Modification of mesenchymal stem cells for cardiac regeneration.

Song, Heesang,Song, Byeong-Wook,Cha, Min-Ji,Choi, In-Geol,Hwang, Ki-Chul Ashley Publications Ltd 2010 Expert opinion on biological therapy Vol.10 No.3

<P>Mesenchymal stem cells (MSCs) have the greatest potential for use in cell-based therapy of human heart diseases, especially in myocardial infarcts. The therapeutic potential of MSCs in myocardial repair is based on the ability of MSCs to directly differentiate into cardiac tissue and on the paracrine actions of factors released from MSCs. However, the major obstacle in the clinical application of MSC-based therapy is the poor viability of the transplanted cells due to harsh microenvironments like ischemia, inflammation and/or anoikis in the infarcted myocardium. Recently, various approaches have been implemented in an effort to improve the survival of implanted MSCs through ex vivo manipulation of MSCs.</P>

Resolution of a clinical AmpliChip CYP450 Test no call: discovery and characterization of novel CYP2D6*1 haplotypes.

Gaedigk, Andrea,Garcia-Ribera, Carles,Jeong, Hye-Eun,Shin, Jae-Gook,Hernandez-Sanchez, Juanjo,Hernandez-Sanchez, Juanjo T Ashley Publications 2014 Pharmacogenomics Vol.15 No.9

<P>A Han Chinese patient failed CYP2D6 genotype analysis with the AmpliChip CYP450 Test. The CYP2D6 gene locus of the patient and her son were extensively genotyped including copy number variation and gene resequencing. Two SNPs were discovered on the patient's CYP2D6*1 allele, -498C>A and 1661G>C, while the son's CYP2D6*1 allele had -498C>A only. AmpliChip failure was attributed to the presence of a CYP2D6*1 allele carrying the 1661G>C SNP. Functional analyses of -498C>A did not reveal altered activity in vitro or in vivo suggesting that both novel CYP2D6*1 subvariants are functional. The implementation of pharmacogenetics-guided drug therapy relies on accurate clinical-grade genotype analysis. Although the AmpliChip is a reliable platform, numerous allelic (sub)variants and gene arrangements are not detected or may trigger no calls. While such cases may be rare, the clinical/genetic testing community must be aware of the challenges of CYP2D6 testing on the AmpliChip platform and implications regarding accuracy of test results.</P>

Targeting major vault protein in senescence-associated apoptosis resistance.

Ryu, Sung Jin,Park, Sang Chul Ashley Publications 2009 Expert opinion on therapeutic targets Vol.13 No.4

<P>BACKGROUND: Recent studies have shown that major vault protein (MVP) is involved in intracellular signaling, cell survival, differentiation and innate immunity and that it is not directly responsible for nucleo-cytoplasmic drug transport in multi-drug-resistant cancer cell lines. Recently, we reported that MVP increases with age both in vitro and in vivo, and that age-related upregulation of MVP facilitates apoptosis resistance of senescent human diploid fibroblasts (HDFs) based on the interaction with c-Jun-mediated downregulation of bcl-2. OBJECTIVES: To discuss the role of MVP in cell survival and signaling in the development of resistance to apoptosis exhibited by senescent HDFs. CONCLUSIONS: MVP represents a versatile platform for regulation of cellular signaling and survival and is a potential therapeutic target for modulation of resistance to apoptosis, implicated in aging modulation and cancer treatment.</P>

Potential application of adipose-derived stem cells and their secretory factors to skin: discussion from both clinical and industrial viewpoints.

