cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1568532
title: Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer

description: Loss of 3p11-p14 is a frequent event in epithelial cancer and a candidate prognostic biomarker in cervical cancer. In addition to loss, promoter methylation can participate in gene silencing and promote tumor aggressiveness. We have performed a complete mapping of promoter methylation at 3p11-p14 in two independent cohorts of cervical cancer patients (n = 149, n = 121), using Illumina 450K methylation arrays. The aim was to investigate whether hyperm-ethylation was frequent and could contribute to gene silencing and disease aggressiveness either alone or combined with loss. By comparing the methylation level of individual CpG sites with corresponding data of normal cervical tissue, 26 out of 41 genes were found to be hypermethylated in both cohorts. The frequency of patients with hypermethylation of these genes was found to be higher at tumor stages of 3 and 4 than in stage 1 tumors. Seventeen of the 26 genes were transcriptionally downregulated in cancer compared to normal tissue, whereof 6 genes showed a significant correlation between methylation and expression. Integrated analysis of methylation, gene dosage, and expression of the 26 hypermethylated genes identified 3 regulation patterns encompassing 8 hypermethylated genes; a methylation driven pattern (<i>C3orf14, GPR27, ZNF717</i>), a gene dosage driven pattern (<i>THOC7, PSMD6</i>), and a combined methylation and gene dosage driven pattern (<i>FHIT, ADAMTS9, LRIG1</i>). In survival analysis, patients with both hypermethylation and loss of <i>LRIG1</i> had a worse outcome compared to those harboring only hypermethylation or none of the events. <i>C3orf14</i> emerged as a novel methylation regulated suppressor gene, for which knockdown was found to promote invasive growth in human papilloma virus (HPV)-transformed keratinocytes. In conclusion, hypermethylation at 3p11-p14 is common in cervical cancer and may exert a selection pressure during carcinogenesis alone or combined with loss. Information on both events could lead to improved prognostic markers.
DOI: 10.6084/m9.figshare.1568530
title: Development of a method for functional aspect identification in parotid using dynamic contrast-enhanced magnetic resonance imaging and concurrent stimulation

description: Development of a method for functional aspect identification in parotid using dynamic contrast-enhanced magnetic resonance imaging and concurrent stimulation
DOI: 10.6084/m9.figshare.1568532.v1
title: Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer

description: Loss of 3p11-p14 is a frequent event in epithelial cancer and a candidate prognostic biomarker in cervical cancer. In addition to loss, promoter methylation can participate in gene silencing and promote tumor aggressiveness. We have performed a complete mapping of promoter methylation at 3p11-p14 in two independent cohorts of cervical cancer patients (n=149, n=121), using Illumina 450K methylation arrays. The aim was to investigate whether hypermethylation was frequent and could contribute to gene silencing and disease aggressiveness either alone or combined with loss. By comparing the methylation level of individual CpG sites with corresponding data of normal cervical tissue, 26 out of 41 genes were found to be hypermethylated in both cohorts. The frequency of patients with hypermethylation of these genes was found to be higher at tumor stages of 3 and 4 than in stage 1 tumors. Seventeen of the 26 genes were transcriptionally downregulated in cancer compared to normal tissue, whereof six genes showed a significant correlation between methylation and expression. Integrated analysis of methylation, gene dosage, and expression of the 26 hypermethylated genes identified three regulation patterns encompassing eight hypermethylated genes; a methylation driven pattern (<i>C3orf14, GPR27, ZNF717</i>), a gene dosage driven pattern (<i>THOC7, PSMD6</i>), and a combined methylation and gene dosage driven pattern (<i>FHIT, ADAMTS9, LRIG1</i>). In survival analysis, patients with both hypermethylation and loss of <i>LRIG1</i> had a worse outcome compared to those harboring only hypermethylation or none of the events. <i>C3orf14</i> emerged as a novel methylation regulated suppressor gene, for which knockdown was found to promote invasive growth in human papilloma virus (HPV)-transformed keratinocytes. In conclusion, hypermethylation at 3p11-p14 is common in cervical cancer and may exert a selection pressure during carcinogenesis alone or combined with loss. Information on both events could lead to improved prognostic markers.
DOI: 10.6084/m9.figshare.1568532.v3
title: Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer

