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1.
Cancer Immunol Immunother ; 69(7): 1375-1387, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32078016

ABSTRACT

Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3-13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4+ and/or CD8+ T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4+ and CD8+ T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.Trial registration ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).


Subject(s)
Antigens, Neoplasm/immunology , Cancer Vaccines/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Dendritic Cells/immunology , Glioblastoma/therapy , Lung Neoplasms/therapy , Precision Medicine , Adolescent , Adult , Aged , Biomarkers, Tumor/genetics , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/immunology , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Glioblastoma/immunology , Glioblastoma/pathology , Humans , Immunization , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Survival Rate
2.
Int J Mol Sci ; 20(10)2019 May 25.
Article in English | MEDLINE | ID: mdl-31130605

ABSTRACT

An understanding of the interaction between the antibody and its targeted antigen and knowing of the epitopes are critical for the development of monoclonal antibody drugs. Complement factor H (CFH) is implied to play a role in tumor growth and metastasis. An autoantibody to CHF is associated with anti-tumor cell activity. The interaction of a human monoclonal antibody Ab42 that was isolated from a cancer patient with CFH polypeptide (pCFH) antigen was analyzed by molecular docking, molecular dynamics (MD) simulation, free energy calculation, and computational alanine scanning (CAS). Experimental alanine scanning (EAS) was then carried out to verify the results of the theoretical calculation. Our results demonstrated that the Ab42 antibody interacts with pCFH by hydrogen bonds through the Tyr315, Ser100, Gly33, and Tyr53 residues on the complementarity-determining regions (CDRs), respectively, with the amino acid residues of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448 on the pCFH antigen. In conclusion, this study has explored the mechanism of interaction between Ab42 antibody and its targeted antigen by both theoretical and experimental analysis. Our results have important theoretical significance for the design and development of relevant antibody drugs.


Subject(s)
Antibodies, Monoclonal/immunology , Peptides/immunology , Antibodies, Monoclonal/chemistry , Antigen-Antibody Reactions , Autoantibodies/chemistry , Autoantibodies/immunology , Complement Factor H/chemistry , Complement Factor H/immunology , Complementarity Determining Regions/chemistry , Complementarity Determining Regions/immunology , Epitopes/chemistry , Epitopes/immunology , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Neoplasms/immunology , Peptides/chemistry , Protein Conformation
3.
Phys Rev Lett ; 116(20): 205003, 2016 May 20.
Article in English | MEDLINE | ID: mdl-27258873

ABSTRACT

Coherent transition radiation in the terahertz (THz) region with energies of sub-mJ/pulse has been demonstrated by relativistic laser-driven electron beams crossing the solid-vacuum boundary. Targets including mass-limited foils and layered metal-plastic targets are used to verify the radiation mechanism and characterize the radiation properties. Observations of THz emissions as a function of target parameters agree well with the formation-zone and diffraction model of transition radiation. Particle-in-cell simulations also well reproduce the observed characteristics of THz emissions. The present THz transition radiation enables not only a potential tabletop brilliant THz source, but also a novel noninvasive diagnostic for fast electron generation and transport in laser-plasma interactions.

4.
Int J Biol Macromol ; 268(Pt 2): 131910, 2024 May.
Article in English | MEDLINE | ID: mdl-38679267

ABSTRACT

In this study, polysaccharides (RRTPs) were extracted from Rosa roxburghii Tratt pomace by hot water or ultrasound (US)-assisted extraction. The structural properties and potential prebiotic functions of RRTPs were investigated. Structural characterization was conducted through HPAEC, HPGPC, GC-MS, FT-IR and SEM. Chemical composition analysis revealed that RRTPs extracted by hot water (RRTP-HW) or US with shorter (RRTP-US-S) or longer duration (RRTP-US-L) all consisted of galacturonic acid, galactose, glucose, arabinose, rhamnose and glucuronic acid in various molar ratio. US extraction caused notable reduction in molecular weight of RRTPs but no significant changes in primary structures. Fecal fermentation showed RRTPs could reshape microbial composition toward a healthier balance, leading to a higher production of beneficial metabolites including total short-chain fatty acids, curcumin, noopept, spermidine, 3-feruloylquinic acid and citrulline. More beneficial shifts in bacterial population were observed in RRTP-HW group, while RRTP-US-S had stronger ability to stimulate bacterial short-chain fatty acids production. Additionally, metabolic profiles with the intervention of RRTP-HW, RRTP-US-S or RRTP-US-L were significantly different from each other. The results suggested RRTPs had potential prebiotic effects which could be modified by power US via molecular weight degradation.


