Whole-Genome Sequencing of Salivary ACC
Adenoid cystic carcinomas (ACC) of the salivary glands are challenging to understand, treat, and cure. To better understand the genetic alterations underlying the pathogenesis of these tumors, we performed comprehensive genome analyses of 25 fresh-frozen tumors, including whole-genome sequencing and expression and pathway analyses. In addition to the well-described MYB–NFIB fusion that was found in 11 tumors (44%), we observed five different rearrangements involving the NFIB transcription factor gene in seven tumors (28%). Taken together, NFIB translocations occurred in 15 of 25 samples (60%, 95% CI, 41%–77%). ...
Source: Cancer Prevention Research - March 30, 2016 Category: Cancer & Oncology Authors: Rettig, E. M., Talbot, C. C., Sausen, M., Jones, S., Bishop, J. A., Wood, L. D., Tokheim, C., Niknafs, N., Karchin, R., Fertig, E. J., Wheelan, S. J., Marchionni, L., Considine, M., Fakhry, C., Papadopoulos, N., Kinzler, K. W., Vogelstein, B., Ha, P. K., Tags: Research Articles Source Type: research
MyD88 and Inflammation in Gastric Tumorigenesis
It has been established that COX-2 and downstream signaling by prostaglandin E2 (PGE2) play a key role in tumorigenesis through generation of inflammatory microenvironment. Toll-like receptor (TLR) signaling through myeloid differentiation factor 88 (MyD88) also regulates inflammatory responses in tumors. However, the relationship between these distinct pathways in tumorigenesis is not yet fully understood. We herein investigated the role of MyD88 in gastric tumorigenesis using Gan mice, which develop inflammation-associated gastric tumors due to the simultaneous activation of the COX-2/PGE2 pathway and Wnt signaling. Nota...
Source: Cancer Prevention Research - March 1, 2016 Category: Cancer & Oncology Authors: Maeda, Y., Echizen, K., Oshima, H., Yu, L., Sakulsak, N., Hirose, O., Yamada, Y., Taniguchi, T., Jenkins, B. J., Saya, H., Oshima, M. Tags: Research Articles Source Type: research
Alkylation Damage Protects against Hepatocellular Carcinoma
Hepatocellular carcinoma is increasingly important in the United States as the incidence rate rose over the last 30 years. C3HeB/FeJ mice serve as a unique model to study hepatocellular carcinoma tumorigenesis because they mimic human hepatocellular carcinoma with delayed onset, male gender bias, approximately 50% incidence, and susceptibility to tumorigenesis is mediated through multiple genetic loci. Because a human O6-methylguanine-DNA methyltransferase (hMGMT) transgene reduces spontaneous tumorigenesis in this model, we hypothesized that hMGMT would also protect from methylation-induced hepatocarcinogenesis. To test t...
Source: Cancer Prevention Research - March 1, 2016 Category: Cancer & Oncology Authors: Herzig, M. C. S., Zavadil, J. A., Street, K., Hildreth, K., Drinkwater, N. R., Reddick, T., Herbert, D. C., Hanes, M. A., McMahan, C. A., Reddick, R. L., Walter, C. A. Tags: Research Articles Source Type: research
Piperlongumine and Gemcitabine in Pancreatic Cancer
Pancreatic cancer is an aggressive malignancy, which generally respond poorly to chemotherapy. Hence, novel agents that are safe and effective are highly needed. The aim of this study was to investigate whether piperlongumine, a natural product isolated from the fruit of the pepper Piper longum, has any efficacy against human pancreatic cancer when used either alone or in combination with gemcitabine in vitro and in a xenograft mouse model. In vitro, piperlongumine inhibited the proliferation of pancreatic cancer cell lines, potentiated the apoptotic effects of gemcitabine, inhibited the constitutive and inducible activati...
Source: Cancer Prevention Research - March 1, 2016 Category: Cancer & Oncology Authors: Wang, Y., Wu, X., Zhou, Y., Jiang, H., Pan, S., Sun, B. Tags: Research Articles Source Type: research
Efficacy and Safety of Exemestane in the Prevention Setting
This phase II trial evaluated clinical markers of efficacy and safety of exemestane in postmenopausal women at increased risk for breast cancer. Postmenopausal women (n = 42) at risk for invasive breast cancer received 25 mg exemestane daily for 2 years along with calcium and vitamin D. The primary outcome was change in mammographic density (MD) after one year. Secondary outcomes included change in serum steroid hormones as well as change in trefoil protein 1 (TFF1) and proliferating cell nuclear antigen (PCNA) in breast tissue. Safety and tolerability were also assessed. MD decreased at 1 year and was significant at 2 yea...
