Adjuvant therapy in renal cell carcinoma

Publication date: Available online 23 September 2017
Source:Cancer Treatment Reviews
Author(s): Francesco Massari, Vincenzo Di Nunno, Chiara Ciccarese, Jeffrey Graham, Camillo Porta, Francesca Comito, Marta Cubelli, Roberto Iacovelli, Daniel Y.C. Heng
Several drugs have demonstrated clinical activity in metastatic renal cell carcinoma (mRCC). The identification of key metabolic pathways has led to the development of novel targeted therapies which have drastically changed the treatment paradigm of mRCC. Moreover, immune-checkpoint inhibitors have recently shown significant activity in advanced disease. Despite these advancements, the role of adjuvant therapy in localized, non-metastatic RCC remains unclear. The utility of many of these agents in the adjuvant setting is currently being actively explored. In this review, we will summarize the main clinical trials investigating adjuvant therapy in renal cell carcinoma, focusing primarily on immunotherapy and targeted agents.



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Patterns and the Occurrence of KRAS Mutations in Metastatic Colorectal Cancers—a Study from Indian Regional Cancer Centre

Abstract

Mutation analysis of the KRAS oncogene is established as a predictive biomarker in Colorectal cancer (CRC). Many prospective clinical trials have shown that only CRCs with wild-type KRAS respond to anti-epidermal growth factor receptor (EGFR) treatment. Hence, mutation analysis is mandatory before treatment of metastatic CRCs. There are very few studies on the KRAS mutation status in the Indian setting. Hence, this study was done to document the patterns of KRAS mutations in CRCs reporting to a regional cancer centre in South India. Among 150 cases of metastatic colorectal cancer reporting over a period of 20 months, 48 random cases were analyzed for the KRAS mutational status of codons 12 and 13 of the KRAS gene by genomic sequencing. KRAS mutations in codons 12 and 13 were present in 9/48 (18.75%) of all analyzed CRCs. The common types of mutations were glycine to aspartate on codon 12 (p.G12D), glycine to valine on codon 12 (p.G12 V), and glycine to aspartate on codon 13 (p.G13D).

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Patterns and the Occurrence of KRAS Mutations in Metastatic Colorectal Cancers—a Study from Indian Regional Cancer Centre

Abstract

Mutation analysis of the KRAS oncogene is established as a predictive biomarker in Colorectal cancer (CRC). Many prospective clinical trials have shown that only CRCs with wild-type KRAS respond to anti-epidermal growth factor receptor (EGFR) treatment. Hence, mutation analysis is mandatory before treatment of metastatic CRCs. There are very few studies on the KRAS mutation status in the Indian setting. Hence, this study was done to document the patterns of KRAS mutations in CRCs reporting to a regional cancer centre in South India. Among 150 cases of metastatic colorectal cancer reporting over a period of 20 months, 48 random cases were analyzed for the KRAS mutational status of codons 12 and 13 of the KRAS gene by genomic sequencing. KRAS mutations in codons 12 and 13 were present in 9/48 (18.75%) of all analyzed CRCs. The common types of mutations were glycine to aspartate on codon 12 (p.G12D), glycine to valine on codon 12 (p.G12 V), and glycine to aspartate on codon 13 (p.G13D).

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An atypical presentation of cardiac tamponade and periorbital swelling in a patient with eosinophilic granulomatosis with polyangiitis: a case report

Eosinophilic granulomatosis with polyangiitis is a rare, necrotizing systemic vasculitis associated with asthma and hypereosinophilia. Its cause and pathophysiology are still being elucidated.

http://ift.tt/2wKQqu1

Genomic signatures as predictive biomarkers of homologous recombination deficiency in ovarian cancer

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Adriaan Vanderstichele, Pieter Busschaert, Siel Olbrecht, Diether Lambrechts, Ignace Vergote
DNA repair deficiency is a common hallmark of many cancers and is increasingly recognised as a target for cancer therapeutics. Selecting patients for these treatments requires a functional assessment of multiple redundant DNA repair pathways. With the advent of whole-genome sequencing of cancer genomes, it is increasingly recognised that multiple signatures of mutational and chromosomal alterations can be correlated with specific DNA repair defects. The clinical relevance of this approach is underlined by the use of poly-(ADP-ribose) polymerase inhibitors (PARPi) in homologous recombination (HR) deficient high-grade serous ovarian cancers. Beyond deleterious mutations in HR-related genes such as BRCA1/2, it is recognised that HR deficiency endows ovarian cancers with specific signatures of base substitutions and structural chromosomal variation. Multiple metrics quantifying loss-of-heterozygosity (LOH) events were proposed and implemented in trials with PARPi. However, it was shown that some of the HR-deficient cases, i.e. CDK12–mutated tumours, were not associated with high LOH-based scores, but with distinct patterns of genomic alterations such as tandem duplication. Therefore, more complex signatures of structural genomic variation were identified and quantified. Ultimately, optimal prediction models for treatments targeting DNA repair will need to integrate multiples of these genomic signatures and will also need to assess multiple resistance mechanisms such as genomic reversion events that partially or fully re-activate DNA repair.



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PIKHER2: A phase IB study evaluating buparlisib in combination with lapatinib in trastuzumab-resistant HER2-positive advanced breast cancer

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Mathilde Guerin, Keyvan Rezai, Nicolas Isambert, Mario Campone, Aurélie Autret, Jihane Pakradouni, Magali Provansal, Jacques Camerlo, Renaud Sabatier, François Bertucci, Emmanuelle Charafe-Jauffret, Alice Hervieu, Jean-Marc Extra, Patrice Viens, François Lokiec, Jean-Marie Boher, Anthony Gonçalves
BackgroundPhosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin pathway is frequently activated in HER2-positive breast cancer and may play a major role in resistance to trastuzumab. Buparlisib is a pan-class-I PI3K inhibitor with potent and selective activity against wild-type and mutant PI3K p110 isoforms.Patients and methodsPIKHER2 phase IB study aimed primarily to determine a maximum tolerated dose (MTD) and propose a recommended phase II dose (RP2D) for buparlisib in combination with lapatinib in HER2-positive, trastuzumab-resistant, advanced breast cancer. Oral buparlisib (40, 60 or 80 mg) and lapatinib (750, 1000 or 1250 mg) were administered daily. A modified continuous reassessment method using an adaptive Bayesian model guided the dose escalation of both agents. Secondary end-points included antitumour activity and pharmacokinetic (PK) assessments.ResultsA total of 24 patients were treated across five dose levels. Dose-limiting toxicities included transaminases elevation, vomiting, stomatitis, hyperglycemia and diarrhoea. MTD was declared at buparlisib 80 mg/d + lapatinib 1250 mg/d, but toxicities and early treatment discontinuation rate beyond cycle 1 led to select buparlisib 80 mg + lapatinib 1000 mg/d as the RP2D. Main drug-related adverse events included diarrhoea, nausea, skin rash, asthenia, depression, anxiety and transaminases increase. There was no significant evidence for drug–drug PK interaction. Disease control rate was 79% [95% confidence interval [CI] 57–92%], one patient obtained a complete remission, and six additional patients experienced stable disease for ≥ 24 weeks (clinical benefit rate of 29% [95% CI 12–51%]).ConclusionCombining buparlisib and lapatinib in HER2-positive trastuzumab-resistant advanced breast cancer was feasible. Preliminary evidence of antitumour activity was observed in this heavily pre-treated population.Trial registration IDNCT01589861.



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Determination of poor prognostic immune features of tumour microenvironment in non-smoking patients with lung adenocarcinoma

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Tomonari Kinoshita, Chie Kudo-Saito, Reiko Muramatsu, Tomonobu Fujita, Miyuki Saito, Haruna Nagumo, Toshiharu Sakurai, Shinobu Noji, Emi Takahata, Tomonori Yaguchi, Nobuo Tsukamoto, Yuichiro Hayashi, Kaoru Kaseda, Ikuo Kamiyama, Takashi Ohtsuka, Kenji Tomizawa, Masaki Shimoji, Tetsuya Mitsudomi, Hisao Asamura, Yutaka Kawakami
We have previously demonstrated that the prognostic significance of tumour-infiltrating CD8⁺ T cells significantly differs according to histological type and patient smoking habits in non-small cell lung cancer (NSCLC). This work suggested that infiltrating CD8⁺ T cells may not be activated sufficiently in the immunosuppressive microenvironment in non-smokers with adenocarcinoma. To understand the immunogenic microenvironment in NSCLC, we characterised immune cells comprehensively by performing an immunohistochemical evaluation using an alternative counting method and multicolour staining method (n = 234), and assessed immune-related gene expression by using genetic analytical approaches (n = 58). We found that high infiltration of activated CD8⁺ T cells expressing interferon gamma (IFN-γ) and granzyme was correlated with postoperative survival in patients with non-adenocarcinoma. On the contrary, CD8⁺ T-cell accumulation was identified as a worse prognostic factor in patients with adenocarcinoma, particularly in non-smokers. Infiltrating CD8⁺ T cells were significantly less activated in this microenvironment with high expression of various immunoregulation genes. Potentially immunoregulatory CD8⁺ FOXP3⁺ T cells and immunodysfunctional CD8⁺ GATA3⁺ T cells were increased in adenocarcinoma of non-smokers. CD4⁺ FOXP3⁺ regulatory T cells expressing chemokine receptor-4 (CCR4)- and chemokine ligand (CCL17)-expressing CD163⁺ M2-like macrophages also accumulated correlatively and significantly in adenocarcinoma of non-smokers. These characteristic immune cells may promote tumour progression possibly by creating an immunosuppressive microenvironment in non-smoking patients with lung adenocarcinoma. Our findings may be helpful for refining the current strategy of personalised immunotherapy including immune-checkpoint blockade therapy for NSCLC.



