Next Issue
Volume 4, June
Previous Issue
Volume 3, December
 
 
From the start of 2016, the journal uses article numbers instead of page numbers to identify articles. If you are required to add page numbers to a citation, you can do with using a colon in the format [article number]:1–[last page], e.g. 10:1–20.

Diseases, Volume 4, Issue 1 (March 2016) – 15 articles

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Select all
Export citation of selected articles as:
1125 KiB  
Review
Prader-Willi Syndrome: The Disease that Opened up Epigenomic-Based Preemptive Medicine
by Takeo Kubota, Kunio Miyake, Natsuyo Hariya, Vuong Tran Nguyen Quoc and Kazuki Mochizuki
Diseases 2016, 4(1), 15; https://doi.org/10.3390/diseases4010015 - 11 Mar 2016
Cited by 3 | Viewed by 18296
Abstract
Prader-Willi syndrome (PWS) is a congenital neurodevelopmental disorder caused by loss of function of paternally expressed genes on chromosome 15 due to paternal deletion of 15q11–q13, maternal uniparental disomy for chromosome 15, or an imprinting mutation. We previously developed a DNA methylation-based PCR [...] Read more.
Prader-Willi syndrome (PWS) is a congenital neurodevelopmental disorder caused by loss of function of paternally expressed genes on chromosome 15 due to paternal deletion of 15q11–q13, maternal uniparental disomy for chromosome 15, or an imprinting mutation. We previously developed a DNA methylation-based PCR assay to identify each of these three genetic causes of PWS. The assay enables straightforward and rapid diagnosis during infancy and therefore allows early intervention such as nutritional management, physical therapy, or growth hormone treatment to prevent PWS patients from complications such as obesity and type 2 diabetes. It is known that various environmental factors induce epigenomic changes during the perinatal period, which increase the risk of adult diseases such as type 2 diabetes and intellectual disabilities. Therefore, a similar preemptive approach as used in PWS would also be applicable to acquired disorders and would make use of environmentally-introduced “epigenomic signatures” to aid development of early intervention strategies that take advantage of “epigenomic reversibility”. Full article
(This article belongs to the Special Issue Prader-Willi Syndrome)
Show Figures

Graphical abstract

1623 KiB  
Review
Effect of Dietary Bioactive Compounds on Mitochondrial and Metabolic Flexibility
by Jose C. E. Serrano, Anna Cassanye, Meritxell Martín-Gari, Ana Belen Granado-Serrano and Manuel Portero-Otín
Diseases 2016, 4(1), 14; https://doi.org/10.3390/diseases4010014 - 10 Mar 2016
Cited by 32 | Viewed by 9556
Abstract
Metabolic flexibility is the capacity of an organism to adequately respond to changes in the environment, such as nutritional input, energetic demand, etc. An important player in the capacity of adaptation through different stages of metabolic demands is the mitochondrion. In this context, [...] Read more.
Metabolic flexibility is the capacity of an organism to adequately respond to changes in the environment, such as nutritional input, energetic demand, etc. An important player in the capacity of adaptation through different stages of metabolic demands is the mitochondrion. In this context, mitochondrial dysfunction has been attributed to be the onset and center of many chronic diseases, which are denoted by an inability to adapt fuel preferences and induce mitochondrial morphological changes to respond to metabolic demands, such as mitochondrial number, structure and function. Several nutritional interventions have shown the capacity to induce changes in mitochondrial biogenesis/degradation, oxidative phosphorylation efficiency, mitochondrial membrane composition, electron transfer chain capacity, etc., in metabolic inflexibility states that may open new target options and mechanisms of action of bioactive compounds for the treatment of metabolic diseases. This review is focused in three well-recognized food bioactive compounds that modulate insulin sensitivity, polyphenols, ω-3 fatty acids and dietary fiber, by several mechanism of action, like caloric restriction properties and inflammatory environment modulation, both closely related to mitochondrial function and dynamics. Full article
Show Figures

