Journal articles on the topic 'American Association of Park Superintendents'
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1
Ferguson, Maria. "Washington View: Big ideas for a new day." Phi Delta Kappan 102, no. 5 (January 26, 2021): 61–62. http://dx.doi.org/10.1177/0031721721992570.
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As the United States has begun to make the transition from one presidential administration to the next, organizations with an interest in education have weighed in on what they think the Biden administration should focus on. Maria Ferguson shares recommendations from the Center for American Progress, AASA: The School Superintendents Association, Organizations Concerned About Rural Education, and advocates for social and emotional learning.
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Bojorquez, Ietza, and Lina Ojeda-Revah. "Urban public parks and mental health in adult women: Mediating and moderating factors." International Journal of Social Psychiatry 64, no. 7 (August 16, 2018): 637–46. http://dx.doi.org/10.1177/0020764018795198.
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Background: The association of green spaces such as urban public parks and mental health might vary according to personal characteristics and characteristics of the park and be mediated by the use of the park. Aims: We investigate the association between urban public park coverage and mental health in adult women, the moderation of this association by personal and park-related characteristics, and the mediation of the association by use of public space. Methods: Combining data from a cross-sectional survey of the adult female population of Tijuana (Mexico) in 2014, and a study of public spaces in 2013, we analyzed the association between park coverage in buffers of 400 and 800 m from participants’ homes and score in the Center for Epidemiologic Studies-Depression scale (CES-D). We tested for mediation by use of park and interaction of urban park coverage with personal and park characteristics. Results: Urban public park coverage in the 400-m buffer had an inverse association with CES-D score that was moderated by age (significant only for younger participants), with no evidence of mediation. Park coverage in the 800-m buffer also had an inverse association with CES-D score, moderated by age and occupation (significant for younger participants and homemakers), and a mediated association was also observed. There was no interaction between park coverage and park characteristics in their association with CES-D score. Conclusion: Our results confirm the potential of public parks to improve mental health and suggest that this effect could be more important at some stages in the life course for women. The upper-middle-income, Latin American country setting adds to the current knowledge that is mostly based on high-income countries.
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Penha, Renata Cristina Oliveira, Danielle Silva Yamamoto, Isabel Aparecida Porcatti de Walsh, Gualberto Ruas, and Marilita Falangola Accioly. "Analysis of cardiovascular risks in practitioners of unsupervised exercises." Fisioterapia em Movimento 27, no. 4 (December 2014): 523–30. http://dx.doi.org/10.1590/0103-5150.027.004.ao04.
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Introduction Physical exercise is recommended by health professionals for the prevention of cardiovascular events; for it is important that practitioners follow recommendations of qualified professionals. Objectives To analyze the cardiovascular risks and the physical exercise of regulars of a municipal public park. Materials and methods 110 regulars of a municipal public park were evaluated by questionnaire and physical examination, 60 men and 50 women with a mean age of 48.8 ± 11.76 years. Cardiovascular risk was classified according to the American Table and physical activity following the recommendations of the American College of Sports Medicine and the American Heart Association. Results Regarding the classification of cardiovascular risk, 54% of the studied population presented potential risk and 31% moderate. As for physical exercise, 58% were considered inactive, 14% active and 28% were very active. 90% received no professional guidelines. Conclusion The public park goers have cardiovascular risk and do exercise without individualized guidance.
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Hilliard, Ann Toler, and Edward Newsome, Jr. "Effective Communication And Creating Professional Learning Communities Is A Valuable Practice For Superintendents." Contemporary Issues in Education Research (CIER) 6, no. 4 (September 29, 2013): 353. http://dx.doi.org/10.19030/cier.v6i4.8102.
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As the chief executive officer, the superintendent must demonstrate high quality performance at every level in order to impact student achievement. In order to be an effective superintendent, the individual must have knowledge and skills in educational leadership and be able to articulate information clearly and precisely about the school district, state and federal accountability systems, policy related to student achievement and personnel practices. The American Association of School Administrators states that the superintendent must know policy for collective bargaining processes for the state/local schools, school district policy and administrative regulations, district finances and budget matters, model the use of technology for instruction and management and should know the role of the Board of Education (AASA, 2011). Superintendents do not work alone, but work in collaboration with school personnel, leadership teams, broader communities and the Board of Education to ensure a productive school system. The responsibilities of the superintendent are many. The superintendent has the task to supervise the general conduct of district schools, instructional curriculum, handle school district management affairs, hiring appropriate personnel and dismissal of personnel based on state policy through the human resources management office. For the local schools, the superintendent should seek ways to encourage the practices of learning communities within the school district for the purpose of working together to improve teaching instructional skills based on the needs of students and if effective will promote higher student learning (Stoll, 2006). This study will focus on skills and knowledge needed for superintendents, what parents want, value of data, strategic planning, effective communication, learning community practices of ethics and morals, technology as a resource, and the characteristics of high performing schools.
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Harris, Carmen D., Prabasaj Paul, Xingyou Zhang, and Janet E. Fulton. "Park Access among School-Age Youth in the United States." Journal of Physical Activity and Health 12, s1 (January 2015): S94—S101. http://dx.doi.org/10.1123/jpah.2015-0119.
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Background:Fewer than 30% of U.S. youth meet the recommendation to be active > 60 minutes/day. Access to parks may encourage higher levels of physical activity.Purpose:To examine differences in park access among U.S. school-age youth, by demographic characteristics and urbanicity of block group.Methods:Park data from 2012 were obtained from TomTom, Incorporated. Population data were obtained from the 2010 U.S. Census and American Community Survey 2006–2010. Using a park access score for each block group based on the number of national, state or local parks within one-half mile, we examined park access among youth by majority race/ethnicity, median household income, median education, and urbanicity of block groups.Results:Overall, 61.3% of school-age youth had park access—64.3% in urban, 36.5% in large rural, 37.8% in small rural, and 35.8% in isolated block groups. Park access was higher among youth in block groups with higher median household income and higher median education.Conclusion:Urban youth are more likely to have park access. However, park access also varies by race/ethnicity, median education, and median household. Considering both the demographics and urbanicity may lead to better characterization of park access and its association with physical activity among youth.
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Tokaryuk, Alla, and Oksana Vanzar. "Complete analysis of the vegetation cover of The Park-Monument of Landscape Art of Local Value «Park-Square» (Chernivtsi, Myron Korduba Street)." Biolohichni systemy 11, no. 1 (June 20, 2019): 101–6. http://dx.doi.org/10.31861/biosystems2019.01.101.
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The results of floristic, coenotic and biotopic research of the phytocenosis cultures variety of the vegetation cover of the park-monument of landscape art of local value «Park-square» (Chernivtsi, Myron Korduba Street) are resented. Species composition of aboriginal (11 species) and introduced (19) woody plants is established. A complex evaluation of exotic dendroflora on the main biomorphological, bioecological and decorative indicators was carried out. It was revealed that most plants belong to a group of decorative and highly decorative plants in the absence of low-decoterative plants. It is established that the phytocenosis cultures of the park-square are characterized by the highest class of perspective and use with maximum recreational load. It has been investigated, that under condition of optimization of structure of existing plantings with participation of beautiful flowering bushes and decorative herbaceous species, the increase of their general esthetic estimation will be provided. The coenotic and ecological purpose for the lawns of the park was characterized. The park's lawn cover is assigned to the association Lolio-Plantaginetum majoris (Linkola 1921) Beger alliance Polygono-Coronopodion Sissingh 1969 order Polygono arenastri-Poetalia annuae Tx. in Géhu et al. 1972 corr. Rivas-Mart. et al. 1991 class Polygono-Poеtea annuae Rivas-Mart. 1975, and intended for mesophytic, hemihydrocontrastphilic, hemiaerophobic, subacidophilic, semi-autotrophic, acarbonphilic, nitrophilic conditions. On the territory of the park, 19 species of alien plants xenophytes were identified with the predominance of kenophytes of North American origin, epecophytes that are confined to anthropogenic-transformed growing areas. The most dangerous among alien plants is a quarantine allergic species Ambrosia artemisiifolia, single species of which are found at the park territory and is assigned to the association groups Lolio-Plantaginetum majoris. Threats of biomonoforming of park phytocenosis cultures were analyzed and the priority of studying of alien plants in the protected areas of the city was justified.
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Halifax, Shawn. "McLeod Plantation Historic Site." Public Historian 40, no. 3 (August 1, 2018): 252–77. http://dx.doi.org/10.1525/tph.2018.40.3.252.
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In 2015 the Charleston County Park and Recreation Commission opened McLeod Plantation Historic Site. What remains of the former 1,693-acre Sea Island cotton plantation is 37 acres, 14 historic structures, and an African American cemetery. Interpretation of the former plantation is focused on the African American struggle to achieve freedom, justice, and equality from 1851 through 1990. The cultural history interpretation coordinator and co-author of the National Association for Interpretation award winning exhibits at the site explores the development, implementation, and adjustments made to interpretation since the opening and comments on the current state of Black museums in America.
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Harper, Kristine, Louis W. Uccellini, Eugenia Kalnay, Kenneth Carey, and Lauren Morone. "50th Anniversary of Operational Numerical Weather Prediction." Bulletin of the American Meteorological Society 88, no. 5 (May 1, 2007): 639–50. http://dx.doi.org/10.1175/bams-88-5-639.
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The National Centers for Environmental Prediction (NCEP), Air Force Weather Agency (AFWA), Fleet Numerical Meteorology and Oceanography Center (FNMOC), National Weather Association, and American Meteorological Society (AMS) cosponsored a “Symposium on the 50th Anniversary of Operational Numerical Weather Prediction,” on 14–17 June 2004 at the University of Maryland, College Park in College Park, Maryland. Operational numerical weather prediction (NWP) in the United States started with the Joint Numerical Weather Prediction Unit (JNWPU) on 1 July 1954, staffed by members of the U.S. Weather Bureau, the U.S. Air Force and the U.S. Navy. The origins of NCEP, AFWA, and FNMOC can all be traced to the JNWPU. The symposium celebrated the pioneering developments in NWP and the remarkable improvements in forecast skill and support of the nation's economy, well being, and national defense achieved over the last 50 years. This essay was inspired by the presentations from that symposium.
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Whisnant, Anne Mitchell, and Marla R. Miller. "Pulling from Outside, Pushing from Inside." Public Historian 38, no. 4 (November 1, 2016): 264–92. http://dx.doi.org/10.1525/tph.2016.38.4.264.
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In 2011, the Organization of American Historians (OAH) released Imperiled Promise: The State of History in the National Park Service, a multi-year team-authored study commissioned by the NPS Chief Historian. The study offered twelve findings assessing strengths and challenges facing history practice across the agency, and made almost one hundred recommendations that aimed to support that work. The report’s fifth anniversary offers an opportunity to review how Imperiled Promise’s proposals have fared. We find that, although the report has been positively received and many of its perspectives and specific suggestions embraced, the persistent structural issues it identified continue to hinder full realization of the parks’ promise. The OAH, National Council on Public History (NCPH), American Historical Association (AHA), and other professional associations, as well as their members, must continue to advocate strongly and consistently for NPS history.