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Cancer as an ecomolecular disease and a neoplastic consortium

Publication date: Available online 23 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Santiago Ramón y Cajal, Claudia Capdevila, Javier Hernandez-Losa, Leticia de Mattos, Abhishek Ghosh, Julie Lorent, Ola Larsson, Trond Aasen, Lynne-Marie Postovit, Ivan Topisirovic
Current anticancer paradigms largely target driver mutations considered integral for cancer cell survival and tumor progression. Although initially successful, many of these strategies are unable to overcome the tremendous heterogeneity that characterizes advanced tumors, resulting in the emergence of resistant disease. Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in wide phenotypic and molecular heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells and the tumor microenvironment. In this context, cancer may be perceived as an "ecomolecular" disease that involves cooperation between several neoplastic clones and their interactions with immune cells, stromal fibroblasts, and other cell types present in the microenvironment. This collaboration is mediated by a variety of secreted factors. Cancer is therefore analogous to complex ecosystems such as microbial consortia.In the present article, we comment on the current paradigms and perspectives guiding the development of cancer diagnostics and therapeutics and the potential application of systems biology to untangle the complexity of neoplasia. In our opinion, conceptualization of neoplasia as an ecomolecular disease is warranted. Advances in knowledge pertinent to the complexity and dynamics of interactions within the cancer ecosystem are likely to improve understanding of tumor etiology, pathogenesis, and progression. This knowledge is anticipated to facilitate the design of new and more effective therapeutic approaches that target the tumor ecosystem in its entirety.



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Bilateral Breast and Axillary Lymph Nodes Metastases of an Ovarian Serous Cystadenocarcinoma

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Bilateral Breast and Axillary Lymph Nodes Metastases of an Ovarian Serous Cystadenocarcinoma

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18F-FDG PET image biomarkers improve prediction of late radiation-induced xerostomia

Current prediction of radiation-induced xerostomia 12months after radiotherapy (Xer12m) is based on mean parotid gland dose and baseline xerostomia (Xerbaseline) scores. The hypothesis of this study was that prediction of Xer12m is improved with patient-specific characteristics extracted from 18F-FDG PET images, quantified in PET image biomarkers (PET-IBMs).

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A retrospective cohort study to assess adjuvant concurrent chemoradiation (CCRT) compared to adjuvant radiation therapy (RT) in the treatment of grade 2 and 3 extremity soft tissue sarcomas

To evaluate the efficacy and tolerance of adjuvant concurrent chemoradiation (CCRT) as treatment of grade 2 and 3 (G2-3) localized extremity soft tissue sarcomas (STS) by comparing CCRT with standard adjuvant radiation therapy (RT).

http://ift.tt/2fIiNhU

Patient-specific bolus for range shifter air gap reduction in intensity-modulated proton therapy of head-and-neck cancer studied with Monte Carlo based plan optimization

Intensity-modulated proton therapy (IMPT) of superficial lesions requires pre-absorbing range shifter (RS) to deliver the more shallow spots. RS air gap minimization is important to avoid spot size degradation, but remains challenging in complex geometries such as in head-and-neck cancer (HNC). In this study, clinical endpoints were investigated for patient-specific bolus and for conventional RS solutions, making use of a Monte Carlo (MC) dose engine for IMPT optimization.

http://ift.tt/2xn6Zf6

Spatiotemporal fractionation schemes for liver stereotactic body radiotherapy

Dose prescription in stereotactic body radiotherapy (SBRT) for liver tumors is often limited by the mean liver dose. We explore the concept of spatiotemporal fractionation as an approach to facilitate further dose escalation in liver SBRT.

http://ift.tt/2fJfZBn

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.

http://ift.tt/2xYaZTZ

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

http://ift.tt/2xqjTGG

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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HIF pathway and c-Myc as biomarkers for response to sunitinib in metastatic clear-cell renal cell carcinoma

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Targeting the androgen receptor in triple-negative breast cancer: current perspectives

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Approach to MPN Symptom Assessment

Abstract

Purpose of Review

Myeloproliferative neoplasms (MPNs) are recognized for their debilitating symptom burdens. The purpose of this review is to understand the complexity of the MPN symptom burden and identify how validated MPN Patient Reported Outcome (PRO) tools may be integrated into clinical practice to assess the MPN symptom burden.

Recent Findings

Significant heterogeneity exists both within and between MPN subtypes. Surrogates of disease burden such as risk scores and MPN chronicity often fail to correlate with symptomatic burden. Validated MPN PROs allow for precise and rapid assessment of the MPN symptom burden in clinical and trial settings. Their growing use among investigators has resulted in improved understanding of how the MPN disease burden and overall patient experience is impacted by novel and traditional therapies.

Summary

PRO tools are an integral part of National Comprehensive Cancer Center (NCCN) guidelines for MPN treatment and should be regularly employed in disease burden assessment.

http://ift.tt/2xY2Dvz

Approach to MPN Symptom Assessment

Abstract

Purpose of Review

Myeloproliferative neoplasms (MPNs) are recognized for their debilitating symptom burdens. The purpose of this review is to understand the complexity of the MPN symptom burden and identify how validated MPN Patient Reported Outcome (PRO) tools may be integrated into clinical practice to assess the MPN symptom burden.

Recent Findings

Significant heterogeneity exists both within and between MPN subtypes. Surrogates of disease burden such as risk scores and MPN chronicity often fail to correlate with symptomatic burden. Validated MPN PROs allow for precise and rapid assessment of the MPN symptom burden in clinical and trial settings. Their growing use among investigators has resulted in improved understanding of how the MPN disease burden and overall patient experience is impacted by novel and traditional therapies.

Summary

PRO tools are an integral part of National Comprehensive Cancer Center (NCCN) guidelines for MPN treatment and should be regularly employed in disease burden assessment.

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Status of implementation and organization of cancer screening in the European Union Member States - summary results from the second European screening report

Abstract

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N=80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only.

Substantial improvement in screening implementation using population-based approach was documented. Among the age-eligible women, 94.7% were residents of Member States implementing or planning population-based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3% and 51.3% in 2016 and 2007 respectively. Most significant improvement was documented for colorectal cancer screening with roll-out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population-based screening increased to 72.4% of the age-eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2%-111% for breast cancer, 7.6%-105% for cervical cancer and 1.8%-127% for colorectal cancer in the target populations.

In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes. This article is protected by copyright. All rights reserved.

http://ift.tt/2yxnVNB

Status of implementation and organization of cancer screening in the European Union Member States - summary results from the second European screening report

Abstract

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N=80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only.

Substantial improvement in screening implementation using population-based approach was documented. Among the age-eligible women, 94.7% were residents of Member States implementing or planning population-based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3% and 51.3% in 2016 and 2007 respectively. Most significant improvement was documented for colorectal cancer screening with roll-out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population-based screening increased to 72.4% of the age-eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2%-111% for breast cancer, 7.6%-105% for cervical cancer and 1.8%-127% for colorectal cancer in the target populations.

In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes. This article is protected by copyright. All rights reserved.

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Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer

Abstract

Background

To identify clinically relevant genomic rearrangement signatures in high-grade serous ovarian cancer (HGSOC), we conducted a retrospective analysis of sequenced HGSOC whole-tumor genomes.

Methods

Clinical data and whole-genome sequencing (WGS) reads were obtained for primary HGSOC tumors sequenced by the Australian Ovarian Cancer Study (AOCS; n = 80). Genomic rearrangements were identified, and non-negative matrix factorization (NMF) was used to extract rearrangement signatures. The cohort was then dichotomized around the median signature contribution, and overall survival (OS) was analyzed. An independent cohort from The Cancer Genome Atlas (TCGA) ovarian cancer study (n = 490) was also examined. The TCGA cohort was dichotomized around the median similarity between tumor copy number profile and a prognostic rearrangement signature, and OS was analyzed. Outcomes were assessed using Kaplan-Meier and multivariable Cox regression methods. All statistical tests were two-sided.

Results

We identified five genomic rearrangement signatures (Ov.RS1-5) in HGSOC. Ov.RS3 exhibited 10 kilobase to 10 megabase deletions and tandem duplications, and patients whose tumors exhibited a high contribution from Ov.RS3 had poor OS. The median OS was 22.7 months (95% confidence interval [CI] = 20.2 to 39.0 months) in the Ov.RS3-high group vs 38.2 months (95% CI = 22.7 to 69.1 months) in the Ov.RS3-low group (hazard ratio [HR] = 1.86, 95% CI = 1.12 to 3.09, P = .02). For the independent TCGA cohort, median OS rates were 38.0 months (95% CI = 35.3 to 41.4 months) in the Ov.RS3 high-similarity group vs 48.9 months (95% CI = 44.1 to 57.1 months) in the Ov.RS3 low-similarity group (HR = 1.54, 95% CI = 1.21 to 1.97, P < .001).

Conclusion

A novel genomic rearrangement signature is associated with poor prognosis in HGSOC.

http://ift.tt/2yycC7Q

Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer

Abstract

Background

To identify clinically relevant genomic rearrangement signatures in high-grade serous ovarian cancer (HGSOC), we conducted a retrospective analysis of sequenced HGSOC whole-tumor genomes.

Methods

Clinical data and whole-genome sequencing (WGS) reads were obtained for primary HGSOC tumors sequenced by the Australian Ovarian Cancer Study (AOCS; n = 80). Genomic rearrangements were identified, and non-negative matrix factorization (NMF) was used to extract rearrangement signatures. The cohort was then dichotomized around the median signature contribution, and overall survival (OS) was analyzed. An independent cohort from The Cancer Genome Atlas (TCGA) ovarian cancer study (n = 490) was also examined. The TCGA cohort was dichotomized around the median similarity between tumor copy number profile and a prognostic rearrangement signature, and OS was analyzed. Outcomes were assessed using Kaplan-Meier and multivariable Cox regression methods. All statistical tests were two-sided.

