Issues
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Cover Image
Cover Image
Celastrol, an active compound extracted from the Chinese medicine as used as a natural remedy for years. Although Celastrol has been shown to induce leukemia cell apoptosis, the involved molecular target has not been identified. Furthermore, whether Celastrol has antitumor activity in vivo has never been demonstrated. By the chemical structure and computational modeling analysis, Yang et al. hypothesized that Celastrol has proteasome-inhibitory and, therefore, antitumor activities. Indeed, Celastrol potently and preferentially inhibits the chymotrypsin-like activity of purified 20S proteasome (IC50 = 2.5 µM) and 26S proteasome in human prostate cancer cells (1-5 µM) and tumors (1-3 mg/kg/day). Proteasome inhibition in vivo by Celastrol is accompanied by significant apoptosis and tumor growth inhibition (65-93%). Our results demonstrate that Celastrol is a natural proteasome inhibitor that has great potential for cancer prevention and treatment. The remaining challenge is to design, synthesize, and evaluate more potent and selective Celastrol analogs with no or little toxicity as proteasome inhibitors to suppress human tumor growth in clinical settings. The cover figure shows the chemical structure of Celastrol and its computational modeling image that demonstrates two carbons, C2 and C6 (indicated in red). These carbons possess high susceptibility toward a nucleophilic attack by the proteasome, suggesting that one or both could interact with and inhibit the proteasome. For details, see the article by Yang et al. on page 4758 of this issue.
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Journal Archive
Cancer Research (1941-Present; volumes 1-current)
(ISSN 0008-5472) Published twice monthly since 1987. From 1941-1986, published monthly.The American Journal of Cancer (1931-1940; volumes 15-40)
(ISSN 0099-7374) Published quarterly in 1931, bimonthly in 1932, and monthly from 1933 to 1940. The journal changed title to Cancer Research in 1941.The Journal of Cancer Research (1916-1930); volumes 1-14)
(ISSN 0099-7013) Published quarterly from 1916 through 1930 (publication was suspended from November 1922 to March 1924). The journal changed title to The American Journal of Cancer in 1931.Table of Contents
Reviews
Meeting Report
Priority Report
Molecular Biology, Pathobiology, and Genetics
Comparative Genome Analysis Identifies the Vitamin D Receptor Gene as a Direct Target of p53-Mediated Transcriptional Activation
Integrative Genomic Analysis of Protein Kinase C (PKC) Family Identifies PKCι as a Biomarker and Potential Oncogene in Ovarian Carcinoma
Gene Expression Profiling Shows Medullary Breast Cancer Is a Subgroup of Basal Breast Cancers
Dysregulated Human Myeloid Nuclear Differentiation Antigen Expression in Myelodysplastic Syndromes: Evidence for a Role in Apoptosis
Cell, Tumor, and Stem Cell Biology
p130Cas as a New Regulator of Mammary Epithelial Cell Proliferation, Survival, and HER2-Neu Oncogene–Dependent Breast Tumorigenesis
The Interaction Mode of Premalignant Schwann and Immune Effector Cells during Chemically Induced Carcinogenesis in the Rat Peripheral Nervous System Is Strongly Influenced by Genetic Background
MET Overexpression Turns Human Primary Osteoblasts into Osteosarcomas
Inhibition of the Phosphatidylinositol 3′-Kinase Pathway Promotes Autocrine Fas-Induced Death of Phosphatase and Tensin Homologue–Deficient Prostate Cancer Cells
Experimental Therapeutics, Molecular Targets, and Chemical Biology
Selective Toxicity of NSC73306 in MDR1-Positive Cells as a New Strategy to Circumvent Multidrug Resistance in Cancer
Luteolin Promotes Degradation in Signal Transducer and Activator of Transcription 3 in Human Hepatoma Cells: An Implication for the Antitumor Potential of Flavonoids
IMC-EB10, an Anti-FLT3 Monoclonal Antibody, Prolongs Survival and Reduces Nonobese Diabetic/Severe Combined Immunodeficient Engraftment of Some Acute Lymphoblastic Leukemia Cell Lines and Primary Leukemic Samples
Immunology
Identification of a New Cancer/Germline Gene, KK-LC-1, Encoding an Antigen Recognized by Autologous CTL Induced on Human Lung Adenocarcinoma
Endocrinology
Clinical Research
Immunization of Stage IV Melanoma Patients with Melan-A/MART-1 and gp100 Peptides plus IFN-α Results in the Activation of Specific CD8+ T Cells and Monocyte/Dendritic Cell Precursors
Epidemiology and Prevention
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