Σάββατο, 23 Σεπτεμβρίου 2017

Cancers, Vol. 9, Pages 129: Alcohol Misuse Link to POEMS Syndrome in a Patient

Cancers, Vol. 9, Pages 129: Alcohol Misuse Link to POEMS Syndrome in a Patient

Cancers doi: 10.3390/cancers9100129

Authors: John Neary Susan Goodwin Lawrence Cohen Manuela Neuman

Previously called Crow–Fukase syndrome, POEMS syndrome is characterized by poly-neuropathy, osteo-sclerotic myeloma, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. Extremely elevated levels of serum vascular endothelial growth factor (VEGF) are characteristic of the syndrome. Chronic hepatitis B (HBV) and C (HCV) infections can also be present in POEMS. The pathogenesis of the syndrome is not well understood. The link between chronic alcohol consumption and this malignant condition has not been reported until now. In addition, no previous study has evaluated the influence of cytokine and chemokines or viruses in the severity and evolution of POEMS. Objectives: (1) to describe a heavy-alcohol user, who was diagnosed with POEMS; (2) to demonstrate the utility of quantitative measurement of serum levels of VEGF in the diagnosis of POEMS and the monitoring of therapeutic interventions; (3) to demonstrate that overproduction of pro-inflammatory cytokines is a characteristic of POEMS. Methods: We describe a case of a POEMS patient presenting HCV and who is a heavy drinker; we compare the serum levels of cytokines and chemokines between the POEMS patient with 80 patients with HCV, 12 healthy controls, and 80 individuals with alcoholic liver disease (ALD). We quantified (ELISA pg/mL) the levels of VEGF, Interferon gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), Regulated-upon-Activation Normal-T-cell-Expressed and presumably-Secreted (RANTES), and Nuclear Factor kappa-B (NFκB). Results: In POEMS patients, VEGF levels were elevated versus control or other diseases, TNFα levels were higher versus control, but lower when compared with HCV or ALD patients. VEGF levels in POEMS patients decreased with therapeutic intervention. Conclusions: Chronic alcohol misuse can be a strong risk factor to rare malignancies such as POEMS syndrome. Extreme elevation of VEGF levels is diagnostic for POEMS syndrome, and should be followed to assess response to therapy. In addition, other comorbidities should be considered individually to ensure personalized therapeutic intervention.



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Cancers, Vol. 9, Pages 129: Alcohol Misuse Link to POEMS Syndrome in a Patient

Cancers, Vol. 9, Pages 129: Alcohol Misuse Link to POEMS Syndrome in a Patient

Cancers doi: 10.3390/cancers9100129

Authors: John Neary Susan Goodwin Lawrence Cohen Manuela Neuman

Previously called Crow–Fukase syndrome, POEMS syndrome is characterized by poly-neuropathy, osteo-sclerotic myeloma, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. Extremely elevated levels of serum vascular endothelial growth factor (VEGF) are characteristic of the syndrome. Chronic hepatitis B (HBV) and C (HCV) infections can also be present in POEMS. The pathogenesis of the syndrome is not well understood. The link between chronic alcohol consumption and this malignant condition has not been reported until now. In addition, no previous study has evaluated the influence of cytokine and chemokines or viruses in the severity and evolution of POEMS. Objectives: (1) to describe a heavy-alcohol user, who was diagnosed with POEMS; (2) to demonstrate the utility of quantitative measurement of serum levels of VEGF in the diagnosis of POEMS and the monitoring of therapeutic interventions; (3) to demonstrate that overproduction of pro-inflammatory cytokines is a characteristic of POEMS. Methods: We describe a case of a POEMS patient presenting HCV and who is a heavy drinker; we compare the serum levels of cytokines and chemokines between the POEMS patient with 80 patients with HCV, 12 healthy controls, and 80 individuals with alcoholic liver disease (ALD). We quantified (ELISA pg/mL) the levels of VEGF, Interferon gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), Regulated-upon-Activation Normal-T-cell-Expressed and presumably-Secreted (RANTES), and Nuclear Factor kappa-B (NFκB). Results: In POEMS patients, VEGF levels were elevated versus control or other diseases, TNFα levels were higher versus control, but lower when compared with HCV or ALD patients. VEGF levels in POEMS patients decreased with therapeutic intervention. Conclusions: Chronic alcohol misuse can be a strong risk factor to rare malignancies such as POEMS syndrome. Extreme elevation of VEGF levels is diagnostic for POEMS syndrome, and should be followed to assess response to therapy. In addition, other comorbidities should be considered individually to ensure personalized therapeutic intervention.