Graphical abstract

1043 KiB  
Review
Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics
by Emma D. Spikol, Caroline E. Laverriere, Maya Robnett, Gabriela Carter, Erin Wolfe and Eric Glasgow
Diseases 2016, 4(1), 13; https://doi.org/10.3390/diseases4010013 - 08 Mar 2016
Cited by 8 | Viewed by 6281
Abstract
Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic [...] Read more.
Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic basis of PWS, the mechanisms underlying the pathogenesis of the disorder remain poorly understood. Treatment for PWS consists mainly of palliative therapies; curative therapies are sorely needed. Zebrafish, Danio rerio, represent a promising way forward for elucidating physiological problems such as obesity and identifying new pharmacotherapeutic options for PWS. Over the last decade, an increased appreciation for the highly conserved biology among vertebrates and the ability to perform high-throughput drug screening has seen an explosion in the use of zebrafish for disease modeling and drug discovery. Here, we review recent advances in developing zebrafish models of human disease. Aspects of zebrafish genetics and physiology that are relevant to PWS will be discussed, and the advantages and disadvantages of zebrafish models will be contrasted with current animal models for this syndrome. Finally, we will present a paradigm for drug screening in zebrafish that is potentially the fastest route for identifying and delivering curative pharmacotherapies to PWS patients. Full article
(This article belongs to the Special Issue Prader-Willi Syndrome)
Show Figures

Graphical abstract

494 KiB  
Review
Uric Acid for Cardiovascular Risk: Dr. Jekyll or Mr. Hide?
by Cristina Vassalle, Annamaria Mazzone, Laura Sabatino and Clara Carpeggiani
Diseases 2016, 4(1), 12; https://doi.org/10.3390/diseases4010012 - 26 Feb 2016
Cited by 23 | Viewed by 7501
Abstract
Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that this [...] Read more.
Uric acid (UA) is a potent endogenous antioxidant. However, high concentrations of this molecule have been associated with cardiovascular disease (CVD) and renal dysfunction, involving mechanisms that include oxidative stress, inflammatory processes, and endothelial injury. Experimental and in vitro results suggest that this biomarker behaves like other antioxidants, which can shift from the physiological antioxidant action to a pro-oxidizing effect according to their level and to microenvironment conditions. However, data on patients (general population or CAD cohorts) are controversial, so the debate on the role of hyperuricemia as a causative factor for CVD is still ongoing. Increasing evidence indicates UA as more meaningful to assess CVD in women, even though this aspect needs deeper investigation. It will be important to identify thresholds responsible for UA “biological shift” from protective to harmful effects in different pathological conditions, and according to possible gender-related differences. In any case, UA is a low-tech and inexpensive biomarker, generally performed at patient’s hospitalization and, therefore, easily accessible information for clinicians. For these reasons, UA might represent a useful additive tool as much as a CV risk marker. Thus, in view of available evidence, progressive UA elevation with levels higher than 6 mg/dL could be considered an “alarm” for increased CV risk. Full article
Show Figures