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Hu, Caixia. "Shake Shack IPO Analysis." Journal of Contemporary Educational Research 5, no. 9 (September 30, 2021): 49–54. http://dx.doi.org/10.26689/jcer.v5i9.2535.
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The restaurant industry is one of the largest and fastest growing sectors in the economy in the United States. According to the National Restaurant Association (NRA), the food service industry is the third largest industry accounting for more than 4% of the country’s gross domestic product (GDP). Shake Shack is an American fast food restaurant chain based in New York City. It started out as a food cart at Madison Square Park in 2000, and its popularity grew steadily. Shake Shack is currently one of the best fast-food restaurants in the world. This article discusses the successful business model of Shake Shack through IPO analysis.
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Seleb, David J., and Jodi Kolo. "Our Path to Engagement, Learning, and Stewardship: The Oak Park Public Library, the American Library Association, and the Harwood Institute." Public Library Quarterly 36, no. 2 (April 3, 2017): 123–35. http://dx.doi.org/10.1080/01616846.2017.1312194.
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Cho, Wansang, Solchan Won, Yoona Choi, Jong Beom Park, Jun-Gyu Park, Sihyeong Yi, Caroline E. Kim, Chintam Narayana, Dong-Sup Lee, and Seung Bum Park. "Abstract 2585: Targeted protein upregulation strategy potentiates STING agonist immunotherapy." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2585. http://dx.doi.org/10.1158/1538-7445.am2022-2585.
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Abstract As cancer immunotherapy has been emerged as a new pillar of cancer therapy, many strategies modulating host immunity were suggested for cancer treatment. Stimulator of interferon genes (STING) is a promising target for anticancer immunotherapy. However, dysregulated STING expression, or poor pharmacokinetic profiles of STING agonists pose major challenges. Recently, modulating target protein levels via the ubiquitin-proteasome system, such as proteolysis-targeting chimera (PROTAC), has broadened the scope of pharmacological inventions. Herein, we propose UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to overcome these limitations. We discovered the small molecule SB24011 that inhibits STING-E3 ligase interaction, thereby induces the blockade of E3 ligase-mediated STING degradation. As a result, SB24011 enhanced the STING agonist-mediated immune responses by upregulating cellular STING protein level. Thus, co-administration of SB24011 markedly improved the immuno-oncological efficacy of STING agonist cGAMP and anti-PD-1 therapy for tumor regression and robust systemic antitumor response. Taken together, we successfully demonstrated that targeted STING protein upregulation is a promising strategy for cancer immunotherapy. Citation Format: Wansang Cho, Solchan Won, Yoona Choi, Jong Beom Park, Jun-Gyu Park, Sihyeong Yi, Caroline E. Kim, Chintam Narayana, Dong-Sup Lee, Seung Bum Park. Targeted protein upregulation strategy potentiates STING agonist immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2585.
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Stasi, Selina Marie, John Otto Spengler, Jay Maddock, Lisako McKyer, and Heather Clark. "Shared-Use Decisions Among Administrators of Physical Activity Facilities in Pasadena, TX." Health Promotion Practice 21, no. 6 (April 29, 2019): 926–33. http://dx.doi.org/10.1177/1524839919847669.
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Background and Purpose. The American Heart Association recommends community-based research on shared use of physical activity (PA) spaces. Pasadena, a community in southeast Houston, Texas with lower socioeconomic status and racial/ethnic diversity, was the setting for our study. Efforts to increase access to PA in Pasadena include building the evidence on PA resources. The purpose of this research was to utilize survey data in a community setting to inform and target efforts around sharing PA spaces. Method. An online survey was administered to K-12 school ( n = 25) and park ( n = 30) administrators, church leaders ( n = 10), community organizations ( n = 2), a health care center, and a local business. Results. Park facilities in Pasadena shared by agreement with two high schools and three baseball/softball leagues were ballfields, tennis courts, and jogging paths. No park facilities were shared with faith-based organizations. Four parks communicated daily, and five schools communicated with parks quarterly about providing opportunities for PA. Key facilitators to sharing facilities were building relationships and collaboration, service to the community, and improving health. Key barriers were cost, maintenance, staffing, and prioritizing use with limited time, facilities, and resources. Conclusions. This study is the first of its kind to address shared use at the community level and suggests opportunities to improve communication and partnerships between parks, schools, and churches. This research will inform ongoing efforts to promote access by identifying barriers and motivators among stakeholder groups to help facilitate shared use agreements.
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Guchhait, Koushik, Hyeon Seung Yoon, Seungheon Shin, Hyun-Su An, Hye Seung Nam, Francisco D. Yanqui-Rivera, Samara M. Oña, et al. "Abstract LB157: Cereblon inhibits prostate cancer progression and metastasis by negatively regulating 6PGD." Cancer Research 83, no. 8_Supplement (April 14, 2023): LB157. http://dx.doi.org/10.1158/1538-7445.am2023-lb157.
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Abstract As the third enzyme of the pentose phosphate pathway (PPP), abnormally elevated levels of 6-phosphogluconate dehydrogenase (6PGD) have been documented in various human cancers. We demonstrate that reduced cereblon (CRBN) protein expression is the underlying mechanism of elevated 6PGD expression in metastatic prostate cancer cells. We establish 6PGD as a new endogenous substrate for CRBN by demonstrating that it interacts directly with CRBN and is ubiquitinated by CRL4CRBN. In addition, CRBN negatively regulates prostate cancer cell progression and metastasis, as abnormally high 6PGD, in the absence of sufficient CRBN, enhances the metastatic potential of prostate cancer in vitro and in vivo. Our findings show convincingly that carbohydrate metabolism regulated by 6PGD is linked to prostate cancer metastasis via CRBN. Based on these data, we propose that the 6PGD-CRBN axis may be a suitable target for further research into new therapeutics for mitigating prostate cancer metastasis. Citation Format: Koushik Guchhait, Hyeon Seung Yoon, Seungheon Shin, Hyun-Su An, Hye Seung Nam, Francisco D. Yanqui-Rivera, Samara M. Oña, Miguel Á. Mendez, Seokjae Park, Eun-Kyoung Kim, Jong Yeon Hwang, Jee-Young Han, Doo Yong Chung, Daeho Park, Su-Geun Yang, Chul-Seung Park, Steve K. Cho. Cereblon inhibits prostate cancer progression and metastasis by negatively regulating 6PGD [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB157.
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Bokhari, Kamran A. "The 36th Annual Meeting of the Middle East Studies Association of North America." American Journal of Islam and Society 20, no. 1 (January 1, 2003): 163–66. http://dx.doi.org/10.35632/ajis.v20i1.1889.
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The 36th annual meeting of the Middle East Studies Association of NorthAmerica (MESA), was held at the Wardman Park Hotel, Washington, DC,November 23-26, 2002. This conference, possibly the largest gathering ofscholars and students of the Middle East, took place in an atmosphere saturatedby 9/11 and Washington’s plans for an all-out war against Iraq, aswell as considerable right-wing and pro-Zionist pressure applied by suchmembers of the epistemic community of scholars, journalists, and policyanalysts as Daniel Pipes (the Middle East Forum) and Martin Kramer, aone-time director and currently a senior research fellow at Tel AvivUniversity’s Moshe Dayan Center for Middle Eastern and African Studies.Both are behind Campus Watch (http://www.campus-watch.org), whichmonitors academic discourse that opposes American foreign policy towardthe Muslim world and its one-sided support for Israel, and which maintainson its website a list of “un-American” academicians and apologists for“militant Islam” and rogue regimes.November 23, the first day, was reserved for the business meetings ofall groups having an institutional affiliation with MESA. The panels, presentedas parallel sessions, began on Sunday at 8:30 a.m. Also featured wasa presidential address by the outgoing president, a plenary session, a bookexhibition, an art gallery, and a film fest. MESA organizers reported that1,900 people attended the 156-panel event, along with 80 exhibitions.The first session featured panels on popular culture and identity in theMaghreb, women and development, issues in contemporary Iran, intellectualsand ideas in the making of the Turkish Republic, history of the Ottomanborderlands, legitimation of authority in early period of Islam, comparativeperceptions of the “other” in Israeli and Palestinian textbooks, comparativeanalysis of political Islam, religious conversion and identity, and the Arabicqasidah. There was also a roundtable discussion on water issues and a thematicconversation on 9/11 and the Muslim public sphere. In the following ...
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Park, Su Hwan, Yun-Yong Park, and Jong-Ho Lee. "Abstract 3087: The m6A methyltransferase RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism." Cancer Research 84, no. 6_Supplement (March 22, 2024): 3087. http://dx.doi.org/10.1158/1538-7445.am2024-3087.
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Abstract N6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remains unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to non-basal like BC and linked it to worse clinical outcome. Gene expression profiling uncovered correlations between RBM15 and serine and glycine metabolism genes including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences overall m6A levels and, specifically, m6A of serine and glycine metabolism genes via direct binding to target RNA. Further RBM15 effects on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism suggesting RBM15 as a new therapeutic target in BC. Citation Format: Su Hwan Park, Yun-Yong Park, Jong-Ho Lee. The m6A methyltransferase RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3087.
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Kami Reddy, Karthik Reddy, Jun Hyoung Park, Roni J. Bollag, Martha K. Terris, Seth P. Lerner, Minhaj Siddiqui, Yair Lotan, Jianjun Gao, Benny Abraham Kaipparettu, and Nagireddy Putluri. "Abstract 7060: Mitochondrial metabolism and racial disparity of bladder cancer." Cancer Research 84, no. 6_Supplement (March 22, 2024): 7060. http://dx.doi.org/10.1158/1538-7445.am2024-7060.
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Abstract Bladder cancer mortality is significantly higher in African American patients compared to their European American counterparts. This inferior survival of African American cancer patients is driven at least in part by distinctive intrinsic tumor biology, more specifically altered metabolic activity. However, underlying molecular mechanism for the African American bladder cancer mortality are largely unexplored. Our pioneering metabolomic findings demonstrate alterations in metabolic pathways between African American and European American bladder cancer, specifically those involved in driving energy metabolism. Along these line, we observed increased electron transport chain activity and ATP production in African American bladder cancer could be a result of distinctive rewiring of energy metabolism compared to their European American counterparts. We further performed gene set enrichment analysis by mapping metabolites to genes and observed that oxidative phosphorylation pathway was uniquely enriched in African American tumors compared to European American tumors. In addition, from in vitro assays, mitochondrial complex protein and activity were altered in African American bladder cancer. To determine the role of glutamine mediated increased electron transport chain activity and ATP production in African American bladder cancer, we evaluated the metabolic flux using 13C labeled tracers in both African American and European American bladder cancer cell lines. Metabolic flux analysis revealed that African American cell lines are more glutamine dependent and that producing increased tricarboxylic acid intermediates. Overall, our data indicate that elevated mitochondrial metabolism and oxidative phosphorylation driven by enhanced glutaminolysis may facilitate African American bladder cancer progression. These findings provide the rationale to use mitochondrial-specific inhibitors to target at least a subset of African American bladder cancer patients. Citation Format: Karthik Reddy Kami Reddy, Jun Hyoung Park, Roni J. Bollag, Martha K. Terris, Seth P. Lerner, Minhaj Siddiqui, Yair Lotan, Jianjun Gao, Benny Abraham Kaipparettu, Nagireddy Putluri. Mitochondrial metabolism and racial disparity of bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7060.
