP and less ankle flexion at BP than NL2. In the frontal plane, NL1 displayed less ROM in the hip joint and significantly less hip abduction ROM at the backward phase (BP). In the transverse plane, NL1 had a significantly greater ROM in the hip joint and displayed significantly less hip ROM at the BP. The level differences presented in this study could help table tennis athletes to improve performance and coaches to develop technical training.

6.
Front Immunol ; 14: 1158137, 2023.
Article in English | MEDLINE | ID: mdl-37033942

ABSTRACT

Introduction: Test anxiety is a common issue among college students, which can affect their physical and psychological health. However, effective interventions or therapeutic strategies are still lacking. This study aims to evaluate the potential effects of Lactobacillus plantarum JYLP-326 on test anxious college students. Methods: Sixty anxious students were enrolled and randomly allocated to the placebo group and the probiotic group. Both groups were instructed to take placebo and JYLP-326 products twice per day for three weeks, respectively. Thirty unanxious students with no treatments were assigned to a regular control group. The anxiety, depression, and insomnia questionnaires were used to measure students' mental states at the baseline and the end of this study. 16S rRNA sequencing and untargeted metabolomics were performed to analyze the changes in the gut microbiota and fecal metabolism. Results: The questionnaire results suggested that JYLP-326 administration could relieve the symptoms of anxiety, depression, and insomnia in test anxious students. The gut microbiomes of the placebo group showed a significantly greater diversity index than the control group (p < 0.05). An increased abundance of Bacteroides and Roseburia at the genus level was observed in the placebo group, and the relative abundance of Prevotella and Bifidobacterium decreased. Whereas, JYLP-326 administration could partly restore the disturbed gut microbiota. Additionally, test anxiety was correlated with disordered fecal metabolomics such as a higher Ethyl sulfate and a lower Cyclohexylamine, which could be reversed after taking JYLP-326. Furthermore, the changed microbiota and fecal metabolites were significantly associated with anxiety-related symptoms. Conclusion: The results indicate that the intervention of L. plantarum JYLP-326 could be an effective strategy to alleviate anxiety, depression, and insomnia in test anxious college students. The potential mechanism underlying this effect could be related to the regulation of gut microbiota and fecal metabolites.


Subject(s)
Gastrointestinal Microbiome , Lactobacillus plantarum , Mental Disorders , Probiotics , Test Anxiety , Humans , Anxiety/diagnosis , Anxiety/therapy , Depression/diagnosis , Depression/therapy , Gastrointestinal Microbiome/genetics , Gastrointestinal Microbiome/physiology , Lactobacillus plantarum/genetics , Lactobacillus plantarum/metabolism , RNA, Ribosomal, 16S/genetics , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep Initiation and Maintenance Disorders/therapy , Test Anxiety/psychology , Test Anxiety/therapy , Probiotics/therapeutic use , Mental Disorders/microbiology , Mental Disorders/therapy , Surveys and Questionnaires , Feces/chemistry , Feces/microbiology
7.
Bioengineering (Basel) ; 9(6)2022 Jun 04.
Article in English | MEDLINE | ID: mdl-35735489

ABSTRACT

With the progress and innovation of table tennis technology, individualized training programs may deserve special attention. This study aimed to analyze elite table tennis athletes in chasse-step, with a particular focus on sex-based biomechanical differences. A total of 36 (18 males and 18 females) elite table tennis athletes performed topspin forehand of chasse-step. Angles and moments of hip, knee, and ankle joints were calculated using OpenSim (v4.2) with marker trajectories and ground reaction forces were measured via Vicon motion capture system and AMTI in-ground force platform. Males had greater hip and knee flexion angles during the entire motion phase and greater internal rotation angles of the hip during the forward swing phase. The joint stiffness of knee in males was greater than females in the frontal plane. Females in the forward swing phase showed greater hip flexion, adduction, and internal rotation moments than males. It was suggested that the difference may be due to the limitation of anatomical structures in sexes. Male table tennis athletes should strengthen lower extremity muscle groups to improve performance, while female table tennis athletes should focus on hip joint groups to avoid injury. The sex differences presented in this study could help coaches and athletes to develop individualized training programs for table tennis.