Figure 1

204 KiB  
Review
Antioxidants and Cardiovascular Risk Factors
by Daniela Pellegrino
Diseases 2016, 4(1), 11; https://doi.org/10.3390/diseases4010011 - 17 Feb 2016
Cited by 23 | Viewed by 5513
Abstract
Cardiovascular disease (CVD), the world’s primary cause of death and disability, represents a global health problem and involves a great public financial commitment in terms of both inability to work and pharmaceutical costs. CVD is characterized by a cluster of disorders, associated with [...] Read more.
Cardiovascular disease (CVD), the world’s primary cause of death and disability, represents a global health problem and involves a great public financial commitment in terms of both inability to work and pharmaceutical costs. CVD is characterized by a cluster of disorders, associated with complex interactions between multiple risk factors. The early identification of high cardiovascular risk subjects is one of the main targets of primary prevention in order to reduce the adverse impact of modifiable factors, from lifestyle changes to pharmacological treatments. The cardioprotective effect of food antioxidants is well known. Indeed, a diet rich in fruits and vegetables results in an increase in serum antioxidant capacity and a decrease in oxidative stress. In contrast, studies on antioxidant supplementation, even those that are numerically significant, have revealed no clear benefit in prevention and therapy of CVD. Both short- and long-term clinical trials have failed to consistently support cardioprotective effects of supplemental antioxidant intake. The aim of this review is to evaluate the antioxidant effects on the main cardiovascular risk factors including hypertension, dyslipidemia, diabetes. Full article
523 KiB  
Review
Targeted Therapy of Hepatitis B Virus-Related Hepatocellular Carcinoma: Present and Future
by Sarene Koh, Anthony Tanoto Tan, Lietao Li and Antonio Bertoletti
Diseases 2016, 4(1), 10; https://doi.org/10.3390/diseases4010010 - 15 Feb 2016
Cited by 8 | Viewed by 6521
Abstract
Cancer immunotherapy using a patient’s own T cells redirected to recognize and kill tumor cells has achieved promising results in metastatic melanoma and leukemia. This technique involves harnessing a patient’s T cells and then delivering a gene that encodes a new T cell [...] Read more.
Cancer immunotherapy using a patient’s own T cells redirected to recognize and kill tumor cells has achieved promising results in metastatic melanoma and leukemia. This technique involves harnessing a patient’s T cells and then delivering a gene that encodes a new T cell receptor (TCR) or a chimeric antigen receptor (CAR) that allow the cells to recognize specific cancer antigens. The prospect of using engineered T cell therapy for persistent viral infections like hepatitis B virus (HBV) and their associated malignancies is promising. We recently tested in a first-in-man clinical trial, the ability of HBV-specific TCR-redirected T cells to target HBsAg-productive hepatocellular carcinoma (HCC) and demonstrated that these redirected T cells recognized HCC cells with HBV–DNA integration [1] We discuss here the possibility to use HBV-specific TCR-redirected T cells targeting hepatitis B viral antigens as a tumor specific antigen in patients with HBV-related HCC, and the potential challenges facing the development of this new immunotherapeutic strategy. Full article
(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
Show Figures