Results

We identified five genomic rearrangement signatures (Ov.RS1-5) in HGSOC. Ov.RS3 exhibited 10 kilobase to 10 megabase deletions and tandem duplications, and patients whose tumors exhibited a high contribution from Ov.RS3 had poor OS. The median OS was 22.7 months (95% confidence interval [CI] = 20.2 to 39.0 months) in the Ov.RS3-high group vs 38.2 months (95% CI = 22.7 to 69.1 months) in the Ov.RS3-low group (hazard ratio [HR] = 1.86, 95% CI = 1.12 to 3.09, P = .02). For the independent TCGA cohort, median OS rates were 38.0 months (95% CI = 35.3 to 41.4 months) in the Ov.RS3 high-similarity group vs 48.9 months (95% CI = 44.1 to 57.1 months) in the Ov.RS3 low-similarity group (HR = 1.54, 95% CI = 1.21 to 1.97, P < .001).

Conclusion

A novel genomic rearrangement signature is associated with poor prognosis in HGSOC.

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Fulminant myocardial bleeding: another clinical course of vascular Ehlers-Danlos Syndrome

Vascular Ehlers-Danlos Syndrome (vEDS) is a dominantly inherited connective tissue disorder characterised by colon rupture and arterial aneurysm, dissection and rupture. A patient was diagnosed with vEDS after a spontaneous colon rupture when he was brought to our institute because of sudden chest pain. An ECG revealed wide regional ST elevation, which was initially suggestive of acute myocarditis. On the second day, haemodynamics suddenly deteriorated because of a rapid accumulation of bloody pericardial effusion, and the patient died. Autopsy revealed an excessive spontaneous myocardial haemorrhage owing to fragility, which suggested an underlying disease—vEDS.

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Congenital melanocytic nevus mimicking a turban tumour in an 18-year-old Filipino male

Congenital melanocytic nevi (CMN) are nevi that are present at birth or arise within the first few weeks of life. They are often found on the trunk, head and neck and extremities. We report herein an unusual presentation of a CMN as a cerebriform tumour presenting as secondary cutis verticis gyrata on the scalp of an 18-year-old Filipino male.

http://ift.tt/2wNrDkh

Microbubble-enhanced ultrasound to demonstrate urethral transection in a case of penile fracture

A 47-year-old man attended the emergency department following trauma during sexual intercourse after which he developed penile swelling and haematuria several hours later. A penile fracture was suspected but given the slightly atypical history, ultrasound was performed to look for a fracture. Given the history of haematuria, both a standard Doppler ultrasound and a microbubble-enhanced retrograde ultrasound urethrogram were performed. The Doppler confirmed the suspected diagnosis of penile fracture, and microbubble urethrogram demonstrated a urethral injury. This facilitated prompt surgical treatment and helped guide the surgical approach. Retrograde microbubble enhanced ultrasound urethrogram is a novel technique that can be used in conjunction with standard ultrasound to confirm the presence of a concurrent urethral rupture in penile fracture.

http://ift.tt/2xvtm12

Case of methaemoglobinaemia caused by tree oils and kerosene

We report a case of a young man who allegedly consumed 100 mL of an indigenous pesticide which is used for the killing of rats in households in India. The constituents were azadirachtin oil (40%), tea oil (15%), pine oil (25%) and kerosene oil (20%). He presented to us with shortness of breath and altered sensorium and was found to have fMetHb (fraction of methaemoglobin) level of 80%, which has been postulated to have a fatal outcome. He responded to a low dose of methylene blue along with intravenous vitamin C and the level of fMetHb came down to 20% within 1 hour. His sensorium improved markedly with a decrease in fMetHb to non-toxic levels and he was discharged 5 days after admission. A literature review pertaining to these constituents individually or in combination causing methaemoglobinaemia is discussed in the context of this case.

http://ift.tt/2wNo0L4

Catastrophic cement reaction following cementation for megaprosthesis for proximal femoral fracture

Bone cement implantation syndrome (BCIS) is a well-described and potentially fatal complication of orthopaedic surgery involving pressurised bone cement. Although also described for certain spinal procedures, it is most commonly associated with cemented hip and knee arthroplasty and with cemented hemiarthroplasty following neck of femur fracture in particular.

Donaldson et alproposed the definition of BCIS as a syndrome "characterized by hypoxia, hypotension or both and/or unexpected loss of consciousness occurring around the time of cementation, prosthesis insertion, reduction of the joint or, occasionally, limb tourniquet deflation in a patient undergoing cemented bone surgery". Other features include increased vascular resistance, cardiac arrhythmias and cardiac arrest post cement use.

We describe a case of a patient who suffered a catastrophic reaction to cement during surgery for a comminuted proximal femoral fracture.

http://ift.tt/2xv9ZW0

Endoscopic surgical management of a large Morel-Lavallee lesion

The Morel-Lavallée lesion is a closed degloving injury that usually occurs following high-energy trauma. We present a case demonstrating endoscopic management of this lesion. A 44-year-old man fell from scaffolding. Initial assessment demonstrated no significant injury. An ultrasound scan 2 days post injury revealed a large fluid collection along the lateral right thigh. This subsequently became infected and did not respond to antibiotic therapy.

Due to the extent of the lesion, we were reluctant to perform a traditional open drainage. An endoscopic probe was inserted at the proximal and distal poles of the lesion and the wound debrided.

This resulted in a rapid improvement in symptoms and a complete resolution of the lesion at 1 year postsurgery, with no wound-associated morbidity.

This is only the second description of endoscopic debridement of a large, acute Morel-Lavallée lesion, with an excellent outcome.

http://ift.tt/2wNOFHz

Disseminated herpes zoster causing acute respiratory distress syndrome in an immunocompetent patient

Disseminated cutaneous varicella herpes zoster with visceral involvement is rare and seen almost exclusively in immunocompromised patients. We describe an unusual case of fulminant herpes zoster (HZ) in a healthy, immunocompetent 37-year-old woman. She initially presented to an urgent care centre with a classic HZ rash localised to her neck, and upper respiratory symptoms and was treated with prednisone and cephalexin. Within 1 week, the rash became diffuse and her clinical status rapidly deteriorated with development of severe acute respiratory distress syndrome. Varicella zoster infection was confirmed via skin biopsy, bronchial viral PCR and serology for varicella antibodies. She was successfully treated with intravenous acyclovir and aggressive supportive care. Though physicians readily recognise typical zoster infection, this case reminds clinicians that HZ infection can be fulminant and potentially life-threatening in younger, immunocompetent individuals. Early recognition and antiviral therapy is important to reduce morbidity and mortality.

http://ift.tt/2xvxbU7

The entrapped twin: a case of fetus-in-fetu

Fetus-in-fetu (FIF) is a rare entity in which malformed parasitic twin grows inside the body of its twin. It is most commonly presented with mass in the abdomen. We present a case of a 15-year-old boy who presented with abdominal mass since infancy. Radiological investigations are suggestive of FIF. Intraoperatively, malformed fetus in a sac was found and excised. Postoperatively the patient recovers well and was put on follow-up.

http://ift.tt/2wNLKid

Nasofrontal dermoid sinus

Description

A 19-year-old woman presented with recurrent episodes of headache and intermittent caseous discharge from a midline pit near the rhinion, since childhood. There was no fever, nausea, vomiting or seizure. Physical examination revealed a widened nasal bridge and a midline aperture with a protruding hair. Patient's neurological examination was normal. A contrast-enhanced CT scan of the head showed a small hypodense lesion at the anterior basifrontal region. T1-weighted MRI images identified a hyperintense intracranial lesion, which showed suppression with fat suppression sequences. T2-weighted images also revealed a high signal lesion modelling the cerebral parenchyma (figure 1), with a small tract going up to the nasal bridge (figure 2). The patient was diagnosed with a nasofrontal dermoid cyst with the extracranial nasal sinus tract and surgical excision was proposed. The histopathological analysis confirmed the previous diagnosis.

Figure 1

Coronal T2-weighted MRI image showing a hyperintense...

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Successful treatment using rituximab in a patient with refractory polymyositis complicated by scleroderma renal crisis

Corticosteroids are the first-line treatment for patients with inflammatory myopathies. Myositis can be a clinical feature of scleroderma (polymyositis–scleroderma overlap syndrome), and treatment of this syndrome is a challenge for clinicians because moderate to high doses of corticosteroids are considered a risk factor for development of acute kidney injury in affected patients. We report here the case of a 56-year-old woman with scleroderma who developed polymyositis and was successfully treated with rituximab. Initial treatment of the polymyositis with prednisolone 40 mg/day was rapidly tapered to 2.5 mg/day due to development of scleroderma renal crisis, for which four weekly infusions of rituximab (500 mg; off-label) were given. She responded well to rituximab in addition to prednisolone 2.5 mg/day. Rituximab may improve inflammatory myopathies, even in cases where high-dose corticosteroids should be avoided due to complications. Rituximab should be considered as a treatment option in cases of refractory polymyositis.

http://ift.tt/2wNBPt5

Extreme bony pelvic deformity in a renal transplant patient

A 35-year-old female renal transplant recipient was referred to the metabolic bone clinic because of a 15 cm loss of height. She was noted to have thoracic kyphosis and vertebral X-ray confirmed a wedge fracture of the eighth thoracic vertebra. She was managed accordingly but on subsequent follow-up mentioned in passing that her gynaecologist had been unable to obtain a cervical smear for routine screening. This led to further questioning, and the patient reported intermittent urinary stress incontinence, feelings of vaginal fullness and severe dyspareunia. It became apparent that these symptoms had been ongoing for 4 years, but the patient had not brought them to the attention of a healthcare practitioner due to feelings of embarrassment and her religious beliefs. These complaints prompted radiological investigation, which revealed extensive bony pelvic deformity, thought to be an extreme manifestation of chronic kidney disease mineral and bone disorder.

http://ift.tt/2xw4x5n

Rapidly enlarging lipoma

Lipoma is a common subcutaneous tumour composed of fat tissue. It may occur as a sporadic solitary lesion or as multiple lesions. They often grow very slowly. They vary between 2 and 10 cm in size. There are rarely any subjective symptoms. Lipomas do not usually require treatment unless they are big enough to be symptomatic. We reported a 75-year-old man with a rapidly enlarging and ulcerated mass on his right upper thigh.

