The Second-Generation PGI2 Analogue Treprostinil Fails to Chemoprevent Tumors in a Murine Lung Adenocarcinoma Model
Prostacyclin (prostaglandin I2, PGI2) overproduction in FVB/N mice prevents the formation of carcinogen and tobacco smoke–induced adenomas, and administration of the oral prostacyclin analogue iloprost to wild-type mice also prevented carcinogen-induced mouse lung adenoma formation. Former smokers taking oral iloprost showed improved bronchial dysplasia histology compared with placebo. Next-generation oral prostacyclin analogues, like treprostinil, were developed for the treatment of pulmonary arterial hypertension (PAH). On the basis of our prior studies with iloprost, we performed preclinical studies examining the ...
Source: Cancer Prevention Research - October 31, 2017 Category: Cancer & Oncology Authors: Dwyer-Nield, L., Hickey, G. A., Friedman, M., Choo, K., McArthur, D. G., Tennis, M. A., New, M. L., Geraci, M., Keith, R. L. Tags: Research Articles Source Type: research
Caloric Restriction Prevents Carcinogen-Initiated Liver Tumorigenesis in Mice
Caloric restriction (CR) and endurance exercise elicit wide-ranging health benefits including reduced risk of select cancers. In addition, diet composition influences oncogenesis, although its interactions with exercise and CR are not well understood. Therefore, to investigate the potential interactions between diet and lifestyle interventions on liver tumorigenesis, the carcinogen diethylnitrosamine was administered to 72 male C57Bl/6 mice that were subsequently fed diets enriched with lard (CTL) or olive oil and were further stratified to voluntary wheel running (Ex) or 30% CR for 49 weeks. Although Ex and diet compositi...
Source: Cancer Prevention Research - October 31, 2017 Category: Cancer & Oncology Authors: Ploeger, J. M., Manivel, J. C., Boatner, L. N., Mashek, D. G. Tags: Research Articles Source Type: research
Alterations in Bronchial Airway miRNA Expression for Lung Cancer Detection
We have previously shown that gene expression alterations in normal-appearing bronchial epithelial cells can serve as a lung cancer detection biomarker in smokers. Given that miRNAs regulate airway gene expression responses to smoking, we evaluated whether miRNA expression is also altered in the bronchial epithelium of smokers with lung cancer. Using epithelial brushings from the mainstem bronchus of patients undergoing bronchoscopy for suspected lung cancer (as part of the AEGIS-1/2 clinical trials), we profiled miRNA expression via small-RNA sequencing from 347 current and former smokers for which gene expression data we...
Source: Cancer Prevention Research - October 31, 2017 Category: Cancer & Oncology Authors: Pavel, A. B., Campbell, J. D., Liu, G., Elashoff, D., Dubinett, S., Smith, K., Whitney, D., Lenburg, M. E., Spira, A., for the AEGIS Study Team Tags: Research Articles Source Type: research
Targeting Aberrant p70S6K Activation for Estrogen Receptor-Negative Breast Cancer Prevention
The prevention of estrogen receptor–negative (ER–) breast cancer remains a major challenge in the cancer prevention field, although antiestrogen and aromatase inhibitors have shown adequate efficacy in preventing estrogen receptor–positive (ER+) breast cancer. Lack of commonly expressed, druggable targets is a major obstacle for meeting this challenge. Previously, we detected the activation of Akt signaling pathway in atypical hyperplasic early-stage lesions of patients. In the current study, we found that Akt and the downstream 70 kDa ribosomal protein S6 kinase (p70S6K) signaling pathway was highly acti...
Source: Cancer Prevention Research - October 31, 2017 Category: Cancer & Oncology Authors: Wang, X., Yao, J., Wang, J., Zhang, Q., Brady, S. W., Arun, B., Seewaldt, V. L., Yu, D. Tags: Research Articles Source Type: research
Gene Methylation Biomarkers in Sputum and Plasma as Predictors for Lung Cancer Recurrence
Detection of methylated genes in exfoliated cells from the lungs of smokers provides an assessment of the extent of field cancerization, is a validated biomarker for predicting lung cancer, and provides some discrimination when interrogated in blood. The potential utility of this 8-gene methylation panel for predicting tumor recurrence has not been assessed. The Eastern Cooperative Oncology Group initiated a prevention trial (ECOG-ACRIN5597) that enrolled resected stage I non–small cell lung cancer patients who were randomized 2:1 to receive selenized yeast versus placebo for 4 years. We conducted a correlative bioma...
