Prevention Research最新文献

{"title":"Abstract LB224: The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients.","authors":"A. Meirovitz, Daniela Nahmias, E. Hermano, O. Maimon, T. Peretz, M. Elkin","doi":"10.1158/1538-7445.AM2021-LB224","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB224","url":null,"abstract":"Obesity serves as a risk factor for estrogen-dependent postmenopausal breast cancer (BC). While the exact association occurring between these two disease states remains unknown, obesity-associated inflammation is thought to be the most likely contributing factor. In addition, obesity has been correlated to changes in gut microbiota composition and a subsequent chronic increase in bacterial endotoxin (lipopolysaccharide [LPS] - canonic ligand of toll-like receptor 4 [TLR4]) blood levels. It was recently shown that BC cells intrinsically express TLR4 and such expression has been associated with decreased patient survival as well as increased tumor growth. We hypothesized that obesity-associated endotoxemia may contribute to BC progression by utilizing TLR-dependent mechanisms and exerting cancer-promoting effects directly (on carcinoma cells) and indirectly (triggering abnormal activation of macrophages). Utilizing a chronic metabolic endotoxemia and breast cancer murine model as well as in vitro experimental systems, we found that continuous exposure to low concentrations of LPS not only promotes BC progression in vivo but stimulates BC cell growth in culture through the activation of key breast cancer-promoting signaling pathways (Stat3, Akt, ERK1/2). Obesity has reached epidemic proportions globally, where elucidation of the molecular mechanisms underlying breast tumor-promoting action of obesity has become of vital importance. Improving the understanding of such mechanisms has the potential to reveal improved efficacious therapy regimens and prevention strategies in a rapidly growing population of obese, breast cancer patients. Citation Format: Amichay Meirovitz, Daniela Nahmias, Esther Hermano, Ofra Maimon, Tamar Peretz, Michael Elkin. The potential effect of chronically increased endotoxin levels on breast carcinoma progression in obese patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB224.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78672855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2553: Using a “train-the-trainer” approach with urban and rural minority community health workers to implement the cancer-Community Awareness Access Research and Education (c-CARE) Project","authors":"Marlo M. Vernon, Ghadeer Albashir, S. J. Sojourner, J. Moore, S. Looney, M. Tingen","doi":"10.1158/1538-7445.AM2021-2553","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2553","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85850290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2571: Paternal epigenetic regulation contributes to the prevention of estrogen receptor-negative mammary cancer with combined broccoli sprouts and green tea polyphenols consumption in transgenic mice","authors":"Shizhao Li, Huixin Wu, T. Tollefsbol","doi":"10.1158/1538-7445.AM2021-2571","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2571","url":null,"abstract":"Breast cancer is one of the leading causes of cancer-related death among women in the United States. It is widely appreciated that abnormal epigenetic alterations act as one of the primary contributors to breast cancer initiation and progression. Parental, including maternal and paternal, nutritional interventions have shown considerable impact on fetal development leading to different susceptibility of offspring to various chronic diseases. Moreover, combinatorial dietary administration to parents could be more efficacious in ameliorating epigenetic aberrations and changing cancer risk in an individual9s later life. The bioactive dietary broccoli sprouts (BSp) and green tea polyphenol (GTP) are important epigenetic modulators that can prevent various cancers. Our study focusses on investigating the effect of paternal dietary BSp and GTP administration on mammary cancer prevention of their offspring. Two spontaneous breast cancer transgenic mouse models, C3(1)/SV40 and Her2/neu, were employed in this study. Male C3(1)/SV40 or Her2/neu transgenic mice were randomly assigned into four groups and treated with: control AIN-93G diet, 26% BSp (w/w) in food pellets, 0.5% GTPs (w/v) in drinking water or combined BSp and GTPs from 3 wks of age until 10 wks of age. Treated male mice of different groups were then mated with non-treated female mice. Female pups were selected after their weaning and tumor growth was monitored weekly until the termination of the experiment. Tumor- and epigenetic-related protein expression and histone modifications (methylation and acetylation) were measured. Our study indicated that paternal BSp or/and GTPs administration suppressed tumor growth, decreased tumor incidence, and delayed tumor latency compared with the control in both mouse models. Overall, paternal dietary intervention displayed more efficacy for mammary tumor prevention in C3(1)/SV40 mice and the combination group in this model also showed synergistically effects. Subsequent analysis with the C3(1)/SV40 mouse tumors demonstrated that paternal BSp or/and GTPs treatments upregulated the expression of tumor suppressor proteins, such as P16 and P53, and down-regulated tumor promoting proteins, such as MYC and BMI1. Moreover, altered DNA methylation, histone methylation and acetylation levels were also observed. These results suggested that paternal exposure to BSp and GTPs may contribute to ER-negative mammary tumor prevention in their offspring through epigenetic