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Ko, Hyun Min, Wona Jee, Do-il Park, Somi Park, Ye-Rin Park, Hyeung-Jin Jang, and Ji Hoon Jung. "Abstract 864: Ophiopogonin D increase apoptosis by activating p53 via ribosomal protein L5 and L11 and inhibiting the expression of c-Myc via CNOT2." Cancer Research 82, no. 12_Supplement (June 15, 2022): 864. http://dx.doi.org/10.1158/1538-7445.am2022-864.
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Abstract Extracted from the root tuber of Ophiopogon japonicas, ophiopogon is well known to have an anti-cancer effect. However, the underlying mechanisms are still largely unknown. Here, we report that Ophiopogon D (OP-D) can inhibit colon cancer cell proliferation and induce apoptosis by inhibiting c-Myc expression through activation of p53 and CNOT2 regulation. Our results showed that OP-D induced p53 expression via ribosomal protein L5 or L11 and inhibited c-Myc expression through CNOT2 in a dose-dependent manner. Additionally, OP-D regulated cyclin D1 and CDK4 which are well known as cell cycle regulatory proteins. Consistently, OP-D inhibited the phosphorylation of AKT expression in a dose-dependent manner. Furthermore, OP-D shortened c-Myc’s half-life in a time-dependent manner. Furthermore, CNOT2 knockdown enhanced the inhibitory effect of OP-D on c-Myc in colon cancer cells. Interestingly, OP-D has increased the apoptotic effect of colon cancer cells when combined with doxorubicin or 5-FU, a treatment already used clinically. Altogether, our results suggested that OP-D regulates colon cancer cell survival and induces apoptosis by inhibiting c-Myc expression via activation of p53 and CNOT2 regulation. Citation Format: Hyun Min Ko, Wona Jee, Do-il Park, Somi Park, Ye-Rin Park, Hyeung-Jin Jang, Ji Hoon Jung. Ophiopogonin D increase apoptosis by activating p53 via ribosomal protein L5 and L11 and inhibiting the expression of c-Myc via CNOT2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 864.
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Park, Heegeon, Saehyung Lee, Hayeon Park, Sunghyun Hong, Jaemun Kim, Sungyoul Hong, Ji-hyun Park, Young Kee Shin, Jun Young Choi, and Na Young Kim. "Abstract 6348: ABN202 (αEGFR-interferon-β mutein), a potent antibody-cytokine fusion protein for the treatment of EGFR-positive non-small cell lung cancer." Cancer Research 83, no. 7_Supplement (April 4, 2023): 6348. http://dx.doi.org/10.1158/1538-7445.am2023-6348.
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Abstract ABN202 is an antibody-cytokine fusion protein consisting of interferon-β mutein (ABN102) molecularly fused to a anti-EGFR monoclonal antibody that recognizes the EGFR expressed on various types of cancer cells. In previous studies, we developed ABN102, a bio-better version of recombinant human interferon-β with hyperglycosylation via site-directed mutagenesis to improve stability, productivity, and pharmacokinetics properties. An addition of glycosylation at the N25 residue of ABN102 is expected to reduce the peripheral toxicity of ABN202, as it can shield the IFNAR2 binding interface. In this study, the binding ability and biological activity of ABN202 was evaluated in vitro models. ABN202 downregulates the EGFR protein expression and reduces EGFR phosphorylation by degrading target proteins via internalization in the EGFR-positive NSCLC cell line. In addition, we also determined the direct and indirect anti-cancer activity of ABN202 in preclinical models. Taken together, we suggest that ABN202 has potent anti-cancer activities, via direct cytotoxicity in EGFR-positive tumors and indirectly activating immune cells through Type I IFN signaling. we conclude ABN202 is a promising drug candidate for patients with EGFR-positive NSCLC. Citation Format: Heegeon Park, Saehyung Lee, Hayeon Park, Sunghyun Hong, Jaemun Kim, Sungyoul Hong, Ji-hyun Park, Young Kee Shin, Jun Young Choi, Na Young Kim. ABN202 (αEGFR-interferon-β mutein), a potent antibody-cytokine fusion protein for the treatment of EGFR-positive non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6348.
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Lee, In Hee, Soo Jung Lee, Jeeyeon Lee, Ho Yong Park, Jin Hyang Jung, Nora Jee-Young Park, Ji-Young Park, Yee Soo Chae, and Byeongju Kang. "Abstract 2146: LDH as a surrogate marker for both pCR and survival in breast cancer patient." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2146. http://dx.doi.org/10.1158/1538-7445.am2023-2146.
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Abstract Background: Glucose metabolism in cancer cells produces various glycolytic metabolites, which can affect cancer progression and treatment outcome. Herein we evaluated the association of glucose transporters and enzymes involved in glucose metabolism with clinic-pathological factors and outcomes in breast cancer patients who underwent neoadjuvant chemotherapy(NAC). Methods: We selected 7 target transporters and enzymes(GLUT1, hexokinase 2, lactate dehydrogenase, MCT1, MCT4, IGF1RA, and IGF1RB) involved in glucose metabolism. Their tumoral expressions were scored both quantitively and qualitatively based on tissue microarrays and immunohistochemistry as previously described (Pinheiro et al, 2010) and then evaluated in relationships with pretreatment clinical/pathological characteristics and treatment outcomes including findings of 18F-FDG PET/CT,pathologic complete response(pCR), and relapse in breast cancer(stage IIA-IIIC) patients who underwent anthracycline or taxane-based NAC. Results: Of the 236 enrolled patients, 145(61.4%), 44(18.6%), and 47(19.9%) were luminal, HER2-enriched, and TNBC subtypes. Pathologic CR was determined 50(21.2%) and 57(24.2%) relapses, 42(17.8%) distant relapses, and 28 deaths were observed during median follow-up duration of 64.0 (32.3-114.9) months. The expression rates of the target molecules were 76.0, 31.1, 42.1, 54.9, 67.9, 78.4, and 49.8% for GLUT1, hexokinase 2 (HK2), lactate dehydrogenase(LD), MCT1, MCT4, IGF1RA, and IGF1RB, respectively. Among target molecules in glucose metabolism, LD was significantly associated with pCR(OR=0.251; p-=0.016) and distant disease-free survival (HR= 2.29; P=0.019). Plus, LD expression shows a trend for a high SUVmax of primary tumor 18F-FDG PET/CT(OR=1.797 P=0.060). Conclusion: Tumoral expression of lactate dehydrogenase can be considered as a predictive marker for pCR to NAC and plus prognostic marker for survival in patients with breast cancer. Citation Format: In Hee Lee, Soo Jung Lee, Jeeyeon Lee, Ho Yong Park, Jin Hyang Jung, Nora Jee-Young Park, Ji-Young Park, Yee Soo Chae, Byeongju Kang. LDH as a surrogate marker for both pCR and survival in breast cancer patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2146.
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Gill, Jasmeet K., Gertraud Maskarinec, Song-Yi Park, Lynne Wilkens, and Loic Le Marchand. "Abstract 3407: Physical activity and post-menopausal breast cancer in the Multiethnic Cohort Study." Cancer Research 84, no. 6_Supplement (March 22, 2024): 3407. http://dx.doi.org/10.1158/1538-7445.am2024-3407.
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Abstract Much research has been conducted on the relationship between physical activity and breast cancer, with meta-analyses showing 10 – 21% reduction in breast cancer risk for postmenopausal women with high compared to low level of physical activity. However, few studies have explored this relationship in non-Caucasian women. We analyzed data from 74,177 post-menopausal African American, Caucasian, Japanese American, Latina, and Native Hawaiian women in the Multiethnic Cohort in Hawaii and California. Data on physical activity (hours and metabolic equivalents (METs)) was based on a self-administered questionnaire at baseline (1993–1996). Multivariate Cox proportional hazards models provided estimates of hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for risk factors. We observed no associations between breast cancer risk and hours of moderate/vigorous activity per week (HR=1.01, 95% CI: 0.91-1.10, Ptrend=0.71), MET-hours of moderate/vigorous activity per week (HR=1.03, 95% CI: 0.94-1.13, Ptrend=0.92), and total METs-measured as average MET level per day multiplied by 7 (HR=0.94, 95% CI: 0.86-1.03, Ptrend=0.37) when comparing the highest quartile to the lowest. When examining the data across race/ethnicity, we observed a reduction in risk of breast cancer for total METs (HR=0.75, 95% CI: 0.61-0.94, Ptrend=0.05) among Latina women. Analysis across strata of BMI showed no differences across subgroups. In this study, we did not observe any consistent protective association between physical activity and breast cancer risk. Citation Format: Jasmeet K. Gill, Gertraud Maskarinec, Song-Yi Park, Lynne Wilkens, Loic Le Marchand. Physical activity and post-menopausal breast cancer in the Multiethnic Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3407.
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Sweeney, P. J. "Great Men with Sick Brains & Other Essays by BENGT LJUNGGREN, 130 pp., ill., Park Ridge, IL, American Association of Neurological Surgeons, 1990. $35.00." Neurology 40, no. 7 (July 1, 1990): 1154. http://dx.doi.org/10.1212/wnl.40.7.1154-c.
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Boyle, Joseph, Jessica Yau, Jimmie L. Slade, Derrick A. Butts, Jessica Wimbush, Jong Y. Park, Arif Hussain, et al. "Abstract 809: Neighborhood disadvantage and prostate tumor aggressiveness among African American and European American men." Cancer Research 84, no. 6_Supplement (March 22, 2024): 809. http://dx.doi.org/10.1158/1538-7445.am2024-809.