Subject(s)
Polysaccharides , Prebiotics , Rosa , Rosa/chemistry , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Molecular Weight , Ultrasonic Waves , Fermentation , Chemical Fractionation/methods
5.
J Res Med Sci ; 18(8): 704-6, 2013 Aug.
Article in English | MEDLINE | ID: mdl-24379848

ABSTRACT

BACKGROUND: The objective of this study is to optimize the effective dose of heparin and ligustrazine hydrochloride injection (LHI) for drug combination. MATERIALS AND METHODS: The animal clinical study of LHI was performed by the rat's model of induced arteriovenous shunt thrombosis. Experimental animals were grouped into several groups and separately treated with both LHI (20, 40, 80 mg/kg, i.p.) and heparin (60, 55, and 50 U/kg; 5000 U/ml; Sigma, i.v). The study had used thrombus weight, protein concentration in thrombus homogenate, inhibition rate of thrombosis, and plasma anti-thrombin activity as indications. RESULTS: The group combination (50, 80) got the result of 100% antithrombotic activity with 0 ± 0 mg of thrombus weight, 14 ± 3 µg/ml of protein concentration in thrombus homogenate and 1.5 ± 0.04 U/ml of plasma anti-thrombin activity. Its anti-thrombotic effect was much better than individual groups treated with LHI in a dose of 0 mg/kg and group of combination (0, 80) (P < 0.05) while antithrombotic effect of 55 and 60 U/kg heparin alone was only 37-58%. Therefore, the group of combination (50, 80) was optimal for 100% antithrombotic activity. CONCLUSION: Optimal combined doses of LHI and heparin preventing blood coagulation were determined and the results were available. It may give some hint for the further clinical application on human.

6.
Heliyon ; 9(7): e17711, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37455999

ABSTRACT

Despite the fact that metastasis is the leading cause of death in patients with head and neck squamous cell carcinoma, fundamental questions about the mechanisms that enable or inhibit metastasis remain unanswered. Tetraspanin CD63 has been linked to tumor progression and metastasis. However, few studies have examined the role of CD63 in HNSCC. In this study, we discovered that CD63 levels were abnormally altered in HNSCC tissue compared to adjacent tissue (n = 69 pairs), and that this was linked to prognosis. Through functional in vitro and in vivo experiments, the roles of CD63 in HNSCC were confirmed. Overexpression of CD63 inhibited the progression and metastasis of HNSCC cells. Using mass spectrometry and co-immunoprecipitation assays, we discovered that KRT1 could be a direct interacting partner of CD63. Furthermore, both CD63 and KRT1 expression was significantly decreased in metastatic tissue compared with primary tumor tissue (n = 13 pairs), suggesting that CD63 and KRT1 play a role in reducing the metastasis of HNSCC. In summary, we reveal a previously unrecognized role of CD63 in regulating KRT1-mediated cell cycle arrest in HNSCC cells, and our findings contribute to defining an important mechanism of HNSCC progression and metastasis.