http://ift.tt/2wNNGr4

Asymptomatic pyogenic liver abscesses secondary to Fusobacterium nucleatum and Streptococcus vestibularis in an immunocompetent patient

A 66-year-old male patient presented with symptoms and signs of L4/5 radiculopathy. He was found to be anaemic with elevated inflammatory markers and deranged hepatic enzymes. Imaging revealed lumbar canal stenosis and the presence of pyogenic liver abscesses from which Fusobacterium nucleatum and Streptococcus vestibularis were isolated. The hepatic abscesses were attributed to asymptomatic diverticular perforation. Multiple coexisting incidental infections were discovered, including oesophageal candidiasis, Helicobacter pylori, stool cultures positive for Strongyloides stercoralis, and sputum cultures positive for Enterobacter cloacae, Escherichia coli and Mycobacterium avium. Extensive investigations for possible underlying immunosuppression were negative.

http://ift.tt/2xvAP0q

Severe unicuspid aortic valve stenosis: VACTERL association

Description

A 24-year-old man with a known history of horseshoe kidney leading to end-stage renal disease, scoliosis and small ventricular septal defect consistent with VACTERL association, who presented with worsening dyspnoea on exertion. Transthoracic echocardiogram (TTE) showed a unicuspid aortic valve (UAV) with severe aortic stenosis (AS) (valve area of 0.6 cm² and mean gradient of 44 mm Hg). TTE also showed moderate aortic insufficiency and severely reduced left ventricular systolic function with estimated ejection fraction of 20%. Transoesophageal echocardiography (TEE) confirmed a UAV with single commissure located anteriorly (figure 1A–D; online  and ) and severe AS (figure 1B, C). In preparation for surgical repair, chest CT angiogram showed dilated ascending aorta measuring 4 cm with no evidence of aortic dissection. The patient underwent aortic valve replacement surgery with 21 mm CarboMedics mechanical valve. TEE showed a well-seated prosthesis without evidence of paravalvular leak (figure 1E). The patient...

http://ift.tt/2wNNI2a

PHACE syndrome in a child with segmental IH of face

Description

An 8-month-old female infant was referred for paediatric and dermatology consultation for evaluation of a facial haemangioma with progressive growth since the first days of life. The observation showed a large segmental infantile haemangioma (IH) over the right face (figure 1), a small vulvar haemangioma and exotropia of the right eye.

Figure 1

Right facial segmental infantile haemangioma at the level of the mandible, with extension to the lower lip.

Due to the segmental appearance of the facial IH, we prompted the investigation of PHACE syndrome, an acronym corresponding to a set of alterations: Posterior fossa anomalies, Haemangioma, Arterial lesions, Cardiac abnormalities/coarctation of the aorta alterations and Eye anomalies.1

The MR angiography showed an absence of the right internal carotid artery, with circulation assured through the circle of Willis (figure 2). Ophthalmology assessment revealed microphthalmia and...

http://ift.tt/2xuVbGY

A rare highly aggressive tumour: lymphoepithelioma-like thymic carcinoma

Lymphoepithelioma-likethymic carcinoma is a rare neoplasm that presents with compressive symptoms or as an incidental radiological finding of an anterior mediastinal mass. It is an aggressive carcinoma with a high rate of invasion, metastasis and recurrence. Its diagnosis usually carries a poor prognosis largely due to propensity for late diagnosis. To date, guidance for treatment remains limited. This is a case of lymphoepithelioma-like thymic carcinoma in a young male adult who presented initially with back pain. Despite prompt initiation of chemotherapy with cisplatin, doxorubicin and cyclophosphamide, he had a complicated hospital course leading to demise within 2 months of diagnosis.

http://ift.tt/2wNuvxL

Dog bites and diabetic peripheral neuropathy: a dangerous combination

All animal bites have the potential to cause significant infection. In the UK, dogs are the most common source of bites. Incidence of hospital attendances attributable to dog bites has risen over the last decade. Patient groups at particular risk of bites and/or complications of infection include those at extremes of age, immunosuppressed and patients with diabetes. We report the case of a patient with diabetic peripheral neuropathy, who was admitted on two separate occasions with unprovoked bites to his toes whilst asleep, by his pet dog. He ultimately required terminalisation of the affected digits. Although unusual, this mechanism of injury has been previously described in literature. However, we are unaware of cases reporting multiple separate incidences involving the same patient and animal. We present this case to highlight the perils of untrained pet ownership in diabetic patients with peripheral neuropathy and the importance of prompt medical and surgical treatment of injuries.

http://ift.tt/2xv9YRW

When all else fails: supervised treatment in outpatient for schizophrenia (STOPS)

This was about a case of a patient requiring admission to psychiatry ward twice a year for relapse schizophrenia due to medication non-compliance. Medication adherence was previously monitored by her husband. However, following the death of her husband, she stopped treatment. The lack of insight and poor family support further contributed to her relapse. She presented with positive and negative symptoms of schizophrenia during her relapse, neglecting her hygiene and oral intake. She was also found to have anaemia as a result of poor diet when she was in relapse. Community psychiatry services had attempted to ensure compliance with postdischarge plan but failed as patient was not present every home visits. Supervised treatment in outpatient for schizophrenia (STOPS) provided an alternative method to ensure compliance in this patient. Patient has remained in remission for 1 year since the use of STOPS.

http://ift.tt/2wNuHg7

Aftermath of induced inflammation: acute periaortitis due to nivolumab therapy

Description

A 57-year-old man with medical history of left upper lobe metastatic squamous cell carcinoma of lung and seizures due to brain metastasis was admitted with acute-onset low back pain. Patient also had a known history of infrarenal aortic and left common iliac artery aneurysm stable on regular surveillance CT over the past 3 years with the most recent CT scan 1 month prior to presentation showing no signs of inflammation around the infrarenal aneurysmal aorta as seen in figure 1. Positron emission tomography 1 year prior to presentation did not show signs of inflammation in the region of aortic aneurysm as shown in figure 2. For his metastatic lung cancer, he was initially started on carboplatin and gemcitabine therapy but unfortunately had progression of cancer in left lung on the regimen. Subsequently, he was placed on nivolumab therapy. After being on the medication for 9 months, patient presented with acute...

http://ift.tt/2xvs4mY

Confusion and abdominal symptoms following a rugby tackle

A 19-year-old man was sent to the emergency department following a pitch-side assessment for suspected concussion, unexplained upper abdominal tenderness and vomiting, following a high-impact tackle during a rugby match. A Focussed Assessment with Sonography for Trauma (FAST) scan performed in the emergency department suggested intra-abdominal free fluid, and subsequent head and abdominal CT imaging showed no intracranial lesion but confirmed a significant haemoperitoneum due to large splenic tear and bleeding. An emergency splenectomy was performed, which confirmed the rupture of an enlarged spleen with blood loss of almost 2 L into the peritoneal cavity. The patient made a full recovery following surgery. A subsequent histological examination revealed granulomatous inflammation characteristic of infectious mononucleosis. This unique case illustrates that physically fit patients with early hypovolaemic shock can present with symptoms mimicking concussion.

http://ift.tt/2wNHZt9

Table of Contents

Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





http://ift.tt/2yjXom4

ASTRO – Program Description/Statement of Need

Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





http://ift.tt/2xpKR1e

Continuing Medical Education

Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





http://ift.tt/2yktePV

ASTRO 2017 Officers and Board of Directors

Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





http://ift.tt/2xpY7mL

The antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts

Summary

We investigated the combinatorial effects of pentoxifylline (PTX) on the efficacy of gemcitabine (GEM) in a human pancreatic tumor xenograft model. PTX significantly improved the efficacy of GEM, as shown by a 50% reduction in tumor growth rate at 4 weeks of treatment compared with that in animals given GEM alone. The fluorescent drug doxorubicin (DOX) was used to test whether drug delivery was improved by PTX, contributing to the improved efficacy of GEM. PTX given for 2 weeks prior to DOX administration improved drug distribution by 1.8- to 2.2-fold with no changes in vessel density, suggesting that improvement in drug delivery was not related to vascular mechanism. Instead, collagen I content in tumor stroma was significantly reduced, as was the expression of α-SMA of cancer-associated fibroblasts (CAFs) and connective tissue growth factor (CTGF) by PTX pretreatment. Overall, our data demonstrated that increased efficacy of GEM by PTX was associated with improved drug delivery to tumor tissue, which may be attributed to decreased expression of CTGF and subsequent reduction in the stromal collagen matrix in the PDAC tumor. These results supported usefulness of PTX in combination with chemotherapy for targeting drug delivery barriers associated with the stromal matrix, which should be further evaluated for clinical development.

This article is protected by copyright. All rights reserved.

http://ift.tt/2xpOww1

Table of Contents

Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





from Cancer via ola Kala on Inoreader http://ift.tt/2yjXom4
via IFTTT

ASTRO – Program Description/Statement of Need

Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





from Cancer via ola Kala on Inoreader http://ift.tt/2xpKR1e
via IFTTT

Continuing Medical Education

Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





from Cancer via ola Kala on Inoreader http://ift.tt/2yktePV
via IFTTT

ASTRO 2017 Officers and Board of Directors

Publication date: 1 October 2017
Source:International Journal of Radiation Oncology*Biology*Physics, Volume 99, Issue 2, Supplement





from Cancer via ola Kala on Inoreader http://ift.tt/2xpY7mL
via IFTTT

The antifibrotic effects of pentoxifylline improve the efficacy of gemcitabine in human pancreatic tumor xenografts

Summary

We investigated the combinatorial effects of pentoxifylline (PTX) on the efficacy of gemcitabine (GEM) in a human pancreatic tumor xenograft model. PTX significantly improved the efficacy of GEM, as shown by a 50% reduction in tumor growth rate at 4 weeks of treatment compared with that in animals given GEM alone. The fluorescent drug doxorubicin (DOX) was used to test whether drug delivery was improved by PTX, contributing to the improved efficacy of GEM. PTX given for 2 weeks prior to DOX administration improved drug distribution by 1.8- to 2.2-fold with no changes in vessel density, suggesting that improvement in drug delivery was not related to vascular mechanism. Instead, collagen I content in tumor stroma was significantly reduced, as was the expression of α-SMA of cancer-associated fibroblasts (CAFs) and connective tissue growth factor (CTGF) by PTX pretreatment. Overall, our data demonstrated that increased efficacy of GEM by PTX was associated with improved drug delivery to tumor tissue, which may be attributed to decreased expression of CTGF and subsequent reduction in the stromal collagen matrix in the PDAC tumor. These results supported usefulness of PTX in combination with chemotherapy for targeting drug delivery barriers associated with the stromal matrix, which should be further evaluated for clinical development.

