bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B48: Lack of efficacy of the anti-diabetic drug metformin in the ER+ methylnitrosourea (MNU)-induced and the ER- MMTV-Neu/p53KO models of mammary cancer
Authors: Lubet Ronald A. , Bode Ann M. , Steele Vernon E. , Grubbs Clinton J. 
Published: January 2011

Abstract
Metformin, an anti-diabetic drug, activates AMP-activated protein kinase (AMPK), and has generated a great deal of interest as a potential preventive agent for a variety of cancers, including breast. This interest is based both on epidemiologic studies showing that diabetics treated with metformin have a lower incidence of a variety of cancers, and on mechanistic considerations arguing that activation of AMPK is likely to be relevant to cancer treatment and prevention. We examined the preventive efficacy of metformin in ER+ and ER- rodent mammary cancer models. Treatment of Sprague-Dawley female rats at 50 days of age with a single dose of MNU (75 mg/kg BW) resulted in the development of multiple ER+ mammary cancers beginning approximately 7 weeks after MNU treatment. This model has been highly responsive to a wide variety of agents that affect ER+ tumors in humans (SERMs, aromatase inhibitors, pregnancy, ovariectomy). Metformin was administered by gavage (7x/week) at either 150 or 50 mg/kg BW/day beginning 7 days after MNU dosing, and continuing for the duration of the study. Metformin failed to decrease mammary tumor incidence and, in fact, increased tumor multiplicity in this model by approximately 35%. In addition, we are evaluating the ability of metformin to inhibit mammary cancer in MMTV-Neu/p53KO mice (which spontaneously develop ER- cancers). In this study, metformin was administered in the diet at a dose level of 1500 mg/kg diet. Initial supplementation of the diet with this agent began when the mice were 60 days of age, and will continue for 10 months. This study similarly has shown no preventive efficacy of metformin (av. tumors/mice: controls, 2.1; metformin, 2.5). Thus, these initial studies fail to observe any chemopreventive efficacy of metformin in two commonly employed models of ER+ and ER- mammary cancers in rodents. Supported by NCI contract number HHSN261200433001C.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B48.
Abstract B49: Use of MMTV-Neu/P53 KO transgenic mice to screen for potential chemopreventive agents
Authors: Lubet Ronald A. , Grubbs Clinton J. , Juliana Margaret , Bode Ann , Steele Vernon E. , Iwata Kenneth 
Published: January 2011

Abstract
The MMTV-Neu transgenic model of mammary cancer was developed almost 20 years ago in which mice develop Neu over-expressing ER- mammary cancers. Since human ER- Neu over-expressing mammary cancers often also have mutations in P53, a heterozygous KO of P53 was incorporated into the model. We used this model to examine a wide variety of potential chemopreventive agents. The agents were routinely administered to virgin female MMTV-Neu/P53 KO mice beginning when they were 60 days of age. Initiation at this time is somewhat later than is often employed in other laboratories (i.e., agents are typically started when mice are roughly 5-6 weeks of age). Mice were routinely monitored until 360 days of age. In agreement with Brown and colleagues (e.g., Cancer Res. 62: 6376-6380, 2002), it was found both RXR agonists (Targretin, UAB-30) and EGFR 1 and/or 2 inhibitors (Tarceva, Lapatinib) were highly effective in preventing the development of these cancers. More surprisingly, tamoxifen which is ineffective as a therapeutic agent against ER- breast cancer in women was effective in this model. It was also observed that a wide variety of agents were ineffective; including Atorvastatin, rosiglitazone (a PPAR gamma agonist), SAHA (an HDAC inhibitor), metformin, and a soy isoflavones mixture. In separate studies, mice bearing small palpable mammary tumors were treated for five days with these various agents, and examined for alterations in potential biomarkers; including proliferation. Effective agents (e.g., Iressa, Tarceva, and Targretin) strongly inhibited cancer cell proliferation, whereas ineffective agents failed to significantly inhibit proliferation. Thus, such a short-term assay might be employed to determine potential chemopreventive compounds. Short-term treatment with the EGFR inhibitors also decreased levels of expression of phosphorylated EGFR and downstream proteins; e.g., AKT/ERK. Supported by NCI contract number HHSN26120043301C.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B49.
Abstract B5: Personal and social predictors of sharing genetic test results within the family
Authors: Daly Mary B. , Montgomery Susan , Barsevick Andrea , Egleston Brian , Bingler Ruth , Ruth Karen , Miller Suzanne , Malick John 
Published: January 2011

