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Article ; Online: Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.

2024 Volume 10, Issue 1, Page(s) 39

Abstract: Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic ... ...

Abstract	Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/β-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.
MeSH term(s)	Humans ; Squamous Cell Carcinoma of Head and Neck/genetics ; Epigenomics ; Dysbiosis ; Mouth Neoplasms/genetics ; Mouth Neoplasms/metabolism ; Mouth Neoplasms/pathology ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Bacteria ; Fusobacterium nucleatum ; Head and Neck Neoplasms/genetics ; Epigenesis, Genetic ; Microbiota ; Tumor Microenvironment
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2817021-0
ISSN	2055-5008 ; 2055-5008
ISSN (online)	2055-5008
ISSN	2055-5008
DOI	10.1038/s41522-024-00511-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Determinants and Interactions of Oral Bacterial and Fungal Microbiota in Healthy Chinese Adults.

Cheung, Man Kit / Chan, Jason Y K / Wong, Martin C S / Wong, Po Yee / Lei, Pu / Cai, Liuyang / Lan, Linlin / Ho, Wendy C S / Yeung, Apple C M / Chan, Paul K S / Chen, Zigui

Microbiology spectrum

2022 Volume 10, Issue 1, Page(s) e0241021

Abstract: Numerous studies have examined the composition of and factors shaping the oral bacterial microbiota in healthy adults; however, similar studies on the less dominant yet ecologically and clinically important fungal microbiota are scarce. In this study, we ...

Abstract	Numerous studies have examined the composition of and factors shaping the oral bacterial microbiota in healthy adults; however, similar studies on the less dominant yet ecologically and clinically important fungal microbiota are scarce. In this study, we characterized simultaneously the oral bacterial and fungal microbiomes in a large cohort of systemically healthy Chinese adults by sequencing the bacterial 16S rRNA gene and fungal internal transcribed spacer. We showed that different factors shaped the oral bacterial and fungal microbiomes in healthy adults. Sex and age were associated with the alpha diversity of the healthy oral bacterial microbiome but not that of the fungal microbiome. Age was also a major factor affecting the beta diversity of the oral bacterial microbiome; however, it only exerted a small effect on the oral fungal microbiome when compared with other variables. After controlling for age and sex, the bacterial microbiota structure was most affected by marital status, recent oral conditions and oral hygiene-related factors, whereas the fungal microbiota structure was most affected by education level, fruits and vegetables, and bleeding gums. Bacterial-fungal interactions were limited in the healthy oral microbiota, with the strongest association existing between Pseudomonas sp. and
MeSH term(s)	Adolescent ; Adult ; Aged ; Bacteria/classification ; Bacteria/genetics ; Bacteria/isolation & purification ; China ; Cohort Studies ; Female ; Fungi/classification ; Fungi/genetics ; Fungi/isolation & purification ; Healthy Volunteers ; Humans ; Male ; Microbiota ; Middle Aged ; Mouth/microbiology ; Mycobiome ; Phylogeny ; Young Adult
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.02410-21
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Article ; Online: Characterization of oral microbiota in HPV and non-HPV head and neck squamous cell carcinoma and its association with patient outcomes.

Chan, Jason Y K / Cheung, Man Kit / Lan, Linlin / Ng, Cherrie / Lau, Eric H L / Yeung, Zenon W C / Wong, Eddy W Y / Leung, Leanne / Qu, Xinyu / Cai, Liuyang / Zhu, Hengyan / Boon, Siaw Shi / Burk, Robert D / Chan, Paul K S / Chen, Zigui

Oral oncology

2022 Volume 135, Page(s) 106245

Abstract: Objective: To investigate the interplay among the oral microbiota, HPV infection, traditional risk factors and patient outcomes in head and neck squamous cell carcinoma (HNSCC).: Materials and methods: A multi-center study of HNSCC patients with ... ...