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Abstract Introduction: African American (AA) men experience greater prostate cancer (PC) incidence and mortality compared to European American (EA) men, but the reasons are not fully understood. Some literature has identified connections between neighborhood disadvantage and aggressive PC, and AA men may be more likely to experience these factors than EA men. However, it is unclear if these associations may vary by race. We tested associations of two neighborhood disadvantage measures (neighborhood socioeconomic deprivation and racial segregation) with prostate tumor aggressiveness, overall and separately by race. We hypothesized that they would be positively associated and that associations would be stronger among AA men. Methods: We leveraged data from the University of Maryland Greenebaum Comprehensive Cancer Center Tumor Registry for AA and EA men who were diagnosed with PC from 2004-2021. We geocoded participants’ addresses at diagnosis to determine census tract-based Area Deprivation Index (ADI) and Racial Isolation Index (RI) values. ADI analyses included men diagnosed in 2005 or later (778 AA men and 687 EA men), and RI analyses included men diagnosed in 2009 or later (606 AA men and 454 EA men) based on data availability. We used logistic regression to model the odds of aggressive PC, defined as a Gleason pattern of 4+3 or a total Gleason score >=8, overall and by race. We fit models with scaled ADI or RI as the exposure variable, adjusting for race, age at diagnosis, and year of diagnosis. We also assessed an interaction between each neighborhood measure and race. Results: Median (interquartile range) ADI scores were 118 (101-137) for AA men and 92 (83-102) for EA men, and RI scores were 0.68 (0.35-0.87) for AA men and 0.11 (0.06-0.20) for EA men, indicating greater neighborhood deprivation and AA residential segregation among AA participants. The greatest values for these scores were concentrated in central and west Baltimore. A one-standard deviation (SD) increase in ADI was associated with significantly greater odds of aggressive tumors for AA men (OR=1.28, 95% CI: 1.10, 1.49; p<0.01), but not for EA men (OR=0.85, 95% CI: 0.67, 1.08; p=0.19), and the p-value for interaction (p<0.01) was statistically significant. Similarly, a one-SD increase in RI was significantly associated with aggressive tumors for AA men (OR=1.24, 95% CI: 1.03, 1.49; p=0.03), but not for EA men (OR=1.23, 95% CI: 0.84, 1.80; p=0.29), although the p-value for interaction was not statistically significant. Conclusions: Neighborhood disadvantage was significantly associated with higher odds of aggressive PC. The association of neighborhood deprivation and tumor aggressiveness was stronger among AA men. Additional analyses will consider other measures, including historical redlining, to further evaluate the relationship of neighborhood disadvantage with prostate tumor aggressiveness. Citation Format: Joseph Boyle, Jessica Yau, Jimmie L. Slade, Derrick A. Butts, Jessica Wimbush, Jong Y. Park, Arif Hussain, Eberechukwu Onukwugha, Cheryl L. Knott, David C. Wheeler, Kathryn Hughes Barry. Neighborhood disadvantage and prostate tumor aggressiveness among African American and European American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 809.
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Alqattan, Hamad, Zoe Morrison, and Jennifer A. Cleland. "A Narrative Synthesis of Qualitative Studies Conducted to Assess Patient Safety Culture in Hospital Settings." Sultan Qaboos University Medical Journal [SQUMJ] 19, no. 2 (September 8, 2019): 91. http://dx.doi.org/10.18295/squmj.2019.19.02.002.
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ABSTRACT: This review aimed to identify methodological aspects of qualitative studies conducted to assess patient safety culture (PSC) in hospital settings. Searches of Google Scholar (Google LLC, Menlo Park, California, USA), MEDLINE® (National Library of Medicine, Bethesda, Maryland, USA), EMBASE (Elsevier, Amsterdam, Netherlands), PsycINFO (American Psychological Association, Washington, District of Columbia, USA) and Web of Science (Clarivate Analytics, Philadelphia, Pennsylvania, USA) databases were used to identify qualitative articles published between 2000 and 2017 that focused on PSC. A total of 22 studies were included in this review and analysis of methodological approaches showed that most researchers adopted purposive sampling, individual interviews, inductive content and thematic analysis. PSC was affected by factors related to staffing, communication, nonhuman resources, organisation and patient-related factors. Most studies lacked theoretical frameworks. However, many commonalities were found across studies. Therefore, it is recommended that future studies adopt a mixed methods approach to gain a better understanding of PSC.Keywords: Patient Safety; Culture; Needs Assessment; Qualitative Research.
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Lee, Minyoung, Yesol Kim, Dasom Son, Sera Lim, and Jong Hoon Park. "Abstract 5681: Identification of dysregulated miRNAs involved in TNBC progression." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5681. http://dx.doi.org/10.1158/1538-7445.am2024-5681.
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Abstract Triple negative breast cancer (TNBC) is the most aggressive type of all breast cancer subtypes. Although various studies have been performed to identify prognostic and therapeutic targets for TNBC, the TNBC specific biomarkers have not yet been elucidated. Herein, we identified dysregulated miRNAs in TNBC via analysis of miRNA microarray in breast cancer tissues and found the oncogenic RNA (miR-374a-5p) and tumor suppressive miRNAs (miR-320c, miR-371b-5p). These miRNAs were closely related to overall survival of TNBC patients and status and involved in TNBC progression or drug responsiveness. Collectively, these results suggest that dysregulated miRNAs might serve as potential prognostic marker or therapeutic target for TNBC. Citation Format: Minyoung Lee, Yesol Kim, Dasom Son, Sera Lim, Jong Hoon Park. Identification of dysregulated miRNAs involved in TNBC progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5681.
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Park, Jong Hoon, Yesol Kim, Je Yeong Ko, Soo-Been Lee, and Minah Park. "Abstract 5825: Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5825. http://dx.doi.org/10.1158/1538-7445.am2022-5825.
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Abstract Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer; however, specific prognostic biomarkers have not yet been developed. In this study, we identified dysregulated microRNAs (miRNAs) in TNBC by profiling miRNA and mRNA expression. In patients with TNBC, miR-371b-5p expression was reduced, and miR-371b-5p overexpression significantly mitigated TNBC cell growth, migration, and invasion. In addition, we found that expression of cold shock domain-containing protein E1 (CSDE1), a direct target gene of miR-371b-5p, was upregulated in TNBC cells, and inhibition of CSDE1 expression alleviated TNBC cell growth by regulating RAC1 transcription. Mechanistically, CSDE1, phosphorylated C-terminal domain (p-CTD) of RNA polymerase II (RNAPII), and CDK7 form a complex, and downregulation of CSDE1 leads to weak interaction between RNAPII p-CTD and CDK7, resulting in a decrease in RNAPII p-CTD expression to reduce RAC1 transcript levels in CSDE1-deficient TNBC cells. Our data demonstrate that miR-371b-5p is a tumor-suppressive miRNA that regulates the CSDE1/Rac1 axis and could be a potential prognostic biomarker for TNBC. Citation Format: Jong Hoon Park, Yesol Kim, Je Yeong Ko, Soo-Been Lee, Minah Park. Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5825.
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Jeong, Sumin, Yuna Park, Eunah Jeong, and Sukjoon Yoon. "Abstract 2092: Consensus analysis of associated target-biomarker pairs in cancers." Cancer Research 83, no. 7_Supplement (April 4, 2023): 2092. http://dx.doi.org/10.1158/1538-7445.am2023-2092.
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Abstract The heterogeneity of cancers limits the reproducibility of target-biomarker relationships in diverse cohorts or sample groups. Here, we carried out consensus analyses of associated data pairs to improve the consistency (reproducibility) of prognostic power of biomarkers and anticancer efficacy of targets. All of RNA expression, patient survival, CRIRSPR/shRNA screening data were integrated from TCGA, GDSC and CCLE datasets. While >90% of prognostic RNA expression found in given sample sets were not reproduced (i.e., not significant) in other test sets, those hits exhibiting consensus prognostic powers in diverse subtypes or lineages, were more significant in test sets than non-consensus hits. In the analysis of the association between CRISPR knockout and RNA expression data, the lineage consensus of the association increased the reproducibility in the validation using sh/siRNA knockdown and qPCR data. Further experimental validations reveal that ITGAV is an effective anticancer target in diverse lineages, significantly associated with prognostic RNA expression of several consensus biomarker genes. In conclusion, the consensus analysis was useful to prioritize reproducible targets and biomarkers from omics data. It has been implemented in Q-omics software (http://qomics.io) for general cancer research. Citation Format: Sumin Jeong, Yuna Park, Eunah Jeong, Sukjoon Yoon. Consensus analysis of associated target-biomarker pairs in cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2092.
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Kim, Dooho, Jong Woo Park, Jung-Ae Kim, Jeong-Hoon Kim, Tae Sub Park, and Joonghoon Park. "Abstract 5954: Big data-driven discovery of novel oncogenic fusion genes for anticancer therapy." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5954. http://dx.doi.org/10.1158/1538-7445.am2024-5954.
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Abstract The integration of big data analytics with cancer research is catalyzing a transformative approach in cancer treatment, primarily focusing on the discovery of novel and efficacious anticancer targets. Our study presents an advanced algorithm, specifically crafted to exploit the extensive data available in the field of oncology. We started with the genomic and clinical information of 8,864 patients with 33 different cancers (TCGA). Then we implemented the following algorithm to discover anti-cancer targets by analyzing the clinical significance (cBioPortal), drug development status (Cortellis), and oncogenicity (DepMap) of candidate genes: Candidate genes = {gene | gene ∈ Genes, [Frequency(gene) > 50, Drug(gene) ∈ {'biological testing', 'preclinical stage'}, Association(gene) ≥ 0.4, Publication(gene) ≤ 200] ∨ [Publication(gene) ≥ 200 ∧ Boolean(gene)]}. We employed this algorithm to analyze fusion genes, which represent promising anti-cancer targets known for their potential to elicit substantial clinical responses, but there is a high demand for new ones. We identified four druggable therapeutic targets out of a total of 15,291 fusion genes through the algorithm: frame-shifted FGFR3-TACC3, in-framed DLK1-RPS11, frame-shifted CHP1-RAD51B, and in-framed TBC1D22A-SMYD3. We conducted in vitro validation studies of these fusion genes in NIH3T3 cell lines, and it confirmed that all of the fusion genes not only produce mRNA and protein levels but also induce oncogenic effects on cellular behavior. In the case of FGFR3-TACC3, the introduced fusion gene induced mRNA (p < 0.05) and protein expression (p < 0.05) even when frame-shifted. In addition, the proliferation rate of transformed cells increased more than 4-fold on day 10 (p < 0.0001) and colony formation increased more than 5-fold on day 21 (p < 0.01) compared to wild-type cells. These results demonstrate the tumorigenicity of the fusion genes. Taken together, this study emphasizes the crucial role of big data in propelling oncology research forward. The algorithm we developed can offer a new pathway for creating innovative cancer treatment, marking a significant advancement in the realm of personalized cancer therapy. Citation Format: Dooho Kim, Jong Woo Park, Jung-Ae Kim, Jeong-Hoon Kim, Tae Sub Park, Joonghoon Park. Big data-driven discovery of novel oncogenic fusion genes for anticancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5954.
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Cha, Mi Young, Gihyeon Kim, Changho Park, Bu-Nam Jeon, Kyung Mi Park, Hansoo Park, and Chan-Young Ock. "Abstract 7522: Association between the CNTN4 expression and responsiveness to pembrolizumab in gastric cancer." Cancer Research 84, no. 6_Supplement (March 22, 2024): 7522. http://dx.doi.org/10.1158/1538-7445.am2024-7522.