7.
Pathol Oncol Res ; 28: 1610699, 2022.
Article in English | MEDLINE | ID: mdl-36330052

ABSTRACT

Purpose: This study aimed to investigate the applicability of plasma extracellular vesicles (EVs) miR-99a-5p as a potential head and neck squamous cell carcinoma (HNSCC) diagnostic biomarker. Methods: The miRNA expression of HNSCC tissue and plasma EVs were profiled by small RNA sequencing. qRT-PCR was performed to detect miR-99a-5p expression in HNSCC (n = 93) and benign disease (n = 39) plasma EVs and formalin-fixed and paraffin-embedded (FFPE) tissue (n = 110). We constructed receiver-operating characteristic curves to investigate the diagnostic efficiency of plasma EVs miR-99a-5p. Results: Tumor tissue exhibited lower miR-99a-5p than para-tumor tissue. Patients with high miR-99a-5p expression exhibited significantly more p16 positive status. In contrast, HNSCC plasma EVs harbored more miR-99a-5p than the benign disease group. Plasma EVs miR-99a-5p distinguished HNSCC with area under the curve (AUC) of 0.7494 (95% CI: 0.6692-0.8296; p < 0.0001), with 61.54% sensitivity and 75.27% specificity, respectively. Furthermore, plasma EVs miR-99a-5p also distinguished early HNSCC with AUC of 0.7394 (95% CI: 0.6284-0.8504; p = 0.0002), with 79.07% sensitivity and 61.54% specificity, respectively. Conclusion: Plasma EVs miR-99a-5p is a potential biomarker for predicting early HNSCC.


Subject(s)
Extracellular Vesicles , Head and Neck Neoplasms , MicroRNAs , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , Extracellular Vesicles/genetics , Extracellular Vesicles/metabolism , Biomarkers, Tumor/metabolism , Head and Neck Neoplasms/genetics
8.
World J Clin Cases ; 9(31): 9386-9394, 2021 Nov 06.
Article in English | MEDLINE | ID: mdl-34877274

ABSTRACT

BACKGROUND: The main treatment methods for cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy and so on. Patients often feel anger, anxiety, depression, and other negative psychological reactions in the process of treatment. AIM: To explore the effects of cognitive behavioral therapy on the personality characteristics of cancer patients. METHODS: According to the matching design requirements, 150 cancer patients were divided into 3 groups based on sex, age, condition, and cultural background. Patients in the control group received conventional treatment. Patients in experimental group 1 received an intervention based on conventional treatment combined with cognitive behavioral therapy. Patients in experimental group 2 received family members' participation in addition to the treatment given in experimental group 1. An Eysenck personality questionnaire was used to investigate all the patients before and after the intervention, and the scores for psychosis, introversion, neuroticism, and concealment degree were analyzed. RESULTS: Compared with the control group, for experimental group 1 and experimental group 2 before and after the intervention, the four dimensions of mental quality, neuroticism, introversion and concealment degree all decreased, and the difference was statistically significant (P < 0.05). After the intervention, there were no obvious or statistically significant differences (P > 0.05) among the control group, experimental group 1, and experimental group 2 for two personality traits, psychoticism and neuroticism, both inside and outside degree and all four dimensions. CONCLUSION: Simple cognitive behavioral therapy could not change the personality characteristics of cancer patients quickly, but the patients' personality characteristics were significantly improved after treatment.

9.
Genes Dis ; 8(5): 677-688, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34291139

ABSTRACT

Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Hence, we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo. In this study, we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo. Compared with that in normal epidermal melanocytes (PIG1), the expression of SFRP5 was increased in vitiligo melanocytes (PIG3V). To investigate the effect of SFRP5 on melanin synthesis, PIG1 cells were infected with recombinant SFRP5 adenovirus (AdSFRP5), and PIG3V cells were infected with recombinant siSFRP5 adenovirus (AdsiSFRP5). The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor (MITF) and its target proteins via suppression of the Wnt/ß-catenin signaling pathway. Accordingly, SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V cells. Moreover, SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor (TCF/LEF) in PIG1 cells. Furthermore, this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the ß-catenin agonist, SKL2001. The inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse model. Hence, our results indicate that SFRP5 can inhibit melanogenesis in melanocytes. Additionally, our findings showed that SFRP5 plays a vital role in the development of vitiligo, and thus may serve as a potential therapeutic target for vitiligo.