Abstract	Objective: To investigate the interplay among the oral microbiota, HPV infection, traditional risk factors and patient outcomes in head and neck squamous cell carcinoma (HNSCC). Materials and methods: A multi-center study of HNSCC patients with paired tumor and control tissues. We characterized the oral microbiota and HPV infection of tissues in 166 Chinese adults by sequencing the bacterial 16S rRNA V3-V4 and HPV L1 regions, respectively, and examined the associations among the oral microbiota, HPV and clinical features. Results: A total of 15.7% of the surveyed HNSCC patients were positive for HPV DNA, with infection rates varying from 66.7% in oropharyngeal SCC to 10.4% in oral cavity SCC (OSCC). No HPV infection was detected in the surveyed hypopharyngeal SCC. HPV16 was largely the predominant type. HPV infection in non-OSCC, especially oropharyngeal SCC, was associated with advanced N stage and superior survival outcomes. Oral microbiota dysbiosis was observed in HNSCC tumors, with differentially abundant taxa mainly associated with HNSCC subtype, T stage, survival/relapse, HPV infection, and smoking. Notably, the enrichment of Fusobacterium in tumor tissues of OSCC patients was associated with no smoking, early T stage, early N stage, and better 3-year disease-specific survival. Conclusion: Our findings underscore the involvement of oral microbiota dysbiosis in OSCC pathogenesis, Fusobacterium is involved with improved OSCC patient outcomes, especially in patients lacking traditional risk factors. Understanding the complex interactions among the oral microbiota, HPV infection and other risk factors for HNSCC will provide important insights into the pathogenesis of HNSCC.
MeSH term(s)	Adult ; Humans ; Squamous Cell Carcinoma of Head and Neck/complications ; Head and Neck Neoplasms/complications ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/complications ; Neoplasm Recurrence, Local ; Papillomavirus Infections ; Carcinoma, Squamous Cell/pathology ; Mouth Neoplasms ; Microbiota ; Papillomaviridae/genetics
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2022-11-12
Publishing country	England
Document type	Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1120465-5
ISSN	1879-0593 ; 0964-1955 ; 1368-8375
ISSN (online)	1879-0593
ISSN	0964-1955 ; 1368-8375
DOI	10.1016/j.oraloncology.2022.106245
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Zs.A 4869: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article: Restoration of the Oral Microbiota After Surgery for Head and Neck Squamous Cell Carcinoma Is Associated With Patient Outcomes.

Chan, Jason Y K / Ng, Cherrie W K / Lan, Linlin / Fung, Sherwood / Li, Jing-Woei / Cai, Liuyang / Lei, Pu / Mou, Qianqian / Meehan, Katie / Lau, Eric H L / Yeung, Zenon / Chan, K C Allen / Wong, Eddy W Y / Chan, Paul K S / Chen, Zigui

Frontiers in oncology

2021 Volume 11, Page(s) 737843

Abstract: Objective: To evaluate the dynamics of the oral microbiome and associated patient outcomes following treatment of head and neck squamous cell carcinoma (HNSCC).: Materials and methods: This was a prospective cohort study at a tertiary academic center ...

Abstract	Objective: To evaluate the dynamics of the oral microbiome and associated patient outcomes following treatment of head and neck squamous cell carcinoma (HNSCC). Materials and methods: This was a prospective cohort study at a tertiary academic center in Hong Kong SAR of patients with head and neck squamous cell carcinoma evaluating the oral microbiome in pre- and postsurgery oral rinses (at 1, 3, and 6 months) with 16S rRNA gene V3-V4 amplicon sequencing. Results: In total, 76 HNSCC patients were evaluated. There was a significantly depressed alpha diversities of oral microbial communities observed in HNSCC oral rinse samples within the first 6 months post-surgery when compared to presurgery or healthy controls. Distant clustering between pre- and postsurgery was also observed ( Conclusions: Oral microbiome dysbiosis associated with HNSCC is dynamic. These dynamics of the oral microbiome postsurgery are also associated with patient treatment and outcomes and may serve as potential biomarkers for patient management in HNSCC.
Language	English
Publishing date	2021-10-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.737843
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Article ; Online: Proteomic Analysis of Circulating Extracellular Vesicles Identifies Potential Biomarkers for Lymph Node Metastasis in Oral Tongue Squamous Cell Carcinoma.

Qu, Xinyu / Leung, Thomas C N / Ngai, Sai-Ming / Tsai, Sau-Na / Thakur, Abhimanyu / Li, Wing-Kar / Lee, Youngjin / Leung, Leanne / Ng, Tung-Him / Yam, Judy / Lan, Linlin / Lau, Eric H L / Wong, Eddy W Y / Chan, Jason Y K / Meehan, Katie

Cells

2021 Volume 10, Issue 9

Abstract: Lymph node metastasis is the most reliable indicator of a poor prognosis for patients with oral tongue cancers. Currently, there are no biomarkers to predict whether a cancer will spread in the future if it has not already spread at the time of diagnosis. ...