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Abstract Even though numerous strategies for controlling malignant tumors have been established with immunotherapies, a solution for non-favorable responses to immunotherapy is still unclear. To address this unsolved problem, we previously suggested that a new immune checkpoint, CNTN4, is expressed on the tumor side and suppresses T cell-dependent immune activation. We further investigated the association between the clinical outcome of pembrolizumab and the expression of CNTN4 in the gastric cancer cohort using bulk RNA sequencing data to establish a clinical strategy for targeting CNTN4. We split the patients into high- or low-group based on the expression of CNTN4 and CD274 (PD-L1) with the median of those two genes and analyzed for the responses. As a result, patients who had low-CNTN4 expression and high-CD274 expression were favorable to the pembrolizumab (Objective response rate, ORR; 64.3% [9/14]). However, patients who had high-CNTN4 expression and high-CD274 expression showed unfavorable responses (ORR; 0% [0/9]. Ꭓ2 = 5.951, P = 0.002). We also figured out that non-responders (NRs, N = 33) had a relatively lower expression of CD274 (p = 0.0012) and a higher expression of CNTN4 (p = 0.0015) compared to responders (Rs, N =12). Furthermore, in CD274-high patients, NRs showed significantly higher CNTN4 expression than Rs (Fold change = 2.17. P = 0.0086). Immune-related cytokine genes, such as IFNG, GZMA, and CXCL9, were negatively correlated to CNTN4 expression (R = -0.69, P = 2 × 10−4; R = -0.52, P = 0.0108; R= -0.54, and P = 0.0077, respectively.). In addition to the cancer cells, cancer-associated fibroblast, important for immunotherapy, was deconvoluted from bulk RNA data and showed higher CNTN4 expressions in NRs than Rs (Fold change = 3.3, P = 0.002). When classifying tumor tissue based on TCGA molecular subtypes, genomically stable (GS) type and chromosomal instability (CIN) were more observed in the NRs compared to the Rs with poor prognosis. CIN and GS type patients showed higher CNTN4 and lower CD274 expression than other TCGA subtypes. We also figured out that all CNTN4-high patients were composed of CIN or GS types. Similarly, higher CNTN4 expression and lower CD274 expression were observed in CIN and GS gastric patients from the TCGA database. Moreover, overall survival (OS) and progression-free survival (PFS) were poorer in CNTN4-high patients (OS: median of CNTN4-high = 9.73 [95% CI= 4.77-NA] months, median of CNTN4-low = NA [95% CI= 9.03-NA] months, P = 0.072. Hazard ratio = 2.15 [95% CI = 0.917-5.037], P = 0.078) (PFS: median of CNTN4-high = 2.10 [95% CI= 1.33-3.97] months, median of CNTN4-low = 5.47 [95% CI= 2.80-NA] months, P = 0.0004. Hazard ratio = 3.303 [95% CI = 1.647-6.624], P = 0.0008).Together, we suggest that CNTN4 is a potential ICP candidate for gastric cancer patients unfavorable to pembrolizumab treatment. The anti-CNTN4 antibody GENA-104A16 is under the IND submission stage for clinical studies. Citation Format: Mi Young Cha, Gihyeon Kim, Changho Park, Bu-Nam Jeon, Kyung Mi Park, Hansoo Park, Chan-Young Ock. Association between the CNTN4 expression and responsiveness to pembrolizumab in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7522.
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Lee, Jieun, Sunguk Shin, Seung-been Lee, Yieri Yoo, Sangjun Lee, So Hyun Kang, Eunju Lee, et al. "Abstract 6135: Microbiome profiling through the various gastrointestinal environment of gastric cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6135. http://dx.doi.org/10.1158/1538-7445.am2022-6135.
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Abstract The association between cancer and microbiome dysbiosis across anatomically related multiple body sites has not been comprehensively investigated. The purpose of our study is to profile microbial diversity and composition through the various gastrointestinal environment of gastric cancer (GC). We performed V3-V4 16S rRNA gene sequencing analysis for matched samples of gastric tumor, normal gastric mucosa, gastric juice and stool from 30 GC patients. Amplicon sequence variant (ASV) profile was compared among the four body sites at genus level. In this study, we found that mean alpha diversity was lowest in normal gastric mucosa and stool exhibited the largest amount of alpha diversity compared with others. Beta-diversity analysis showed significant differences in microbiota composition for each sample. The microbiome dysbiosis was significantly independent in gastrointestinal environment of gastric cancer. Helicobacter abundance in tumor tissue was significantly lower than in matched normal tissue and gastric juice while the trend was opposite for Lactobacillus. Additionally, the level of Helicobacter was considerably lower in patients with lymphatic invasion. The bacterial community that significantly correlated with tumor samples compared to normal mucosa, gastric juice, and stool were 49, 27, and 11 genus, respectively. Lactobacillus and Delftia had higher abundance and Rothia and Collnsella had lower abundance in tumor tissue compare with normal mucosa. Especially, Delftia was seen only in the tumor tissue not normal gastric mucosa, gastric juice and stool. Pentose phosphate pathway was significantly enriched in tumor tissue and normal mucosa. There is a unique microbiome pattern through the various gastrointestinal environment of gastric cancer. Our analysis shows enriched Delftia abundance only in the tumor tissue except other sample type. Citation Format: Jieun Lee, Sunguk Shin, Seung-been Lee, Yieri Yoo, Sangjun Lee, So Hyun Kang, Eunju Lee, Young Suk Park, Sang-Hoon Ahn, Kyoung Un Park, Hyung-Ho Kim, Nak Jung Kwon, Yun-Suhk Suh. Microbiome profiling through the various gastrointestinal environment of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6135.
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Choi, Ji Won, Kwangsung Ahn, Sangsoo Kim, Dong-Il Park, and Soo-kyung Park. "Abstract 6253: RNA-seq based somatic variant calling and gene expression analysis reveals tumor heterogeneity and metastatic potential in colorectal cancers." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6253. http://dx.doi.org/10.1158/1538-7445.am2022-6253.
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Abstract Colorectal cancer (CRC) is the third common malignant tumor and the second most responsible for worldwide cancer deaths. Also, RNAseq technology has been used for two purposes: to find exonic regions on the genome and quantify the expression level of the gene. We tried to validate the pipeline for identifying somatic variants from RNA-seq data, mainly following GATK4 somatic calling pipelines with some optimizing modifications. It is intended to examine whether somatic mutations driven from RNAseq data are associated with the biological behaviors of the individual colorectal cancer cells. We found that key genes (i.e., tumor suppressor genes such as APC and p53) are mostly mutated by T to C (in the non-coding region) or C to T (in the coding region) transitions, so that causes missense and nonsense mutations. However, highly mutated genes did not show significant expressional changes compared to the normal tissue. Otherwise, genes related to the metastatic potentials were observed to have highly increased expression. Our results can substantially verify the reliability of the somatic mutation calling approach using RNAseq data to call cancer-driving mutation and confirm an increase of extracellular matrix metabolism in the CRC. Citation Format: Ji Won Choi, Kwangsung Ahn, Sangsoo Kim, Dong-Il Park, Soo-kyung Park. RNA-seq based somatic variant calling and gene expression analysis reveals tumor heterogeneity and metastatic potential in colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6253.
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Park, Jong Hoon, Jee Won Park, Yesol Kim, Jaehee Jun, and Yejin Ahn. "Abstract 5826: Autophagy regulates cancer stem cell properties in triple negative breast cancer via miR-181a-mediated regulation of ATG5/ATG2B." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5826. http://dx.doi.org/10.1158/1538-7445.am2022-5826.
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Abstract Autophagy has a dual role in the maintenance of cancer stem cells (CSCs), but the precise relationship between autophagy and cancer stemness requires further investigation. In this study, it was found that luminal and triple-negative breast cancer require distinct therapeutic approaches because of their different expressions of autophagy flux. We identified that autophagy flux was inhibited in triple-negative breast cancer (TNBC) CSCs. Moreover, miRNA-181a (miR-181a) is upregulated both in TNBC CSCs and patients. ATG5 and ATG2B participate in the early formation of autophagosomes and were revealed as targets of miR-181a. Inhibition of miR-181a expression led to attenuation of TNBC cancer stemness and an increase in autophagy flux. Furthermore, treatment with curcumin led to attenuation of cancer stemness in TNBC CSCs; the expression of ATG5 and ATG2B was enhanced and there was an increase of autophagy flux. These results indicated that ATG5 and ATG2B are involved in the suppression of cancer stemness in TNBC. In summary, autophagy inhibits cancer stemness through the miR-181a-regulated mechanism in TNBC. Promoting tumor-suppressive autophagy using curcumin may be a potential method for the treatment of TNBC. Citation Format: Jong Hoon Park, Jee Won Park, Yesol Kim, Jaehee Jun, Yejin Ahn. Autophagy regulates cancer stem cell properties in triple negative breast cancer via miR-181a-mediated regulation of ATG5/ATG2B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5826.
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Park, Tae Jun, Seok Yun Kang, Jang Hee Kim, Hyun Woo Lee, Yong Won Choi, Soon Sang Park, and Young-Kyoung Lee. "Abstract 6801: Cellular senescence involves spatial evolution in colorectal cancer." Cancer Research 84, no. 6_Supplement (March 22, 2024): 6801. http://dx.doi.org/10.1158/1538-7445.am2024-6801.
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Abstract Cancer evolution is a continuous process involving cellular changes that promote progression and metastasis. Recent studies demonstrate that cancer evolution is spatially associated: a phenomenon called “the spatial evolution of cancer.” In our data, colorectal cancer cells gradually evolve from an adenoid to a collective invasion morphology, ultimately developing a partial epithelial-mesenchymal transition phenotype as they form an invasive front. Trajectory analysis showed that cancer cells at the invasive front of a tumor exhibit a totally different gene expression pattern from those at the center, and that cellular senescence plays a crucial role in this transition. Epigenetic changes in the promoter/exon1 region of the CDKN2A gene caused by increased reactive oxygen species level are crucial for expression of p16INK4A and induction of senescence in the cancer cells. Two types of senescent tumor cells (type I and type II) were observed, and they played different roles in cancer progression due to different gene expression. Type II senescent tumor cells (p16INK4A+/LAMC2+/MMP7+), a final evolved form of cancer cells, are strongly associated with local invasion and lymph node metastasis of colorectal cancer and worsen the prognosis for patients. Citation Format: Tae Jun Park, Seok Yun Kang, Jang Hee Kim, Hyun Woo Lee, Yong Won Choi, Soon Sang Park, Young-Kyoung Lee. Cellular senescence involves spatial evolution in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6801.
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Lee, Sieun, Jihye Park, Eun Ju Kim, Seongran Cho, Sungsoo Park, Jonathan M. Kurie, and Young-Ho Ahn. "Abstract 4265: ZEB1-regulated hyaluronan network in the lung tumor microenvironment." Cancer Research 84, no. 6_Supplement (March 22, 2024): 4265. http://dx.doi.org/10.1158/1538-7445.am2024-4265.
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Abstract In the tumor microenvironment, hyaluronan surrounds neighboring cells as one of the major components of the extracellular matrix and stimulates the epithelial-mesenchymal transition (EMT) of various epithelial cancer cells. However, the mechanism of how the hyaluronic network is formed by cancer cells and regulates cancer progression and metastasis has not been known in detail. Therefore, we investigated the role of the hyaluronan network built-up by cancer cells in regulating cancer progression and metastasis in the tumor microenvironment. Our study demonstrated that ZEB1, an EMT-inducing transcription factor, reconstructs the hyaluronan network to induce the expression of ITIH2, a hyaluronan-binding protein, and hyaluronic acid synthase-2 (HAS2), ZEB1 was also shown to control the isoform switching of CD44, a hyaluronan receptor. ITIH2 knockdown and HAS inhibition reduced the formation of hyaluronan cables and inhibited cancer cell migration and invasion. In addition, the treatment of a specific ITIH2 inhibitor identified through deep learning-based screening suppressed the formation of hyaluronan cables, cell migration, and metastasis. These findings suggest that targeting the hyaluronan network could be a novel strategy for suppressing lung cancer progression and metastasis in the tumor microenvironment. Citation Format: Sieun Lee, Jihye Park, Eun Ju Kim, Seongran Cho, Sungsoo Park, Jonathan M Kurie, Young-Ho Ahn. ZEB1-regulated hyaluronan network in the lung tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4265.
