PAK1 Deletion Impairs Intestinal Tumorigenesis
p21-activated kinase 1 (PAK1) is a serine/threonine kinase that is overexpressed in colorectal cancer. PAK1 is a target of mesalamine [5-aminosylicylic acid (5-ASA)], a common drug for the treatment of ulcerative colitis with prospective chemopreventive properties. Here, we investigated whether PAK1 deletion impedes tumorigenesis in murine intestinal cancer models. Ten-week-old APCmin or APCmin/PAK1–/– mice were monitored for 8 weeks, euthanized, and assessed for tumor number and size. Six- to 8-week-old PAK1–/– and wild-type (WT) mice received one 10 mg/kg intraperitoneal injection of azoxymethane ...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Dammann, K., Khare, V., Harpain, F., Lang, M., Kurtovic, A., Mesteri, I., Evstatiev, R., Gasche, C. Tags: Research Articles Source Type: research
ER{beta} Expression and Breast Cancer Risk Prediction for Women with Atypias
Estrogen receptor (ER) β is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERβ expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERβ expression was examined by immunohistochemistry in a well-characterized 171-women cohort with atypical hyperplasia diagnosed 1967–1991. Nuclear ERβ percent and intensity was scored in the atypia and adjacent nor...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Hieken, T. J., Carter, J. M., Hawse, J. R., Hoskin, T. L., Bois, M., Frost, M., Hartmann, L. C., Radisky, D. C., Visscher, D. W., Degnim, A. C. Tags: Research Articles Source Type: research
Fish Oil and Butyrate Effects on Colon Cell Kinetics
We have shown that dietary fish oil is protective against experimentally induced colon cancer, and the protective effect is enhanced by coadministration of pectin. However, the underlying mechanisms have not been fully elucidated. We hypothesized that fish oil with butyrate, a pectin fermentation product, protects against colon cancer initiation by decreasing cell proliferation and increasing differentiation and apoptosis through a p27Kip1-mediated mechanism. Rats were provided diets of corn or fish oil, with/without butyrate, and terminated 12, 24, or 48 hours after azoxymethane (AOM) injection. Proliferation (Ki-67), dif...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Hong, M. Y., Turner, N. D., Murphy, M. E., Carroll, R. J., Chapkin, R. S., Lupton, J. R. Tags: Research Articles Source Type: research
Calcium and Biomarkers of Inflammation and Oxidative Stress
Inflammation and oxidative stress play important roles in colorectal carcinogenesis. There is strong evidence that calcium reduces risk for colorectal neoplasms, possibly through its ability to bind bile acids and prevent their colonic toxicity (which occurs via an oxidative mechanism and results in an inflammatory response). In a previously reported pilot, randomized, controlled trial among sporadic colorectal adenoma patients we found that those on 2.0 g/day of calcium, relative to those on placebo, had an estimated drop in a combined cytokine z-score of 48% (P = 0.18) over 6 months. To follow-up these promising prelimin...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Yang, B., Gross, M. D., Fedirko, V., McCullough, M. L., Bostick, R. M. Tags: Research Articles Source Type: research
Prostanoid Metabolites and Colorectal Adenoma Occurrence
Aspirin has been shown to protect against colorectal neoplasms; however, the optimal chemopreventive dose and underlying mechanisms are unclear. We aimed to study the relationship between prostanoid metabolites and aspirin's effect on adenoma occurrence. We used data from the Aspirin/Folate Polyp Prevention Study, in which 1,121 participants with a recent adenoma were randomized to placebo or two doses of aspirin (81 or 325 mg/d) to be taken until the next surveillance colonoscopy, anticipated about 3 years later. Urinary metabolites of prostanoids (PGE-M, PGI-M, and dTxB2) were measured using liquid chromatography/mass sp...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Fedirko, V., Bradshaw, P. T., Figueiredo, J. C., Sandler, R. S., Barry, E. L., Ahnen, D. J., Milne, G. L., Bresalier, R. S., Baron, J. A. Tags: Research Articles Source Type: research