Abstract	Lymph node metastasis is the most reliable indicator of a poor prognosis for patients with oral tongue cancers. Currently, there are no biomarkers to predict whether a cancer will spread in the future if it has not already spread at the time of diagnosis. The aim of this study was to quantitatively profile the proteomes of extracellular vesicles (EVs) isolated from blood samples taken from patients with oral tongue squamous cell carcinoma with and without lymph node involvement and non-cancer controls. EVs were enriched using size exclusion chromatography (SEC) from pooled plasma samples of patients with non-nodal and nodal oral tongue squamous cell carcinoma (OTSCC) and non-cancer controls. Protein cargo was quantitatively profiled using isobaric labelling (iTRAQ) and two-dimensional high-performance liquid chromatography followed by tandem mass spectrometry. We identified 208 EV associated proteins and, after filtering, generated a short list of 136 proteins. Over 85% of the EV-associated proteins were associated with the GO cellular compartment term "extracellular exosome". Comparisons between non-cancer controls and oral tongue squamous cell carcinoma with and without lymph node involvement revealed 43 unique candidate EV-associated proteins with deregulated expression patterns. The shortlisted EV associated proteins described here may be useful discriminatory biomarkers for differentiating OTSCC with and without nodal disease or non-cancer controls.
MeSH term(s)	Aged ; Biomarkers, Tumor/metabolism ; Extracellular Vesicles/metabolism ; Female ; Humans ; Lymph Nodes/metabolism ; Lymph Nodes/pathology ; Lymphatic Metastasis/pathology ; Male ; Middle Aged ; Mouth Neoplasms/metabolism ; Mouth Neoplasms/pathology ; Proteome/metabolism ; Proteomics/methods ; Squamous Cell Carcinoma of Head and Neck/metabolism ; Squamous Cell Carcinoma of Head and Neck/pathology ; Tongue Neoplasms/metabolism ; Tongue Neoplasms/pathology
Chemical Substances	Biomarkers, Tumor ; Proteome
Language	English
Publishing date	2021-08-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10092179
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Article ; Online: Inhibition of human MCF-7 breast cancer cells and HT-29 colon cancer cells by rice-produced recombinant human insulin-like growth binding protein-3 (rhIGFBP-3).

Cheung, Stanley C K / Long, Xiaohang / Liu, Lizhong / Liu, Qiaoquan / Lan, Linlin / Tong, Peter C Y / Sun, Samuel S M

PloS one

2013 Volume 8, Issue 10, Page(s) e77516

Abstract: Background: Insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I) to form a ...

Abstract	Background: Insulin-like growth factor binding protein-3 (IGFBP-3) is a multifunctional molecule which is closely related to cell growth, apoptosis, angiogenesis, metabolism and senescence. It combines with insulin-like growth factor-I (IGF-I) to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and reduce insulin requirement in patients with diabetes. IGFBP-3 alone has been shown to have anti-proliferation effect on numerous cancer cells. Methodology/principal findings: We reported here an expression method to produce functional recombinant human IGFBP-3 (rhIGFBP-3) in transgenic rice grains. Protein sorting sequences, signal peptide and endoplasmic reticulum retention tetrapeptide (KDEL) were included in constructs for enhancing rhIGFBP-3 expression. Western blot analysis showed that only the constructs with signal peptide were successfully expressed in transgenic rice grains. Both rhIGFBP-3 proteins, with or without KDEL sorting sequence inhibited the growth of MCF-7 human breast cancer cells (65.76 ± 1.72% vs 45.00 ± 0.86%, p < 0.05; 50.84 ± 1.97% vs 45.00 ± 0.86%, p < 0.01 respectively) and HT-29 colon cancer cells (65.14 ± 3.84% vs 18.01 ± 13.81%, p < 0.05 and 54.7 ± 9.44% vs 18.01 ± 13.81%, p < 0.05 respectively) when compared with wild type rice. Conclusion/significance: These findings demonstrated the feasibility of producing biological active rhIGFBP-3 in rice using a transgenic approach, which will definitely encourage more research on the therapeutic use of hIGFBP-3 in future.
MeSH term(s)	Breast Neoplasms/pathology ; Cell Proliferation/drug effects ; Colonic Neoplasms/pathology ; Glycosylation ; HT29 Cells ; Humans ; Insulin-Like Growth Factor Binding Protein 3/biosynthesis ; Insulin-Like Growth Factor Binding Protein 3/genetics ; Insulin-Like Growth Factor Binding Protein 3/metabolism ; Insulin-Like Growth Factor Binding Protein 3/pharmacology ; MCF-7 Cells ; Oryza/genetics ; Plants, Genetically Modified ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Recombinant Proteins/pharmacology
Chemical Substances	Insulin-Like Growth Factor Binding Protein 3 ; Recombinant Proteins
Language	English
Publishing date	2013-10-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0077516
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Article ; Online: Microtubule network is required for insulin-induced signal transduction and actin remodeling.