10.
World J Gastroenterol ; 27(43): 7530-7545, 2021 Nov 21.
Article in English | MEDLINE | ID: mdl-34887647

ABSTRACT

BACKGROUND: Severe acute pancreatitis (SAP) is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options. N6-methyladenosine (m6A) modification of circRNAs plays important roles in physiological and pathological processes. However, the roles of m6A circRNA in the pathological process of SAP remains unknown. AIM: To identify transcriptome-wide map of m6A circRNAs and to determine their biological significance and potential mechanisms in SAP. METHODS: The SAP in C57BL/6 mice was induced using 4% sodium taurocholate salt. The transcriptome-wide map of m6A circRNAs was identified by m6A-modified RNA immunoprecipitation sequencing. The biological significance of circRNAs with differentially expressed m6A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The underlying mechanism of m6A circRNAs in SAP was analyzed by constructing of m6A circRNA-microRNA networks. The expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m6A process in SAP. RESULTS: Fifty-seven circRNAs with differentially expressed m6A peaks were identified by m6A-modified RNA immunoprecipitation sequencing, of which 32 were upregulated and 25 downregulated. Functional analysis of these m6A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP, such as regulation of autophagy and protein digestion. In m6A circRNA-miRNA networks, several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m6A circRNAs, such as miR-24-3p, miR-26a, miR-92b, miR-216b, miR-324-5p and miR-762. Notably, the total m6A level of circRNAs was reduced, while the demethylase alkylation repair homolog 5 was upregulated in SAP. CONCLUSION: m6A modification of circRNAs may be involved in the pathogenesis of SAP. Our findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new potential therapeutic targets for SAP.


Subject(s)
MicroRNAs , Pancreatitis , Acute Disease , Adenosine/analogs & derivatives , Animals , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Pancreatitis/chemically induced , Pancreatitis/genetics , RNA, Circular
11.
J Agric Food Chem ; 69(1): 88-100, 2021 Jan 13.
Article in English | MEDLINE | ID: mdl-33356208

ABSTRACT

Insect resistance to insecticides is an increasingly serious problem, and the resistant mechanisms are complicated. The resistance research based on the chemosensory pathway is one of the hot problems at present, but the specific binding mechanism of chemosensory genes and insecticides remains elusive. The binding mechanism of AlepGOBP2 (belong to insect chemosensory gene) with two insecticides was investigated by computational and experimental approaches. Our calculation results indicated that four key residues (Phe12, Ile52, Ile94, and Phe118) could steadily interact with these two insecticides and be assigned as hotspot sites responsible for their binding affinities. The significant alkyl-π and hydrophobic interactions involved by these four hotspot residues were found to be the driving forces for their binding affinities, especially for two residues (Phe12 and Ile94) that significantly contribute to the binding of chlorpyrifos, which were also validated by our binding assay results. Furthermore, we also found that the AlepGOBP2-chlorpyrifos/phoxim complexes can be more efficiently converged in the residue-specific force field-(RSFF2C) and its higher accuracy and repeatability in protein dynamics simulation, per-residue free energy decomposition, and computational alanine scanning calculations have also been achieved in this paper. These findings provided useful insights for efficient and reliable calculation of the binding mechanism of relevant AlepGOBPs with other insecticides, facilitating to develop new and efficient insecticides targeting the key sites of AlepGOBP2.