Abstract
Purpose: As testing for cancer susceptibility gene mutations becomes more prevalent, there is a growing need to understand the challenges faced by probands as they attempt to share genetic test results with family members. This study reports on a communication skills intervention, guided by the Theory of Planned Behavior (TPB), to improve the process of communication.
Methods: Participants seeking BRCA1/2 genetic testing were randomized to a communication skills-building intervention or a wellness control. Primary outcome was the number of first degree adult relatives with whom results were shared and ease of sharing. Questionnaires addressed TPB tenets and psychosocial factors.
Results: 233 participants shared test results with 743 of their 907 eligible relatives (81.9%). There was no significant difference between intervention and control in sharing test results, or in the level of sharing-related distress. When data from both arms were combined, the proband's perception of her relative's opinion about genetic testing and her confidence in effectively sharing results were strong predictors of sharing. Results were more likely to be shared with female relatives and with children.
Conclusion: While this data does not support a communication intervention in improving the sharing of genetic test results, it does identify the importance of the proband's perception of her relative's opinion of genetic testing and her perceived ability to relay this information. It highlights the selective nature of sharing, with male relatives and parents less likely to be recipients.
Impact: Psychosocial factors play a significant role in the communication of genetic test results within families.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B5.
Abstract B50: Antiproliferative activity of the polar extract of Justicia spicigera on LNCaP cells
Authors: Fernández-Pomares Cynthia , Bravo-Ávila Myriam , Muñoz-Muñiz Omar , Juárez-Aguilar Enrique , Domínguez-Ortiz Miguel Ángel , Hernández-Aguilar María Elena 
Published: January 2011

Abstract
Justicia spicigera is a Mexican plant employed in traditional medicine for treatment of anemia, stomach illness and skin diseases. Furthermore, it has been suggested that this plant has anticancer properties on leukemia patients and in other types of cancer. However, the scientific evidence supporting these properties is not sufficient. The aim of this study was to evaluate the effect of Justicia spicigera on proliferation and viability of the androgen-dependent human prostate cancer cell line, LNCaP.A polar extract was obtained by exhaustive maceration with water and ethanol (v/v) of the air parts of the plant. The phytochemical analysis by the color test and thin layer chromatography (TLC) showed the presence of antioxidant compounds like coumarins, flavonoids and anthocyanins, which was corroborated by Nuclear Magnetic Resonance (H1 NMR). At the same time, the extract showed the presence of polyphenolic compounds detected by the Folin-Ciocalteu's reagent. The reducing power and the free radical scavenging capacity, was not too high in comparison with other less polar extracts of this plant, this could be explained by the high rate of glycosylation of the compounds in the sample. In the other hand, the polar extract of Justicia spicigera showed an antiproliferative activity on LNCaP cells since 500 g/ml of extract, measured by the MTT assay and direct cell account. Interestingly, cell morphology was not affected under these conditions. Likewise, the same extract did not show a relevant citotoxic effect (MTT assay) or an affectation on cellular viability (trypan blue assay) of LNCaP cells. Our study showed an antiproliferative effect of the polar extract of Justicia spicigera on LNCaP cells suggesting a potential use as anticancer agent. Further studies should focus on the characterization of compounds responsible of the effects observed on LNCaP cells, as well as in the definition of the mechanisms by which they affect the growth of these cells.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B50.
Abstract B51: Prevention of mouse lung tumors by combinations containing SAHA and atorvastin
Authors: Pereira Michael A. , Casto Bruce C. , Lubet Ronald A. , Steele Veron E. 
Published: January 2011

