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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
Tuesday, October 18, 2016
Advances in Synergistic Combinations of Chinese Herbal Medicine for the Treatment of Cancer
Article Details
Advances in Synergistic Combinations of Chinese Herbal Medicine
for the Treatment of Cancer
Author(s):
Xue-Qing Hu, Yang Sun, Eric Lau,
Ming Zhao and Shi-Bing SuPages 346-356 (11)
Abstract:
The complex pathology of cancer development requires correspondingly complex treatments. The traditional application of individual single-target drugs fails to sufficiently treat cancer with durable therapeutic effects and tolerable adverse events. Therefore, synergistic combinations of drugs represent a promising way to enhance efficacy, overcome toxicity and optimize safety. Chinese Herbal Medicines (CHMs) have long been used as such synergistic combinations. Therefore, we summarized the synergistic combinations of CHMs used in the treatment of cancer and their roles in chemotherapy in terms of enhancing efficacy, reducing side effects, immune modulation, as well as abrogating drug resistance. Our conclusions support the development of further science-based holistic modalities for cancer care.
Keywords:
Cancer treatment, Chinese
medicine, drug resistance, effect, immunity, side effects, synergistic
combination.
Affiliation:
Department of Research Center for
Traditional Chinese Medicine Complexity System, Shanghai University of
Traditional Chinese Medicine, Shanghai, China.
Graphical Abstract:
For More Information Please Visit Our Website Current Cancer Drug Targets
Monday, October 10, 2016
Indian Authors have made substantial contributions to Bentham Science Journal Current Cancer Drug Targets
Journal Name: Current Cancer Drug Targets
Article Title: DNA Methyltransferase-1 Inhibitors as Epigenetic Therapy for Cancer
Author(s): Varinder Singh, Prince Sharma and Neena Capalash
Abstract
Author(s): Varinder Singh, Prince Sharma and Neena Capalash
Abstract
DNA methylation is an epigenetic modification involved in gene expression regulation. In cancer, the DNA methylation pattern becomes aberrant, causing an array of tumor suppressor genes to undergo promoter hypermethylation and become transcriptionally silent. Reexpression of methylation silenced tumor suppressor genes by inhibiting the DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) has emerged as an effective strategy against cancer. The expression of DNA methyltransferase 1 (DNMT1) being high in S-phase of cell cycle makes it a specific target for methylation inhibition in rapidly dividing cells as in cancer. This review discusses nucleoside analogues (azacytidine, decitabine, zebularine, SGI-110, CP-4200), non-nucleoside ihibitors both synthetic (hydralazine, RG108, procaine, procainamide, IM25, disulfiram) and natural compounds (curcumin, genistein, EGCG, resveratrol, equol, parthenolide) which act through different mechanisms to inhibit DNMTs. The issues of bioavailability, toxicity, side effects, hypomethylation resistance and combinatorial therapies have also been highlighted.
For more information, visit:http://benthamscience.com/journal/contents.php?journalID=ccdt&issueID=109879
For details on this article, visit:http://benthamscience.com/journal/abstracts.php?journalID=ccdt&articleID=109882
Courtesy by: Bentham Insight
Tuesday, October 4, 2016
Podcast Targeting MDM4 as a Novel Therapeutic Approach for Hematologic Malignancies
Podcast Targeting MDM4 as a Novel Therapeutic Approach for Hematologic Malignancies
Open Access Plus Article in the journal Current Cancer Drug Targets
The article entitled ‘Pleiotropic Role of HSF1 in Neoplastic Transformation’ in the journal Current Cancer Drug Targets, 2014, 14, 144-155, is now open for all to view and access.
Abstract
Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC50 values in the range of 11.17 to 26.13μmol/L, whereas RWPE-1cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXOresponsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy.
– See more at:http://www.eurekaselect.com/126880/article#sthash.Z6xu5W21.dpuf
Issue ::: Current Cancer Drug Targets, 16 Issue 7
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes.
Current Cancer Drug Targets publishes original research articles, letters, reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
Articles from the journal Current Cancer Drug Targets, 16 Issue 7
- Protein Geranylgeranyltransferase Type 1 as a Target in Cancer
- nMET, A New Target in Recurrent Cancer
- RBM15 Functions in Blood Diseases
- Understanding Molecular Pathways and Targets of Brachyury in Epithelial-mesenchymal Transition (EMT) in Human Cancers
- Roles of Interferon Regulatory Factors in Chronic Myeloid Leukemia
- BRCA1-Associated Triple-Negative Breast Cancer and Potential Treatment for Ruthenium-Based Compounds
- MT1-MMP Activation of TGF-β Signaling Enables Intercellular Activation of an Epithelial-mesenchymal Transition Program in Cancer
- Persistent GP130/STAT3 Signaling Contributes to the Resistance of Doxorubicin, Cisplatin, and MEK Inhibitor in Human Rhabdomyosarcoma Cells
- Bispecific Antibodies for Targeted Delivery of Dendritic Polyglycerol (dPG) Prodrug Conjugates
For details on the articles, please visit this link :: http://bit.ly/2bvWR9P
courtesy by: Bentham Insight
Issue ::: Current Cancer Drug Targets
Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes.
