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Diseases, Volume 3, Issue 4 (December 2015) – 10 articles , Pages 221-415

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Open AccessReview
Puzzle Pieces: Neural Structure and Function in Prader-Willi Syndrome
Diseases 2015, 3(4), 382-415; https://doi.org/10.3390/diseases3040382 - 17 Dec 2015
Cited by 9 | Viewed by 2596
Abstract
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a behavioural phenotype encompassing hyperphagia, intellectual disability, social and behavioural difficulties, and propensity to psychiatric illness. Research has tended to focus on the cognitive and behavioural investigation of these features, and, [...] Read more.
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a behavioural phenotype encompassing hyperphagia, intellectual disability, social and behavioural difficulties, and propensity to psychiatric illness. Research has tended to focus on the cognitive and behavioural investigation of these features, and, with the exception of eating behaviour, the neural physiology is currently less well understood. A systematic review was undertaken to explore findings relating to neural structure and function in PWS, using search terms designed to encompass all published articles concerning both in vivo and post-mortem studies of neural structure and function in PWS. This supported the general paucity of research in this area, with many articles reporting case studies and qualitative descriptions or focusing solely on the overeating behaviour, although a number of systematic investigations were also identified. Research to date implicates a combination of subcortical and higher order structures in PWS, including those involved in processing reward, motivation, affect and higher order cognitive functions, with both anatomical and functional investigations indicating abnormalities. It appears likely that PWS involves aberrant activity across distributed neural networks. The characterisation of neural structure and function warrants both replication and further systematic study. Full article
(This article belongs to the Special Issue Prader-Willi Syndrome)
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Open AccessReview
Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future
Diseases 2015, 3(4), 360-381; https://doi.org/10.3390/diseases3040360 - 01 Dec 2015
Cited by 10 | Viewed by 2070
Abstract
Systemic chemotherapy is one of the most important treatment modalities for advanced hepatocellular carcinoma (HCC). Before the introduction of sorafenib, cytotoxic agents, hormonal therapies, or many combinations of these were the mainly used modalities for systemic chemotherapy of advanced HCC. However, such regimens [...] Read more.
Systemic chemotherapy is one of the most important treatment modalities for advanced hepatocellular carcinoma (HCC). Before the introduction of sorafenib, cytotoxic agents, hormonal therapies, or many combinations of these were the mainly used modalities for systemic chemotherapy of advanced HCC. However, such regimens were of only limited value in clinical practice, because some randomized controlled studies comparing promising regimens with no treatment or doxorubicin alone failed to show any overall survival advantage. In two pivotal phase III placebo-controlled studies, the SHARP trial and the Asia-Pacific trial, sorafenib was demonstrated to significantly delay the time to progression and the overall survival time in patients with advanced HCC. Therefore, sorafenib therapy has come to be acknowledged as a standard therapy for advanced HCC worldwide. After the introduction of sorafenib, a number of phase III trials of various molecular-targeted agents vs. sorafenib as first-line chemotherapy and of various molecular-targeted agents vs. placebo as second-line chemotherapy have been conducted to determine if any of these agents could offer a survival benefit, however, none of the agents examined so far has been demonstrated to provide any survival benefit over sorafenib or placebo. Recently, favorable treatment efficacies have been reported in some clinical trials of molecular-targeted agents in the biomarker-enriched population. Development of individualized cancer treatments using molecular-targeted agents based on the results of genome-sequencing is aggressively ongoing. Furthermore, immune-oncologic agents, such as anti-CTLA-4 antibody and anti-PD-1/PD-L1 antibody, have been reported to provide promising outcomes. Thus, various novel systemic chemotherapeutic agents are currently under development, and further improvements in the treatment outcomes are expected. Full article
(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
Open AccessReview
An Integrated Outlook on the Metagenome and Metabolome of Intestinal Diseases
Diseases 2015, 3(4), 341-359; https://doi.org/10.3390/diseases3040341 - 06 Nov 2015
Cited by 2 | Viewed by 2181
Abstract
Recently, metagenomics and metabolomics are the two most rapidly advancing “omics” technologies. Metagenomics seeks to characterize the composition of microbial communities, their operations, and their dynamically co-evolving relationships with the habitats they occupy, whereas metabolomics studies unique chemical endpoints (metabolites) that specific cellular [...] Read more.