Abstract
The use of combinations of chemopreventive agents is a promising strategy for increasing efficacy while lowering toxicity to prevent cancer, including lung cancer. To test whether this strategy of using combinations would enhance efficacy, combinations containing SAHA and atorvastatin were evaluated for their ability to prevent mouse lung tumors. Lung tumors were induced in female strain A/J mice (8-9 week-old) by administering i.p. an injection of 16 mg/kg vinyl carbamate once a week for three weeks. Two weeks after the last injection of vinyl carbamate, some of the mice started to receive in their diet, either 500mg/kg SAHA, 18, 60 or 180 mg/kg atorvastatin, combinations containing SAHA and one of the three dose levels of atorvastatin, or the Control Diet. Mice were sacrificed either at 21 or 32 weeks after the first dose of vinyl carbamate. At week 21, SAHA, the low (18 mg/kg diet) and high (180 mg/kg) concentrations of atorvastatin, and the three combinations containing SAHA and atorvastatin decreased the multiplicity of lung tumors/mouse, while at Week 32, lung tumor multiplicity was reduced by only SAHA (31.5 ± 1.6 lung tumors/mouse) and the combinations containing SAHA with either 60 or 180 mg/kg concentration of atorvastatin (21.9 ± 1.7 and 24.7 ± 1.9 lung tumors/mouse, respectively) compared to the yield in the Control Group of 42.7 ± 1.6 lung tumors/mouse. At both sacrifices, the combinations containing SAHA and the middle and high concentrations of atorvastatin demonstrated greater efficacy in decreasing tumor multiplicity than either SAHA or atorvastatin administered alone (p-value ≤ 0.05). At Week 21, both the size of the lung tumors and the multiplicity of adenocarcinomas were decreased by SAHA, 180 mg/kg atorvastatin and all three combinations, while at Week 32 only the combinations containing SAHA with either 60 or 180 mg/kg atorvastatin (0.160 ± 0.094 and 0.041 ± 0.041 lung adenocarcinomas/mouse, respectively) decreased the size of the lung tumors and the multiplicity of adenocarcinomas (1.44 ± 0.25 lung adenocarcinomas/mouse, p-value ≤ 0.05). Although, the ability of the two chemopreventive agents and the combinations to decrease the occurrence of lung tumors, to slow the growth of the tumors, and to slow their progression to carcinomas decreased with time, the efficacy of the combinations was still significant at the Week 32 sacrifice. Hence, the combinations of SAHA and atorvastatin demonstrated greater and more prolonged efficacy in preventing and slowing the progression of mouse lung tumors supporting the concept of using combinations of chemopreventive agents for cancer prevention. Supported in part by N01-CN-35116 from NCI.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B51.
Abstract B54: Prevention of mouse lung tumors by combinations of budesonide and Targretin or SAHA
Authors: Casto Bruce C. , Schmalbrock Petra M.F. , Wassenaar Peter A. , Heverhagen Johannes T. , Pereira Michael A. 
Published: January 2011

Abstract
Individual chemopreventive drugs have been shown to prevent and slow the growth and progression of mouse lung tumors. Combinations of these chemopreventive agents have been proposed as a strategy for increasing efficacy, while lowering drug toxicity. In addition, non-invasive procedures such as MRI have been suggested as a means to determine the ability of drugs to inhibit the growth of tumors and avoid using serial sacrifices. Three drugs representing different mechanisms of action (budesonide, a nonsteroidal anti-inflammatory; Targretin, a selective activator of RXR; and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor) were used singly and in combination to inhibit development of mouse lung tumors. Lung tumors were induced in female Strain A/J mice by i.p. administration of 100 mg/kg 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol (NNK) once a week for four consecutive weeks. Two weeks after the fourth dose of NNK, the mice started to receive a diet (AIN-76A) containing either1.6 mg/kg budesonide, 160 mg/kg Targretin, 500 mg/kg SAHA, or combinations of budesonide plus either Targretin or SAHA. At Week 21, the multiplicity of lung tumors in control mice (28.13 ± 1.62) was significantly reduced to 10.50 ± 0.74, 15.96 ± 0.90, and 12.42 ± 1.57 by budesonide, Targretin, and SAHA, respectively. The combinations containing budesonide plus Targretin or SAHA demonstrated significantly more inhibition of total tumors than either agent acting alone, resulting in 7.25 ± 0.87 and 5.00 ±1.16 tumors/mouse, respectively. The multiplicity of carcinomas was also significantly reduced by budesonide, Targretin, and SAHA from 5.10 ± 0.83 in control mice to 0.88 ± 0.21, 1.12 ± 0.27, and 0.37 ± 0.15, respectively, whereas the combinations demonstrated a greater efficacy than either agent acting alone, yielding 0.10 ± 0.07, and 0.12 ± 0.12 for the combinations containing Targretin or SAHA, respectively. Mice administered budesonide,
Targretin or the control diet were monitored by MRI at Weeks 21, 26 and 31 after the first dose of NNK and groups sacrificed at Weeks 21 and 31 after MRI for tumor counts. The two drugs (budesonide and Targretin) significantly reduced the size and number of tumors when monitored by MRI. At week 21, it was demonstrated by MRI that Targretin and budesonide significantly reduced the multiplicity of total lung tumors by 32% and 64%, respectively, from controls. In conclusion, relative to their individual effects, combinations containing budesonide and either Targretin or SAHA demonstrated greater efficacy in inhibiting both the occurrence of mouse lung tumors and their progression to carcinomas. Supported in part by NCI grant 5R21CA135335.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B54.
Abstract B58: Discovery of a novel drug KBU2046 that inhibits conversion of human prostate cancer to a metastatic phenotype
Authors: Xu Li , Farmer Rebecca , huang xiaoke , Pavese Janet , Voll Eric , Irene Ogden , Biddle Margaret , Nibbs Antoinette , Valsecchi Matias , Scheidt Karl , Bergan Raymond 
Published: January 2011