description: Loss of 3p11-p14 is a frequent event in epithelial cancer and a candidate prognostic biomarker in cervical cancer. In addition to loss, promoter methylation can participate in gene silencing and promote tumor aggressiveness. We have performed a complete mapping of promoter methylation at 3p11-p14 in two independent cohorts of cervical cancer patients (n = 149, n = 121), using Illumina 450K methylation arrays. The aim was to investigate whether hyperm-ethylation was frequent and could contribute to gene silencing and disease aggressiveness either alone or combined with loss. By comparing the methylation level of individual CpG sites with corresponding data of normal cervical tissue, 26 out of 41 genes were found to be hypermethylated in both cohorts. The frequency of patients with hypermethylation of these genes was found to be higher at tumor stages of 3 and 4 than in stage 1 tumors. Seventeen of the 26 genes were transcriptionally downregulated in cancer compared to normal tissue, whereof 6 genes showed a significant correlation between methylation and expression. Integrated analysis of methylation, gene dosage, and expression of the 26 hypermethylated genes identified 3 regulation patterns encompassing 8 hypermethylated genes; a methylation driven pattern (<i>C3orf14, GPR27, ZNF717</i>), a gene dosage driven pattern (<i>THOC7, PSMD6</i>), and a combined methylation and gene dosage driven pattern (<i>FHIT, ADAMTS9, LRIG1</i>). In survival analysis, patients with both hypermethylation and loss of <i>LRIG1</i> had a worse outcome compared to those harboring only hypermethylation or none of the events. <i>C3orf14</i> emerged as a novel methylation regulated suppressor gene, for which knockdown was found to promote invasive growth in human papilloma virus (HPV)-transformed keratinocytes. In conclusion, hypermethylation at 3p11-p14 is common in cervical cancer and may exert a selection pressure during carcinogenesis alone or combined with loss. Information on both events could lead to improved prognostic markers.
DOI: 10.25345/c5n17d
title: MassIVE MSV000086083 - Plasma Proteome Signature of Sepsis: a Functionally Connected Protein Network
title: Protein network integration from proteins in mouse plasma.
DOI: 10.6084/m9.figshare.1568530.v1
title: Development of a method for functional aspect identification in parotid using dynamic contrast-enhanced magnetic resonance imaging and concurrent stimulation

description: Development of a method for functional aspect identification in parotid using dynamic contrast-enhanced magnetic resonance imaging and concurrent stimulation
DOI: 10.6084/m9.figshare.1568532.v2
title: Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer

description: Loss of 3p11-p14 is a frequent event in epithelial cancer and a candidate prognostic biomarker in cervical cancer. In addition to loss, promoter methylation can participate in gene silencing and promote tumor aggressiveness. We have performed a complete mapping of promoter methylation at 3p11-p14 in two independent cohorts of cervical cancer patients (n = 149, n = 121), using Illumina 450K methylation arrays. The aim was to investigate whether hyperm-ethylation was frequent and could contribute to gene silencing and disease aggressiveness either alone or combined with loss. By comparing the methylation level of individual CpG sites with corresponding data of normal cervical tissue, 26 out of 41 genes were found to be hypermethylated in both cohorts. The frequency of patients with hypermethylation of these genes was found to be higher at tumor stages of 3 and 4 than in stage 1 tumors. Seventeen of the 26 genes were transcriptionally downregulated in cancer compared to normal tissue, whereof 6 genes showed a significant correlation between methylation and expression. Integrated analysis of methylation, gene dosage, and expression of the 26 hypermethylated genes identified 3 regulation patterns encompassing 8 hypermethylated genes; a methylation driven pattern (<i>C3orf14, GPR27, ZNF717</i>), a gene dosage driven pattern (<i>THOC7, PSMD6</i>), and a combined methylation and gene dosage driven pattern (<i>FHIT, ADAMTS9, LRIG1</i>). In survival analysis, patients with both hypermethylation and loss of <i>LRIG1</i> had a worse outcome compared to those harboring only hypermethylation or none of the events. <i>C3orf14</i> emerged as a novel methylation regulated suppressor gene, for which knockdown was found to promote invasive growth in human papilloma virus (HPV)-transformed keratinocytes. In conclusion, hypermethylation at 3p11-p14 is common in cervical cancer and may exert a selection pressure during carcinogenesis alone or combined with loss. Information on both events could lead to improved prognostic markers.
DOI: 10.6084/m9.figshare.1568530.v3
title: Development of a method for functional aspect identification in parotid using dynamic contrast-enhanced magnetic resonance imaging and concurrent stimulation