Yang, Jin-Ah,Chung, Hyung-Min,Won, Chong-Hyun,Sung, Jong-Hyuk Ashley Publications Ltd 2010 Expert opinion on biological therapy Vol.10 No.4

<P>Importance of the field: Adipose tissue is one of the richest sources of mesenchymal stem cells. Even more interesting is the fact that adipose-derived stem cells (ASCs) show an outstanding ability to regenerate damaged skin. Thus, ASCs are a popular and feasible treatment in clinical dermatology. Areas covered in this review: This review discusses the potential applications of ASCs and conditioned medium of ASC (ASC-CM) to skin, and briefly touches on the mechanisms by which ASCs promote skin regeneration. What the reader will gain: Clinically, processed lipo-aspirated (PLA) cells are commonly used for treatment of aged skin; however, the use of PLA cells for cosmetic purposes is not convenient, because PLA cells are prepared from patients. Alternatively, cosmetics that contain ASC-CM can be pre-made from healthy volunteers such that they are immediately available for clinical treatment of aged skin. Cell-based therapies are adequate for improvement of wrinkles or for soft tissue augmentation, whereas ASC-CM has merit for amelioration of skin tone. When culturing ASCs for the production of cosmetic raw materials, hypoxic culture conditions and transduction of specific genes into ASCs may increase the regenerative protein content of the conditioned medium. Take home message: Application of ASCs and ASC-CM to dermatology shows promising results for skin regeneration.</P>

Microenvironmental targeting of Wnt/b-catenin signals for hematopoietic stem cell regulation

ASHLEY PUBLICATIONS 2010 Expert opinion on biological therapy Vol.10 No.9

Pharmacological treatment of chronic fatigue syndrome: focusing on the role of antidepressants.

Pae, Chi-Un,Marks, David M,Patkar, Ashwin A,Masand, Prakash S,Luyten, Patrick,Serretti, Alessandro Ashley Publications 2009 Expert opinion on pharmacotherapy Vol.10 No.10

<P>Chronic fatigue syndrome (CFS) is characterized by chronic, medically unexplained fatigue associated with effort- and stress-intolerance, widespread pain, and impairment in sleep and concentration. Although this constellation of symptoms is highly prevalent in clinical practice, the pathophysiological mechanisms underlying CFS are poorly understood. Current evidence indicates similarities in symptomatology, and possibly etiology and pathogenesis, between CFS and depression. Additionally, there is significant overlap between CFS and the syndrome of fibromyalgia for which antidepressants have shown consistent efficacy. Data regarding antidepressant treatment of CFS is less copious and less uniformly positive, such that antidepressant use in CFS remains controversial. The current review aims to summarize available data related to antidepressants and other psychotropic agents in CFS to provide a platform for clinicians to make decisions in their treatment of this challenging syndrome. We identified relevant studies through a PubMed literature search with a combination of the following search terms: 'fatigue,' 'depression,' 'antidepressant,' 'etiology' (e.g., 'neurobiology,' 'neurotransmitter,' 'genetic'), 'diagnosis,' and 'treatment' (e.g., 'antidepressant' plus the specific name). In addition, studies were also identified via the reference sections of retrieved articles. The authors thoroughly reviewed major findings from the scanned literatures and eventually synthesized them, providing summary, interpretation, and future directions.</P>

HLA-B*5901 is strongly associated with methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

Kim, Sae-Hoon,Kim, Myunghwa,Lee, Kyung Wha,Kim, Sang-Heon,Kang, Hye-Ryun,Park, Heung-Woo,Jee, Young-Koo Ashley Publications 2010 Pharmacogenomics Vol.11 No.6

<P>Aims: The carbonic anhydrase inhibitor methazolamide infrequently causes Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). An association between these diseases and the HLA-B59 serotype has been suggested in case reports. This study examined the disease-associated B*59 allele and investigated the association of these diseases with other HLA class I alleles. Methods: We performed high-resolution HLA-A, -B and -C genotyping in five patients with methazolamide-induced SJS/TEN using a PCR-sequencing-based typing method and analyzed the association between HLA-class I alleles and occurrence of methazolamide-induced SJS/TEN. Results: B*5901 and Cw*0102 alleles were observed in all patients and A*2402 was observed in four patients. The B*5901 allele showed the strongest association with methazolamide-induced SJS/TEN (p < 0.001; odds ratio: 249.8; 95% CI: 13.4-4813.5), followed by Cw*0102 (p = 0.004; odds ratio: 22.1; 95% CI: 1.2-414.3), when compared with the general population as a control. The frequency of the patients carrying B*5901, Cw*0102 and A*2402 simultaneously was significantly higher than that in the general population (p < 0.001; odds ratio: 110.1; 95% CI: 11.7-1038.6). Conclusion: A strong association was observed between HLA-B*5901 and methazolamide-induced SJS/TEN in Korean patients. HLA-B*5901 may be a useful screening marker for predicting methazolamide-induced SJS/TEN in patients of Korean and Japanese ancestry.</P>

Antioxidant and mitochondrial protective effects of oxidized metabolites of oltipraz.