Subject(s)
Chlorpyrifos/chemistry , Insect Proteins/chemistry , Moths/metabolism , Organothiophosphorus Compounds/chemistry , Receptors, Odorant/chemistry , Receptors, Odorant/metabolism , Animals , Chlorpyrifos/metabolism , Insect Proteins/metabolism , Molecular Dynamics Simulation , Moths/chemistry , Organothiophosphorus Compounds/metabolism , Protein Binding
12.
Zool Res ; 42(4): 492-501, 2021 Jul 18.
Article in English | MEDLINE | ID: mdl-34235898

ABSTRACT

Fish morphological phenotypes are important resources in artificial breeding, functional gene mapping, and population-based studies in aquaculture and ecology. Traditional morphological measurement of phenotypes is rather expensive in terms of time and labor. More importantly, manual measurement is highly dependent on operational experience, which can lead to subjective phenotyping results. Here, we developed 3DPhenoFish software to extract fish morphological phenotypes from three-dimensional (3D) point cloud data. Algorithms for background elimination, coordinate normalization, image segmentation, key point recognition, and phenotype extraction were developed and integrated into an intuitive user interface. Furthermore, 18 key points and traditional 2D morphological traits, along with 3D phenotypes, including area and volume, can be automatically obtained in a visualized manner. Intuitive fine-tuning of key points and customized definitions of phenotypes are also allowed in the software. Using 3DPhenoFish, we performed high-throughput phenotyping for four endemic Schizothoracinae species, including Schizopygopsis younghusbandi, Oxygymnocypris stewartii, Ptychobarbus dipogon, and Schizothorax oconnori. Results indicated that the morphological phenotypes from 3DPhenoFish exhibited high linear correlation (>0.94) with manual measurements and offered informative traits to discriminate samples of different species and even for different populations of the same species. In summary, we developed an efficient, accurate, and customizable tool, 3DPhenoFish, to extract morphological phenotypes from point cloud data, which should help overcome traditional challenges in manual measurements. 3DPhenoFish can be used for research on morphological phenotypes in fish, including functional gene mapping, artificial selection, and conservation studies. 3DPhenoFish is an open-source software and can be downloaded for free at https://github.com/lyh24k/3DPhenoFish/tree/master.


Subject(s)
Fishes/anatomy & histology , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/veterinary , Software , Animals , Fishes/classification , Imaging, Three-Dimensional/methods , Reproducibility of Results , Species Specificity
13.
Mitochondrial DNA B Resour ; 6(2): 425-427, 2021 Feb 09.
Article in English | MEDLINE | ID: mdl-33628878

ABSTRACT

'Yunning No.1' lemon, a mutant of Eureka lemon, is originally found in Yunnan province of China and is the main cultivated lemon variety there. In this study, we assembled and annotated its chloroplast genome using Illumina Hiseq-2500 whole genome re-sequencing data. Its chloroplast genome is 160,141 bp in size, containing a 87,754 bp large single copy region, a 18,385 bp small single copy region and a pair of 27,001 bp inverted repeat region. Like many citrus species, 114 unique genes (including 80 protein-coding genes, 30 tRNAs and 4 rRNAs) could be identified from the chloroplast genome of 'Yunning No.1'. Phylogenetic analysis revealed that the 'Yunning No.1' chloroplast genome was closest to Citrus maxima.

14.
Am J Transl Res ; 12(9): 5381-5398, 2020.
Article in English | MEDLINE | ID: mdl-33042426

ABSTRACT

Osteosarcoma (OS) is the most common type of primary bone cancer. Even with advances in early diagnosis and aggressive treatment, the overall prognosis for OS remains to be further elevated. Lycorine was an isoquinoline alkaloid mainly existed in the bulb of lyco salvia miltiorrhiza and was shown to inhibit several types of cancer. In the present study, we investigated the anti-OS activity of lycorine and the possible underlying mechanism. We found that lycorine inhibited cell proliferation of human OS cells while had lower cytotoxcity against normal cells, and triggered cell cycle arrest at the G1/S transition. Moreover, we validated that lycorine promoted apoptosis via death receptor pathway and mitochondrial pathway, suppressed migration and invasion by reversing epithelial mesenchymal transition (EMT) and suppressing the degradation of extracellular matrix (ECM) in vitro. In addition, orthotopic implantation model of 143B OS cells further confirmed that lycorine suppressed OS growth and lung metastasis in vivo. Mechanically, lycorine reduced the protein level of ß-catenin and its' downstream molecule c-Myc. Furthermore, lycorine also decreased the phosphorylation of ERK1/2 and AKT. Together, our results reveal that lycorine may inhibit tumor growth of OS cells possibly through suppressing Wnt/ß-catenin, ERK1/2 and PI3K/AKT signaling pathway.