regulations and the combined addition of bioactive botanicals could be a more promising approach for coping with breast cancer initiation and progression in humans. Citation Format: Shizhao Li, Huixin Wu, Trygve Tollefsbol. Paternal epigenetic regulation contributes to the prevention of estrogen receptor-negative mammary cancer with combined broccoli sprouts and green tea polyphenols consumption in transgenic mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87814108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2584: Leukemia latency in the mCG-PML-RARα mouse model is impacted by sex and obesity","authors":"John W R Kincaid, Annie E. Hill-Baskin, N. Berger","doi":"10.1158/1538-7445.AM2021-2584","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2584","url":null,"abstract":"Human leukemias have been reported to show sexual dimorphism in both incidence and behavior. However, few studies of this observation have been conducted in animal models. We used the C57BL/6J mouse, genetically engineered to contain the PML-RARA fusion gene at the mouse cathepsin G (mCG) locus, as a model (B6.mCG-PML-RARα) of acute promyelocytic leukemia (APL) to interrogate the impact of sex and diet variation on disease latency as measured by leukemia-free survival. At 30 days of age, control (WT) and mutant (mCG+/PR) mice were separated by sex and provided with high fat (HF) [57% coconut oil fat] or low fat (LF) [10% coconut oil fat] diets. Mice were followed with serial blood collections and sacrificed when peripheral blood revealed signs of leukemia development including elevated granulocytes (WBC >20 K/μL), anemia (Hb 425 days was observed. In contrast, male mCG+/PR mice fed LF diets showed a reduced MLFS of 360 days of age, indicating a difference in latency of 65 days, thereby demonstrating sexual dimorphism in the appearance of APL. HF diet accelerated the appearance of APL in both female (MLFS = 277 days of age) and male mCG+/PR mice (MLFS = 277 days of age), which also displayed a difference in latency of 65 days. Thus, HF diet accelerated appearance of APL by 148 days in male and 148 days in female mCG+/PR mice. There were no signs of leukemia development in WT mice on either HF or LF diets. There was no splenomegaly observed in WT mice on either HF or LF diets. Thus, although HF diet and obesity accelerate the onset of APL in B6.mCG-PML-RARα mice, sexual dimorphism remains, with females showing extended latency compared to males under conditions of both HF and LF diets. Overall, our studies provide a robust mouse model to study the mechanisms by which sex impacts leukemia latency, as well as demonstrate that obesity accelerates leukemia development without affecting sexual dimorphism. Citation Format: John W. Kincaid, Annie E. Hill-Baskin, Nathan A. Berger. Leukemia latency in the mCG-PML-RARα mouse model is impacted by sex and obesity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2584.","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85752377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract SY17-02: Multiantigen vaccines for colon cancer prevention","authors":"S. Sei","doi":"10.1158/1538-7445.AM2021-SY17-02","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-SY17-02","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85263547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2580: Synergistic effect of magnesium with metformin for the prevention of liver and colorectal cancer","authors":"L. Fan, D. Yu, Xiangzhu Zhu, Xuehong Zhang, Xiang Huang, H. Murff, M. Azcarate-Peril, M. Shrubsole, Q. Dai","doi":"10.1158/1538-7445.AM2021-2580","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2580","url":null,"abstract":"The obesity epidemic has dramatically increased the type 2 diabetes (T2D) prevalence in the US over the past two decades. Previous studies have relatively consistently found individuals with T2D are at increased risks of cancer, including liver and colorectal cancer in which insulin resistance may play an important role. However, the mechanism remains largely unknown. Metformin, the primary first-line medication for the treatment of T2D, has been shown to improve insulin resistance and be linked to a reduced risk of hepatocellular carcinoma (HCC) and colorectal cancer (CRC). Two recent Cell and Cell metabolism publications identified that imidazole propionate (ImP), a microbial metabolite of histidine, significantly increased in patients with T2D and causally induced insulin resistance in mice. Furthermore, the therapeutic effects of metformin on insulin resistance disappeared when ImP was elevated, indicating that ImP plays a key role in developing insulin resistance and resistance to metformin treatment. Our recent work together with a subsequent study from others demonstrated higher magnesium (Mg) intake is associated with a substantially reduced risk of HCC, HCC mortality and mortality from liver diseases. Accumulative evidence, including our prior work, has also linked higher Mg intake to a reduced risk of colorectal neoplasia. Previous studies found that the process of the histidine utilization (Hut) system to metabolize histidine in some bacterial taxa depends on concentrations of divalent metal ion Mg2+. We hypothesize that low availability of Mg2+ in gut microbiota could terminate the Hut system and increase the production of intermediate metabolites, including ImP, over other end products. This will lead to increased levels of ImP in the gut and, in turn, liver and circulation. We tested our hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (registered at clinicaltrials.gov as NCT01105169), a precision-based randomized trial enrolling 240 participants at high risk of Mg