Current Cancer Drug Targets publishes original research articles, letters, reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer.
As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
Articles from the journal Current Cancer Drug Targets, Volume 16 Issue 4:
- Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin
- A New Therapeutic Era in GCB and ABC Diffuse Large B-cell Lymphom a Molecular Subtypes: A Cell of Origin-Driven Review
- New Insights into the Molecular Resistance Mechanisms of Chronic Myeloid Leukemia
- Advances in Synergistic Combinations of Chinese Herbal Medicine for the Treatment of Cancer
- Development of Linker-Conjugated Nanosize Lipid Vesicles: A Strategy for Cell Selective Treatment in Breast Cancer
- Epigallocatechin-3-gallate Increases RXRγ-mediated Pro-apoptotic and Anti-invasive Effects in Gastrointestinal Cancer Cell Lines
For details on the articles, please visit this link :: http://bit.ly/1szzeRm
courtesy by Bentham Insight
Friday, August 12, 2016
Friday, June 24, 2016
Pleiotropic Role of HSF1 in Neoplastic Transformation
Author(s):
Natalia Vydra, Agnieszka Toma and Wieslawa WidlakPages 144-155 (12)
Abstract:
HSF1 (Heat Shock transcription Factor 1) is the main transcription factor activated in response to proteotoxic stress. Once activated, it induces an expression of heat shock proteins (HSPs) which enables cells to survive in suboptimal conditions. HSF1 could be also activated by altered kinase signaling characteristic for cancer cells, which is a probable reason for its high activity found in a broad range of tumors. There is rapidly growing evidence that HSF1 supports tumor initiation and growth, as well as metastasis and angiogenesis. It also modulates the sensitivity of cancer cells to therapy. Functions of HSF1 in cancer are connected with HSPs’ activity, which generally protects cells from apoptosis, but also are independent of its classical targets. HSF1-dependent regulation of non-HSPs genes plays a role in cell cycle progression, glucose metabolism, autophagy and drug efflux. HSF1 affects the key cell-survival and regulatory pathways, including p53, RAS/MAPK, cAMP/PKA, mTOR and insulin signaling. Although the exact mechanism of HSF1 action is still somewhat obscure, HSF1 is becoming an attractive target in anticancer therapies, whose inhibition could enhance the effects of other treatments.
Keywords:
Cancer, drug resistance, genomic instability, HSF1 inhibitors, HSPs, metastasis, p53 signaling.
Affiliation:
Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.
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Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo
Author(s):
Rui Zhou, Zongliang Lu, Kai Liu, Jing Guo, Jie Liu, Yong Zhou, Jian Yang, Mantian Mi and Hongxia XuPages 860-871 (12)
Abstract:
Platycodin D (PD), a major saponin derived from Platycodin grandiflorum, exerted cytotoxicity against prostate cancer cell lines (PC3, DU145 and LNCaP cells) with IC50 values in the range of 11.17 to 26.13μmol/L, whereas RWPE-1cells (a non-malignant human prostate epithelial cell line) were not significantly affected. A further study in these cell lines showed that PD could potently affect cell proliferation (indicated by the bromodeoxyuridine assay), induce cell apoptosis (determined by Annexin V-FITC flow cytometry) and cause cell cycle arrest (indicated by PI staining). After being treated with PD for 48 hours, DU145 and LNCaP cells were arrested in the G0 /G1 phase, and PC3 cells were arrested in the G2/M phase. A Western blotting analysis indicated that PD increased the expression of the FOXO3a transcription factor, decreased the expression of p-FOXO3a and MDM2 and increased the expression of FOXO-responsive genes, p21 and p27. MDM2 silencing (transiently by siRNA-MDM2) increased the PD-induced FOXO3a protein expression, while MDM2 overexpression (in cells transiently transfected with a pcDNA3-MDM2 plasmid) decreased the PD-induced expression of the FOXO3a protein. Moreover, PD dose-dependently inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. A Western blotting analysis of the excised xenograft tumors indicated that similar changes in protein expression also occurred in vivo. These results suggest that PD exhibits significant activity against prostate cancer in vitro and in vivo. The FOXO3a transcription factor appears to be involved in the activity of PD. Together, all of these findings provide a basis for the future development of this agent for human prostate cancer therapy.
Keywords:
Cell cycle, FOXO3a, MDM2, Platycodin D, prostate cancer.