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Trichostatin A preferentially reverses the upregulation of gene expression levels induced by gain of chromosome 7 in colorectal cancer cell lines

Abstract

Epithelial cancers are defined by a tumor-specific distribution of chromosomal aneuploidies that are maintained when cells metastasize and are conserved in cell lines derived from primary tumors. Correlations between genomic copy number and gene expression have been observed for different tumors including, colorectal (CRC), breast and pancreatic cancer. These ploidy-driven transcriptional deregulations are characterized by low-level expression changes of most genes on the affected chromosomes. The emergence of these aberrations at an early stage of tumorigenesis and the strong selection for the maintenance of these aneuploidies suggests that aneuploidy-dependent transcriptional deregulations might contribute to cellular transformation and maintenance of the malignant phenotype. The histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) has anticancer effects and is well known to lead to large scale gene expression changes. Here we assessed if TSA could disrupt the aneuploidy-driven gene expression in the aneuploid colon cancer cell line SW480 and the artificially generated aneuploid cell line DLD-1 + 7. We found that TSA increases transcriptional activity throughout the genome, yet inhibits aneuploidy-induced gene expression changes on chromosome 7. Among the TSA affected genes on chromosome 7 we identified potential CRC oncogenes. These experiments represent the first attempt to explain how histone acetylation affects aneuploidy-driven gene expression changes. This article is protected by copyright. All rights reserved.



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Trichostatin A preferentially reverses the upregulation of gene expression levels induced by gain of chromosome 7 in colorectal cancer cell lines

Abstract

Epithelial cancers are defined by a tumor-specific distribution of chromosomal aneuploidies that are maintained when cells metastasize and are conserved in cell lines derived from primary tumors. Correlations between genomic copy number and gene expression have been observed for different tumors including, colorectal (CRC), breast and pancreatic cancer. These ploidy-driven transcriptional deregulations are characterized by low-level expression changes of most genes on the affected chromosomes. The emergence of these aberrations at an early stage of tumorigenesis and the strong selection for the maintenance of these aneuploidies suggests that aneuploidy-dependent transcriptional deregulations might contribute to cellular transformation and maintenance of the malignant phenotype. The histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) has anticancer effects and is well known to lead to large scale gene expression changes. Here we assessed if TSA could disrupt the aneuploidy-driven gene expression in the aneuploid colon cancer cell line SW480 and the artificially generated aneuploid cell line DLD-1 + 7. We found that TSA increases transcriptional activity throughout the genome, yet inhibits aneuploidy-induced gene expression changes on chromosome 7. Among the TSA affected genes on chromosome 7 we identified potential CRC oncogenes. These experiments represent the first attempt to explain how histone acetylation affects aneuploidy-driven gene expression changes. This article is protected by copyright. All rights reserved.



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Clinical significance of SLP-2 in hepatocellular carcinoma tissues and its regulation in cancer cell proliferation, migration, and EMT

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The effects of nonsteroidal anti-inflammatory drugs in the incident and recurrent risk of hepatocellular carcinoma: a meta-analysis

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DNA ploidy and S-phase fraction analysis in peritoneal carcinomatosis from ovarian cancer: correlation with clinical pathological factors and response to chemotherapy

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