Liu, Li-Zhong / Cheung, Stanley C K / Lan, Lin-Lin / Ho, Stanley K S / Chan, Juliana C N / Tong, Peter C Y

Molecular and cellular endocrinology

2013 Volume 365, Issue 1, Page(s) 64–74

Abstract: Both microtubule and actin are required for insulin-induced glucose uptake. However, the roles of these two cytoskeletons and their relationship in insulin action still remain unclear. In this work, we examined the morphological change of microtubule/ ... ...

Abstract	Both microtubule and actin are required for insulin-induced glucose uptake. However, the roles of these two cytoskeletons and their relationship in insulin action still remain unclear. In this work, we examined the morphological change of microtubule/actin and their involvement in insulin signal transduction using rat skeletal muscle cells. Insulin rapidly led to microtubule clustering from ventral to dorsal surface of the cell. Microtubule filaments were rearranged to create space where new actin structures formed. Disruption of microtubule prevented insulin-induced actin remodeling and distal insulin signal transduction, with reduction in surface glucose transporter isoform 4 (GLUT4) and glucose uptake. Though microtubule mediated actin remodeling through PKCζ, reorganization of microtubule depended on tyrosine phosphorylation of insulin receptor, the mechanism is different from insulin-induced actin remodeling, which relied on the activity of PI3-kinase and PKCζ. We propose that microtubule network is required for insulin-induced signal transduction and actin remodeling in skeletal muscle cells.
MeSH term(s)	Actin Cytoskeleton/metabolism ; Animals ; Biological Transport ; Cell Line ; Cell Membrane/metabolism ; Cell Polarity ; Glucose/metabolism ; Glucose Transporter Type 4/metabolism ; Insulin/metabolism ; Kinetics ; Microtubules/metabolism ; Myoblasts, Skeletal/cytology ; Myoblasts, Skeletal/metabolism ; Phosphatidylinositol 3-Kinase/metabolism ; Phosphorylation ; Protein Kinase C/metabolism ; Protein Processing, Post-Translational ; Protein Transport ; Rats ; Receptor, Insulin/metabolism ; Signal Transduction
Chemical Substances	Glucose Transporter Type 4 ; Insulin ; Slc2a4 protein, rat ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; Receptor, Insulin (EC 2.7.10.1) ; protein kinase C zeta (EC 2.7.11.1) ; Protein Kinase C (EC 2.7.11.13) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2013-01-05
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2012.09.005
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Article: Microtubule network is required for insulin-induced signal transduction and actin remodeling

Liu, Li-Zhong / Cheung, Stanley C.K / Lan, Lin-Lin / Ho, Stanley K.S / Chan, Juliana C.N / Tong, Peter C.Y

Molecular and cellular endocrinology. 2013 Jan. 5, v. 365, no. 1

2013

Abstract	Both microtubule and actin are required for insulin-induced glucose uptake. However, the roles of these two cytoskeletons and their relationship in insulin action still remain unclear. In this work, we examined the morphological change of microtubule/actin and their involvement in insulin signal transduction using rat skeletal muscle cells. Insulin rapidly led to microtubule clustering from ventral to dorsal surface of the cell. Microtubule filaments were rearranged to create space where new actin structures formed. Disruption of microtubule prevented insulin-induced actin remodeling and distal insulin signal transduction, with reduction in surface glucose transporter isoform 4 (GLUT4) and glucose uptake. Though microtubule mediated actin remodeling through PKCζ, reorganization of microtubule depended on tyrosine phosphorylation of insulin receptor, the mechanism is different from insulin-induced actin remodeling, which relied on the activity of PI3-kinase and PKCζ. We propose that microtubule network is required for insulin-induced signal transduction and actin remodeling in skeletal muscle cells.
Keywords	actin ; glucose ; glucose transporters ; insulin ; insulin receptors ; microtubules ; myocytes ; phosphorylation ; protein kinase C ; rats ; signal transduction ; skeletal muscle ; tyrosine
Language	English
Dates of publication	2013-0105
Size	p. 64-74.
Publishing place	Elsevier Ireland Ltd
Document type	Article
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2012.09.005
Database	NAL-Catalogue (AGRICOLA)

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: The Intersection between Oral Microbiota, Host Gene Methylation and Patient Outcomes in Head and Neck Squamous Cell Carcinoma.