8.
Dis Markers ; 2022: 8762936, 2022.
Article in English | MEDLINE | ID: mdl-35634440

ABSTRACT

Airborne diseases are transmitted by pathogens in the air. The complex microbial environment in wards is usually considered a major cause of nosocomial infection of various diseases which greatly influences the health of patients with chronic diseases, whereas the illuminant of wards impacts on the microbe especially the disease marker strain is seldom studied. In the present study, high-throughput sequencing was used to study the effect of yellow light on airborne microbial composition, and changes of transcriptome of marker strains Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which were isolated from wards, were further studied after the irradiation by yellow light. High-throughput sequencing results indicated that yellow light significantly decreased α-diversity. The relative abundance of Firmicutes at the phylum level, and Clostridium sensu stricto 1, Paraclostridium at the genus level were significantly reduced. RNA sequencing results declared that yellow light significantly downregulated the genes associated with flagella, heme transport system and carbohydrate, amino acid metabolism in E. coli, and the genes related to arginine biosynthesis and the biosynthesis of isoleucine, leucine, and valine in S. aureus. Meanwhile, yellow light significantly upregulated the genes relating to porphyrin metabolism in P. aeruginosa. In conclusion, our work reveals the impacts of yellow light on the microbe in wards, pointing out the application value of yellow light in the prevention of infectious diseases in clinical practice.


Subject(s)
Staphylococcus aureus , Transcriptome , Escherichia coli/genetics , Humans , Sequence Analysis, RNA , Staphylococcus aureus/genetics
9.
Breast Cancer Res ; 23(1): 12, 2021 01 25.
Article in English | MEDLINE | ID: mdl-33494814

ABSTRACT

BACKGROUND: MicroRNAs have been reported to participate in tumorigenesis, treatment resistance, and tumor metastasis. Novel microRNAs need to be identified and investigated to guide the clinical prognosis or therapy for breast cancer. METHOD: The copy number variations (CNVs) of MIR3613 from Cancer Genome Atlas (TCGA) or Cancer Cell Line Encyclopedia (CCLE) were analyzed, and its correlation with breast cancer subtypes or prognosis was investigated. The expression level of miR-3613-3p in tumor tissues or serum of breast cancer patients was detected using in situ hybridization and qPCR. Gain-of-function studies were performed to determine the regulatory role of miR-3613-3p on proliferation, apoptosis, and tumor sphere formation of human breast cancer cells MDA-MB-231 or MCF-7. The effects of miR-3613-3p on tumor growth or metastasis in an immunocompromised mouse model of MDA-MB-231-luciferase were explored by intratumor injection of miR-3613-3p analogue. The target genes, interactive lncRNAs, and related signaling pathways of miR-3613-3p were identified by bioinformatic prediction and 3'-UTR assays. RESULTS: We found that MIR3613 was frequently deleted in breast cancer genome and its deletion was correlated with the molecular typing, and an unfavorable prognosis in estrogen receptor-positive patients. MiR-3613-3p level was also dramatically lower in tumor tissues or serum of breast cancer patients. Gain-of-function studies revealed that miR-3613-3p could suppress proliferation and sphere formation and promote apoptosis in vitro and impeded tumor growth and metastasis in vivo. Additionally, miR-3613-3p might regulate cell cycle by targeting SMS, PAFAH1B2, or PDK3 to restrain tumor progression. CONCLUSION: Our findings indicate a suppressive role of miR-3613-3p in breast cancer progression, which may provide an innovative marker or treatment for breast cancer patients.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , MicroRNAs/genetics , RNA Interference , 3' Untranslated Regions , Cell Cycle/genetics , Cell Line, Tumor , Cell Proliferation , Computational Biology/methods , Databases, Genetic , Female , Gene Expression Profiling , Humans , Neoplastic Stem Cells/metabolism , Signal Transduction
10.
Front Cell Dev Biol ; 9: 709669, 2021.
Article in English | MEDLINE | ID: mdl-35087823