This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2xpOww1
via IFTTT

Macro- and Microelement Status in Animal and Human Hypertension: the Role of the ACE Gene I/D Polymorphism

Abstract

Genetic factors that predispose to hypertension may contribute to element disturbances observed in hypertensive patients. We tested the hypothesis that the deletion allele of the angiotensin-converting enzyme (ACE) gene is associated with element imbalances in hypertension. The concentrations of elements in genetically predisposed to hypertension rats (SHRs) and their controls (WKY rats) were also examined. ICP-MS was used for elemental analysis of human hair and animal fur. Genotyping was performed by PCR. We also measured micronuclei frequency and distribution of peripheral blood leukocytes in cell cycle phases by flow cytometry and studied the correlations of these parameters with element contents. In general, the tendency for higher levels of toxic and lower levels of essential elements is observed in hypertension, specifically in patients carrying the D allele. Hypertensive men had significantly higher Be, V, Cr, As, Mo, Ag, Sb, and Na levels and lower Ca, Zn, Ba, and U levels compared with control subjects; the differences were not significant for Mg, Al, K, Mn, Fe, Co, Ni, Cu, Se, Cd, Tl, Pb, and Th. The D allele was associated with higher Be, Mo, and Th levels and lower Zn, Se, and Tl levels. The concentrations of Ca, Co, Mo and U were higher in SHR than those in the WKY rats. Mo, an antagonist of Cu, positively correlated with the S-phase cells, and Cu positively correlated with micronuclei frequency. The results suggest an involvement of the ACE I/D polymorphism in element imbalances in hypertension and attract attention to the possible significant role of genetic factors in Mo accumulation.

http://ift.tt/2wNCn23

Serum Level of Zinc and Copper in Sudanese Women with Polycystic Ovarian Syndrome

Abstract

The study aimed to evaluate the serum level of zinc and copper in women with polycystic ovarian syndrome (PCOS). A case-control study was conducted at Saad Abualila infertility center (Khartoum, Sudan). The cases were women who had a PCOS based on Rotterdam criteria. The controls were infertile women with no evidence of PCOS. The socio-demographic characteristics and medical history data were gathered using questionnaires. Zinc and copper levels were measured using atomic absorption spectrophotometer. While there was no difference in zinc and copper levels between the two groups (50 women in each arm), mean (SD) of body mass index (BMI) was significantly higher in women with PCOS compared to the controls [28.4 (4.2) vs. 25.6 (5.7) kg/m²; P = 0.006], respectively. There were no significant differences in the level of luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH, prolactin, testosterone, cholesterol, triglycerides and low-density lipoprotein (LDL) between the cases and the controls. In linear regression analyses, none of the investigated factors were associated with PCOS. Zinc and copper were not associated with PCOS in this setting.

http://ift.tt/2xuN5hy

Trace Element Levels in Scalp Hair of School Children in Shigatse, Tibet, an Endemic Area for Kaschin-Beck Disease (KBD)

Abstract

Kaschin-Beck disease (KBD) is an endemic osteoarthritis, and the etiology is closely related with levels of trace elements in the human body. Currently, it is clear that the selenium (Se) status of children in KBD areas is lower than that in non-KBD areas in the Tibetan Plateau, whereas role of other elements are yet unknown. This study aimed to assess some essential trace elements (Se, Mo, Mn, Zn, Fe, Cu, Co, and Sr) in children using scalp hair as a biomarker, and 157 samples from school children aged 8–14 years old were collected from both KBD and non-KBD areas in Shigatse, Tibet. Se and Mo were measured by inductive coupled plasma mass spectrometry, and the other elements were determined by inductive coupled plasma optical emission spectrometry. Compared with the non-KBD areas, Se, Mo, Mn, Fe, Zn, Co, and Sr levels of children in KBD areas were found to be significantly different (P < 0.05); while in linear discriminant analysis, only Se and Zn were found to contribute to the KBD prevalence in the study area. The hair Se level of children in KBD areas ranged from 0.115 to 0.299 mg/kg, while in non-KBD areas it ranged from 0.135 to 0.519 mg/kg. The Zn content of children's hair was between 83 and 207 mg/kg in KBD areas, while it was 37 and 219 mg/kg in non-KBD areas. Lower Se and higher Zn levels in children in KBD areas was found when compared with non-KBD groups. In addition, Mo levels were found to be different between KBD areas and non-KBD areas on the opposite side of the Yarlung Zangbo River, but no close relationship was shown because there was no difference compared with the non-KBD area on the same side of the river. Our observations suggest that Se deficiency is still an important factor for the occurrence and prevalence of KBD, while the relationship between Zn and KBD needs to be further explored in the Tibetan Plateau.

http://ift.tt/2wO5Sko

Dietary Intake of Minerals, Vitamins, and Trace Elements Among Geriatric Population in India

Abstract

The geriatric population is at a high risk of developing deficiencies of essential micronutrients such as minerals, vitamins, and trace elements and their related deficiency signs and symptoms. Scarce data is available on the dietary intake of essential micronutrients among geriatric subjects in India. Hence, to fill the gap in the existing knowledge, a community-based cross-sectional study was conducted during 2015–2016 in District Nainital, Uttarakhand State, India. A total of 255 geriatric subjects were enrolled from 30 clusters (villages) identified by using population proportionate to size sampling methodology. Data were collected on sociodemographic profile and dietary intake of essential micronutrients (24-h dietary recall, food frequency questionnaire) from all the geriatric subjects. A high percentage of geriatric subjects did not consume the recommended daily intake for essential micronutrients such as energy (78%), protein (78%), calcium (51%), thiamine (33%), riboflavin (64%), niacin (88%), vitamin C (42%), iron (72%), folic acid (72%), magnesium (48%), zinc (98%), copper (81%) and chromium (89%) adequately. Food groups rich in essential micronutrients such as pulses, green leafy vegetables, roots and tubers, other vegetables, fruits, nonvegetarian food items, and milk and milk products were consumed irregularly by the subjects. The overall intake of energy and essential micronutrients was inadequate among the geriatric population in India, possibly due to poor quality and quantity of the diet consumed.

http://ift.tt/2xv1XfO

Experimental Research Showing the Reduction of Naloxone-Place Aversion by Oral Zinc Administration in Rats

Abstract

Previous studies showed the attenuation of both morphine-dependence and morphine-place preference by zinc. Conditioned place preference and aversion are experimental models frequently used to test the reward-stimulating, respectively the aversive effects induced by different stimuli or substances. Addictive substances usually induce place preference (exhibit reward-stimulating properties), while their antagonists determine place-avoidance (aversion). The present study aimed to assess the effect determined by zinc sulphate oral administration (2 and 4 mg/kg/day, 14 days, prior to habituation) on the place aversion induced by two naloxone doses (1.5 and 2.5 mg/kg/administration). The results show a robust, dose-dependent reduction of the aversion determined by both naloxone doses (the aversion induced by 1.5 mg/kg naloxone was reduced with 15%—the lower zinc dose and with 24%—the higher zinc dose; the aversion induced by 2.5 mg/kg naloxone was reduced with 16%—the lower zinc dose and with 29%—the higher zinc dose). This represents a new proof of the interactions between zinc and opioidergic system and a further argument for dietary zinc supplementation in patients on opioids for cancer-related chronic pain.

http://ift.tt/2wNHL5d

The Concentration of Vanadium in Pathologically Altered Human Kidneys

Abstract

Vanadium has a unique and beneficial effect on both humans and animal organisms; however, excessive amount of the above-mentioned metal can cause many alterations in tissues and organs, including the kidneys. The aim of the study was to determine the concentration of vanadium (V) in the kidneys removed from patients due to lesions of various etiologies, including the rejection of the transplanted kidneys. Additionally, we determined the influence of selected biological and environmental factors on the V concentration. The study material consisted of the kidneys with tumor lesions (n = 27) and extracted kidney grafts (n = 10) obtained from patients from the north-western Poland. The V concentrations were assessed by atomic absorption spectrophotometry emission in inductively coupled argon plasma and expressed in concentrations in dry weight (dw). Statistically significant differences were observed for V concentrations in the renal medulla between the kidneys with tumors and renal grafts, where the lowest concentration of V was observed. The kidneys in more advanced stages of the tumor (T3 + T4) contained more vanadium than the kidneys of T1 + T2 stages and medians were 2.07 and 1.51, respectively. We also compared the V concentration in the kidneys between the renal grafts (K2) and the kidneys with tumor (K1) in two stages of advancement: T1 with T2 (K1_1 + 2) and T3 with T4 (K1_3 + 4). Statistically significant differences were noted between the renal medullae of the above-mentioned groups of kidneys.