Source: Cancer Prevention Research - March 1, 2016 Category: Cancer & Oncology Authors: Gatti-Mays, M. E., Venzon, D., Galbo, C. E., Singer, A., Reynolds, J., Makariou, E., Kallakury, B., Heckman-Stoddard, B. M., Korde, L., Isaacs, C., Warren, R., Gallagher, A., Eng-Wong, J. Tags: Research Articles Source Type: research
Inhibition of Akt Potentiates Rapamycin Skin Chemoprevention
The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced nonmelanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared with those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here, we explored the use of topical rapamycin as a chemopreventive agent in the context of ...
Source: Cancer Prevention Research - March 1, 2016 Category: Cancer & Oncology Authors: Dickinson, S. E., Janda, J., Criswell, J., Blohm-Mangone, K., Olson, E. R., Liu, Z., Barber, C., Petricoin, E. F., Calvert, V. S., Einspahr, J., Dickinson, J. E., Stratton, S. P., Curiel-Lewandrowski, C., Saboda, K., Hu, C., Bode, A. M., Dong, Z., Alberts Tags: Research Articles Source Type: research
ACR Inhibits Lipogenesis to Prevent Hepatocellular Carcinoma
The objective of this study was to gain insights into molecular basis of the antitumorigenic action of ACR from a metabolic point of view. To achieve this, comprehensive cationic and lipophilic liver metabolic profiling was performed in mouse diethylnitrosamine (DEN)-induced hepatic tumorigenesis model using both capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry. ACR significantly counteracted against acceleration of lipogenesis but not glucose metabolism in DEN-treated mice liver, suggesting an important role of lipid metabolic reprogramming in the initia...
Source: Cancer Prevention Research - March 1, 2016 Category: Cancer & Oncology Authors: Qin, X.-Y., Tatsukawa, H., Hitomi, K., Shirakami, Y., Ishibashi, N., Shimizu, M., Moriwaki, H., Kojima, S. Tags: Research Articles Source Type: research
Exercise Dose and Inflammation in Postmenopausal Women
This randomized dose comparison trial examined if higher exercise volume decreased inflammatory biomarkers, associated with postmenopausal breast cancer risk, more than moderate exercise volume. The Breast Cancer and Exercise Trial in Alberta was a two-center, two-armed randomized trial in 400 inactive, healthy, postmenopausal women, aged 50 to 74 years, with a body mass index of 22 to 40 kg/m2. Participants were randomized to high (300 minutes/week) or moderate (150 minutes/week) volumes of aerobic exercise while maintaining usual diet. Fasting blood concentrations of C-reactive protein (CRP), IL6, and TNFα were mea...
Source: Cancer Prevention Research - February 1, 2016 Category: Cancer & Oncology Authors: Friedenreich, C. M., O'Reilly, R., Shaw, E., Stanczyk, F. Z., Yasui, Y., Brenner, D. R., Courneya, K. S. Tags: Research Articles Source Type: research
GSTM1, UGT1A1, and Smoking Status Predict Recurrence of NMIBC
This study establishes a connection between GSTM1, UGT1A1, and tobacco exposure as prognostic markers of NMIBC recurrence in bladder cancer patients. These findings warrant validation in larger cohorts. Cancer Prev Res; 9(2); 189–95. ©2015 AACR. (Source: Cancer Prevention Research)
Source: Cancer Prevention Research - February 1, 2016 Category: Cancer & Oncology Authors: Lacombe, L., Fradet, V., Levesque, E., Pouliot, F., Larue, H., Bergeron, A., Hovington, H., Caron, A., Nguile-Makao, M., Harvey, M., Fradet, Y., Guillemette, C. Tags: Research Articles Source Type: research
Unconjugated Bilirubin Inhibits Metastasis in NPC
In this study, we investigated the prognostic value of unconjugated bilirubin (UCB), which was previously considered a byproduct of heme catabolism, in NPC patients and examined the effects of UCB on NPC metastasis. The receiver operating characteristic analysis–generated UCB cutoff point for DMFS was 9.7 μmol/L. We found that higher UCB levels were significantly associated with favorable distant metastasis-free survival (DMFS, 93.3% vs. 84.2%, P < 0.001) in NPC patients and was an independent predictor for DMFS (HR, 0.416; 95% confidence interval, 0.280–0.618; P < 0.001). We next found that UCB treatm...