Abstract
Epidemiological evidence, preclinical studies and prospective phase II studies in humans indicate that the isoflavone, genistein, will inhibit the conversion of human prostate cells to an invasive, and ultimately, a metastatic phenotype. Though promising, genistein exerts many additional effects that have the potential for future toxicity in humans. We therefore sought to discover a new drug with improved efficacy and most importantly, with high specificity. Starting from an isoflavone chemical scaffold, we employed a fragment-based chemical synthesis diversification approach, and coupled it to three in vitro screens: 1) cell invasion (efficacy), 2) cell growth inhibition (an indicator of general toxicity), and 3) several measures of estrogenic activity. From multiple synthesis/biological assay iterations we developed a refined structure-activity relationship map, thereby leading us to discover KBU2046. KBU2046 represents a new and chemically distinct class of bioactive compounds. It has greater anti-invasion efficacy than genistein, and more importantly, no cell toxicity or estrogenic activity. Extensive toxicity studies in mice were negative. At low nanomolar blood concentrations, KBU2046 will prevent orthotopically implanted human prostate cancer cells from forming metastasis in a dose-responsive fashion. In summary, we have successfully discovered and developed a compound that prevents progression to a metastatic phenotype for human prostate cancer. We are in the process of bringing KBU2046 into the clinic, with the goal of preventing death from the second most common cause of cancer related death in men.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B58.
Abstract B59: The effect of resveratrol on azoxymethane (AOM)-induced colon carcinogenesis in mice with aberrant crypt foci (ACF)
Authors: Sakai Eiji , Endo Hiroki , Uchiyama Takashi , Hosono Kunihiro , Michiko Sugiyama , Takahashi Hirokazu , Nakajima Atsushi 
Published: January 2011

Abstract
Introduction: Resveratrol (trans-3,4,5-trihydroxy-trans-stilbene) is a naturally occurring phytoalexin with antioxidant and antiinflammatory properties. Moreover, recent studies suggest that resveratrol possesses anticancer effects on the major stages (initiation, promotion and progression) of malignant transformation. The present study was designed to investigate the effect of resveratrol on azoxymethane (AOM)-induced colon carcinogenesis in mice with aberrant crypt foci (ACF).
Methods and Results: 8-week-old male C57/BL6 mice were randomly assorted into experimental five groups and administered several doses resveratrol (0.1, 1, 10, 50mg/kg/day). All mice were injected twice (1 week apart) of 10 mg/kg AOM, and sacrificed 6weeks after the first injection of AOM. Colon and rectum were stained with methylene blue for the determination of ACF. The number of ACF was significantly decreased in groups of mice treated with resveratrol in dose-dependent manner.
Discussion: Colorectal cancer (CRC) poses a major clinical challenge in the developed world where the disease is common. However chemoprevention is defined as the use of natural, synthetic or chemical agents to reverse, suppress or prevent carcinogenic progress. No drug is confirmed for CRC chemoprevention. Present study demonstrated resveratrol may have chemopreventive effect for CRC. Resveratrol considered to be a food supplement and a relatively safe natural medication, so seems to be tolerated to long-term administration for CRC chemoprevention.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B59.
Abstract B62: Zinc supplementation reduces forestomach tumor burden in N-nitrosomethylbenzylamine-treated mice
Authors: Sun Jin , Liu James , Pan Xueliang , Quimby Donald , Zanesi Nicola , Druck Teresa , Pfeifer Gerd , Croce Carlo M. , Fong Louise , Huebner Kay 
Published: January 2011