According to the previous studies on the concentrations of other heavy metals, renal grafts accumulate less vanadium than cancerous kidneys, what can be associated with the immunosuppressive drugs taken by patients after the transplantation.

http://ift.tt/2xvufXF

Effects of Excess Dietary Fluoride on Serum Biochemical Indices, Egg Quality, and Concentrations of Fluoride in Soft Organs, Eggs, and Serum of Laying Hens

Abstract

This study was conducted to investigate the effects of excess dietary fluoride (F) on serum biochemical indices, egg quality, and concentrations of F in soft tissues, eggs, and serum of laying hens. Commercial laying hens (n = 576, 51 weeks of age) were randomly allotted to 6 treatments with 6 replicates of 16 birds. The basal diets contained fluorine inclusions at a level of 16 mg/kg, and graded sodium fluoride was added to the basal diet to achieve fluorine inclusions, respectively, at a level of 200, 400, 600, 800, and 1000 mg/kg in the experimental diets. Dietary F levels at 600, 800, and 1000 mg/kg decreased (P < 0.05) albumin height and yolk color, while eggshell strength and eggshell thickness significantly decreased at 800 and 1000 mg/kg, respectively, compared with the control group. Fluoride concentrations in eggshell, albumin, yolk, liver, kidney, ovary, and oviduct responded to dietary F levels positively, and F concentrations in eggshell were the highest. Fluorine concentrations in albumin and yolk increased with the feeding time at the same dietary F levels (P < 0.05). Dietary F level at 400 mg/kg increased serum calcium level and activity of glutamic oxalacetic transaminase (P < 0.05). In conclusion, dietary F levels at 600 mg/kg decreased albumin height and yolk color, while eggshell strength and eggshell thickness significantly decreased at 800 and 1000 mg/kg, respectively. F concentrations in soft tissues, albumin, yolk, and eggshell of layers had a positive correlation with dietary F levels. By disturbing Ca and phosphorus metabolism, dietary F levels affected the formation of eggshell, reducing eggshell strength and eggshell thickness.

http://ift.tt/2wNoDEn

Role of Selenium from Different Sources in Prevention of Pulmonary Arterial Hypertension Syndrome in Broiler Chickens

Abstract

Pulmonary arterial hypertension (PAH) syndrome in broilers is associated with hypoxia, which prevails at high altitude. Oxidative stress is the pathogenic mechanism underlying PAH. Because selenium is key element in the structure of antioxidant enzymes, we evaluated pulmonary hypertensive responses in broiler chickens fed with diets supplemented with organic or nano-selenium. One hundred forty-four broilers (starting at 5 days old) were fed with (i) control group: birds received a standard diet; (ii) nano-selenium group: birds were fed with basal diet supplemented with nano-selenium at 0.3 mg/kg; and (iii) organic selenium group: birds received basal diet supplemented with organic selenium at 0.3 mg/kg. We assessed growth performance, carcass characteristics, antioxidant variables, blood parameters, and small intestine morphology. Although Se supplementation did not affect growth performance, carcass traits, and organ weight (P > 0.05), the right to total ventricular weight ratio (RV:TV), malondialdehyde concentration in the liver, and heterophil to lymphocyte ratio were significantly lower in the nano-selenium group relative to the control (P < 0.05). Chickens that received nano-selenium also elicited significantly higher antibody titers after 24 h of an injection of sheep red blood cells (P < 0.05). Nano-selenium supplementation also significantly increased villus height, absorptive surface area, and lamina propria thickness relative to the control (P < 0.05) in different segments of the small intestine. In contrast, organic selenium supplement improved intestinal morphometry only in the jejunum. We conclude that dietary supplementation of 0.30 mg/kg nano-selenium could prevent right ventricular hypertrophy as reflected by reduced RV:TV, reduced levels of lipid peroxidation in the liver, and improved gut function.

http://ift.tt/2xv8as1

The Effects of Agaricus blazei Murill Polysaccharides on Cadmium-Induced Apoptosis and the TLR4 Signaling Pathway of Peripheral Blood Lymphocytes in Chicken

Abstract

In this study, we investigated the effects of Agaricus blazei Murill polysaccharides (ABP) on cadmium (Cd)-induced apoptosis and the TLR4 signaling pathway of chicken peripheral blood lymphocytes (PBLs). Seven-day-old healthy chickens were randomly divided into four groups, and each group contained 20 males. The cadmium-supplemented diet group (Cd group) was fed daily with full feed that contained 140 mg cadmium chloride (CdCl₂)/kg and 0.2 mL saline. The A. blazei Murill polysaccharide diet group (ABP group) was fed daily with full feed with 0.2 mL ABP solution (30 mg/mL) by oral gavage. The cadmium-supplemented plus A. blazei Murill polysaccharide diet group (Cd + ABP group) was fed daily with full feed containing 140 mg CdCl₂/kg and 0.2 mL ABP solution (30 mg/mL) by gavage. The control group was fed daily with full feed with 0.2 mL saline per day. We measured the apoptosis rate and messenger RNA (mRNA) levels of apoptosis genes (caspase-3, Bax, and Bcl-2), the mRNA levels of TLR4 and TLR4 signaling pathway-related factors (MyD88, TRIF, NF-κB, and IRF3), the TLR4 protein expression, and the concentrations of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in chicken PBLs. The results showed that the PBL apoptosis rate was significantly increased, the mRNA levels of caspase-3 and Bax were significantly increased, while that of Bcl-2 was significantly reduced. The Bax/Bcl-2 ratio was significantly increased in the Cd group at 20, 40, and 60 days after treatment compared with that in the control group. After treatment with ABP, the above changes were clearly suppressed. At the same time, ABP reduced the concentrations of IL-1β, IL-6, and TNF-α induced by Cd. We also found that ABP inhibited the TLR4 mRNA level and protein expression and inhibited the mRNA levels of MyD88, TRIF, NF-κB, and IRF3. The results demonstrated that Cd could induce apoptosis, activate the TLR4 signaling pathway, and induce the expression of inflammatory cytokines in chicken PBLs, and that the administration of ABP clearly inhibited Cd-induced effects on chicken PBLs.

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The Cytotoxicity and Genotoxicity of Particulate and Soluble Cobalt in Human Urothelial Cells

Abstract

Cobalt use is increasing particularly due to its use as one of the primary metals in cobalt-chromium-molybdenum (CoCrMo) metal-on-metal prosthetics. CoCrMo is a high-strength, wear-resistant alloy with reduced risk for prosthetic loosening and device fracture. More than 500,000 people receive hip implants each year in the USA which puts them at potential risk for exposure to metal ions and particles released by the prosthetic implants. Data show cobalt ions released from prosthetics reach the bloodstream and accumulate in the bladder. As patients with failed hip implants show increased urinary and blood cobalt levels, no studies have considered the effects of cobalt on human urothelial cells. Accordingly, we investigated the cytotoxic and genotoxic effects of particulate and soluble cobalt in urothelial cells. Exposure to both particulate and soluble cobalt resulted in a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ions. Based on intracellular cobalt ion levels, we found, when compared to particulate cobalt, soluble cobalt was more cytotoxic, but induced similar levels of genotoxicity. Interestingly, at similar intracellular cobalt ion concentrations, soluble cobalt induced cell cycle arrest indicated by a lack of metaphases not observed after particulate cobalt treatment. These data indicate that cobalt compounds are cytotoxic and genotoxic to human urothelial cells and solubility may play a key role in cobalt-induced toxicity.

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Gene Silencing of Selenoprotein K Induces Inflammatory Response and Activates Heat Shock Proteins Expression in Chicken Myoblasts

Abstract

In the present study, specific small interfering RNA (siRNA) for selenoprotein K (Selk) gene was designed and transfected into chicken myoblasts. Then, the expressions of inflammatory factors (including induced nitric oxide synthase [iNOS], nuclear factor-kappa B [NF-κB], heme-oxygenase-1 [HO-1], cyclooxygenase-2 [COX-2], and prostaglandin E synthase [PTGEs]), inflammation-related cytokines (including interleukin [IL]-1β, IL-6, IL-7, IL-8, IL-17, and interferon [IFN]-γ), and heat shock proteins (HSPs) (including HSP27, HSP40, HSP60, HSP70, and HSP90) were examined at 24 and 72 h after transfection. The results showed that messenger RNA (mRNA) expressions of iNOS, NF-κB, HO-1, COX-2, IL-6, IL-7, IL-8, HSP 27, HSP 40, HSP 60, HSP 70, and HSP 90 were significantly increased (p < 0.05) at 24 and 72 h after siRNA transfection, and the mRNA expressions of PTGEs, IL-1β, IL-17, and IFN-γ were significantly increased and decreased (p < 0.05) at 24 and 72 h after siRNA transfection. The results also showed that the protein expressions of iNOS, NF-κB, HO-1, COX-2, HSP60, HSP70, and HSP90 were significantly increased (p < 0.05) at 24 and 72 h after siRNA transfection. The correlation analysis and principal component analysis (PCA) showed that PTGEs, IL-1β, IL-17, IFN-γ, HSP40, and HSP90 might play special roles in response to Selk silencing in chicken myoblasts. These results indicated that Selk silencing induced inflammation response by affecting the expression levels of inflammatory factors and inflammation-related cytokines, and the heat shock proteins might play protective roles in this response in chicken myoblasts.

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The Reference Intervals of Hair Trace Element Content in Hereford Cows and Heifers ( Bos taurus )

Abstract

The objective of the present study was to assess hair trace element content in Hereford heifers and cows (Bos taurus) living in South Ural region and calculate the site-specific reference intervals. Hair trace element content in 150 cows and heifers farmed in the Southern Urals of Russia was assessed using inductively coupled plasma mass-spectrometry. Dietary trace element content corresponded to the adequate values as estimated by recommendations of USSR State Agriculture Committee and U.S. National Research Council. Comparative analysis demonstrated that heifers are characterized by significantly higher hair Se (3-fold), Hg (4-fold), and Sn (46%) content, whereas cows had significantly higher levels of hair Co (56%), I (33%), Si (2-fold), V (27%), B (55%), Cd (19%), Pb (47%), and Sr (23%). At the same time, no significant group difference in hair Cr, Cu, Fe, Li, Mn, Zn, As, and Ni was detected between Hereford cows and heifers. The reference intervals and 90% confidence intervals for the lower and upper limits were calculated in agreement with the American Society for Veterinary Clinical Pathology Quality Assurance and Laboratory Standard Guidelines.