Chen, Zigui / Wong, Po Yee / Ng, Cherrie W K / Lan, Linlin / Fung, Sherwood / Li, Jing W / Cai, Liuyang / Lei, Pu / Mou, Qianqian / Wong, Sunny H / Wu, William K K / Li, Ryan J / Meehan, Katie / Lui, Vivian W Y / Chow, Chit / Lo, Kwok W / Chan, Amy B W / Boon, Siaw Shi / Lau, Eric H L /

Yeung, Zenon / Chan, Kwan C Allen / Wong, Eddy W Y / Cheng, Alfred S L / Yu, Jun / Chan, Paul K S / Chan, Jason Y K

Cancers

2020 Volume 12, Issue 11

Abstract: The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a ... ...

Abstract	The role of oral microbiota in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Here we sought to evaluate the association of the bacterial microbiome with host gene methylation and patient outcomes, and to explore its potential as a biomarker for early detection or intervention. Here we performed 16S rRNA gene amplicon sequencing in sixty-eight HNSCC patients across both tissue and oral rinse samples to identify oral bacteria with differential abundance between HNSCC and controls. A subset of thirty-one pairs of HNSCC tumor tissues and the adjacent normal tissues were characterized for host gene methylation profile using bisulfite capture sequencing. We observed significant enrichments of
Language	English
Publishing date	2020-11-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12113425
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Article ; Online: Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivo studies.

Cheung, Stanley Ck / Liu, Li-Zhong / Lan, Lin-Lin / Liu, Qiao-Quan / Sun, Samuel Sm / Chan, Juliana Cn / Tong, Peter Cy

BMC biotechnology

2011 Volume 11, Page(s) 37

Abstract: Background: Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone ... ...

Abstract	Background: Human insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains. Results: The plant-codon-optimized hIGF-I was introduced into rice via Agrobacterium-mediated transformation. To enhance the stability and yield of rhIGF-I, the endoplasmic reticulum-retention signal and glutelin signal peptide were used to deliver rhIGF-I to endoplasmic reticulum for stable accumulation. We found that only glutelin signal peptide could lead to successful expression of hIGF-I and one gram of hIGF-I rice grain possessed the maximum activity level equivalent to 3.2 micro molar of commercial rhIGF-I. In vitro functional analysis showed that the rice-derived rhIGF-I was effective in inducing membrane ruffling and glucose uptake on rat skeletal muscle cells. Oral meal test with rice-containing rhIGF-I acutely reduced blood glucose levels in streptozotocin-induced and Zucker diabetic rats, whereas it had no effect in normal rats. Conclusion: Our findings provided an alternative expression system to produce large quantities of biologically active rhIGF-I. The provision of large quantity of recombinant proteins will promote further research on the therapeutic potential of rhIGF-I.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Biological Transport ; Blood Glucose/metabolism ; Cells, Cultured ; DNA, Complementary/metabolism ; Diabetes Mellitus, Experimental ; Disease Models, Animal ; Gene Expression Regulation, Plant ; Glutens/genetics ; Humans ; Insulin-Like Growth Factor I/administration & dosage ; Insulin-Like Growth Factor I/biosynthesis ; Insulin-Like Growth Factor I/genetics ; Insulin-Like Growth Factor I/pharmacology ; Muscle, Skeletal/cytology ; Muscle, Skeletal/metabolism ; Oligopeptides ; Oryza/chemistry ; Oryza/genetics ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Plants, Genetically Modified/chemistry ; Plants, Genetically Modified/genetics ; Promoter Regions, Genetic/genetics ; Protein Sorting Signals ; Rats ; Rats, Zucker ; Recombinant Proteins/administration & dosage ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Recombinant Proteins/pharmacology ; Seeds/chemistry ; Seeds/genetics ; Starch/analysis ; Transformation, Genetic
Chemical Substances	Blood Glucose ; DNA, Complementary ; Oligopeptides ; Plant Extracts ; Protein Sorting Signals ; Recombinant Proteins ; lysyl-aspartyl-glutamyl-leucine (113516-56-6) ; Insulin-Like Growth Factor I (67763-96-6) ; Glutens (8002-80-0) ; Starch (9005-25-8)
Language	English
Publishing date	2011-04-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1472-6750
ISSN (online)	1472-6750
DOI	10.1186/1472-6750-11-37
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