Metformin and Risk of Prostate Cancer
The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4–6 and high-grade Gleason 7–10) using logistic reg...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Feng, T., Sun, X., Howard, L. E., Vidal, A. C., Gaines, A. R., Moreira, D. M., Castro-Santamaria, R., Andriole, G. L., Freedland, S. J. Tags: Research Articles Source Type: research
Isoflavone Bioavailability of Soy Breads in Prostate Cancer
Epidemiologic associations suggest that populations consuming substantial amounts of dietary soy exhibit a lower risk of prostate cancer. A 20-week randomized, phase II, crossover trial was conducted in 32 men with asymptomatic prostate cancer. The crossover involved 8 weeks each of soy bread (SB) and soy–almond bread (SAB). The primary objective was to investigate isoflavone bioavailability and metabolite profile. Secondary objectives include safety, compliance, and assessment of biomarkers linked to prostate carcinogenesis. Two distinct SBs were formulated to deliver approximately 60 mg aglycone equivalents of isof...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Ahn-Jarvis, J. H., Clinton, S. K., Grainger, E. M., Riedl, K. M., Schwartz, S. J., Lee, M.-L. T., Cruz-Cano, R., Young, G. S., Lesinski, G. B., Vodovotz, Y. Tags: Research Articles Source Type: research
Immune Effects of Soy Bread in Patients with Prostate Cancer
We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Lesinski, G. B., Reville, P. K., Mace, T. A., Young, G. S., Ahn-Jarvis, J., Thomas-Ahner, J., Vodovotz, Y., Ameen, Z., Grainger, E., Riedl, K., Schwartz, S., Clinton, S. K. Tags: Research Articles Source Type: research
Early Methylation Changes in Oral Tumorigenesis
In conclusion, AGTR1, FOXI2, and PENK promoter methylation and LINE1 hypomethylation may be associated with an increased risk of OSCC development in patients with OPLs. Cancer Prev Res; 8(11); 1027–35. ©2015 AACR. (Source: Cancer Prevention Research)
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Foy, J.-P., Pickering, C. R., Papadimitrakopoulou, V. A., Jelinek, J., Lin, S. H., William, W. N., Frederick, M. J., Wang, J., Lang, W., Feng, L., Zhang, L., Kim, E. S., Fan, Y. H., Hong, W. K., El-Naggar, A. K., Lee, J. J., Myers, J. N., Issa, J.-P., Lip Tags: Research Articles Source Type: research
Droplet Digital PCR Analysis of Surgical Margins
Molecular deep surgical margin analysis has been shown to predict locoregional recurrences of head and neck squamous cell carcinoma (HNSCC). To improve the accuracy and versatility of the analysis, we used a highly tumor-specific methylation marker and highly sensitive detection technology to test DNA from surgical margins. Histologically cancer-negative deep surgical margin samples were prospectively collected from 82 eligible HNSCC surgeries by an imprinting procedure (n = 75) and primary tissue collection (n = 70). Bisulfite-treated DNA from each sample was analyzed by both conventional quantitative methylation-specific...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Hayashi, M., Guerrero-Preston, R., Sidransky, D., Koch, W. M. Tags: Research Articles Source Type: research
FDA Guidance Needed on Preventive Cancer Vaccines
Cancer vaccines based on antigens derived from self molecules rather than pathogens have been under basic and clinical investigations for many years. Up until very recently, they had been tested primarily in the setting of metastatic disease with the goal to engage the immune system in slowing down disease progression. Many therapeutic vaccine trials, either investigator initiated or led by pharmaceutical companies, have been completed and many are currently ongoing, following the FDA Guidance on therapeutic cancer vaccines published in 2011. In recent years, the target of cancer vaccines is being shifted to early cancer a...