Abstract
Zinc deficiency is associated with high incidences of esophageal and other human cancers. In addition, zinc status in plasma and white blood cells is a better indicator of tumor burden and stage of the disease in head and neck cancer patients than overall nutritional status. Research in rodents found that zinc insufficiency leads to a highly proliferative hyperplastic condition in the upper gastrointestinal tract. Zn replenishment reduces the incidence of lingual, esophageal, and forestomach tumors in Zn-deficient rats and mice. While previous animal studies focused on the effect of Zn deficiency on cancer prevention and development, in this study we investigated the effect of Zn supplementation on carcinogenesis in Zn-sufficient mice of wild type and three tumor suppressor-deficient mouse strains, Fhit−/−, Fhit−/−Nit1−/−, and Fhit−/−Rassf1a−/−. About fifty mice from each strain received 6-8 doses of N-nitrosomethylbenzylamine (NMBA). Half the mice then received Zn supplemented water while another half received regular water. Sixteen weeks after last NMBA administration, mice were sacrificed and tumors were found only in forestomach. Mice without Zn supplementation had developed more tumors than Zn-supplemented mice: wild type C57BL/6 mice developed an average of 7.0 vs 5.0 tumors for Zn supplemented (p&lt;0.05); Zn-supplemented Fhit−/− mice averaged 5.7 vs 8.0 for control mice (p&lt; 0.01); Zn-supplemented Fhit−/−Nit1−/− mice averaged 5.4 vs 9.2 for control mice (p&lt; 0.01); and Zn-supplemented Fhit−/−Rassf1a−/−mice averaged 5.9 vs 9.1 for control mice (p&lt; 0.01). Zn supplementation reduced tumor burdens by 28% (wild type) to 42% (Fhit−/−Nit1−/−). Histological analysis of forestomach tissues also showed significant decreases in severity of preneoplastic and neoplastic lesions in Zn-supplemented cohorts of each mouse strain. Thus, Zn supplementation significantly reduced tumor burdens in mice with multiple tumor suppressor deficiencies. When Zn supplementation was begun at 7 weeks after the final carcinogen dose, the reduction in tumor burden was the same as observed when supplementation began immediately after carcinogen dosing, suggesting that Zn supplementation may affect tumor progression rather than tumor initiation. Our study suggests that Zn could have an important role in tumor prevention and perhaps treatment of specific human cancers and should be more thoroughly studied in preclinical models.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B62.
Abstract B64: Zinc supplementation has antitumor effects in 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis
Authors: Fong Louise Y.Y. , Jiang Yubao , Rawahneh Maysoon L. , Croce Carlo M. , Farber John L. , Huebner Kay 
Published: January 2011

Abstract
Zinc (Zn)-deficiency promotes esophageal/tongue tumorigenesis in rats by causing cell proliferation and changes in gene expression and Zn-replenishment inhibits tumorigenesis by attenuating cell proliferation and abnormal gene expression. Whether Zn has antitumor activities in a Zn-sufficient animal, however, is unknown. Here we examined the effects of Zn supplementation on tongue carcinogenesis in Zn-sufficient male Sprague-Dawley rats formerly exposed for 8 weeks to the carcinogen 4-nitroquinoline 1-oxide (NQO) at 10 and 20-30 ppm dose levels. Immediately after the cessation of NQO exposure, Zn gluconate (0, 20 ppm) was administered in the drinking water and continued for 10-13 weeks. At both NQO levels, Zn-supplemented rats had fewer tongue lesions than respective controls (10 ppm NQO: 5.2 ± 0.4 vs 8.6 ± 0.7, P&lt;0.001; 20-30 ppm NQO: 10.6 ± 1.1 vs. 18.4 ± 1.2, P&lt;0.01). Additionally, Zn-supplementation reduced the incidence of early tongue squamous cell carcinomas (SCC) from 40% [10/25] to 11.5% [3/26] (P=0.027) and that of invasive SCC from 93.8% [15/16] to 47.1% [8/17] (P=0.007) in rats exposed to 10 and 20-30 ppm NQO, respectively. The cell proliferative activity, as measured by quantitative proliferating cell nuclear antigen (PCNA)-immunohistochemistry, was significantly lower in the nontumorous tongue epithelia from Zn-supplemented rats than untreated controls (P&lt;0.001). Compared with invasive tongue SCC from controls, Zn treatment led to less proliferative tongue SCCs with reduced immunostaining of cyclin D1, COX-2, NF-kB p65, and p53 proteins but increased apoptotic index. Thus, our finding that Zn inhibits tongue cancer progression in Zn-sufficient as in Zn-deficient animals should lead to prevention and therapeutic possibilities for oral cancer. Supported by National Institute of Health Grants R01CA118560 (LYYF) and R01 CA115965 (CMC).
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B64.