deficiency. Among 68 participants (34 treatment/34 placebo), we found that compared to the placebo, Mg treatment significantly reduced ImP by 39.9% compared to a 6.0% increase in the placebo arm after adjustment for baseline ImP (P=0.02). However, we found Mg treatment did not significantly affect the levels of trans-urocanate, the precursor of ImP. Since Mg deficiency leads to insulin resistance and as high as 50% of patients with T2D have hypomagnesemia, Mg deficiency may lead to an increased risk of ImP and, in turn, resistance to metformin which subsequently increases risk of HCC and CRC. Thus, futures studies should evaluate whether the joint use of Mg supplementation and metformin synergistically maximizes the efficacy of metformin and minimizes the treatment resistance on insulin resistance and, subsequently, prevention of HCC and CRC. Citation Format: Lei Fan, Danxia Yu, Xiangzhu Zhu, Xuehong Zhang, Xiang Huang, Harvey J. Murff, M. Andr","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73836402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2525: Low frequency TP53 mutations in airway epithelial cells serve as lung cancer risk biomarker","authors":"D. J. Craig, E. Crawford, P. Massion, Thomas Morrison, J. Willey","doi":"10.1158/1538-7445.AM2021-2525","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2525","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72961864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2540: Belief in research, religious coping, and willingness to participate in clinical trials among African Americans with hematologic malignancies: a pilot study","authors":"Marjorie Petty","doi":"10.1158/1538-7445.AM2021-2540","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2540","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72993471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 111: Accurate multi-cancer detection using methylated DNA markers and proteins in plasma","authors":"Slava Katerov, A. Vaccaro, Jacquelyn Hennek, J. Carlson, W. Taylor, D. Mahoney, J. Kisiel, H. Allawi","doi":"10.1158/1538-7445.AM2021-111","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-111","url":null,"abstract":"","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76918688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract 2607: Promotion of low-dose computed tomography for early-stage lung cancer detection","authors":"Monica Saravana Vela, J. Berei, Katrina Dovalovsky, S. Sreenivasappa, J. Ross, Luigi Moruzzi, S. Martell, W. Schulz, N. Puri","doi":"10.1158/1538-7445.AM2021-2607","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2607","url":null,"abstract":"Background: Lung cancer is the leading cause of cancer-related deaths in the United States. In 2019, 23.5% of deaths from cancer in the United States were attributed to lung cancer, a greater proportion than those from breast, prostate, pancreatic, and ovarian cancers combined. Lung cancer9s high mortality rate is largely due to the fact that approximately 75% of new cases are diagnosed in late stages. On a local level, Winnebago County has 17% higher incidence and mortality rates due to lung cancer than the corresponding national rates. Low-dose computed tomography (LDCT) is a valuable lung screening technique that utilizes 90% less ionizing radiation than a conventional chest CT scan. Hypothesis/Aims: Increased awareness of LDCT in clinical and community settings will lead to increased detection of lung cancer in early stages and decreased mortality. Study Design: We spread information on the new U.S. Preventive Services Task Force guidelines to both smokers and physicians in Winnebago County. We evaluated the number of LDCT screenings in Winnebago County between June 2015-March 2019, and recorded the number and stage classifications of lung cancer cases detected after these screenings. We also surveyed physicians and smokers on their likelihood of recommending LDCT to others after our seminars. Lastly, we created a Facebook page (Northern Illinois Lung Cancer Screening Project) to continue promoting LDCT screening in a socially distanced manner. Results: 15 seminars and 37 public awareness booths targeting an estimated 300 physicians and 1,450 smokers were conducted to increase knowledge of LDCT. 2,076 patients underwent LDCT screening at local hospitals. 28 patients were diagnosed with lung cancer, with 17 cases being early stage. 1,000 additional individuals were found to have small lung nodules. According to our surveys, 100% of attendees felt motivated to tell others about LDCT screening after attending our seminars. These studies are also being extended to Boone, Ogle, and Stephenson Counties, which have high incidence of mortality rates attributed to lung cancer. In an alternative effort to promote lung cancer screening in Northern Illinois, we created a Facebook page where we publish posts weekly and have reached over 1109 people and garnered 142 engagements from users. Conclusions: 17 local community members were diagnosed with early stage lung cancer, thus improving their prognosis and increasing therapy options. These community-based studies are being expanded to surrounding areas to expand the reach and effectiveness of our studies. Citation Format: Monica Saravana Vela, Joseph Berei, Katrina Dovalovsky, Shylendra Sreenivasappa, Joseph Ross, Luigi Moruzzi, Sandra Martell, William Schulz, Neelu Puri. Promotion of low-dose computed tomography for early-stage lung cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cance","PeriodicalId":20290,"journal":{"name":"Prevention Research","volume":"49 8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77575534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}