15.
Chin Phys Lett ; 37(5): 058701, 2020 May.
Article in English | MEDLINE | ID: mdl-38619931

ABSTRACT

Coronavirus Disease 2019 (COVID-19), caused by the novel coronavirus, has spread rapidly across China. Consequently, there is an urgent need to sort and develop novel agents for the prevention and treatment of viral infections. A rapid structure-based virtual screening is used for the evaluation of current commercial drugs, with structures of human angiotensin converting enzyme II (ACE2), and viral main protease, spike, envelope, membrane and nucleocapsid proteins. Our results reveal that the reported drugs Arbidol, Chloroquine and Remdesivir may hinder the entry and release of virions through the bindings with ACE2, spike and envelope proteins. Due to the similar binding patterns, NHC (ß-d-N4-hydroxycytidine) and Triazavirin are also in prospects for clinical use. Main protease (3CLpro) is likely to be a feasible target of drug design. The screening results to target 3CL-pro reveal that Mitoguazone, Metformin, Biguanide Hydrochloride, Gallic acid, Caffeic acid, Sulfaguanidine and Acetylcysteine seem be possible inhibitors and have potential application in the clinical therapy of COVID-19.

16.
Cancer Manag Res ; 11: 8977-8989, 2019.
Article in English | MEDLINE | ID: mdl-31695490

ABSTRACT

PURPOSE: Glioblastoma multiforme (GBM) is a highly malignant tumor of the central nervous system. Although primary GBM patients receive extensive therapies, tumors may recur within months, and there is no objective and scientific method to predict prognosis. Adoptive immunotherapy holds great promise for GBM treatment. However, the expression profiles of the tumor-associated antigens (TAAs) and tumor immune microenvironment (TME) genes used in immunotherapy of GBM patients have not been fully described. The present study aimed to develop a predictive tool to evaluate patient survival based on full analysis of the expression levels of TAAs and TME genes. METHODS: Expression profiles of a panel of 87 TAAs and 8 TME genes significantly correlated with poor prognosis were evaluated in 44 GBM patients and 10 normal brain tissues using quantitative real-time polymerase chain reaction (qRT-PCR). A linear formula (the LASSO algorithm based in the R package) weighted by regression coefficients was used to develop a multi-element expression score to predict prognosis; this formula was cross-validated by the leave-one-out method in different GBM cohorts. RESULTS: After analysis of gene expression, clinical features, and overall survival (OS), a total of 8 TAAs (CHI3L1, EZH2, TRIOBP, PCNA, PIK3R1, PRKDC, SART3 and EPCAM), 1 TME gene (FOXP3) and 4 clinical features (neutrophil-to-lymphocyte (NLR), number of basophils (BAS), age and treatment with standard radiotherapy and chemotherapy) were included in the formula. There were significant differences between high and low scoring groups identified using the formula in different GBM cohorts (TCGA (n=732) and GEO databases (n=84)), implying poor and good prognosis, respectively. CONCLUSION: The multi-element expression score was significantly associated with OS of GBM patients. The improve understanding of TAAs and TMEs and well-defined formula could be implemented in immunotherapy for GBM to provide better care.