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Ko, Dongmi, Juyeon Seo, Seongjae Kim, Soeun Park, Minsu Park, Kee Dal Nam, Yong koo Kang, et al. "Abstract 5800: Anti-metastatic potential of pitavastatin in triple-negative breast cancer via targeting breast cancer stem-like properties and STAT3 signaling." Cancer Research 83, no. 7_Supplement (April 4, 2023): 5800. http://dx.doi.org/10.1158/1538-7445.am2023-5800.
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Abstract Triple-negative breast cancer (TNBC) is the most deadly and aggressive phenotype, with a higher rate of metastatic recurrence. TNBC does yet have a suitable treatment option other than cytotoxic anticancer drugs. Although pitavastatin has been shown to exert anti-proliferative effects and cytotoxicity in various types of cancer cells, the precise mechanisms underlying pitavastatin’s anti-cancer effects in TNBC have not been fully elucidated. We sought to investigate the mechanism of pitavastatin-induced apoptosis and its effects on cancer stem cell (CSC)-like characteristics in TNBC. Exposure to pitavastatin induced mitochondria-mediated apoptotic cell death in BT549 and 4T1 cells. Mitochondrial dysfunction was accompanied with a robust production of reactive oxygen species (ROS) and collapse of mitochondrial membrane potential (MMP), resulting in subsequent activation of caspase-3/-7 and PARP cleavage. Pitavastatin effectively suppressed CSC-like properties in TNBC via targeting CD44+/CD24- and CD49f+/CD24- phenotypes, as well as impediment of mammosphere formation in vitro. This phenomenon was accompanied with dysregulation of STAT3 survival pathway, concomitant with significant downregulation of cyclin D1, survivin and vimentin. Pitavastatin effectively targets both the proliferating TNBC tumor cells and CSCs via the dysregulation of STAT3 and suppression of CSC-like properties, markedly reducing angiogenesis and tumor growth, coinciding with decreased Ki-67 expression. It is noteworthy that pitavastatin considerably suppressed metastasis, coinciding with significant reduction of MMP-2, MMP-9 and VEGF in the circulating blood of mice. Our findings highlight that pitavastatin may be potentially effective for the treatment of metastatic TNBC. Citation Format: Dongmi Ko, Juyeon Seo, Seongjae Kim, Soeun Park, Minsu Park, Kee Dal Nam, Yong koo Kang, Sora Seock, Eunsun Jung, Yoon-Jae Kim, Jaeyoun Park, Ji Young Kim, Jae Hong Seo. Anti-metastatic potential of pitavastatin in triple-negative breast cancer via targeting breast cancer stem-like properties and STAT3 signaling. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5800.
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Cha, Mi Young, Hyunuk Kim, Seungmin Byun, Youngeun Ha, Kitae Park, Hyunkyung Yu, Bu-Nam Jeon, et al. "Abstract 740: CNTN4 as a novel target for solid cancer with antibody-drug conjugate." Cancer Research 84, no. 6_Supplement (March 22, 2024): 740. http://dx.doi.org/10.1158/1538-7445.am2024-740.
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Abstract As a novel immune checkpoint, we previously confirmed that contactin 4 (CNTN4) regulates T cell activity negatively by binding to amyloid precursor protein (APP) on T cells. CNTN4 is highly expressed in various types of tumors, including gallbladder, pancreas, stomach, endometrium, liver, prostate, bladder cancer, melanoma, and other tumors, with positive rates over 70% through immunohistochemistry analysis in contrast to low-level expression in normal tissues. Based on the tumor-specific expression profile of CNTN4, we evaluated the potential of CNTN4 as a novel target for antibody-drug conjugate (ADC). First, the internalization of the anti-CNTN4 antibody in the IND submission stage, GENA-104A16, into CNTN4-positive cancer cells was confirmed. For investigation of the potential of targeting CNTN4 using ADC, clinically validated various linker-payloads (MMAE, MMAF, SN-38, and exatecan derivate) were conjugated to GENA-104A16 using thiol maleimide conjugation with average drug-to-antibody ratio (DAR) in the range of 4.0 to 4.8. After preparing ADCs, we confirmed the binding affinity for CNTN4 was maintained as high even after the payload conjugation through an ELISA. In vitro studies have demonstrated the highly cytotoxic effect of MMAF conjugate among the conjugates of GENA-104A16 on CNTN4-positive cancer cells compared to negative cancer cells. And there was no cytotoxic effect on normal cells. Furthermore, treating MMAF conjugate of GENA-104A16 showed promising efficacy in the Pan02 pancreatic orthotopic mouse model and the patient-derived xenograft model. These results suggest that CNTN4 could be a highly potential ADC target that could expand the options for cancer treatment strategies. Citation Format: Mi Young Cha, Hyunuk Kim, Seungmin Byun, Youngeun Ha, Kitae Park, Hyunkyung Yu, Bu-Nam Jeon, Mira Kim, Soojung Moon, Kyung Mi Park, Hansoo Park. CNTN4 as a novel target for solid cancer with antibody-drug conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 740.
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Tonelli, Claudia, Georgi N. Yordanov, Yuan Hao, Astrid Deschênes, Erin Brosnan, Abishek Doshi, Youngkyu Park, Jonathan Preall, and David A. Tuveson. "Abstract 6081: The transcription factor SPDEF promotes the survival of mucinous pancreatic ductal adenocarcinoma of the classical subtype." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6081. http://dx.doi.org/10.1158/1538-7445.am2022-6081.
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Abstract Pancreatic ductal adenocarcinoma (PDA) is characterized by intra-tumoral heterogeneity. Using single-cell RNA sequencing, we reveal multiple tumor subpopulations distinguished by their differentiation state and associated with different stages of tumor progression. We identify SPDEF as a factor required for tumorigenesis in pancreatic cancer cells of epithelial and mucinous nature. SPDEF levels correlate with glandular differentiation and high secretory activity, which are characteristic features of human PDA of the classical subtype. SPDEF can drive mucus production in pancreatic cancer cells and is essential for the growth of mucus-secreting tumors by regulating endoplasmic reticulum (ER) activity. These findings offer insights into the factors controlling differentiation in PDA and may inform new therapeutic strategies with improved efficacy. Citation Format: Claudia Tonelli, Georgi N. Yordanov, Yuan Hao, Astrid Deschênes, Erin Brosnan, Abishek Doshi, Youngkyu Park, Jonathan Preall, David A. Tuveson. The transcription factor SPDEF promotes the survival of mucinous pancreatic ductal adenocarcinoma of the classical subtype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6081.
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Miranda, Adam X., Emily Hodges, and Ben Ho Park. "Abstract 3726: Functional genomic dissection of PIK3CA hotspot mutations using a multi-lineage isogenic breast cell model." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3726. http://dx.doi.org/10.1158/1538-7445.am2022-3726.
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Abstract PIK3CA is the most commonly mutated gene in breast cancer, and in breast cancer there are two hotspot mutations that represent an outsized proportion of PIK3CA mutations. Previous research suggests that there are distinct prognostic and cell signaling differences induced by these mutational isoforms, however there is currently only one targeted treatment approved for PIK3CA mutant breast cancer. The goal of our research is to leverage a comprehensive multi-lineage isogenic breast cell line model to further interrogate the unique effects of these PIK3CA mutations on breast cells using assays to assess gene expression and chromatin state. Insights gained from these assays shed light on disrupted pathways that may prove to be new targets for PIK3CA mutation-specific treatment of breast cancer. Citation Format: Adam X. Miranda, Emily Hodges, Ben Ho Park. Functional genomic dissection of PIK3CA hotspot mutations using a multi-lineage isogenic breast cell model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3726.
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Zhang, Shengzhe, Kee-Bum Kim, Yuanjian Huang, Dong-Wook Kim, Bongjun Kim, Kyung-Pil Ko, Gengyi Zou, et al. "Abstract 1714: CRACD/KIAA1211 loss drives cell plasticity and immune evasion of small cell lung cancer." Cancer Research 83, no. 7_Supplement (April 4, 2023): 1714. http://dx.doi.org/10.1158/1538-7445.am2023-1714.
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Abstract Small cell lung carcinoma (SCLC) is a lethal neuroendocrine type of lung cancer with limited therapeutic options. Despite recent advances in cancer immunotherapy, its efficacy is limited to a small subset of SCLC patient tumors. The molecular origin of the refractoriness to immunotherapy remains elusive. CRACD (Capping protein inhibiting regulator of actin dynamics; KIAA1211/CRAD) gene is frequently mutated and transcriptionally downregulated in SCLC. Cracd knockout (KO) causes the transformation of preneoplastic neuroendocrine cells and significantly accelerates SCLC development in a mouse model initiated by the loss of Rb1, Trp53, and Rbl2 in the lung epithelium. Cracd KO induces tumor cell plasticity generating deregulated cell lineage trajectories of SCLC tumors. Strikingly, Cracd KO SCLC tumors display the complete loss of CD8+ T cells due to epigenetic suppression of the MHC-I pathway. Furthermore, single-cell transcriptomic analyses of SCLC patient samples classified SCLC by concurrent features: CRACD inactivation and tumor antigen presentation impairment. This study suggests CRACD as a tumor suppressor of SCLC that regulates proliferation and immune recognition of cells, providing novel insight into the mechanism of SCLC evading immune surveillance. Citation Format: Shengzhe Zhang, Kee-Bum Kim, Yuanjian Huang, Dong-Wook Kim, Bongjun Kim, Kyung-Pil Ko, Gengyi Zou, Jie Zhang, Sohee Jun, Nicole A. Kirk, Ye Eun Hwang, Young Ho Ban, Joseph M. Chan, Charles M. Rudin, Kwon-Sik Park, Jae-Il Park. CRACD/KIAA1211 loss drives cell plasticity and immune evasion of small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1714.
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Berglund, Anders, Kosj Yamoah, Carlos Diaz Osterman, Julie Dutil, Jaime Matta, Gilberto Ruiz-Deya, Liang Wang, et al. "Abstract 1896: Dysregulation of DNA methylation in prostate cancer among African American men." Cancer Research 83, no. 7_Supplement (April 4, 2023): 1896. http://dx.doi.org/10.1158/1538-7445.am2023-1896.