Figure 1

196 KiB  
Article
The Developmental Trajectory of Self-Injurious Behaviours in Individuals with Prader Willi Syndrome, Autism Spectrum Disorder and Intellectual Disability
by Lauren J. Rice, Kylie M. Gray, Patricia Howlin, John Taffe, Bruce J. Tonge and Stewart L. Einfeld
Diseases 2016, 4(1), 9; https://doi.org/10.3390/diseases4010009 - 06 Feb 2016
Cited by 11 | Viewed by 5555
Abstract
In the present study we examined the nature and developmental trajectory of self-injurious behaviour in Prader Willi syndrome (PWS) and autism spectrum disorder (ASD). The development of interventions is greatly aided by understanding gene to behaviour pathways, and this requires an accurate description [...] Read more.
In the present study we examined the nature and developmental trajectory of self-injurious behaviour in Prader Willi syndrome (PWS) and autism spectrum disorder (ASD). The development of interventions is greatly aided by understanding gene to behaviour pathways, and this requires an accurate description of the behaviour phenotype, that is, which types and natural history of self-injurious behaviour are more common in PWS and ASD and which are shared with other forms of developmental disability. Self-injury displayed by individuals with PWS and individuals with ASD was compared with that reported in a group of individuals with intellectual disability due to mixed aetiology (ID group). Three self-injurious behaviours (head banging, skin-picking and hitting and/or biting self) were measured on five occasions over 18 years using the Developmental Behaviour Checklist (DBC) a well-validated caregiver report measure. Rates of skin picking were higher in individuals with PWS and hitting and/or biting self was higher in individuals with ASD compared to the ID group. Rates of head banging were similar across the three groups. Over time, skin-picking and head banging increased with age for individuals with ASD and hitting and/or biting self increased for the PWS group. In the PWS and mixed ID groups head banging decreased with age. These findings suggest that the typology and developmental trajectories of self-injurious behaviours differ between those with PWS and ASD. Full article
(This article belongs to the Special Issue Prader-Willi Syndrome)
645 KiB  
Editorial
Acknowledgement to Reviewers of Diseases in 2015
by Diseases Editorial Office
Diseases 2016, 4(1), 8; https://doi.org/10.3390/diseases4010008 - 26 Jan 2016
Viewed by 3319
Abstract
The editors of Diseases would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...] Full article
2609 KiB  
Article
Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics
by Rosa Ragone, Fabio Sallustio, Sara Piccinonna, Monica Rutigliano, Galleggiante Vanessa, Silvano Palazzo, Giuseppe Lucarelli, Pasquale Ditonno, Michele Battaglia, Francesco Paolo Fanizzi and Francesco Paolo Schena
Diseases 2016, 4(1), 7; https://doi.org/10.3390/diseases4010007 - 22 Jan 2016
Cited by 61 | Viewed by 5074
Abstract
Renal cell carcinoma (RCC) is a heterogeneous cancer often showing late symptoms. Until now, some candidate protein markers have been proposed for its diagnosis. Metabolomics approaches have been applied, predominantly using Mass Spectrometry (MS), while Nuclear Magnetic Resonance (NMR)-based studies remain limited. There [...] Read more.
Renal cell carcinoma (RCC) is a heterogeneous cancer often showing late symptoms. Until now, some candidate protein markers have been proposed for its diagnosis. Metabolomics approaches have been applied, predominantly using Mass Spectrometry (MS), while Nuclear Magnetic Resonance (NMR)-based studies remain limited. There is no study about RCC integrating NMR-based metabolomics with transcriptomics. In this work, 1H-NMR spectroscopy combined with multivariate statistics was applied on urine samples, collected from 40 patients with clear cell RCC (ccRCC) before nephrectomy and 29 healthy controls; nine out of 40 patients also provided samples one-month after nephrectomy. We observed increases of creatine, alanine, lactate and pyruvate, and decreases of hippurate, citrate, and betaine in all ccRCC patients. A network analysis connected most of these metabolites with glomerular injury, renal inflammation and renal necrosis/cell death. Interestingly, intersecting metabolites with transcriptomic data from CD133+/CD24+ tumoral renal stem cells isolated from ccRCC patients, we found that both genes and metabolites differentially regulated in ccRCC patients belonged to HIF-α signaling, methionine and choline degradation, and acetyl-CoA biosynthesis. Moreover, when comparing urinary metabolome of ccRCC patients after nephrectomy, some processes, such as the glomerular injury, renal hypertrophy, renal necrosis/cell death and renal proliferation, were no more represented. Full article
(This article belongs to the Special Issue Advances and Applications of Metabolomics in Human Diseases)
Show Figures

Figure 1

694 KiB  
Review
Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer
by María Angeles Martín, Luis Goya and Sonia Ramos
Diseases 2016, 4(1), 6; https://doi.org/10.3390/diseases4010006 - 22 Jan 2016
Cited by 23 | Viewed by 10415
Abstract
Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to [...] Read more.
Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to interfere at the three stages of cancer. Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective approach in colorectal cancer prevention. In this review, we look over different in vitro and in vivo studies that have identified potential targets and mechanisms whereby cocoa and their flavonoids could interfere with colonic cancer. In addition, evidence from human studies is also illustrated. Full article
Show Figures