description: Development of a method for functional aspect identification in parotid using dynamic contrast-enhanced magnetic resonance imaging and concurrent stimulation
DOI: 10.6084/m9.figshare.1568530.v2
title: Development of a method for functional aspect identification in parotid using dynamic contrast-enhanced magnetic resonance imaging and concurrent stimulation

description: Development of a method for functional aspect identification in parotid using dynamic contrast-enhanced magnetic resonance imaging and concurrent stimulation
DOI: 10.6084/m9.figshare.1568520
title: Bioinformatic analysis of specific genes in diabetic nephropathy

description: <i>Objective</i>: We attempt to explore the pathogenesis and specific genes with aberrant expression in diabetic nephropathy (DN). <i>Methods</i>: The gene expression profile of GSE1009 was downloaded from Gene Expression Omnibus database, including 3 normal function glomeruli and DN glomeruli from cadaveric donor kidneys. The differentially expressed genes (DEGs) were analyzed and the aberrant gene-related functions were predicted by informatics methods. The protein–protein interaction (PPI) networks for DEGs were constructed and the functional sub-network was screened. <i>Results</i>: A total of 416 DEGs were found to be differentially expressed in DN samples comparing with normal controls, including 404 up-regulated genes and 12 down-regulated genes. DEGs were involved in the process of combination to saccharides and the decline of tissue repairing ability of the organisms. The genes of <i>VEGFA, ACTG1, HSP90AA1</i> had high degree in the PPI network. The main biological process of genes in the sub-network was related with cell proliferation and signal transmitting of cell membrane receptor. <i>Conclusion</i>: Significant nodes in PPI network provide new insights to understand the mechanism of DN. <i>VEGFA, ACTG1</i> and <i>HSP90AA1</i> may be the potential targets in the DN treatment.
DOI: 10.6084/m9.figshare.1568520.v1
title: Bioinformatic analysis of specific genes in diabetic nephropathy

description: <i>Objective</i>: We attempt to explore the pathogenesis and specific genes with aberrant expression in diabetic nephropathy (DN). <i>Methods</i>: The gene expression profile of GSE1009 was downloaded from Gene Expression Omnibus database, including 3 normal function glomeruli and DN glomeruli from cadaveric donor kidneys. The differentially expressed genes (DEGs) were analyzed and the aberrant gene-related functions were predicted by informatics methods. The protein–protein interaction (PPI) networks for DEGs were constructed and the functional sub-network was screened. <i>Results</i>: A total of 416 DEGs were found to be differentially expressed in DN samples comparing with normal controls, including 404 up-regulated genes and 12 down-regulated genes. DEGs were involved in the process of combination to saccharides and the decline of tissue repairing ability of the organisms. The genes of <i>VEGFA, ACTG1, HSP90AA1</i> had high degree in the PPI network. The main biological process of genes in the sub-network was related with cell proliferation and signal transmitting of cell membrane receptor. <i>Conclusion</i>: Significant nodes in PPI network provide new insights to understand the mechanism of DN. <i>VEGFA, ACTG1</i> and <i>HSP90AA1</i> may be the potential targets in the DN treatment.
DOI: 10.6084/m9.figshare.1568517
title: Glutamine contributes to maintenance of mouse embryonic stem cell self-renewal through PKC-dependent downregulation of HDAC1 and DNMT1/3a

