Premalignancy in Prostate Cancer
High-grade prostatic intraepithelial neoplasia (PIN) has been accepted as the main precursor lesion to invasive adenocarcinoma of the prostate, and this is likely to be the case. However, in an unknown number of cases, lesions fulfilling the diagnostic criteria for high-grade PIN may actually represent intra-acinar or intraductal spread of invasive carcinoma. Intriguingly, this possibility would not contradict many of the findings of previous epidemiologic studies linking high-grade PIN to carcinoma or molecular pathologic studies showing similar genomic (e.g., TMPRSS2-ERG gene fusion) as well as epigenomic and molecular p...
Source: Cancer Prevention Research - July 30, 2016 Category: Cancer & Oncology Authors: De Marzo, A. M., Haffner, M. C., Lotan, T. L., Yegnasubramanian, S., Nelson, W. G. Tags: Review: Molecular Pathogenesis of Premalignancy Series Source Type: research
Chemoprevention of Prostate Cancer
This article attempts to critically assess whether the notion that chemoprevention of prostate cancer has no future is warranted. Risk of prostate cancer is modifiable and chemoprevention of prostate cancer, particularly fatal/lethal cancer, is both needed and possible. However, the approach to prostate cancer–chemopreventive agent development has not followed a rational and systematic process. To make progress, the following steps are necessary: (i) identification of intermediate biomarkers predictive of fatal/lethal disease; (ii) development of a rational approach to identification of candidate agents, including hi...
Source: Cancer Prevention Research - July 30, 2016 Category: Cancer & Oncology Authors: Bosland, M. C. Tags: Commentary Source Type: research
Intratumoral Heterogeneity: Sources and Significance
Advances in DNA sequencing have created new opportunities to better understand the biology of cancers. Attention is currently focused on precision medicine: does a cancer carry a mutation that is targetable with already available drugs? But, the timing at which multiple, targetable mutations arise during the adenoma to carcinoma sequence remains unresolved. Borras and colleagues identified mutations and allelic imbalance in at-risk mucosa and early polyps in the human colon. Their analyses indicate that mutations in key genes can arise quite early during tumorigenesis and that polyps are often multiclonal with at least two...
Source: Cancer Prevention Research - July 30, 2016 Category: Cancer & Oncology Authors: Sievers, C. K., Leystra, A. A., Clipson, L., Dove, W. F., Halberg, R. B. Tags: Commentary Source Type: research
Disease Interception
Malignant diseases develop slowly over time and are often preceded by identifiable premalignancies. As malignancy progresses, so does genomic complexity and the ability of cancers to evade most therapeutic interventions. Accordingly, with some notable exceptions, a relatively low percentage of advanced cancers are effectively treated and even fewer are cured. Despite this appreciation, much less attention has been paid to intercepting the disease process compared with that of treating well-established and refractory disease. One frequently cited reason is that the pharmaceutical industry is not interested in these pursuits...
Source: Cancer Prevention Research - July 30, 2016 Category: Cancer & Oncology Authors: Hait, W. N., Lebowitz, P. F. Tags: Commentary Source Type: research
Pancreatic Cancer Prevention by Phospho-Aspirin
In conclusion, our findings indicate that phospho-aspirin has strong anticancer efficacy in preclinical models of pancreatic cancer, warranting its further evaluation. Cancer Prev Res; 9(7); 624–34. ©2016 AACR. (Source: Cancer Prevention Research)
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Mattheolabakis, G., Papayannis, I., Yang, J., Vaeth, B. M., Wang, R., Bandovic, J., Ouyang, N., Rigas, B., Mackenzie, G. G. Tags: Research Articles Source Type: research
Effect of 5MeCDDO on Various Cancers
The preventive efficacy of the triterpenoid 5MeCDDO was tested in two models of mammary cancer, the Min model of intestinal cancer, and a chemically induced model of head and neck cancer. In one model of mammary cancer, female Sprague-Dawley rats were administered MNU at 50 days of age, and 5MeCDDO (27 ppm) was administered in the diet beginning 5 days later for the duration of the study; 5MeCDDO was ineffective. In contrast, in a model examining initiation of mammary cancers by the procarcinogen dimethyl-benzanthracene, 5, 6-benzoflavone (500 ppm, an Ah receptor agonist) or 5MeCDDO (27 or 2.7 ppm) decreased tumor multipli...
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Lubet, R. A., Townsend, R., Clapper, M. L., Juliana, M. M., Steele, V. E., McCormick, D. L., Grubbs, C. J. Tags: Research Articles Source Type: research
DADS Prevents Colorectal Cancer in Mice
There is a strong belief that garlic has medicinal properties and may even reduce the risk of developing certain cancers including those of the gastrointestinal tract. The chemopreventive effects of garlic may be attributed to the anti-inflammatory properties of the sulfur-containing constituents of garlic, which includes diallyl disulfide (DADS). Here, we demonstrate that DADS prevented colorectal tumorigenesis in a mouse model of colitis-induced colorectal cancer. Supplementation with 85 ppm of DADS (60 mg daily human equivalent dose) in the diet of FVB/N mice treated with chemical carcinogen azoxymethane (AOM) and colon...