Source: Cancer Prevention Research - October 31, 2017 Category: Cancer & Oncology Authors: Belinsky, S. A., Leng, S., Wu, G., Thomas, C. L., Picchi, M. A., Lee, S. J., Aisner, S., Ramalingam, S., Khuri, F. R., Karp, D. D. Tags: Research Articles Source Type: research
NRG Oncology/National Surgical Adjuvant Breast and Bowel Project Decision-Making Project-1 Results: Decision Making in Breast Cancer Risk Reduction
This study highlights the importance of social and cultural aspects for SERM decision making, most importantly personal beliefs and experiences. HCPs' recommendations play a statistically significant role in decision making and are more likely to be followed if in line with patients' attitudes. Results indicate the need for developing interventions for HCPs that not only focus on the presentation of medical information but, equally as important, on addressing patients' beliefs and experiences. Cancer Prev Res; 10(11); 625–34. ©2017 AACR.
See related editorial by Crew, p. 609 (Source: Cancer Prevention Research)
Source: Cancer Prevention Research - October 31, 2017 Category: Cancer & Oncology Authors: Holmberg, C., Bandos, H., Fagerlin, A., Bevers, T. B., Battaglia, T. A., Wickerham, D. L., McCaskill-Stevens, W. J. Tags: Research Articles Source Type: research
Primary Immunoprevention of Epithelial Ovarian Carcinoma by Vaccination against the Extracellular Domain of Anti-Müllerian Hormone Receptor II
Epithelial ovarian carcinoma (EOC) is the most prevalent form of ovarian cancer in the United States, representing approximately 85% of all cases and causing more deaths than any other gynecologic malignancy. We propose that optimized control of EOC requires the incorporation of a vaccine capable of inducing safe and effective preemptive immunity in cancer-free women. In addition, we hypothesize that ovarian-specific self-proteins that are "retired" from autoimmune-inducing expression levels as ovaries age but are expressed at high levels in emerging EOC may serve as vaccine targets for mediating safe and effective primary...
Source: Cancer Prevention Research - October 31, 2017 Category: Cancer & Oncology Authors: Mazumder, S., Johnson, J. M., Swank, V., Dvorina, N., Martelli, E., Ko, J., Tuohy, V. K. Tags: Research Articles Source Type: research
What Factors Influence Decision-Making about Breast Cancer Chemoprevention among High-Risk Women?
Estrogen exposure is one of the strongest risk factors for breast cancer development. Chemoprevention with selective estrogen receptor modulators (SERM), such as tamoxifen and raloxifene, has been shown in randomized controlled trials to reduce breast cancer incidence by up to 50% among high-risk women. Despite the strength of this evidence, there is significant underutilization of chemoprevention. Given the relatively few modifiable breast cancer risk factors, SERM use provides an important strategy for the primary prevention of this disease. Understanding factors which influence chemoprevention decision-making will infor...
Source: Cancer Prevention Research - October 31, 2017 Category: Cancer & Oncology Authors: Crew, K. D. Tags: Editorials Source Type: research
Targeting "Retired Antigens" for Cancer Immunoprevention
Identification of immune targets for cancer immunoprevention, or immunotherapy, has historically focused on tumor-associated (self) antigens or neoantigens expressed on malignant cells. For self-antigens, overcoming tolerance can be a difficult challenge. Neoantigens do not suffer from this limitation, but the lack of recurrent mutations yielding common neoantigens that can be exploited in vaccines is a problem for many tumor types. Targeting "retired antigens," a specialized type of self-antigen, may have considerable advantages. Antigens no longer expressed in mature or aged individuals should pose reduced risk of autoim...
Source: Cancer Prevention Research - October 31, 2017 Category: Cancer & Oncology Authors: Shoemaker, R. H., Forsthuber, T. G. Tags: Editorials Source Type: research
Topically Applied Carvedilol Attenuates Solar Ultraviolet Radiation Induced Skin Carcinogenesis
In previous studies, the β-blocker carvedilol inhibited EGF-induced epidermal cell transformation and chemical carcinogen-induced mouse skin hyperplasia. As exposure to ultraviolet (UV) radiation leads to skin cancer, the present study examined whether carvedilol can prevent UV-induced carcinogenesis. Carvedilol absorbs UV like a sunscreen; thus, to separate pharmacological from sunscreen effects, 4-hydroxycarbazole (4-OHC), which absorbs UV to the same degree as carvedilol, served as control. JB6 P+ cells, an established epidermal model for studying tumor promotion, were used for evaluating the effect of carvedilol o...
Source: Cancer Prevention Research - October 1, 2017 Category: Cancer & Oncology Authors: Huang, K. M., Liang, S., Yeung, S., Oiyemhonlan, E., Cleveland, K. H., Parsa, C., Orlando, R., Meyskens, F. L., Andresen, B. T., Huang, Y. Tags: Research Articles Source Type: research
Tobacco-Specific Carcinogens Induce Hypermethylation, DNA Adducts, and DNA Damage in Bladder Cancer
Smoking is a major risk factor for the development of bladder cancer; however, the functional consequences of the carcinogens in tobacco smoke and bladder cancer–associated metabolic alterations remain poorly defined. We assessed the metabolic profiles in bladder cancer smokers and non-smokers and identified the key alterations in their metabolism. LC/MS and bioinformatic analysis were performed to determine the metabolome associated with bladder cancer smokers and were further validated in cell line models. Smokers with bladder cancer were found to have elevated levels of methylated metabolites, polycyclic aromatic ...