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A Preliminary Study about the Potential Effects of Heavy Metals on the Human Male Reproductive Parameters in HIV-Infected Population in China

Abstract

Due to the inconsistent effects of human immunodeficiency virus (HIV) on the human male reproduction in previous studies and the impacts of environmental exposures, such as heavy metals, on male reproduction receiving little attention in HIV-infected population, the aim of present study was to investigate whether heavy metals have potential effects on reproductive parameters in HIV-infected men. The current study assessed the associations between semen quality or serum hormone and concentration of the three heavy metal toxicants (lead (Pb), cadmium (Cd), and zinc (Zn)) in seminal, urine, and serum, and 50 HIV-infected men were recruited in the present study. Concentrations of Pb, Cd, and Zn were measured in three fluids by graphite furnace atomic absorption spectrophotometer. Semen analyses were performed according to World Health Organization criteria. Serum samples were analyzed for follicle-stimulating hormone, luteinizing hormone, and testosterone. HIV RNA viral load was determined by HIV virus loads kit. Spearman's rank correlations were used for correlation analyses. The results showed that the concentrations of Pb, Cd, and Zn were significantly correlated with semen quality and serum hormone. HIV-1 virus loads were significantly associated with increased seminal Pb. However, HIV-1 virus loads were not statistically associated with semen quality and serum hormone. Our findings suggested that environmental heavy metals had potential effects on reproductive parameters in HIV-infected men in China.

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Relationships Between Element Contents in Polish Children’s and Adolescents’ Hair

Abstract

Environment, sex, and age are the main factors which determine the elemental composition of hair. The objective of the study is to determine the contents of calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), iron (Fe), lead (Pb), and cadmium (Cd) in girls' and boys' hair in five age groups (within 1–19-year range) corresponding to successive human ontogenesis phases as well as to evaluate the relationships between these elements. Quantitative analysis has been carried out using atomic absorption spectrometry (AAS). Experimental results were analyzed using classic and principal component (PCA) statistical analyses. In particular, differences between contents of particularly Ca, Mg, and Zn in girls' and boys' hair were found, and substantial differences between age groups were stated. In general, larger amounts of Ca, Mg, and Zn as compared to boys' hair have been observed for girls' hair and higher toxic element (Pb, Cd) contents for boys were measured in some age groups. An increasing trend was found for bioelements (Ca, Mg, Zn) both for girls and boys in all age groups, while for Cu and Fe content, changes are insignificant and even decreasing for teenagers. The most frequently correlating element pairs are Ca–Mg, Ca–Zn, Mg–Zn, and Pb–Cd. Classic and PCA statistics show, in general, a satisfactory consistence. The elemental composition of hair varies depending on the gender and age of children and young people.

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A Rat Experimental Study of the Relationship Between Fluoride Exposure and Sensitive Biomarkers

Abstract

Chronic excessive fluoride exposure impairs human health and damages not only the skeletal system and the teeth but also the soft tissues such as the brain, liver, kidneys, pancreas and spinal cord. However, there is limited research regarding the exposure levels and sensitive biomarkers. This study was aimed to establish the relationship between fluoride exposure and sensitive biomarkers. Ninety-six rats were randomly divided into six groups, with each group exposed to 0, 2, 4, 8, 16 and 32 mg NaF/(kg.bw), respectively. Correlation analysis of the exposure levels, the tissue distributions and the effects was done, and the possible mathematical relationship between the exposure and sensitive biomarkers is discussed. Our findings revealed that the level of serum fluoride can serve as one of the sensitive indicators to reflect the ex-exposure levels (in the present article, ex-exposure means the fluoride exposure pathway from the outside, which differs from the burden of the organism). Furthermore, an equation determining the external exposure dose of serum fluoride was obtained by fitting the coefficient 0.901. Simultaneously, enzyme levels were closely compared with the burden of the tissue, which showed that the activities of alkaline phosphatase significantly correlated with serum fluoride levels (R ² = −0.259, p < 0.05), as well as with the fluoride levels of the lung (R ² = 0.463, ρ < 0.01), the thymus (R ² = 0.429, ρ < 0.05) and the ovary/testicle (R ² = 0.685, ρ < 0.01). Results suggested that excessive fluoride exposure might affect reproduction by altering the activities of alkaline phosphatase. In addition, some indicators related to immunity and calcium absorption exhibited sensitivity to tissue burden, among which activating transcriptional factor 4 (ATF4), an important indicator involved in bone metabolism, was found sensitive to the ex-exposure level. These findings highlight the gap between health effects in epidemiology research and the total intake amount of fluoride from the environment. This study presents a novel insight into the method of establishing the relationship between fluoride exposure and sensitive biomarkers.

http://ift.tt/2wNs6TK

Alterations of Mg 2+ After Hemorrhagic Shock

Abstract

Hemorrhagic shock is generally characterized by hemodynamic instability with cellular hypoxia and diminishing cellular function, resulting from an imbalance between systemic oxygen delivery and consumption and redistribution of fluid and electrolytes. Magnesium (Mg) is the fourth most abundant cation overall and second most abundant intracellular cation in the body and an essential cofactor for the energy production and cellular metabolism. Data for blood total Mg (tMg; free-ionized, protein-bound, and anion-bound forms) and free Mg²⁺ levels after a traumatic injury are inconsistent and only limited information is available on hemorrhagic effects on free Mg²⁺ as the physiologically active form. The aim of this study was to determine changes in blood Mg²⁺ and tMg after hemorrhage in rats identifying mechanism and origin of the changes in blood Mg²⁺. Hemorrhagic shock produced significant increases in blood Mg²⁺, plasma tMg, Na⁺, K⁺, Cl⁻, anion gap, partial pressures of oxygen, glucose, and blood urea nitrogen but significant decreases in RBC tMg, blood Ca²⁺, HCO₃⁻, pH, partial pressures of carbon dioxide, hematocrit, hemoglobin, total cholesterol, and plasma/RBC ATP. During hemorrhagic shock, K⁺, anion gap, and BUN showed significant positive correlations with changes in blood Mg²⁺ level, while Ca²⁺, pH, and T-CHO correlated to Mg²⁺ in a negative manner. In conclusion, hemorrhagic shock induced an increase in both blood-free Mg²⁺ and tMg, resulted from Mg²⁺ efflux from metabolic damaged cell with acidosis and ATP depletion.

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The Effects of Supplementary Cr3 (Chromium(III) Propionate Complex) on the Mineral Status in Healthy Female Rats

Abstract

More and more people use food supplements for various reasons, e.g. to prevent mineral deficiency and diseases (e.g. osteoporosis, diabetes, anaemia). Supplements containing Cr(III) are purchased primarily for weight loss and antidiabetic effects. The aim of this study was to evaluate the effects of supplementary Cr3 {chromium(III) propionate complex, [Cr₃O(O₂CCH₂CH₃)₆(H₂O)₃]NO₃)} on the mineral status in female Wistar rats. The study was carried out on 30 female Wistar rats, divided into five groups (six animals in each): a control group and test groups fed Cr3 supplemented diets with 100, 200, 500 and 1000 mg Cr · kg⁻¹ diet (equivalent to 10, 20, 50 and 100 mg Cr ·kg⁻¹ body mass (b.m.) per day) given as Cr3 for 4 weeks. Supplementary Cr3 increased the Cr content in tissues in a dose-dependent manner. High dietary doses of Cr3, 20 and 100 mg Cr · kg⁻¹ b.m., increased the Cu content in the liver and spleen as well as the Zn content in the kidneys but decreased the liver Ca content. Doses of 50–100 mg Cr ·kg⁻¹ b.m. decreased the serum Fe concentration and the Fe content in the liver and kidneys. Supplementation with Cr3 at doses of 10 and 100 mg Cr ·kg⁻¹ b.m. did not affect the Mg content in the rats' tissues. In conclusion, high dietary doses of Cr3 (10 and 100 mg Cr· kg⁻¹ b.m.) given for 4 weeks affected the mineral status of Fe, Zn, Cu and Ca in the tissues of healthy female Wistar rats.

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Macro- and Microelement Status in Animal and Human Hypertension: the Role of the ACE Gene I/D Polymorphism

Abstract

Genetic factors that predispose to hypertension may contribute to element disturbances observed in hypertensive patients. We tested the hypothesis that the deletion allele of the angiotensin-converting enzyme (ACE) gene is associated with element imbalances in hypertension. The concentrations of elements in genetically predisposed to hypertension rats (SHRs) and their controls (WKY rats) were also examined. ICP-MS was used for elemental analysis of human hair and animal fur. Genotyping was performed by PCR. We also measured micronuclei frequency and distribution of peripheral blood leukocytes in cell cycle phases by flow cytometry and studied the correlations of these parameters with element contents. In general, the tendency for higher levels of toxic and lower levels of essential elements is observed in hypertension, specifically in patients carrying the D allele. Hypertensive men had significantly higher Be, V, Cr, As, Mo, Ag, Sb, and Na levels and lower Ca, Zn, Ba, and U levels compared with control subjects; the differences were not significant for Mg, Al, K, Mn, Fe, Co, Ni, Cu, Se, Cd, Tl, Pb, and Th. The D allele was associated with higher Be, Mo, and Th levels and lower Zn, Se, and Tl levels. The concentrations of Ca, Co, Mo and U were higher in SHR than those in the WKY rats. Mo, an antagonist of Cu, positively correlated with the S-phase cells, and Cu positively correlated with micronuclei frequency. The results suggest an involvement of the ACE I/D polymorphism in element imbalances in hypertension and attract attention to the possible significant role of genetic factors in Mo accumulation.

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Serum Level of Zinc and Copper in Sudanese Women with Polycystic Ovarian Syndrome

Abstract

The study aimed to evaluate the serum level of zinc and copper in women with polycystic ovarian syndrome (PCOS). A case-control study was conducted at Saad Abualila infertility center (Khartoum, Sudan). The cases were women who had a PCOS based on Rotterdam criteria. The controls were infertile women with no evidence of PCOS. The socio-demographic characteristics and medical history data were gathered using questionnaires. Zinc and copper levels were measured using atomic absorption spectrophotometer. While there was no difference in zinc and copper levels between the two groups (50 women in each arm), mean (SD) of body mass index (BMI) was significantly higher in women with PCOS compared to the controls [28.4 (4.2) vs. 25.6 (5.7) kg/m²; P = 0.006], respectively. There were no significant differences in the level of luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH, prolactin, testosterone, cholesterol, triglycerides and low-density lipoprotein (LDL) between the cases and the controls. In linear regression analyses, none of the investigated factors were associated with PCOS. Zinc and copper were not associated with PCOS in this setting.