Recently, metagenomics and metabolomics are the two most rapidly advancing “omics” technologies. Metagenomics seeks to characterize the composition of microbial communities, their operations, and their dynamically co-evolving relationships with the habitats they occupy, whereas metabolomics studies unique chemical endpoints (metabolites) that specific cellular processes leave behind. Remarkable progress in DNA sequencing and mass spectrometry technologies has enabled the comprehensive collection of information on the gut microbiome and its metabolome in order to assess the influence of the gut microbiota on host physiology on a whole-systems level. Our gut microbiota, which consists of prokaryotic cells together with its metabolites, creates a unique gut ecosystem together with the host eukaryotic cells. In this review, we will highlight the detailed relationships between gut microbiota and its metabolites on host health and the pathogenesis of various intestinal diseases such as inflammatory bowel disease and colorectal cancer. Therapeutic interventions such as probiotic and prebiotic administrations and fecal microbiota transplantations will also be discussed. We would like to promote this unique biology-wide approach of incorporating metagenome and metabolome information as we believe that this can help us understand the intricate interplay between gut microbiota and host metabolism to a greater extent. This novel integration of microbiome, metatranscriptome, and metabolome information will help us have an improved holistic understanding of the complex mammalian superorganism, thereby allowing us to gain new and unprecedented insights to providing exciting novel therapeutic approaches for optimal intestinal health. Full article
(This article belongs to the Special Issue Advances and Applications of Metabolomics in Human Diseases)
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Open AccessReview
New Tools for Molecular Therapy of Hepatocellular Carcinoma
Diseases 2015, 3(4), 325-340; https://doi.org/10.3390/diseases3040325 - 30 Oct 2015
Cited by 3 | Viewed by 3014
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, arising from neoplastic transformation of hepatocytes or liver precursor/stem cells. HCC is often associated with pre-existing chronic liver pathologies of different origin (mainly subsequent to HBV and HCV infections), such as fibrosis [...] Read more.
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, arising from neoplastic transformation of hepatocytes or liver precursor/stem cells. HCC is often associated with pre-existing chronic liver pathologies of different origin (mainly subsequent to HBV and HCV infections), such as fibrosis or cirrhosis. Current therapies are essentially still ineffective, due both to the tumor heterogeneity and the frequent late diagnosis, making necessary the creation of new therapeutic strategies to inhibit tumor onset and progression and improve the survival of patients. A promising strategy for treatment of HCC is the targeted molecular therapy based on the restoration of tumor suppressor proteins lost during neoplastic transformation. In particular, the delivery of master genes of epithelial/hepatocyte differentiation, able to trigger an extensive reprogramming of gene expression, could allow the induction of an efficient antitumor response through the simultaneous adjustment of multiple genetic/epigenetic alterations contributing to tumor development. Here, we report recent literature data supporting the use of members of the liver enriched transcription factor (LETF) family, in particular HNF4α, as tools for gene therapy of HCC. Full article
(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
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Open AccessReview
Clinical Development of c-MET Inhibition in Hepatocellular Carcinoma
Diseases 2015, 3(4), 306-324; https://doi.org/10.3390/diseases3040306 - 28 Oct 2015
Cited by 4 | Viewed by 1846
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death. In patients with advanced or unresectable HCC, there are few treatment options. Conventional chemotherapy has limited benefits. Sorafenib, a multi-kinase inhibitor, improves survival, but options for patients intolerant of or progressing [...] Read more.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death. In patients with advanced or unresectable HCC, there are few treatment options. Conventional chemotherapy has limited benefits. Sorafenib, a multi-kinase inhibitor, improves survival, but options for patients intolerant of or progressing on sorafenib are limited. There has been much interest in recent years in molecular therapeutic targets and drug development for HCC. One of the more promising molecular targets in HCC is the cellular-mesenchymal-epithelial transition (c-MET) factor receptor. Encouraging phase II data on two c-MET inhibitors, tivantinib and cabozantinib, has led to phase III trials. This review describes the c-MET/hepatocyte growth factor (HGF) signalling pathway and its relevance to HCC, and discusses the preclinical and clinical trial data for inhibitors of this pathway in HCC. Full article
(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
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Open AccessReview
Targeting FGF19/FGFR4 Pathway: A Novel Therapeutic Strategy for Hepatocellular Carcinoma
Diseases 2015, 3(4), 294-305; https://doi.org/10.3390/diseases3040294 - 28 Oct 2015
Cited by 18 | Viewed by 3151
Abstract
Hepatocellular carcinoma (HCC) is a lethal cancer with limited systemic therapeutic options. Liver carcinogenesis is a complex procedure and various pathways have been found to be deregulated which are potential targets for novel treatments. Aberrant signalling through FGF19 and its receptor FGFR4 seems [...] Read more.
Hepatocellular carcinoma (HCC) is a lethal cancer with limited systemic therapeutic options. Liver carcinogenesis is a complex procedure and various pathways have been found to be deregulated which are potential targets for novel treatments. Aberrant signalling through FGF19 and its receptor FGFR4 seems to be the oncogenic driver for a subset of HCCs and is associated with poor prognosis. Inhibition of the pathway in preclinical models has shown antitumour activity and has triggered further evaluation of this strategy to in vivo models. This review aims to describe the role of the FGF19/FGFR4 pathway in hepatocellular carcinoma and its role as a potential predictive biomarker for novel targeted agents against FGF19/FGFR4 signalling. Full article
(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
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Open AccessReview
The Role of Environmental Factors in the Development of Celiac Disease: What Is New?