description: Although glutamine (Gln) is not an essential amino acid, it is considered a critical substrate in many key metabolic processes that control a variety of physiological functions and are involved in regulating early embryonic development. Thus, we investigated the effect of Gln on regulation of mouse embryonic stem cell (mESC) self-renewal and related signaling pathways. Gln deprivation decreased Oct4 expression as well as expression of cell cycle regulatory proteins. However, Gln treatment retained the expression of cell cycle regulatory proteins and the Oct4 in mESCs, which were blocked by compound 968 (a glutaminase inhibitor). In addition, Gln stimulated PI3K/Akt pathway, which subsequently elicited PKCϵ translocation to membrane without an influx of intracellular Ca<sup>2+</sup>. Inhibition of Akt and PKC blocked Gln-induced Oct4 expression and proliferation. Gln also stimulated mTOR phosphorylation in a time-dependent manner, which abolished by PKC inhibition. Furthermore, Gln increased the cellular population of both Oct4 and bromodeoxyuridine positive cells, suggesting that Gln regulates self-renewal ability of mESCs. Gln induced a decrease in HDAC1, but not in HDAC2, which were blocked by PKC inhibitors. Gln treatment resulted in an increase in global histone acetylation and methylation. In addition, Gln significantly reduced methylation of the Oct4 promoter region through decrease in DNMT1 and DNMT3a expression, which were blocked by PKC and HDAC inhibitors. In conclusion, Gln stimulates mESC proliferation and maintains mESC undifferentiation status through transcription regulation via the Akt, PKCϵ, and mTOR signaling pathways.
DOI: 10.6084/m9.figshare.1568515
title: IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients

description: <b>Objectives</b>: To describe the clinical features, treatment response, and follow-up of a large cohort of Italian patients with immunoglobulin (Ig)G4-related disease (IgG4-RD) referred to a single tertiary care centre. <b>Method</b>: Clinical, laboratory, histological, and imaging features were retrospectively reviewed. IgG4-RD was classified as ‘definite’ or ‘possible’ according to international consensus guidelines and comprehensive diagnostic criteria for IgG4-RD. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI). <b>Results</b>: Forty-one patients (15 females, 26 males) were included in this study: 26 with ‘definite’ IgG4-RD and 15 with ‘possible’ IgG4-RD. The median age at diagnosis was 62 years. The median follow-up was 36 months (IQR 24–51). A history of atopy was present in 30% of patients. The pancreas, retroperitoneum, and major salivary glands were the most frequently involved organs. Serum IgG4 levels were elevated in 68% of cases. Thirty-six patients were initially treated with glucocorticoids (GCs) to induce remission. IgG4-RD RI decreased from a median of 7.8 at baseline to 2.9 after 1 month of therapy. Relapse occurred in 19/41 patients (46%) and required additional immunosuppressive drugs to maintain long-term remission. Multiple flares occurred in a minority of patients. A single case of orbital pseudotumour did not respond to medical therapy and underwent surgical debulking. <b>Conclusions</b>: IgG4-RD is an elusive inflammatory disease to be considered in the differential diagnosis of isolated or multiple tumefactive lesions. Long-term disease control can be achieved with corticosteroids and immunosuppressive drugs in the majority of cases.
DOI: 10.6084/m9.figshare.1568517.v2
title: Glutamine contributes to maintenance of mouse embryonic stem cell self-renewal through PKC-dependent downregulation of HDAC1 and DNMT1/3a

description: Although glutamine (Gln) is not an essential amino acid, it is considered a critical substrate in many key metabolic processes that control a variety of physiological functions and are involved in regulating early embryonic development. Thus, we investigated the effect of Gln on regulation of mouse embryonic stem cell (mESC) self-renewal and related signaling pathways. Gln deprivation decreased Oct4 expression as well as expression of cell cycle regulatory proteins. However, Gln treatment retained the expression of cell cycle regulatory proteins and the Oct4 in mESCs, which were blocked by compound 968 (a glutaminase inhibitor). In addition, Gln stimulated PI3K/Akt pathway, which subsequently elicited PKCϵ translocation to membrane without an influx of intracellular Ca<sup>2+</sup>. Inhibition of Akt and PKC blocked Gln-induced Oct4 expression and proliferation. Gln also stimulated mTOR phosphorylation in a time-dependent manner, which abolished by PKC inhibition. Furthermore, Gln increased the cellular population of both Oct4 and bromodeoxyuridine positive cells, suggesting that Gln regulates self-renewal ability of mESCs. Gln induced a decrease in HDAC1, but not in HDAC2, which were blocked by PKC inhibitors. Gln treatment resulted in an increase in global histone acetylation and methylation. In addition, Gln significantly reduced methylation of the Oct4 promoter region through decrease in DNMT1 and DNMT3a expression, which were blocked by PKC and HDAC inhibitors. In conclusion, Gln stimulates mESC proliferation and maintains mESC undifferentiation status through transcription regulation via the Akt, PKCϵ, and mTOR signaling pathways.
DOI: 10.6084/m9.figshare.1568515.v1
title: IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients

description: <b>Objectives</b>: To describe the clinical features, treatment response, and follow-up of a large cohort of Italian patients with immunoglobulin (Ig)G4-related disease (IgG4-RD) referred to a single tertiary care centre. <b>Method</b>: Clinical, laboratory, histological, and imaging features were retrospectively reviewed. IgG4-RD was classified as ‘definite’ or ‘possible’ according to international consensus guidelines and comprehensive diagnostic criteria for IgG4-RD. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI). <b>Results</b>: Forty-one patients (15 females, 26 males) were included in this study: 26 with ‘definite’ IgG4-RD and 15 with ‘possible’ IgG4-RD. The median age at diagnosis was 62 years. The median follow-up was 36 months (IQR 24–51). A history of atopy was present in 30% of patients. The pancreas, retroperitoneum, and major salivary glands were the most frequently involved organs. Serum IgG4 levels were elevated in 68% of cases. Thirty-six patients were initially treated with glucocorticoids (GCs) to induce remission. IgG4-RD RI decreased from a median of 7.8 at baseline to 2.9 after 1 month of therapy. Relapse occurred in 19/41 patients (46%) and required additional immunosuppressive drugs to maintain long-term remission. Multiple flares occurred in a minority of patients. A single case of orbital pseudotumour did not respond to medical therapy and underwent surgical debulking. <b>Conclusions</b>: IgG4-RD is an elusive inflammatory disease to be considered in the differential diagnosis of isolated or multiple tumefactive lesions. Long-term disease control can be achieved with corticosteroids and immunosuppressive drugs in the majority of cases.
DOI: 10.6084/m9.figshare.1568517.v1
title: Glutamine contributes to maintenance of mouse embryonic stem cell self-renewal through PKC-dependent downregulation of HDAC1 and DNMT1/3a

description: ABSTRACTAlthough glutamine (Gln) is not an essential amino acid, it is considered a critical substrate in many key metabolic processes that control a variety of physiological functions and are involved in regulating early embryonic development. Thus, we investigated the effect of Gln on regulation of mouse embryonic stem cell (mESC) self-renewal and related signaling pathways. Gln deprivation decreased Oct4 expression as well as expression of cell cycle regulatory proteins. However, Gln treatment retained the expression of cell cycle regulatory proteins and the Oct4 in mESCs, which were blocked by compound 968 (a glutaminase inhibitor). In addition, Gln stimulated PI3K/Akt pathway, which subsequently elicited PKCε translocation to membrane without an influx of intracellular Ca<sup>2+</sup>. Inhibition of Akt and PKC blocked Gln-induced Oct4 expression and proliferation. Gln also stimulated mTOR phosphorylation in a time-dependent manner, which abolished by PKC inhibition. Furthermore, Gln increased the cellular population of both Oct4 and bromodeoxyuridine positive cells, suggesting that Gln regulates self-renewal ability of mESCs. Gln induced a decrease in HDAC1, but not in HDAC2, which were blocked by PKC inhibitors. Gln treatment resulted in an increase in global histone acetylation and methylation. In addition, Gln significantly reduced methylation of the Oct4 promoter region through decrease in DNMT1 and DNMT3a expression, which were blocked by PKC and HDAC inhibitors. In conclusion, Gln stimulates mESC proliferation and maintains mESC undifferentiation status through transcription regulation via the Akt, PKCε, and mTOR signaling pathways.