Thursday, December 8, 2016
Tuesday, December 6, 2016
Wednesday, November 30, 2016
Thursday, November 24, 2016
Tuesday, November 8, 2016
Call For Paper
Bentham Science Publishers would like to invite you to submit your research paper for publishing in the Journal of
Wednesday, November 2, 2016
Highlighted Article: Pyrimethamine as a Potent and Selective Inhibitor of Acute Myeloid Leukemia Identified by High-throughput Drug Screening
Pyrimethamine as a Potent and Selective Inhibitor of Acute Myeloid Leukemia Identified by High-throughput Drug Screening
Author(s):
Amit Sharma, Nidhi Jyotsana, Courteney K. Lai, Anuhar Chaturvedi, Razif Gabdoulline, Kerstin Görlich, Cecilia Murphy, Jan E. Blanchard, Arnold Ganser, Eric Brown, John A. Hassell, R. Keith Humphries, Michael Morgan and Michael Heuser Pages 818 - 828 ( 11 )
Abstract:
Hematopoietic stem and progenitor cell differentiation are blocked in acute myeloid leukemia (AML) resulting in cytopenias and a high risk of death. Most patients with AML become resistant to treatment due to lack of effective cytotoxic and differentiation promoting compounds. High MN1 expression confers poor prognosis to AML patients and induces resistance to cytarabine and alltrans-retinoic acid (ATRA) induced differentiation. Using a high-throughput drug screening, we identified the dihydrofolate reductase (DHFR) antagonist pyrimethamine to be a potent inducer of apoptosis and differentiation in several murine and human leukemia cell lines. Oral pyrimethamine treatment was effective in two xenograft mouse models and specifically targeted leukemic cells in human AML cell lines and primary patient cells, while CD34+ cells from healthy donors were unaffected. The antileukemic effects of PMT could be partially rescued by excess folic acid, suggesting an oncogenic function of folate metabolism in AML. Thus, our study identifies pyrimethamine as a candidate drug that should be further evaluated in AML treatment.
Keywords:
AML, apoptosis, differentiation and DHFR, High-throughput drug screening.
Affiliation:
Department of Hematology, Hemostasis, Oncology and Stem cell Transplantation, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Graphical Abstract:
For More Information Please Visit Our Website Current Cancer Drug Targets
Monday, October 24, 2016
Most Cited Article: Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways
Cytochromes P450 and Skin Cancer:
Role of Local Endocrine Pathways
Author(s):
Andrzej T. Slominski, Michal A. Zmijewski, Igor Semak, Blazej
Zbytek, Alexander Pisarchik, Wei Li, Jordan Zjawiony and Robert C. TuckeyPages
77-96 (20)
Abstract:
Skin is the largest body organ forming a metabolically active barrier between external and internal environments. The metabolic barrier is composed of cytochromes P450 (CYPs) that regulate its homeostasis through activation or inactivation of biologically relevant molecules. In this review we focus our attention on local steroidogenic and secosteroidogenic systems in relation to skin cancer, e.g., prevention, attenuation of tumor progression and therapy. The local steroidogenic system is composed of locally expressed CYPs involved in local production of androgens, estrogens, gluco- and mineralo-corticosteroids from cholesterol (initiated by CYP11A1) or from steroid precursors delivered to the skin, and of their metabolism and/or inactivation. Cutaneous 7-hydroxylases (CYP7A1, CYP7B1 and CYP39) potentially can produce 7-hydroxy/oxy-steroids/sterols with modifying effects on local tumorigenesis. CYP11A1 also transforms 7-dehydrocholesterol (7DHC)→22(OH)7DHC→20,22(OH)2-7DHC→7-dehydropregnenolone, which can be further metabolized to other 5,7- steroidal dienes. These 5,7-dienal intermediates are converted by ultraviolet radiation B (UVB) into secosteroids which show pro-differentiation and anti-cancer properties. Finally, the skin is the site of activation of vitamin D3 through two alternative pathways. The classical one involves sequential hydroxylation at positions 25 and 1 to produce active 1,25(OH)2D3, which is further inactivated through hydroxylation at C24. The novel pathway is initiated by CYP11A1 with predominant production of 20(OH)D3 which is further metabolized to biologically active but non-calcemic D3-hydroxyderivatives. Classical and non-classical (novel) vitamin D analogs show pro-differentiation, anti-proliferative and anticancer properties. In addition, melatonin is metabolized by local CYPs. In conclusion cutaneously expressed CYPs have significant effects on skin physiology and pathology trough regulation of its chemical milieu.
Keywords:
CYP, melatonin, secosteroids, skin cancer, steroids, vitamin D.
Affiliation:
Department of Pathology and Laboratory Medicine, University of
Tennessee Health Science Center, 930 Madison Avenue, RM525, Memphis, TN 38163.
For More Information Please Visit Our Website Recent Patents on Anti-Cancer Drug