Figure 1

186 KiB  
Review
Pituitary-Adrenal Axis in Prader Willi Syndrome
by Olivia S. Edgar, Angela K. Lucas-Herald and Mohamad Guftar Shaikh
Diseases 2016, 4(1), 5; https://doi.org/10.3390/diseases4010005 - 19 Jan 2016
Cited by 2 | Viewed by 4419
Abstract
Purpose: Prader Willi syndrome (PWS) is a rare genetic condition that has concurrent endocrinological insufficiencies. The presence of growth hormone deficiency has been well documented, but adrenal insufficiency (AI) is not widely reported. A review was conducted to investigate its prevalence and relevance [...] Read more.
Purpose: Prader Willi syndrome (PWS) is a rare genetic condition that has concurrent endocrinological insufficiencies. The presence of growth hormone deficiency has been well documented, but adrenal insufficiency (AI) is not widely reported. A review was conducted to investigate its prevalence and relevance in PWS in both adults and children. Methodology: A literature review was performed with the search terms “Prader-Willi syndrome” and “adrenal insufficiency”. Results: The review found studies disagree on the prevalence and method of investigation of AI in PWS. Case studies demonstrate that patients with PWS are at risk of premature death, often secondary to respiratory infections. The possibility that this may be the result of the inability to mount an effective cortisol response has been studied, with some evidence confirming AI in PWS patients. Most reports agreed AI is present in PWS, however, Farholt et al. showed no HPA axis dysfunction in adults, suggesting that perhaps it is rare in adults, and children should be the focus of further studies. Conclusion: AI is present in some patients with PWS. Further research is required to ensure optimal treatment can be implemented and to prevent premature deaths related to adrenal insufficiency. Clinicians should have a low threshold for testing the adrenal axis and considering treatment for adrenal insufficiency in PWS patients. Full article
(This article belongs to the Special Issue Prader-Willi Syndrome)
421 KiB  
Article
Obesity and Prader-Willi Syndrome Affect Heart Rate Recovery from Dynamic Resistance Exercise in Youth
by Diobel M. Castner, Susan J. Clark, Daniel A. Judelson and Daniela A. Rubin
Diseases 2016, 4(1), 4; https://doi.org/10.3390/diseases4010004 - 15 Jan 2016
Cited by 3 | Viewed by 6344
Abstract
Following exercise, heart rate decline is initially driven by parasympathetic reactivation and later by sympathetic withdrawal. Obesity delays endurance exercise heart rate recovery (HRR) in both children and adults. Young people with Prader-Willi Syndrome (PWS), a congenital cause for obesity, have shown a [...] Read more.
Following exercise, heart rate decline is initially driven by parasympathetic reactivation and later by sympathetic withdrawal. Obesity delays endurance exercise heart rate recovery (HRR) in both children and adults. Young people with Prader-Willi Syndrome (PWS), a congenital cause for obesity, have shown a slower 60-s endurance exercise HRR compared to lean and obese children, suggesting compromised regulation. This study further evaluated effects of obesity and PWS on resistance exercise HRR at 30 and 60 s in children. PWS (8–18 years) and lean and obese controls (8–11 years) completed a weighted step-up protocol (six sets x 10 reps per leg, separated by one-minute rest), standardized using participant stature and lean body mass. HRR was evaluated by calculated HRR value (HRRV = difference between HR at test termination and 30 (HRRV30) and 60 (HRRV60) s post-exercise). PWS and obese had a smaller HRRV30 than lean (p < 0.01 for both). Additionally, PWS had a smaller HRRV60 than lean and obese (p = 0.01 for both). Obesity appears to delay early parasympathetic reactivation, which occurs within 30 s following resistance exercise. However, the continued HRR delay at 60 s in PWS may be explained by either blunted parasympathetic nervous system reactivation, delayed sympathetic withdrawal and/or poor cardiovascular fitness. Full article
(This article belongs to the Special Issue Prader-Willi Syndrome)
Show Figures

Figure 1

966 KiB  
Article
Phytoconstituents with Radical Scavenging and Cytotoxic Activities from Diospyros shimbaensis
by Per Aronsson, Joan J. E. Munissi, Amra Gruhonjic, Paul A. Fitzpatrick, Göran Landberg, Stephen S. Nyandoro and Mate Erdelyi
Diseases 2016, 4(1), 3; https://doi.org/10.3390/diseases4010003 - 15 Jan 2016
Cited by 8 | Viewed by 6363
Abstract
As part of our search for natural products having antioxidant and anticancer properties, the phytochemical investigation of Diospyros shimbaensis (Ebenaceae), a plant belonging to a genus widely used in East African traditional medicine, was carried out. From its stem and root barks the [...] Read more.
As part of our search for natural products having antioxidant and anticancer properties, the phytochemical investigation of Diospyros shimbaensis (Ebenaceae), a plant belonging to a genus widely used in East African traditional medicine, was carried out. From its stem and root barks the new naphthoquinone 8,8′-oxo-biplumbagin (1) was isolated along with the known tetralones trans-isoshinanolone (2) and cis-isoshinanolone (3), and the naphthoquinones plumbagin (4) and 3,3′-biplumbagin (5). Compounds 2, 4, and 5 showed cytotoxicity (IC50 520–82.1 μM) against MDA-MB-231 breast cancer cells. Moderate to low cytotoxicity was observed for the hexane, dichloromethane, and methanol extracts of the root bark (IC50 16.1, 29.7 and > 100 μg/mL, respectively), and for the methanol extract of the stem bark (IC50 59.6 μg/mL). The radical scavenging activity of the isolated constituents (15) was evaluated on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The applicability of the crude extracts and of the isolated constituents for controlling degenerative diseases is discussed. Full article
Show Figures