Choi, Song Hwa,Kim, Young Mi,Lee, Jung Min,Kim, Sang Geon Ashley Publications, Ltd 2010 Expert opinion on drug metabolism & toxicology Vol.6 No.2

<P>Comprehensive studies indicate that oltipraz exerts cancer chemopreventive effects. Oltipraz has other therapeutic potentials, which include anti-fibrotic effect, inhibition of insulin resistance, mitochondrial protection and cytoprotective effect against oxidative stress. Although antioxidant mechanisms may account for its cancer chemopreventive effect, details on the molecular mechanism still remain to be clarified.</P>

Targeting orphan nuclear receptor SHP in the treatment of metabolic diseases.

Kim, Mi-Kyung,Chanda, Dipanjan,Lee, In-Kyu,Choi, Hueng-Sik,Park, Keun-Gyu Ashley Publications 2010 Expert opinion on therapeutic targets Vol.14 No.4

<P>IMPORTANCE OF THE FIELD: The orphan nuclear receptor small heterodimer partner (SHP; NR0B2) is an atypical nuclear receptor that contains a ligand-binding domain, but lacks the conserved DNA-binding domain. Since its discovery, SHP has been identified as a key transcriptional regulatory factor of genes involved in diverse metabolic pathways. AREAS COVERED IN THIS REVIEW: We performed a Medline/Pubmed search to find published studies on the role of SHP in the regulation of metabolism in the liver, pancreatic islets, blood vessel, and kidney and on the feasibility of using SHP as a therapeutic target in metabolic disease. WHAT THE READER WILL GAIN: In this review, we discuss the function of SHP as regulator of cholesterol, lipid and glucose metabolism, and the role of SHP in metabolic and fibrotic diseases. TAKE HOME MESSAGE: The reviewed studies suggested that SHP could be a major target for therapeutic intervention in metabolic and fibrotic diseases, including metabolic syndrome and its complications. However, for SHP-targeted therapy, there are some outstanding issues, including the small number of known inducers of SHP and the lack of sufficient data in humans.</P>

Gene transfer in the nervous system and implications for transsynaptic neuronal tracing.

Huh, Youngbuhm,Oh, Myung S,Leblanc, Pierre,Kim, Kwang-Soo Ashley Publications Ltd 2010 Expert opinion on biological therapy Vol.10 No.5

<P>IMPORTANCE OF THE FIELD: Neuronal circuitries are determined by specific synaptic connections and they provide the cellular basis of cognitive processes and behavioral functions. To investigate neuronal circuitries, tracers are typically used to identify the original neurons and their projection targets. AREAS COVERED IN THIS REVIEW: Traditional tracing methods using chemical tracers have major limitations such as non-specificity. In this review, we highlight novel genetic tracing approaches that enable visualization of specific neuronal pathways by introducing cDNA encoding a transsynaptic tracer. In contrast to conventional tracing methods, these genetic approaches use cell-type-specific promoters to express transsynaptic tracers such as wheat germ agglutinin and C-terminal fragment of tetanus toxin, which allows labeling of either the input or output populations and connections of specific neuronal type. WHAT THE READER WILL GAIN: Specific neuronal circuit information by these genetic approaches will allow more precise, comprehensive and novel information about individual neural circuits and their function in normal and diseased brains. TAKE HOME MESSAGE: Using tracer gene transfer, neuronal circuit plasticity after traumatic injury or neurodegenerative diseases can be visualized. Also, this can provide a good marker for evaluation of therapeutic effects of neuroprotective or neurotrophic agents.</P>