Source: Cancer Prevention Research - November 2, 2015 Category: Cancer & Oncology Authors: Finn, O. J., Khleif, S. N., Herberman, R. B. Tags: Cancer Immunoprevention Series Source Type: research
Parity-Induced IGF1R DNA Methylation
The most effective natural prevention against breast cancer is an early first full-term pregnancy. Understanding how the protective effect is elicited will inform the development of new prevention strategies. To better understand the role of epigenetics in long-term protection, we investigated parity-induced DNA methylation in the mammary gland. FVB mice were bred or remained nulliparous and mammary glands harvested immediately after involution (early) or 6.5 months following involution (late), allowing identification of both transient and persistent changes. Targeted DNA methylation (109 Mb of Ensemble regulatory features...
Source: Cancer Prevention Research - October 4, 2015 Category: Cancer & Oncology Authors: Katz, T. A., Liao, S. G., Palmieri, V. J., Dearth, R. K., Pathiraja, T. N., Huo, Z., Shaw, P., Small, S., Davidson, N. E., Peters, D. G., Tseng, G. C., Oesterreich, S., Lee, A. V. Tags: Research Articles Source Type: research
Dietary EPA and Leukemia
In this study, we supplemented mice with eicosapentaenoic acid (EPA, C20:5), a polyunsaturated omega-3 fatty acid, at pharmacologic levels, to examine whether the endogenous metabolite, cyclopentenone prostaglandin delta-12 PGJ3 (12-PGJ3), was effective in targeting LSCs in experimental leukemia. EPA supplementation for 8 weeks resulted in enhanced endogenous production of 12-PGJ3 that was blocked by indomethacin, a cyclooxygenase (COX) inhibitor. Using a murine model of chronic myelogenous leukemia (CML) induced by bone marrow transplantation of BCR-ABL–expressing hematopoietic stem cells, mice supplemented with EPA...
Source: Cancer Prevention Research - October 4, 2015 Category: Cancer & Oncology Authors: Finch, E. R., Kudva, A. K., Quickel, M. D., Goodfield, L. L., Kennett, M. J., Whelan, J., Paulson, R. F., Prabhu, K. S. Tags: Research Articles Source Type: research
Prediction and Prophylaxis of HCC and Death
We aimed to evaluate whether hepatitis B virus (HBV) mutations at the core promoter region could improve the prediction and specific prophylaxis of hepatocellular carcinoma (HCC) in chronic HBV-infected patients. A total of 2,114 HBV-infected patients enrolled between August 1998 and December 2007 were followed-up for 18,406 person-years. Of those, 612 received ≥48 week treatments with nucleos(t)ide analogue (NA) and/or IFNα. Baseline HBV mutations were identified by sequencing. Propensity score matching was applied to reduce baseline differences between antiviral and control cohorts. Multivariate Cox regression a...
Source: Cancer Prevention Research - October 4, 2015 Category: Cancer & Oncology Authors: Yin, J., Wang, J., Pu, R., Xin, H., Li, Z., Han, X., Ding, Y., Du, Y., Liu, W., Deng, Y., Ji, X., Wu, M., Yu, M., Zhang, H., Wang, H., Thompson, T. C., Ni, W., Cao, G. Tags: Research Articles Source Type: research
Role of SFRP1 in NPC Metastasis
Distant metastasis remains the predominant mode of treatment failure in nasopharyngeal carcinoma (NPC). Unfortunately, the molecular events underlying NPC metastasis remain poorly understood. Secreted frizzled-related protein 1 (SFRP1) plays an important role in tumorigenesis and progression. However, little is known about the function and mechanism of SFRP1 in NPC. Immunohistochemistry was used to determine SFRP1 expression levels in patients with NPC. SFRP1 function was evaluated using MTT, colony formation, wound-healing, Transwell assays, and in vivo models. The methylation level of SFRP1 in NPC cells was examined usin...
Source: Cancer Prevention Research - October 4, 2015 Category: Cancer & Oncology Authors: Ren, X.-Y., Zhou, G.-Q., Jiang, W., Sun, Y., Xu, Y.-F., Li, Y.-Q., Tang, X.-R., Wen, X., He, Q.-M., Yang, X.-J., Liu, N., Ma, J. Tags: Research Articles Source Type: research