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Saud, S. M., Li, W., Gray, Z., Matter, M. S., Colburn, N. H., Young, M. R., Kim, Y. S. Tags: Research Articles Source Type: research
PEITC, GST, and Volatile Organic Carcinogens
Cigarette smoke contains relatively large quantities of volatile organic toxicants or carcinogens such as benzene, acrolein, and crotonaldehyde. Among their detoxification products are mercapturic acids formed from glutathione conjugation, catalyzed in part by glutathione S-transferases (GST). A randomized phase II clinical trial with a crossover design was conducted to evaluate the effect of 2-phenethyl isothiocyanate (PEITC), a natural product formed from gluconasturtiin in certain cruciferous vegetables, on the detoxification of benzene, acrolein, and crotonaldehyde in 82 cigarette smokers. Urinary mercapturic acids of ...
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Yuan, J.-M., Murphy, S. E., Stepanov, I., Wang, R., Carmella, S. G., Nelson, H. H., Hatsukami, D., Hecht, S. S. Tags: Research Articles Source Type: research
Vitamin D Metabolites and Fecal Bile Acid Concentrations
In conclusion, this is the first study to demonstrate an inverse relationship between circulating levels of 25(OH)D and primary fecal bile acid concentrations. These results support prior data demonstrating that vitamin D plays a key role in bile acid metabolism, and suggest a potential mechanism of action for 25(OH)D in colorectal cancer prevention. Cancer Prev Res; 9(7); 589–97. ©2016 AACR. (Source: Cancer Prevention Research)
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Jacobs, E. T., Haussler, M. R., Alberts, D. S., Kohler, L. N., Lance, P., Martinez, M. E., Roe, D. J., Jurutka, P. W. Tags: Research Articles Source Type: research
Effects of Exercise on Breast Cancer Risk
Observational data indicate that behaviors that shift energetic homeostasis, such as exercise, may decrease the risk of developing breast cancer by reducing the amount of energy-dense, metabolically active adipose tissue. Between December 2008 and April 2013, we conducted a single-blind, 5-month, clinical trial that randomized premenopausal women at high risk of developing breast cancer to one of three groups: 150 min/wk of aerobic exercise (low dose), 300 min/wk of aerobic exercise (high dose), or control. Body composition was assessed using dual-energy x-ray absorptiometry. Background parenchymal enhancement (BPE) was qu...
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Brown, J. C., Kontos, D., Schnall, M. D., Wu, S., Schmitz, K. H. Tags: Research Articles Source Type: research
ISO Inhibits Bladder Cancer Invasion by Inducing FOXO1
Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo. We also found that ISO suppressed human bladder cancer cell invasion accompanied by upr...
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Jiang, G., Wu, A. D., Huang, C., Gu, J., Zhang, L., Huang, H., Liao, X., Li, J., Zhang, D., Zeng, X., Jin, H., Huang, H., Huang, C. Tags: Research Articles Source Type: research
Biomarkers for Squamous Dysplasia and Carcinoma
The 5-year survival rate of esophageal cancer is less than 10% in developing countries, where more than 90% of these cancers are esophageal squamous cell carcinomas (ESCC). Endoscopic screening is undertaken in high incidence areas. Biomarker analysis could reduce the subjectivity associated with histologic assessment of dysplasia and thus improve diagnostic accuracy. The aims of this study were therefore to identify biomarkers for esophageal squamous dysplasia and carcinoma. A publicly available dataset was used to identify genes with differential expression in ESCC compared with normal esophagus. Each gene was ranked by ...
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Couch, G., Redman, J. E., Wernisch, L., Newton, R., Malhotra, S., Dawsey, S. M., Lao-Sirieix, P., Fitzgerald, R. C. Tags: Research Articles Source Type: research
Sulforaphane Prevents Carcinogen-Induced Oral Cancer
Chronic exposure to carcinogens represents the major risk factor for head and neck squamous cell carcinoma (HNSCC). Beverages derived from broccoli sprout extracts (BSE) that are rich in glucoraphanin and its bioactive metabolite sulforaphane promote detoxication of airborne pollutants in humans. Herein, we investigated the potential chemopreventive activity of sulforaphane using in vitro models of normal and malignant mucosal epithelial cells and an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO). Sulforaphane treatment of Het-1A, a normal mucosal epithelial cell line, and...
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Bauman, J. E., Zang, Y., Sen, M., Li, C., Wang, L., Egner, P. A., Fahey, J. W., Normolle, D. P., Grandis, J. R., Kensler, T. W., Johnson, D. E. Tags: Research Articles Source Type: research
Dnmt1 in Genomic Stability during Intestinal Tumorigenesis
Intestinal cancer is a heterogeneous disease driven by genetic mutations and epigenetic changes. Approximately 80% of sporadic colorectal cancers are initiated by mutation and inactivation of the adenomatous polyposis coli (APC) gene, which results in unrestrained intestinal epithelial growth and formation of adenomas. Aberrant DNA methylation promotes cancer progression by the inactivation of tumor suppressor genes via promoter methylation. In addition, global DNA hypomethylation is often seen before the formation of adenomas, suggesting that it contributes to neoplastic transformation. Previous studies employed mice with...
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Sheaffer, K. L., Elliott, E. N., Kaestner, K. H. Tags: Research Articles Source Type: research
Ursodeoxycholic Acid in Patients with Barrett's Esophagus
Prior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett's esophagus and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with Barrett's esophagus. Twenty-nine patients with Barrett's esophagus received UDCA treatment at a daily dose of 13 to 15 mg/kg/day for 6 months. The clinical activity of UDCA was assessed by evaluat...
Source: Cancer Prevention Research - June 29, 2016 Category: Cancer & Oncology Authors: Banerjee, B., Shaheen, N. J., Martinez, J. A., Hsu, C.-H., Trowers, E., Gibson, B. A., Della'Zanna, G., Richmond, E., Chow, H.-H. S. Tags: Research Articles Source Type: research