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Trace Element Levels in Scalp Hair of School Children in Shigatse, Tibet, an Endemic Area for Kaschin-Beck Disease (KBD)

Abstract

Kaschin-Beck disease (KBD) is an endemic osteoarthritis, and the etiology is closely related with levels of trace elements in the human body. Currently, it is clear that the selenium (Se) status of children in KBD areas is lower than that in non-KBD areas in the Tibetan Plateau, whereas role of other elements are yet unknown. This study aimed to assess some essential trace elements (Se, Mo, Mn, Zn, Fe, Cu, Co, and Sr) in children using scalp hair as a biomarker, and 157 samples from school children aged 8–14 years old were collected from both KBD and non-KBD areas in Shigatse, Tibet. Se and Mo were measured by inductive coupled plasma mass spectrometry, and the other elements were determined by inductive coupled plasma optical emission spectrometry. Compared with the non-KBD areas, Se, Mo, Mn, Fe, Zn, Co, and Sr levels of children in KBD areas were found to be significantly different (P < 0.05); while in linear discriminant analysis, only Se and Zn were found to contribute to the KBD prevalence in the study area. The hair Se level of children in KBD areas ranged from 0.115 to 0.299 mg/kg, while in non-KBD areas it ranged from 0.135 to 0.519 mg/kg. The Zn content of children's hair was between 83 and 207 mg/kg in KBD areas, while it was 37 and 219 mg/kg in non-KBD areas. Lower Se and higher Zn levels in children in KBD areas was found when compared with non-KBD groups. In addition, Mo levels were found to be different between KBD areas and non-KBD areas on the opposite side of the Yarlung Zangbo River, but no close relationship was shown because there was no difference compared with the non-KBD area on the same side of the river. Our observations suggest that Se deficiency is still an important factor for the occurrence and prevalence of KBD, while the relationship between Zn and KBD needs to be further explored in the Tibetan Plateau.

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Dietary Intake of Minerals, Vitamins, and Trace Elements Among Geriatric Population in India

Abstract

The geriatric population is at a high risk of developing deficiencies of essential micronutrients such as minerals, vitamins, and trace elements and their related deficiency signs and symptoms. Scarce data is available on the dietary intake of essential micronutrients among geriatric subjects in India. Hence, to fill the gap in the existing knowledge, a community-based cross-sectional study was conducted during 2015–2016 in District Nainital, Uttarakhand State, India. A total of 255 geriatric subjects were enrolled from 30 clusters (villages) identified by using population proportionate to size sampling methodology. Data were collected on sociodemographic profile and dietary intake of essential micronutrients (24-h dietary recall, food frequency questionnaire) from all the geriatric subjects. A high percentage of geriatric subjects did not consume the recommended daily intake for essential micronutrients such as energy (78%), protein (78%), calcium (51%), thiamine (33%), riboflavin (64%), niacin (88%), vitamin C (42%), iron (72%), folic acid (72%), magnesium (48%), zinc (98%), copper (81%) and chromium (89%) adequately. Food groups rich in essential micronutrients such as pulses, green leafy vegetables, roots and tubers, other vegetables, fruits, nonvegetarian food items, and milk and milk products were consumed irregularly by the subjects. The overall intake of energy and essential micronutrients was inadequate among the geriatric population in India, possibly due to poor quality and quantity of the diet consumed.

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Experimental Research Showing the Reduction of Naloxone-Place Aversion by Oral Zinc Administration in Rats

Abstract

Previous studies showed the attenuation of both morphine-dependence and morphine-place preference by zinc. Conditioned place preference and aversion are experimental models frequently used to test the reward-stimulating, respectively the aversive effects induced by different stimuli or substances. Addictive substances usually induce place preference (exhibit reward-stimulating properties), while their antagonists determine place-avoidance (aversion). The present study aimed to assess the effect determined by zinc sulphate oral administration (2 and 4 mg/kg/day, 14 days, prior to habituation) on the place aversion induced by two naloxone doses (1.5 and 2.5 mg/kg/administration). The results show a robust, dose-dependent reduction of the aversion determined by both naloxone doses (the aversion induced by 1.5 mg/kg naloxone was reduced with 15%—the lower zinc dose and with 24%—the higher zinc dose; the aversion induced by 2.5 mg/kg naloxone was reduced with 16%—the lower zinc dose and with 29%—the higher zinc dose). This represents a new proof of the interactions between zinc and opioidergic system and a further argument for dietary zinc supplementation in patients on opioids for cancer-related chronic pain.

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The Concentration of Vanadium in Pathologically Altered Human Kidneys

Abstract

Vanadium has a unique and beneficial effect on both humans and animal organisms; however, excessive amount of the above-mentioned metal can cause many alterations in tissues and organs, including the kidneys. The aim of the study was to determine the concentration of vanadium (V) in the kidneys removed from patients due to lesions of various etiologies, including the rejection of the transplanted kidneys. Additionally, we determined the influence of selected biological and environmental factors on the V concentration. The study material consisted of the kidneys with tumor lesions (n = 27) and extracted kidney grafts (n = 10) obtained from patients from the north-western Poland. The V concentrations were assessed by atomic absorption spectrophotometry emission in inductively coupled argon plasma and expressed in concentrations in dry weight (dw). Statistically significant differences were observed for V concentrations in the renal medulla between the kidneys with tumors and renal grafts, where the lowest concentration of V was observed. The kidneys in more advanced stages of the tumor (T3 + T4) contained more vanadium than the kidneys of T1 + T2 stages and medians were 2.07 and 1.51, respectively. We also compared the V concentration in the kidneys between the renal grafts (K2) and the kidneys with tumor (K1) in two stages of advancement: T1 with T2 (K1_1 + 2) and T3 with T4 (K1_3 + 4). Statistically significant differences were noted between the renal medullae of the above-mentioned groups of kidneys.

According to the previous studies on the concentrations of other heavy metals, renal grafts accumulate less vanadium than cancerous kidneys, what can be associated with the immunosuppressive drugs taken by patients after the transplantation.

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Effects of Excess Dietary Fluoride on Serum Biochemical Indices, Egg Quality, and Concentrations of Fluoride in Soft Organs, Eggs, and Serum of Laying Hens

Abstract

This study was conducted to investigate the effects of excess dietary fluoride (F) on serum biochemical indices, egg quality, and concentrations of F in soft tissues, eggs, and serum of laying hens. Commercial laying hens (n = 576, 51 weeks of age) were randomly allotted to 6 treatments with 6 replicates of 16 birds. The basal diets contained fluorine inclusions at a level of 16 mg/kg, and graded sodium fluoride was added to the basal diet to achieve fluorine inclusions, respectively, at a level of 200, 400, 600, 800, and 1000 mg/kg in the experimental diets. Dietary F levels at 600, 800, and 1000 mg/kg decreased (P < 0.05) albumin height and yolk color, while eggshell strength and eggshell thickness significantly decreased at 800 and 1000 mg/kg, respectively, compared with the control group. Fluoride concentrations in eggshell, albumin, yolk, liver, kidney, ovary, and oviduct responded to dietary F levels positively, and F concentrations in eggshell were the highest. Fluorine concentrations in albumin and yolk increased with the feeding time at the same dietary F levels (P < 0.05). Dietary F level at 400 mg/kg increased serum calcium level and activity of glutamic oxalacetic transaminase (P < 0.05). In conclusion, dietary F levels at 600 mg/kg decreased albumin height and yolk color, while eggshell strength and eggshell thickness significantly decreased at 800 and 1000 mg/kg, respectively. F concentrations in soft tissues, albumin, yolk, and eggshell of layers had a positive correlation with dietary F levels. By disturbing Ca and phosphorus metabolism, dietary F levels affected the formation of eggshell, reducing eggshell strength and eggshell thickness.

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Role of Selenium from Different Sources in Prevention of Pulmonary Arterial Hypertension Syndrome in Broiler Chickens

Abstract

Pulmonary arterial hypertension (PAH) syndrome in broilers is associated with hypoxia, which prevails at high altitude. Oxidative stress is the pathogenic mechanism underlying PAH. Because selenium is key element in the structure of antioxidant enzymes, we evaluated pulmonary hypertensive responses in broiler chickens fed with diets supplemented with organic or nano-selenium. One hundred forty-four broilers (starting at 5 days old) were fed with (i) control group: birds received a standard diet; (ii) nano-selenium group: birds were fed with basal diet supplemented with nano-selenium at 0.3 mg/kg; and (iii) organic selenium group: birds received basal diet supplemented with organic selenium at 0.3 mg/kg. We assessed growth performance, carcass characteristics, antioxidant variables, blood parameters, and small intestine morphology. Although Se supplementation did not affect growth performance, carcass traits, and organ weight (P > 0.05), the right to total ventricular weight ratio (RV:TV), malondialdehyde concentration in the liver, and heterophil to lymphocyte ratio were significantly lower in the nano-selenium group relative to the control (P < 0.05). Chickens that received nano-selenium also elicited significantly higher antibody titers after 24 h of an injection of sheep red blood cells (P < 0.05). Nano-selenium supplementation also significantly increased villus height, absorptive surface area, and lamina propria thickness relative to the control (P < 0.05) in different segments of the small intestine. In contrast, organic selenium supplement improved intestinal morphometry only in the jejunum. We conclude that dietary supplementation of 0.30 mg/kg nano-selenium could prevent right ventricular hypertrophy as reflected by reduced RV:TV, reduced levels of lipid peroxidation in the liver, and improved gut function.

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