17.
Cell Death Dis ; 10(12): 916, 2019 12 04.
Article in English | MEDLINE | ID: mdl-31801947

ABSTRACT

The burgeoning functions of many microRNAs (miRs) have been well study in cancer. However, the level and function of miR-1205 in laryngeal squamous cell cancer remains unknown. In the current research, we validated that miR-1205 was notably downregulated in human laryngeal squamous cell carcinoma (LSCC) samples in comparison with tissues adjacent to LSCC, and correlated with T stage, lymph node metastasis, and clinical stage. Using Kaplan-Meier analysis indicates that high expression of miR-1205 has a favorable prognosis for patients with LSCC. Functional assays show that enforced miR-1205 expression attenuates the migration, growth, and invasion of LSCC cells. And E2F1 is verified to be a target of miR-1205, while E2F1 binds to miR-1205 promoter and transcriptionally inhibits miR-1205 expression. Overexpression of E2F1 reverses the inhibitory impacts of miR-1205 on LSCC cells in part. Importantly, E2F1 is abnormally increased in LSCC tissues, and its protein levels were inversely relevant to miR-1205 expression. High E2F1 protein level is in connection with clinical stage, T stage, lymph node metastasis, and poor prognosis. Consequently, reciprocal regulation of miR-1205 and E2F1 plays a crucial role in the progression of LSCC, suggesting a new miR-1205/E2F1-based clinical application for patients of LSCC.


Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Disease Progression , E2F1 Transcription Factor/genetics , Gene Expression Regulation, Neoplastic , Laryngeal Neoplasms/genetics , Laryngeal Neoplasms/pathology , MicroRNAs/genetics , 3' Untranslated Regions/genetics , Animals , Base Sequence , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cyclin E/metabolism , Down-Regulation/genetics , E2F1 Transcription Factor/metabolism , HEK293 Cells , Humans , Lymphatic Metastasis , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/metabolism , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Survivin/metabolism , Up-Regulation/genetics
18.
Sci Data ; 6: 190009, 2019 02 05.
Article in English | MEDLINE | ID: mdl-30720802

ABSTRACT

Animal genomes in the Qinghai-Tibetan Plateau provide valuable resources for scientists to understand the molecular mechanism of environmental adaptation. Tibetan fish species play essential roles in the local ecology; however, the genomic information for native fishes was still insufficient. Oxygymnocypris stewartii, belonging to Oxygymnocypris genus, Schizothoracinae subfamily, is a native fish in the Tibetan plateau living within the elevation from roughly 3,000 m to 4,200 m. In this report, PacBio and Illumina sequencing platform were used to generate ~385.3 Gb genomic sequencing data. A genome of about 1,849.2 Mb was obtained with a contig N50 length of 257.1 kb. More than 44.5% of the genome were identified as repetitive elements, and 46,400 protein-coding genes were annotated in the genome. The assembled genome can be used as a reference for future population genetic studies of O. stewartii and will improve our understanding of high altitude adaptation of fishes in the Qinghai-Tibetan Plateau.


Subject(s)
Cyprinidae/genetics , Genome , Animals , High-Throughput Nucleotide Sequencing , Molecular Sequence Annotation , Tibet
19.
Opt Express ; 15(24): 16102-9, 2007 Nov 26.
Article in English | MEDLINE | ID: mdl-19550899

ABSTRACT

The robustness and prolongation of multiple filamentation (MF) for femtosecond laser propagation in air are investigated experimentally and numerically. It is shown that the number, pattern, propagation distance, and spatial stability of MF can be controlled by a variable-aperture on-axis pinhole. The random MF pattern can be optimized to a deterministic pattern. In our numerical simulations, we configured double filaments to principlly simulate the experimental MF interactions. It is experimentally and numerically demonstrated that the pinhole can reduce the modulational instability of MF and is favorable for a more stable MF evolution.

20.
Opt Express ; 14(2): 773-8, 2006 Jan 23.
Article in English | MEDLINE | ID: mdl-19503396

ABSTRACT

The spatial evolution of plasma filaments in air induced by femtosecond laser pulses is investigated experimentally. Several major filaments and small scaled additional filaments are detected in the plasma channel. The complicated interaction process of filaments as splitting, fusion and spreading is observed. The major filaments propagate stably, and the small scaled additional filaments can be attracted to the major filaments and merged with them. The major filaments are formed due to the perturbation of initial beam profile and the small scaled filaments are mainly caused by the transverse modulational instability.

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