Affiliation:
Department of Nutrition, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
Graphical Abstract:
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Cancer Stem Cells in Solid and Liquid Tissues of Breast Cancer Patients: Characterization and Therapeutic Perspectives
Author(s):
Rena Chiotaki, Hara Polioudaki and Panayiotis A. TheodoropoulosPages 256-269 (14)
Abstract:
Breast cancer stem cells (BCSCs) represent a heterogeneous subpopulation of rare cells within breast cancer tumors, displaying an enhanced tumor initiating capability and underlying disease progression and therapy resistance. Unraveling their phenotypic, biological and functional profile is a major challenge in the context of diminishing patient mortality. In this review, following a brief description on how cancer stem cells (CSCs) and their microenvironment contribute to tumor preservation and heterogeneity, we summarize the current literature regarding the molecular signature of BCSCs either localized in the primary tumor or circulating in the blood of breast cancer patients. We present recent data on specific stem and epithelial-to-mesenchymal transition (EMT) markers designating the BCSC subpopulation and underline their pathogenic significance. The molecular characterization of BCSCs has promoted the design of novel therapeutic approaches targeting the BCSC subpopulation which are currently being experimentally and clinically evaluated. We highlight recent advances on the development of novel BCSC-targeting therapeutic strategies including the inhibition of cell signaling pathways, differentiation therapy, metabolic interference and nucleotide-, bio- and nano-technology based approaches. Eliminating the chemo- and radio-resistance properties of breast cancer tumor cells via BCSC-directed therapies, combined to conventional therapeutic approaches, will augment the effectiveness of breast cancer treatment and improve the clinical outcome of breast cancer patients.
Keywords:
Breast cancer, cancer stem cells, circulating tumor cells, epithelial-to-mesenchymal transition, targeting of cancer stem cells.
Affiliation:
University of Crete, School of Medicine, P.O. Box 2208, 71003 Heraklion, Greece.
Graphical Abstract:
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A Comprehensive Outline of Trastuzumab Resistance Biomarkers in HER2 Overexpressing Breast Cancer
Author(s):
Otília Menyhart, Libero Santarpia and Balazs GyorffyPages 665-683 (19)
Abstract:
The introduction of trastuzumab for anti-HER2 therapy dramatically changed the clinical outcome for HER2 (ERBB2, neu) positive breast cancer patients. Today, patients eligible for trastuzumab are selected using HER2 expression/amplification status of the primary tumor. However, acquired and inherent resistance to anti-HER2 therapy in these patients poses a significant challenge, and better patient stratification will be needed to improve clinical response.
Here, we provide a wide-ranging overview of potential biomarkers capable of stratifying patients regarding their response to trastuzumab. These include HER2 amplification, impaired access to the binding site (p95HER2, Δ16HER-2, MUC4), augmented signaling through other ERBB family receptors (HER1, HER3, HER4) and their ligands, activation of HER2 targets by alternate heterodimers (EphA2, IGF-1R, GDF15, MUC1*), signaling triggered by downstream members (PIK3CA, PTEN, SRC, mTOR), altered expression of cell cycle and apoptotic regulators (CDKs, p27kip1, Bcl-2), hormone receptor status, resistance to antibody-dependent cellular cytotoxicity (FcγR), and altered miRNA expression signatures.
Multigenic molecular profile analyses have revealed further genes not directly associated with classical oncogenic pathways. Although numerous biomarkers have shown promise in pre-clinical studies, many have delivered controversial results when evaluated in clinical trials. One of the keys for targeting ERBB2 will be to consider the entire ERBB family and downstream associated pathways responsible for the malignant transformation.
The heterogeneity of the disease is likely to represent a significant obstacle to accurately predicting the course of resistance. The future most probably involves the incorporation of multiple biomarkers into a unified predictor enabling selection of patients for superior targeted drug administration.
Keywords:
Breast cancer, dimerization, HER2, molecular subtype, negative predictive biomarkers, survival, trastuzumab, tumor heterogeneity.
Affiliation:
MTA TTK Lendület Cancer Biomarker Research Group, Magyar Tudosok Korutja 2, H-1117 Budapest, Hungary.
Graphical Abstract:
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Advances in Synergistic Combinations of Chinese Herbal Medicine for the Treatment of Cancer
Author(s):
Xue-Qing Hu, Yang Sun, Eric Lau, Ming Zhao and Shi-Bing SuPages 346-356 (11)
Abstract:
The complex pathology of cancer development requires correspondingly complex treatments. The traditional application of individual single-target drugs fails to sufficiently treat cancer with durable therapeutic effects and tolerable adverse events. Therefore, synergistic combinations of drugs represent a promising way to enhance efficacy, overcome toxicity and optimize safety. Chinese Herbal Medicines (CHMs) have long been used as such synergistic combinations. Therefore, we summarized the synergistic combinations of CHMs used in the treatment of cancer and their roles in chemotherapy in terms of enhancing efficacy, reducing side effects, immune modulation, as well as abrogating drug resistance. Our conclusions support the development of further science-based holistic modalities for cancer care.
Keywords:
Cancer treatment, Chinese medicine, drug resistance, effect, immunity, side effects, synergistic combination.
Affiliation:
Department of Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Graphical Abstract:
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