ABSTRACT

Background: Pancreatic cancer (PC) is a highly aggressive gastrointestinal tumor and has a poor prognosis. Evaluating the prognosis validly is urgent for PC patients. In this study, we utilized the RNA-sequencing (RNA-seq) profiles and DNA methylation expression data comprehensively to develop and validate a prognostic signature in patients with PC. Methods: The integrated analysis of RNA-seq, DNA methylation expression profiles, and relevant clinical information was performed to select four DNA methylation-driven genes. Then, a prognostic signature was established by the univariate, multivariate Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses in The Cancer Genome Atlas (TCGA) dataset. GSE62452 cohort was utilized for external validation. Finally, a nomogram model was set up and evaluated by calibration curves. Results: Nine DNA methylation-driven genes that were related to overall survival (OS) were identified. After multivariate Cox and LASSO regression analyses, four of these genes (RIC3, MBOAT2, SEZ6L, and OAS2) were selected to establish the predictive signature. The PC patients were stratified into two groups according to the median risk score, of which the low-risk group displayed a prominently favorable OS compared with the high-risk group, whether in the training (p < 0.001) or validation (p < 0.01) cohort. Then, the univariate and multivariate Cox regression analyses showed that age, grade, risk score, and the number of positive lymph nodes were significantly associated with OS in PC patients. Therefore, we used these clinical variables to construct a nomogram; and its performance in predicting the 1-, 2-, and 3-year OS of patients with PC was assessed via calibration curves. Conclusion: A prognostic risk score signature was built with the four alternative DNA methylation-driven genes. Furthermore, in combination with the risk score, age, grade, and the number of positive lymph nodes, a nomogram was established for conveniently predicting the individualized prognosis of PC patients.

11.
Ther Adv Med Oncol ; 12: 1758835920940946, 2020.
Article in English | MEDLINE | ID: mdl-32728395

ABSTRACT

Serum and glucocorticoid-inducible kinase 1 (SGK1) is an AGC kinase that has been reported to be involved in a variety of physiological and pathological processes. Recent evidence has accumulated that SGK1 acts as an essential Akt-independent mediator of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway in cancer. SGK1 is overexpressed in several tumors, including prostate cancer, colorectal carcinoma, glioblastoma, breast cancer, and endometrial cancer. The functions of SGK1 include regulating tumor growth, survival, metastasis, autophagy, immunoregulation, calcium (Ca2+) signaling, cancer stem cells, cell cycle, and therapeutic resistance. In this review, we introduce the pleiotropic role of SGK1 in the development and progression of tumors, summarize its downstream targets, and integrate the knowledge provided by preclinical studies that the prospect of SGK1 inhibition as a potential therapeutic approach.

12.
Clin Endocrinol (Oxf) ; 92(4): 295-302, 2020 04.
Article in English | MEDLINE | ID: mdl-31945198

ABSTRACT

BACKGROUND AND OBJECTIVE: Parathyroid carcinoma (PC) is a rare malignant neoplasm with a relatively poor prognosis. The loss of parafibromin expression or the presence of CDC73 mutation has been found to be remarkably associated with malignancy in parathyroid tumours. However, the prognostic role of them in PC has not yet been shown due to sampling limitations. We conducted a systematic review and meta-analysis based on individual patient data to clarify the performance of parafibromin immunohistochemical staining and CDC73 gene sequencing in predicting outcomes for patients PC. METHODS: Published studies from PubMed/MEDLINE, EMBASE, Cochrane and Scopus Databases were searched using the terms 'parafibromin', 'CDC73', 'HRPT2' and 'parathyroid' to identify eligible studies. From the included studies, the survival data of patients with PC were extracted, and a Cox proportional hazards model was used to assess hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 193 patients from 9 studies were included in this survival analysis. Negative immunohistochemical staining of parafibromin was shown to be a risk factor for recurrence/metastasis (HR 2.73, P = .002) and death (HR 2.54, P = .004). Patient age ≥ 50 years was significantly related to lower OS (HR 2.37, P = .004) but not to DFS. CDC73 mutation was not statistically related to DFS or OS. CONCLUSIONS: Negative parafibromin staining indicated a higher risk of recurrence/metastasis and mortality. The immunohistochemical staining of parafibromin seems to be more promising in predicting outcomes for patients with PC than the sequencing of CDC73.


Subject(s)
Parathyroid Neoplasms , Humans , Infant, Newborn , Mutation , Neoplasm Recurrence, Local , Parathyroid Neoplasms/genetics , Prognosis , Staining and Labeling , Tumor Suppressor Proteins/genetics
13.
Clin Transl Med ; 8(1): 32, 2019 Dec 23.
Article in English | MEDLINE | ID: mdl-31873828

ABSTRACT

The polycistronic miR-17-92 cluster is instrumental in physiological processes commonly dysregulated in cancer, such as proliferation, the cell cycle, apoptosis, and differentiation. MicroRNA-18a (miR-18a) is one of the most conserved and multifunctional miRNAs in the cluster and is frequently overexpressed in malignant tumors. Altered miR-18a expression has been found in various physiological and pathological processes, including cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), tumorigenesis, cancer invasion and metastasis. In this review, we summarized the molecular basis and regulatory targets of miR-18a in cancer development. Interestingly, miR-18a has a dual functional role in either promoting or inhibiting oncogenesis in different human cancers. The differential miRNA expression in cancers of the same organ at different stages or of various subtypes suggests that this dual function of miR-18a is independent of cancer type and may be attributed to the fundamental differences in tumorigenic mechanisms. Finally, we summarized the current clinical use of miR-18a and discussed its potential uses in cancer therapy.