Figure 1

1089 KiB  
Review
Prader-Willi Syndrome and Schaaf-Yang Syndrome: Neurodevelopmental Diseases Intersecting at the MAGEL2 Gene
by Michael D. Fountain and Christian P. Schaaf
Diseases 2016, 4(1), 2; https://doi.org/10.3390/diseases4010002 - 13 Jan 2016
Cited by 52 | Viewed by 15154
Abstract
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by neonatal hypotonia, developmental delay/intellectual disability, and characteristic feeding behaviors with failure to thrive during infancy; followed by hyperphagia and excessive weight gain later in childhood. Individuals with PWS also manifest complex behavioral phenotypes. Approximately [...] Read more.
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by neonatal hypotonia, developmental delay/intellectual disability, and characteristic feeding behaviors with failure to thrive during infancy; followed by hyperphagia and excessive weight gain later in childhood. Individuals with PWS also manifest complex behavioral phenotypes. Approximately 25% meet criteria for autism spectrum disorder (ASD). PWS is caused by the absence of paternally expressed, maternally silenced genes at chromosome 15q11-q13. MAGEL2 is one of five protein-coding genes in the PWS-critical domain. Truncating point mutations of the paternal allele of MAGEL2 cause Schaaf-Yang syndrome, which has significant phenotypic overlap with PWS, but is also clinically distinct; based on the presence of joint contractures, and a particularly high prevalence of autism spectrum disorder (up to 75% of affected individuals). The clinical and molecular overlap between PWS and Schaaf-Yang syndrome, but also their distinguishing features provide insight into the pathogenetic mechanisms underlying both disorders. Full article
(This article belongs to the Special Issue Prader-Willi Syndrome)
Show Figures

Figure 1

263 KiB  
Review
Hepatocellular Carcinoma: Past and Future of Molecular Target Therapy
by Khanh Nguyen, Kerri Jack and Weijing Sun
Diseases 2016, 4(1), 1; https://doi.org/10.3390/diseases4010001 - 25 Dec 2015
Cited by 11 | Viewed by 4838
Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer related mortality worldwide. The incidence of HCC has been increasing annually. Viral infection, alcohol usage, and other causes of cirrhosis have been identified as major risk factors for HCC development. The [...] Read more.
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer related mortality worldwide. The incidence of HCC has been increasing annually. Viral infection, alcohol usage, and other causes of cirrhosis have been identified as major risk factors for HCC development. The underlying pathogenesis has not been as well defined. There have been multiple hypotheses to the specific mechanisms of hepatocarcinogenesis and they share the common theme of chronic inflammation, increase oxidative stress, and genomic alteration. Therapeutic options of HCC have been primarily local and/or regional including transplantation, resection, and radial frequency ablation, chemoembolization or radio-embolization. For unresectable or metastatic disease, the options are limited. Conventional chemotherapeutic options have been noted to have limited benefit. Sorafenib has been the one and only systemic therapy which has demonstrated modest overall survival benefit. This has led to more extensive research with focus on targeted therapy. Numerous pre-clinical and early phase clinical studies have been noted but failed to show efficacy in later phase clinical trials. In an effort to identify new potential therapeutic options, new understanding of underlying pathways to hepatocarcinogenesis should be one of the main focuses. This leads to development of more molecularly targeted agents to specific pathways, and immunotherapy. This article provides a review of major studies of molecular targeted agents which attempts to target these specific pathways in HCC. Full article
(This article belongs to the Special Issue Targeted Therapy of Hepatocellular Carcinoma: Present and Future)
Previous Issue
Next Issue
Back to TopTop