Source: Cancer Prevention Research - October 1, 2017 Category: Cancer & Oncology Authors: Jin, F., Thaiparambil, J., Donepudi, S. R., Vantaku, V., Piyarathna, D. W. B., Maity, S., Krishnapuram, R., Putluri, V., Gu, F., Purwaha, P., Bhowmik, S. K., Ambati, C. R., von Rundstedt, F.-C., Roghmann, F., Berg, S., Noldus, J., Rajapakshe, K., Go0 Tags: Research Articles Source Type: research
In Silico Systems Biology Analysis of Variants of Uncertain Significance in Lynch Syndrome Supports the Prioritization of Functional Molecular Validation
Lynch syndrome (LS) is a genetic condition secondary to germline alterations in the DNA mismatch repair (MMR) genes with 30% of changes being variants of uncertain significance (VUS). Our aim was to perform an in silico reclassification of VUS from a large single institutional cohort that will help prioritizing functional validation. A total of 54 VUS were detected with 33 (61%) novel variants. We integrated family history, pathology, and genetic information along with supporting evidence from eight different in silico tools at the RNA and protein level. Our assessment allowed us to reclassify 54% (29/54) of the VUS as pro...
Source: Cancer Prevention Research - October 1, 2017 Category: Cancer & Oncology Authors: Borras, E., Chang, K., Pande, M., Cuddy, A., Bosch, J. L., Bannon, S. A., Mork, M. E., Rodriguez-Bigas, M. A., Taggart, M. W., Lynch, P. M., You, Y. N., Vilar, E. Tags: Research Articles Source Type: research
Effect of Green Tea Supplements on Liver Enzyme Elevation: Results from a Randomized Intervention Study in the United States
We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk. The current analysis examined the effect of GTE consumption on liver injury in 1,021 participants (513 in GTE and 508 in placebo arm) with normal baseline levels of liver enzymes. Among women in the GTE arm, alanine aminotransferase (ALT) increased by 5.4 U/L [95% confidence interval (CI),...
Source: Cancer Prevention Research - October 1, 2017 Category: Cancer & Oncology Authors: Yu, Z., Samavat, H., Dostal, A. M., Wang, R., Torkelson, C. J., Yang, C. S., Butler, L. M., Kensler, T. W., Wu, A. H., Kurzer, M. S., Yuan, J.-M. Tags: Research Articles Source Type: research
Prospective Evaluation of Multimodal Optical Imaging with Automated Image Analysis to Detect Oral Neoplasia In Vivo
The 5-year survival rate for patients with oral cancer remains low, in part because diagnosis often occurs at a late stage. Early and accurate identification of oral high-grade dysplasia and cancer can help improve patient outcomes. Multimodal optical imaging is an adjunctive diagnostic technique in which autofluorescence imaging is used to identify high-risk regions within the oral cavity, followed by high-resolution microendoscopy to confirm or rule out the presence of neoplasia. Multimodal optical images were obtained from 206 sites in 100 patients. Histologic diagnosis, either from a punch biopsy or an excised surgical...
Source: Cancer Prevention Research - October 1, 2017 Category: Cancer & Oncology Authors: Quang, T., Tran, E. Q., Schwarz, R. A., Williams, M. D., Vigneswaran, N., Gillenwater, A. M., Richards-Kortum, R. Tags: Research Articles Source Type: research
Early Exposure to a High Fat/High Sugar Diet Increases the Mammary Stem Cell Compartment and Mammary Tumor Risk in Female Mice
Obesity and alterations in metabolic programming from early diet exposures can affect the propensity to disease in later life. Through dietary manipulation, developing mouse pups were exposed to a hyperinsulinemic, hyperglycemic milieu during three developmental phases: gestation, lactation, and postweaning. Analyses showed that a postweaning high fat/high sugar (HF/HS) diet had the main negative effect on adult body weight, glucose tolerance, and insulin resistance. However, dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis revealed that animals born to a mother fed a HF/HS gestation diet, nursed by a mother on a mi...
Source: Cancer Prevention Research - October 1, 2017 Category: Cancer & Oncology Authors: Lambertz, I. U., Luo, L., Berton, T. R., Schwartz, S. L., Hursting, S. D., Conti, C. J., Fuchs-Young, R. Tags: Research Articles Source Type: research