14.
Eur J Radiol ; 121: 108714, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31704598

ABSTRACT

PURPOSE: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been proven to be a prognostic and predictive biomarker for lower grade glioma (LGG). This study aims to build a radiomics model to preoperatively predict the MGMT promoter methylation status in LGG. METHOD: 122 pathology-confirmed LGG patients were retrospectively reviewed, with 87 local patients as the training dataset, and 35 from The Cancer Imaging Archive as independent validation. A total of 1702 radiomics features were extracted from three-dimensional contrast-enhanced T1 (3D-CE-T1)-weighted and T2-weighted MRI images, including 14 shape, 18 first order, 75 texture, and 744 wavelet features respectively. The radiomics features were selected with the least absolute shrinkage and selection operator algorithm, and prediction models were constructed with multiple classifiers. Models were evaluated using receiver operating characteristic (ROC). RESULTS: Five radiomics prediction models, namely, 3D-CE-T1-weighted single radiomics model, T2-weighted single radiomics model, fusion radiomics model, linear combination radiomics model, and clinical integrated model, were built. The fusion radiomics model, which constructed from the concatenation of both series, displayed the best performance, with an accuracy of 0.849 and an area under the curve (AUC) of 0.970 (0.939-1.000) in the training dataset, and an accuracy of 0.886 and an AUC of 0.898 (0.786-1.000) in the validation dataset. Linear combination of single radiomics models and integration of clinical factors did not improve. CONCLUSIONS: Conventional MRI radiomics models are reliable for predicting the MGMT promoter methylation status in LGG patients. The fusion of radiomics features from different series may increase the prediction performance.


Subject(s)
Brain Neoplasms/diagnostic imaging , Brain Neoplasms/metabolism , DNA Modification Methylases/metabolism , DNA Repair Enzymes/metabolism , Glioma/diagnostic imaging , Glioma/metabolism , Magnetic Resonance Imaging/methods , Tumor Suppressor Proteins/metabolism , Adult , Area Under Curve , Brain/diagnostic imaging , Brain/metabolism , Brain Neoplasms/genetics , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Female , Glioma/genetics , Humans , Image Processing, Computer-Assisted/methods , Male , Methylation , Middle Aged , ROC Curve , Reproducibility of Results , Retrospective Studies , Tumor Suppressor Proteins/genetics
15.
Neuroimage Clin ; 23: 101912, 2019.
Article in English | MEDLINE | ID: mdl-31491820

ABSTRACT

The differential diagnosis of primary central nervous system lymphoma from glioblastoma multiforme (GBM) is essential due to the difference in treatment strategies. This study retrospectively reviewed 77 patients (24 with lymphoma and 53 with GBM) to identify the stable and distinguishable characteristics of lymphoma and GBM in 18F-fluorodeocxyglucose (FDG) positron emission tomography (PET) images using a radiomics approach. Three groups of maps, namely, a standardized uptake value (SUV) map, an SUV map calibrated with the normal contralateral cortex (ncc) activity (SUV/ncc map), and an SUV map calibrated with the normal brain mean (nbm) activity (SUV/nbm map), were generated, and a total of 107 radiomics features were extracted from each SUV map. The margins of the ROI were adjusted to assess the stability of the features, and the area under the curve (AUC) of the receiver operating characteristic curve of each feature was compared with the SUVmax to evaluate the distinguishability of the features. Nighty-five radiomics features from the SUV map were significantly different between lymphoma and GBM, 46 features were numeric stable after marginal adjustment, and 31 features displayed better performance than SUVmax. Features extracted from the SUV map demonstrated higher AUCs than features from the further calibrated maps. Tumors with solid metabolic patterns were also separately evaluated and revealed similar results. Thirteen radiomics features that were stable and distinguishable than SUVmax in every circumstance were selected to distinguish lymphoma from glioblastoma, and they suggested that lymphoma has a higher SUV in most interval segments and is more mathematically heterogeneous than GBM. This study suggested that 18F-FDG-PET-based radiomics is a reliable noninvasive method to distinguish lymphoma and GBM.