Diseases 2015, 3(4), 282-293; https://doi.org/10.3390/diseases3040282 - 27 Oct 2015
Cited by 7 | Viewed by 2619
Abstract
Celiac disease (CD) is a systemic immune-mediated disorder caused by the ingestion of gluten-containing grains in genetically susceptible persons. It is one of the most common lifelong disorders, affecting approximately 1% of the general population. The prevalence of CD has increased in developed [...] Read more.
Celiac disease (CD) is a systemic immune-mediated disorder caused by the ingestion of gluten-containing grains in genetically susceptible persons. It is one of the most common lifelong disorders, affecting approximately 1% of the general population. The prevalence of CD has increased in developed countries over recent decades, pointing to the role of additional environmental triggers other than gluten. It has been hypothesized that intestinal infections, the amount and quality of gluten, the intestinal microbiota, and early nutrition are all possible triggers of the switch from tolerance to an immune response to gluten. Two recent randomized controlled trials have been performed to clarify the relationship between the age at which gluten is introduced to a child’s diet and the risk of CD, showing that timing of gluten introduction does not modify the risk of CD. Both trials also showed that breastfeeding compared with no breastfeeding or breastfeeding duration or breastfeeding during gluten introduction have no effect on the risk of CD. The two trials, although not designed to address this issue, have shown that intestinal infections seem not to influence the risk of CD. Further studies are still needed to explore the missing environmental factors of CD for future prevention. Full article
(This article belongs to the Special Issue Celiac Disease)
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Open AccessReview
Synergistic Anticancer Activities of Natural Substances in Human Hepatocellular Carcinoma
Diseases 2015, 3(4), 260-281; https://doi.org/10.3390/diseases3040260 - 22 Oct 2015
Cited by 5 | Viewed by 2010
Abstract
Hepatocellular carcinoma (HCC) is highly resistant to currently available chemotherapeutic agents. The clinical outcome of HCC treatment remains unsatisfactory. Therefore, new effective and well-tolerated therapy strategies are needed. Natural products are excellent sources for the development of new medications for disease treatment. Recently, [...] Read more.
Hepatocellular carcinoma (HCC) is highly resistant to currently available chemotherapeutic agents. The clinical outcome of HCC treatment remains unsatisfactory. Therefore, new effective and well-tolerated therapy strategies are needed. Natural products are excellent sources for the development of new medications for disease treatment. Recently, we and other researchers have suggested that the combined effect of natural products may improve the effect of chemotherapy treatments against the proliferation of cancer cells. In addition, many combination treatments with natural products augmented intracellular reactive oxygen species (ROS). In this review we will demonstrate the synergistic anticancer effects of a combination of natural products with chemotherapeutic agents or natural products against human HCC and provide new insight into the development of novel combination therapies against HCC. Full article
(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
Open AccessArticle
The Effects of Vitamin D Supplementation on Pulmonary Function of Chronic Obstructive Pulmonary Disease Patients, before and after Clinical Trial
Diseases 2015, 3(4), 253-259; https://doi.org/10.3390/diseases3040253 - 16 Oct 2015
Cited by 2 | Viewed by 1906
Abstract
Vitamin D has several extra calcemic effects. Vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients but little is known about it’s association with lung function. Objective: To investigate whether supplementation with vitamin D could improve pulmonary function in [...] Read more.
Vitamin D has several extra calcemic effects. Vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients but little is known about it’s association with lung function. Objective: To investigate whether supplementation with vitamin D could improve pulmonary function in COPD patients. Design: Before and after, double center, clinical trial. Setting: Hazrat Rasoul University Hospital, Tehran, and Imam Khomaini University Hospital, Ahvaz, Iran. Participants: 24 patients with mild to very severe COPD. Intervention: Loading dose of 300,000–600,000 International Units (IU) of vitamin D, then 50000 IU weekly for 12 weeks. Measurements: The outcomes included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), vital capacity (VC), forced expiratory flow between 25%–75% of forced vital capacity (FEF 25%–75%), exercise capacity according to the six minute walk test(6MWT) and the saturation of oxygen during exercise. Results: The mean FEV1 (p-value = 0.866), FVC (p-value = 0.475) and VC (p-value = 0.425) were not significantly different before and after intervention. FEF 25%–75% did not improve with this intervention (p-value = 0.555). The vitamin D supplementation did not have any significant effect on the exercise capacity (p-value=0.175) or the saturation of oxygen (p-value = 0.635). Conclusion: Pulmonary function and exercise capacity did not improve with vitamin D supplementation in COPD patients. Full article
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Open AccessReview
A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma
Diseases 2015, 3(4), 221-252; https://doi.org/10.3390/diseases3040221 - 29 Sep 2015
Cited by 1 | Viewed by 3495
Abstract
Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the [...] Read more.
Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC. Full article
(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
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