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Abstract Men of African ancestry have the higher incidence and mortality rates of prostate cancer (PCa) worldwide. These health disparities may be contributed by environmental or biological factors, such as epigenomics. Differential DNA methylation can influence carcinogenesis and disease progression. Indeed, the most common molecular event in PCa is dysregulation of DNA methylation. Among these epigenetic changes, some specific changes may be associated with poor outcomes. Numerous studies reported that differential DNA methylation influences the likelihood of developing PCa and affects its progression. However, most studies were based on European American patients. There is a need to investigate methylation profiles to evaluate potential African American-specific methylated genes, since differential DNA methylation may influence health disparities in PCa. This study aimed to investigate differentially DNA methylated genes between tumor vs. adjacent normal, and aggressive vs. indolent PCa (based on Gleason Score) in 120 African American patients from Florida. Genomic DNA samples were extracted by macro-dissection from FFPE. DNA methylation patterns were assessed using the human Illumina Infinium Methylation EPIC array. We identified 5,097 differentially methylated CpG-sites (q<0.01, lΔβl > 0.2) A few representative differentially methylated regions (DMRs) include immune genes, such as CD40, OX40L, Galectin 3, and STING, in prostate tumor tissues as compared with normal tissues. There was also a clear global increase of methylation level in the tumor samples compared to the normal tissues. Regarding PCa aggressiveness, 6,775 (Hypo:4,252, and Hyper: 2,523) differentially methylated CpG-sites (q<0.05, lΔβl > 0.1) were identified when two groups GG1 (Gleason score 6) vs GG4/5 (Gleason score 8≤) were compared. Among these 6,775 CpG-sites, many CpG-probes are consistently significant in more than one comparison. For example, 1,182 hyper and 1,660 hypo-methylation sites were identified in the comparison between GG1 and GG2/3 (Gleason score 7), while 362 hyper- and 1,640 hypo-methylation sites were found in the GG2/3 vs GG4/5 comparison. A small fraction of probes (51 hyper and 155 hypomethylated probes) was consistently found in all comparisons. These genes, MMP16, CDH13, CCND2, and SEPT9, were previously reported to have a role in PCa progression. This study identified several differentially methylated genes, associated with risk or aggressiveness. Most of these changes appear to overlap in different comparisons, thus GG1 vs. GG2/3 or GG2/3 vs. GG4/5 comparison. Many differentially methylated genes identified here have previously been associated with PCa risk or tumor aggressiveness. These results will shed light on potential mechanisms contributing to PCa disparities in African American population. Citation Format: Anders Berglund, Kosj Yamoah, Carlos Diaz Osterman, Julie Dutil, Jaime Matta, Gilberto Ruiz-Deya, Liang Wang, Hyun Park, Tamara Lotan, Ryan Putney, Sungjune Kim, Seung Joon Kim, Clement Gwede, Rana Falahat, James Mule, Youngchul Kim, Ratna Chakrabarti, Jong Y. Park. Dysregulation of DNA methylation in prostate cancer among African American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1896.
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Hebert-DeRouen, Mindy C., Li Tao, Salma Shariff-Marco, Juan Yan, Yurii B. Shvetsov, Song-Yi Park, Cheryl L. Albright, et al. "Abstract LB159: Neighborhood obesogenic environment and risk of prostate cancer: The Multiethnic Cohort." Cancer Research 82, no. 12_Supplement (June 15, 2022): LB159. http://dx.doi.org/10.1158/1538-7445.am2022-lb159.
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Abstract Background: Obesity is associated with risk of aggressive prostate cancer. It is not known whether neighborhood obesogenic factors are associated with prostate cancer risk. Methods: Neighborhood socioeconomic status (nSES) and four neighborhood obesogenic environment factors (urbanicity, mixed-land development, unhealthy food environment, and parks) were assessed for associations with prostate cancer risk among 41,563 African American, European American, Japanese American, and Latino males in the Multiethnic Cohort Study (MEC), California site. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for non-aggressive and aggressive prostate cancer, adjusting for individual-level sociodemographic, behavioral, and prostate cancer risk factors. Analyses were stratified by race, ethnicity, and, among Latino males, nativity. Results: Males residing in low SES, compared to high SES, neighborhoods had lower risk of non-aggressive prostate cancer (lowest vs. highest quintile HR=0.81; 95% CI=0.68, 0.95, p-trend 0.024); driven by a similar trend among U.S.-born and foreign-born Latino males. Foreign-born Latino males in neighborhoods with low mixed-land development had increased risk (lowest vs. highest quintile HR=1.52; 95% CI=1.09, 2.12). African American males in neighborhoods with more unhealthy food environments had increased risk of aggressive disease (more vs. none, HR=1.35; 95% CI=1.02, 1.77). Conclusions: Neighborhood SES and obesogenic factors were independently associated with prostate cancer risk; associations varied by race, ethnicity, nativity, and disease aggressiveness. Impact: Upstream structural and social determinants of health that contribute to neighborhood obesogenic characteristics likely impact prostate cancer risk differently across groups defined by race, ethnicity, and nativity and by disease aggressiveness. Citation Format: Mindy C. Hebert-DeRouen, Li Tao, Salma Shariff-Marco, Juan Yan, Yurii B. Shvetsov, Song-Yi Park, Cheryl L. Albright, Kristine Monroe, Loic Le Marchand, Lynne Wilkens, Scarlett L. Gomez, Iona Cheng. Neighborhood obesogenic environment and risk of prostate cancer: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB159.
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Chou, Alisha, Fei Chen, Peggy Wan, Xin Sheng, Song-Yi Park, Daniel O. Stram, Lynne R. Wilkens, Loic Le Marchand, and Christopher A. Haiman. "Abstract C102: Interactions of a polygenic risk score and modifiable lifestyle factors for breast cancer in the Multiethnic Cohort." Cancer Epidemiology, Biomarkers & Prevention 32, no. 1_Supplement (January 1, 2023): C102. http://dx.doi.org/10.1158/1538-7755.disp22-c102.
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Abstract Purpose: A polygenic risk score (PRS) has demonstrated great potential in stratifying breast cancer risk in non-African ancestry populations. Several modifiable lifestyle risk factors have been identified for breast cancer, although little is known regarding their effects among women with varying genetic risk. Methods: In the Multiethnic Cohort (MEC), we conducted a nested case-control study of 3,229 breast cancer cases and 3,921 controls from five major racial/ethnic groups (White, African American, Latino, Japanese American, and Native Hawaiian). We examined a PRS of 313 variants in association with breast cancer risk and evaluated the interaction with selected modifiable lifestyle factors on the risk of breast cancer. The modifiable lifestyle factors examined included body mass index (BMI), physical activity, smoking, alcohol consumption, and five diet quality indexes, such as the Healthy Eating Index (HEI)-2010, the Alternative Healthy Eating Index (AHEI)-2010, the alternate Mediterranean Diet score (aMED), the Dietary Approaches to Stop Hypertension score (DASH), and the Dietary Inflammatory Index (DII). Results: The 313-variant PRS was strongly associated with breast cancer risk across the five racial/ethnic groups, with per standard deviation (SD) odds ratios (OR) of 2.07 (95% CI=1.63-2.63) in Native Hawaiian, 1.72 (95% CI=1.54-1.92) in White, 1.56 (95% CI=1.36-1.77) in Latina, 1.45 (95% CI=1.31-1.60) in Japanese American, and 1.32 (95% CI=1.20-1.44) in African American women. For the lifestyle factors, BMI (OR=0.84, 95% CI=0.75-0.93, for <25 vs. ≥ 25 kg/m2) and alcohol consumption (OR=1.14, 95% CI=1.02-1.26 for drinkers vs. non-drinkers) were significantly associated with breast cancer risk. We also observed a suggestive positive association for smoking (OR=1.14, 95% CI=0.98-1.32 for current vs. never/past smokers) and a suggestive inverse association for AHEI-2010 (OR=0.96, 95%CI=0.91-1.01 per SD increment). No association was observed for physical activity or other dietary indexes. We found that the association of BMI and AHEI-2010 with breast cancer risk depended on PRS. Specifically, among women with above-average genetic risk (50-100% of PRS), the OR of breast cancer was 0.77 (95% CI=0.66-0.88) for women with a BMI <25 kg/m2 (vs. BMI³25 kg/m2), while among women with below-average genetic risk (0-50% of PRS) the OR was 0.96 (95%CI=0.81-1.14, P-heterogeneity=0.04). In contrast, a significant inverse association of AHEI-2010 (per SD) with breast cancer risk was only observed in women with below-average genetic risk (OR=0.90, 95%=0.83-0.97) but not among women with above-average genetic risk (OR=1.00, 95%CI=0.94-1.08, P-heterogeneity=0.04). Conclusions: In line with previous reports, the 313-variant PRS was effective in stratifying breast cancer risk, with diminished transferability for women of African ancestry. Our findings also suggest that maintaining a healthy BMI may offset the genetic risk of breast cancer, while adhering to a healthy dietary pattern may further reduce risk for women with lower genetic risk. Citation Format: Alisha Chou, Fei Chen, Peggy Wan, Xin Sheng, Song-Yi Park, Daniel O. Stram, Lynne R. Wilkens, Loic Le Marchand, Christopher A. Haiman. Interactions of a polygenic risk score and modifiable lifestyle factors for breast cancer in the Multiethnic Cohort [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C102.
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Piao, Xuan-Mei, Young Joon Byun, Chuang-Ming Zheng, Seon-Kyu Kim, Seong-Hwan Park, Kyungchan Min, Hansoo Park, et al. "Abstract 7648: COL6A1 expression as a potential prognostic biomarker for risk stratification of T1HG bladder cancer: Unveiling the aggressive nature of a distinct non-muscle invasive subtype." Cancer Research 84, no. 6_Supplement (March 22, 2024): 7648. http://dx.doi.org/10.1158/1538-7445.am2024-7648.
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Abstract Introduction and Objectives: T1 high grade (T1HG) bladder cancer (BC) is a type of non-muscle invasive BC (NMIBC) that is recognized as an aggressive subtype with a heightened propensity for progression. Current risk stratification methods for NMIBC rely on clinicopathological indicators; however, these approaches do not adequately capture the aggressive nature of T1HG BC. Thus, new, more accurate biomarkers for T1HG risk stratification are needed. Here, we enrolled three different patient cohorts and investigated expression of COL6A1, a key component of the extracellular matrix, at different stages and grades of BC, with a specific focus on T1HG BC. Materials and Methods: Samples from 298 BC patients were subjected to RNA sequencing and real-time PCR. Results: We found that T1HG BC and muscle invasive BC (MIBC) exhibited comparable expression of COL6A1, which was significantly higher than that by other NMIBC subtypes. In particular, T1HG patients who later progressed to MIBC had considerably higher expression of COL6A1 than Ta, T1 low-grade patients, and patients that did not progress, highlighting the aggressive nature and higher risk of progression associated with T1HG BC. Moreover, Cox and Kaplan-Meier survival analyses revealed a significant association between elevated expression of COL6A1 and poor progression-free survival of T1HG BC patients (multivariate Cox hazard ratio, 16.812; 95% confidence interval, 3.283-86.095; P=0.001 and P=0.0002 [log-rank test]). Conclusion: These findings suggest that COL6A1 may be a promising biomarker for risk stratification of T1HG BC, offering valuable insight into disease prognosis and guidance of personalized treatment decisions. Citation Format: Xuan-Mei Piao, Young Joon Byun, Chuang-Ming Zheng, Seon-Kyu Kim, Seong-Hwan Park, Kyungchan Min, Hansoo Park, Sungmin Moon, Kyeong Kim, Ho Won Kang, Won Tae Kim, Seok Joong Yun. COL6A1 expression as a potential prognostic biomarker for risk stratification of T1HG bladder cancer: Unveiling the aggressive nature of a distinct non-muscle invasive subtype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7648.