Subject(s)
Brain Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18 , Glioblastoma/diagnostic imaging , Lymphoma/diagnostic imaging , Machine Learning , Neuroimaging/methods , Positron-Emission Tomography/methods , Radiopharmaceuticals , Aged , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Neuroimaging/standards , Positron-Emission Tomography/standards , Retrospective Studies
16.
Oncogene ; 38(23): 4527-4539, 2019 06.
Article in English | MEDLINE | ID: mdl-30742065

ABSTRACT

The altered metabolism and acidic microenvironment plays an important role in promoting tumor malignant characteristics. A small population of cancer stem cells (CSCs) were considered as a therapy target to reserve tumor relapse, resistance, and metastasis. However, the molecular mechanism that regulates CSCs metabolism remains poorly understood. In this study, we demonstrate a fundamental role of stemness gene LIN28B in maintaining CSCs glycolysis metabolism. Using LIN28B-expressing cancer cell lines, we found that the rate of extracellular acidification, glucose uptake, and lactate secretion are all suppressed by LIN28B knockdown in vitro and in vivo. Importantly, metabolic analyses reveal that CSCs have enhanced aerobic glycolysis metabolic characteristics and the glycolytic product lactate further promotes cancer associated stemness properties. LIN28B silencing suppresses MYC expression that further increases miR-34a-5p level. Furthermore, the glycolysis metabolism of human breast cancer cell line MDA-MB-231 is suppressed by either MYC siRNA or miR-34a-5p mimic. Clinically, high MYC and low miR-34a-5p level are correlated with high LIN28B expression and poor prognosis in human breast cancer patients. Notably, blocking LIN28B/MYC/miR-34a-5p signaling pathway by LIN28B-specific inhibitor causes dramatic inhibition of tumor growth and metastasis in immunodeficient orthotopic mouse models of human breast cancer cell MDA-MB-231. Taken together, our findings offer a preclinical investigation of targeting LIN28B to suppress CSCs glycolysis metabolism and tumor progression that may improve the therapeutic benefit for cancer patients.


Subject(s)
Gene Expression Regulation, Neoplastic , Glucose/metabolism , Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , RNA-Binding Proteins/metabolism , Animals , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Proliferation , Disease Progression , Female , Glycolysis , Humans , Hydrogen-Ion Concentration , Mice , Mice, Inbred NOD , Mice, SCID , MicroRNAs/metabolism , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Transplantation , Prognosis , RNA, Small Interfering/metabolism , Recurrence , Signal Transduction , Tumor Microenvironment
17.
Neuroimage Clin ; 20: 51-60, 2018.
Article in English | MEDLINE | ID: mdl-30069427

ABSTRACT

Antiangiogenic therapy is a universal approach to the treatment of malignant gliomas but fails to prolong the overall survival of newly diagnosed or recurrent glioblastoma patients. Imaging biomarkers are quantitative imaging parameters capable of objectively describing biological processes, pathological changes and treatment responses in some situations and have been utilized for outcome predictions of malignant gliomas in anti-angiogenic therapy. Advanced magnetic resonance imaging techniques (including perfusion-weighted imaging and diffusion-weighted imaging), positron emission computed tomography and magnetic resonance spectroscopy are imaging techniques that can be used to acquire imaging biomarkers, including the relative cerebral blood volume (rCBV), Ktrans, and the apparent diffusion coefficient (ADC). Imaging indicators for a better prognosis when treating malignant gliomas with antiangiogenic therapy include the following: a lower pre- or post-treatment rCBV, less change in rCBV during treatment, a lower pre-treatment Ktrans, a higher vascular normalization index during treatment, less change in arterio-venous overlap during treatment, lower pre-treatment ADC values for the lower peak, smaller ADC volume changes during treatment, and metabolic changes in glucose and phenylalanine. The investigation and utilization of these imaging markers may confront challenges, but may also promote further development of anti-angiogenic therapy. Despite considerable evidence, future prospective studies are critically needed to consolidate the current data and identify novel biomarkers.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Biomarkers, Tumor , Brain Neoplasms/diagnostic imaging , Cerebral Blood Volume/physiology , Diffusion Magnetic Resonance Imaging/methods , Glioma/diagnostic imaging , Angiogenesis Inhibitors/pharmacology , Biomarkers, Tumor/metabolism , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Clinical Trials as Topic/methods , Glioma/drug therapy , Glioma/metabolism , Humans
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