Source: Cancer Prevention Research - February 1, 2016 Category: Cancer & Oncology Authors: Deng, C.-C., Xu, M., Li, J., Luo, X.-L., Zhu, Y.-J., Jiang, R., Zhang, M.-X., Lei, J.-J., Lian, Y.-F., Zou, X., You, R., Chen, L.-Z., Feng, Q.-S., Bei, J.-X., Chen, M.-Y., Zeng, Y.-X. Tags: Research Articles Source Type: research
An Algorithm to Detect HCC
In conclusion, the Doylestown algorithm consolidates clinical laboratory values, with age and gender, which are each individually associated with HCC risk, into a single value that can be used for HCC risk assessment. As such, it should be applicable and useful to the medical community that manages those at risk for developing HCC. Cancer Prev Res; 9(2); 172–9. ©2015 AACR. (Source: Cancer Prevention Research)
Source: Cancer Prevention Research - February 1, 2016 Category: Cancer & Oncology Authors: Wang, M., Devarajan, K., Singal, A. G., Marrero, J. A., Dai, J., Feng, Z., Rinaudo, J. A. S., Srivastava, S., Evans, A., Hann, H.-W., Lai, Y., Yang, H., Block, T. M., Mehta, A. Tags: Research Articles Source Type: research
Black Raspberries Suppress Biomarkers of Oral Carcinogenesis
Black raspberries (BRB) demonstrate potent inhibition of aerodigestive tract carcinogenesis in animal models. However, translational clinical trials evaluating the ability of BRB phytochemicals to impact molecular biomarkers in the oral mucosa remain limited. The present phase 0 study addresses a fundamental question for oral cancer food–based prevention: Do BRB phytochemicals successfully reach the targeted oral tissues and reduce proinflammatory and antiapoptotic gene expression profiles? Patients with biopsy-confirmed oral squamous cell carcinomas (OSCC) administered oral troches containing freeze-dried BRB powder...
Source: Cancer Prevention Research - February 1, 2016 Category: Cancer & Oncology Authors: Knobloch, T. J., Uhrig, L. K., Pearl, D. K., Casto, B. C., Warner, B. M., Clinton, S. K., Sardo-Molmenti, C. L., Ferguson, J. M., Daly, B. T., Riedl, K., Schwartz, S. J., Vodovotz, Y., Buchta, A. J., Schuller, D. E., Ozer, E., Agrawal, A., Weghorst, C. M. Tags: Research Articles Source Type: research
Lobular Involution and Mammographic Density
Elevated mammographic density (MD) is an established breast cancer risk factor. Reduced involution of terminal duct lobular units (TDLU), the histologic source of most breast cancers, has been associated with higher MD and breast cancer risk. We investigated relationships of TDLU involution with area and volumetric MD, measured throughout the breast and surrounding biopsy targets (perilesional). Three measures inversely related to TDLU involution (TDLU count/mm2, median TDLU span, median acini count/TDLU) assessed in benign diagnostic biopsies from 348 women, ages 40–65, were related to MD area (quantified with thres...
Source: Cancer Prevention Research - February 1, 2016 Category: Cancer & Oncology Authors: Gierach, G. L., Patel, D. A., Pfeiffer, R. M., Figueroa, J. D., Linville, L., Papathomas, D., Johnson, J. M., Chicoine, R. E., Herschorn, S. D., Shepherd, J. A., Wang, J., Malkov, S., Vacek, P. M., Weaver, D. L., Fan, B., Mahmoudzadeh, A. P., Palakal, M., Tags: Research Articles Source Type: research
Alternative Dosing of Letrozole in Postmenopausal Women
Aromatase inhibitors (AI) profoundly suppress estrogen levels in postmenopausal women and are effective in breast cancer prevention among high-risk postmenopausal women. Unfortunately, AI treatment is associated with undesirable side effects that limit patient acceptance for primary prevention of breast cancer. A double-blind, randomized trial was conducted to determine whether low and intermittent doses of letrozole can achieve effective estrogen suppression with a more favorable side-effect profile. Overall, 112 postmenopausal women at increased risk for breast cancer were randomized to receive letrozole at 2.5 mg once d...
Source: Cancer Prevention Research - February 1, 2016 Category: Cancer & Oncology Authors: Lopez, A. M., Pruthi, S., Boughey, J. C., Perloff, M., Hsu, C.-H., Lang, J. E., Ley, M., Frank, D., Taverna, J. A., Chow, H.-H. S. Tags: Research Articles Source Type: research
HPV16 Antibodies and Disease Status in Oropharyngeal Cancer
Human papillomavirus (HPV) is responsible for increasing incidence of oropharyngeal cancer. At present, there are no biomarkers in the surveillance algorithm for HPV-positive oropharyngeal cancer (HPV-OPC). HPV16 E6 antibody precedes oropharyngeal cancer diagnosis. If HPV16 E6 indeed precedes primary diagnosis, it is similarly expected to precede disease recurrence and may have a potential role as a biomarker for surveillance of HPV-OPC. To determine whether HPV antibody titers have a potential role as early markers of disease recurrence or prognosis, a retrospective pilot study was designed to determine whether HPV16 earl...
Source: Cancer Prevention Research - February 1, 2016 Category: Cancer & Oncology Authors: Fakhry, C., Qualliotine, J. R., Zhang, Z., Agrawal, N., Gaykalova, D. A., Bishop, J. A., Subramaniam, R. M., Koch, W. M., Chung, C. H., Eisele, D. W., Califano, J., Viscidi, R. P. Tags: Research Articles Source Type: research