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Shin, Dong Wook, Wonyoung Jung, In Young Cho, Jinhyung Jung, Mihee Cho, Hye Yeon Koo, Be-Long Cho, et al. "Abstract 6291: Changes in physical activity and ischemic stroke risk after cancer diagnosis: A nationwide cohort study." Cancer Research 84, no. 6_Supplement (March 22, 2024): 6291. http://dx.doi.org/10.1158/1538-7445.am2024-6291.
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Abstract Background: Physical inactivity is prevalent after cancer treatment, which may pose a greater risk of ischemic stroke in cancer survivors. Objective: To investigate the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. Methods: Cancer survivors without prior history of cardiovascular disease were identified. Pre- and Post-adherence to physical activity was determined within two years from cancer diagnosis. The primary outcome was incident ischemic stroke. Using the Fine-Gray model, sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. Results: Among 269,943 cancer survivors (mean [SD] age 56.3 [12.1] years, 45.7% male), 10.1% remained active, 11.4% became inactive, and 16.6% became active post-diagnosis. During 1,109,566.68 person-years[YMP1] , remaining active both pre- and post-diagnosis was associated with 15% decreased risk of ischemic stroke (sHR 0.85, 95% CI 0.75-0.96), compared to those who remained inactive. Cancer survivors who became active, and inactive post-diagnosis showed a 16%, and 11% lower risk of ischemic stroke (sHR 0.84, 95% CI 0.75-0.93; sHR 0.89, 95% CI 0.79-0.99) than those who remained inactive. Conclusions: Our findings suggest that staying physically active is associated with a reduced risk of ischemic stroke among cancer survivors. Notably, these advantages are not limited to individuals who were physically active before their diagnosis, and it is not too late to start post-diagnosis. Preventive strategies against ischemic stroke in cancer survivors should emphasize the incorporation of regular physical activity at any stage of their cancer journey. Citation Format: Dong Wook Shin, Wonyoung Jung, In Young Cho, Jinhyung Jung, Mihee Cho, Hye Yeon Koo, Be-Long Cho, Jin Ho Park, Hyuk Tae Kwon, Kyungdo Han, Yong-Moon Mark Park. Changes in physical activity and ischemic stroke risk after cancer diagnosis: A nationwide cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6291.
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Jung, Wonyoung, Yong-Moon Mark Park, Sang Hyun Park, Kyungdo Han, Junhee Park, Yohwan Yeo, Jung Kwon Lee, Dale P. Sandler, and Dong Wook Shin. "Abstract 4175: Development of breast cancer risk assessment tool: The Korean decision aid for cancer screening (K-DACS) study." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4175. http://dx.doi.org/10.1158/1538-7445.am2023-4175.
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Abstract Purpose: Widely used breast cancer risk prediction tools are based on data from Western countries, but risk factors may differ for Asian women. Hence, we aimed to develop a risk assessment tool for breast cancer in Asian women, using a nationwide, population-based cohort in Korea. Methods: Women aged ≥ 40 years who participated in both breast cancer screening and general health examination in 2009 were eligible for this study. Age, body mass index (BMI), breast density, lifestyle and reproductive factors, and comorbidities were used to develop 5-year breast cancer risk prediction models in premenopausal (n=771,856) and postmenopausal (n=1,108,047) women at baseline. Backward stepwise selection in the Cox proportional hazards model was used to construct the best-fit risk prediction model, which was then converted into a risk score nomogram, representing an individual probability estimate of incident breast cancer. Model performance was evaluated by discrimination and calibration. Results: Among premenopausal women, high BMI, low parity, short breastfeeding period, early age at menarche, high breast density, history of benign breast mass, and family history of breast cancer contributed to breast cancer risk prediction. The appropriate predictors in postmenopausal women additionally included age, type 2 diabetes, dyslipidemia, late age at menopause, hormone replacement therapy use, except for number of parities. The concordant statistic of risk prediction model was 0.58 (95% confidence interval [CI] 0.57-0.59) for premenopausal women, and 0.64 (95% CI 0.63-0.65) for postmenopausal women. Our model correlated well in the calibration plot in both premenopausal and postmenopausal women.Conclusions: Our breast cancer risk prediction model showed good performance for postmenopausal women, providing the background for risk-based screening recommendations in Asian women. Citation Format: Wonyoung Jung, Yong-Moon Mark Park, Sang Hyun Park, Kyungdo Han, Junhee Park, Yohwan Yeo, Jung Kwon Lee, Dale P. Sandler, Dong Wook Shin. Development of breast cancer risk assessment tool: The Korean decision aid for cancer screening (K-DACS) study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4175.
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Park, Junsik, Yong Jae Lee, Sunghoon Kim, Seungmook Lim, A. Yeong Park, Jamie Jae Eun Kim, Jinhwa Lee, Sang Wun Kim, Su-Hyung Park, and Jung-Yun Lee. "Abstract 4029: HPK1 inhibitor reinvigorates exhausted tumor-infiltrating CD8 T cells and synergizes with anti-PD-1 blockade in gynecologic malignancies." Cancer Research 84, no. 6_Supplement (March 22, 2024): 4029. http://dx.doi.org/10.1158/1538-7445.am2024-4029.
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Abstract HPK1 (Hematopoietic Progenitor Kinase 1) is a negative intracellular immune checkpoint that interferes with the priming and activation of T cells. In recent years, several HPK1 inhibitors have been discovered as novel immune-oncology drugs with promising potential to improve anti-tumor immune responses. However, there has been no study showing the effects and potential application of HPK1 in gynecologic malignancies. Therefore, we investigated the expression and role of HPK1 in tumor-infiltrating CD8 T cells (CD8 TILs) and how the selective small molecule kinase inhibitor, FB849, affected the reinvigoration of exhausted CD8 TILs in gynecologic cancers. We isolated TILs from patients with newly diagnosed endometrial (n=53) and ovarian cancer (n=46). The immunological properties and HPK1 signaling pathway of CD8 TILs were explored using flow cytometry. TILs were in vitro stimulated with anti-CD3 in the presence of FB849 and/or anti-PD-1, and their proliferation was assessed. We observed that HPK1 marked severely exhausted PD-1+CD8 TILs, and high HPK1 expressers had more exhausted PD-1+CD8 TILs compared to low HPK1 expressers. In addition, FB849 could successfully restore the effector function of exhausted CD8 TILs. In particular, the reinvigorating capacity of FB849 was negatively correlated with phosphorylated SLP76+PD-1+CD8 TILs in endometrial cancer. In addition, FB849 further enhanced anti-PD-1-mediated reinvigoration of CD8 TILs in endometrial cancer. However, there was no synergistic effect of FB849 + anti-PD-1 in terms of proliferative capacity in ovarian cancer. Overall, the results of our present study provide a rationale for clinical trials investigating the anti-tumor efficacy of FB849 ± anti-PD-1 tailored to the respective properties of gynecologic malignancies. Citation Format: Junsik Park, Yong Jae Lee, Sunghoon Kim, Seungmook Lim, A Yeong Park, Jamie Jae Eun Kim, Jinhwa Lee, Sang Wun Kim, Su-Hyung Park, Jung-Yun Lee. HPK1 inhibitor reinvigorates exhausted tumor-infiltrating CD8 T cells and synergizes with anti-PD-1 blockade in gynecologic malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4029.
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Park, Hee Geon, Sung Hun Cho, Ha Yeon Park, Mi Gyoung Jo, Ji Hyun Park, Myeung Ryun Seo, Ji Hyun Kim, et al. "Abstract 4084: Potent anti-tumor activity of ABN202 (anti-EGFR antibody-interferon-beta mutein) through direct cytotoxicity and indirect immune activation against non-small cell lung cancer, regardless of EGFR mutation status." Cancer Research 84, no. 6_Supplement (March 22, 2024): 4084. http://dx.doi.org/10.1158/1538-7445.am2024-4084.
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Abstract Epidermal growth factor receptor (EGFR) is overexpressed or mutated in many patients with non-small cell lung cancer (NSCLC). Targeting EGFR mutation by tyrosine kinase inhibitors (TKIs) has significantly improved overall survival (OS) in patients with EGFR mutations. However, many patients experience tumor recurrence due to various resistance mechanisms. Therefore, there is an unmet medical need for new treatment strategies for patients with EGFR-positive NSCLC, regardless of EGFR mutation status. ABN202 is an antibody-cytokine fusion protein (ACFP) that serves as a platform technology compromising the IFN-β mutein (ABN102) fused to various antibodies for specific tumor targeting. In a previous study, we designed ABN202 (αEGFR) to comprise an EGFR targeting antibody (Cetuximab) and IFN-β mutein (ABN102) and we confirmed anti-cancer activities of ABN202 against EGFR-positive NSCLC. In this study, the direct cytotoxicity of ABN202 (αEGFR) was evaluated in human NSCLC cell lines with various driving mutations and EGFR expression levels. The indirect immune activation was tested in human peripheral blood mononuclear cells (PBMCs) and human IFNAR1/2 knock-in (KI) mice. The in vivo efficacy was evaluated in human NSCLC xenograft mouse models and human IFNAR1/2 KI mouse models. ABN202 (αEGFR) demonstrates potent anti-tumor activity through direct cytotoxicity and indirect immune activation in NSCLC, regardless of EGFR mutation status. Taken together, we suggest that ABN202 (αEGFR) is a promising drug candidate against NSCLC, regardless of EGFR mutation status. Citation Format: Hee Geon Park, Sung Hun Cho, Ha Yeon Park, Mi Gyoung Jo, Ji Hyun Park, Myeung Ryun Seo, Ji Hyun Kim, Sung Youl Hong, Kyoung Song, Chan Gyu Lee, Hae Min Jeong, Sae Hyung Lee, Na Young Kim, Jun Young Choi, Young Kee Shin. Potent anti-tumor activity of ABN202 (anti-EGFR antibody-interferon-beta mutein) through direct cytotoxicity and indirect immune activation against non-small cell lung cancer, regardless of EGFR mutation status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4084.
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Park, Ji Min, and Ching-Feng Chiu. "Abstract 6378: The cross-talk between FTH1 and PYCR1 drives pancreatic cancer progression." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6378. http://dx.doi.org/10.1158/1538-7445.am2022-6378.
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Abstract This study is designed to explore the effect of FTH1 on PDAC human pancreatic cancer cells, proline metabolism, and their crosstalk. Considering the high prevalence of pancreatic cancer with an absence of efficient therapy against PDAC, the present study may provide experimental evidence in support of the novel role of FTH1 in proline metabolism and suggest FTH1 as a potential target for PDAC patients. We further focus on the underlying molecular mechanism of how FTH1 cross-talks with PYCR1 and leads KRAS-mutated PDAC cell growth, investigating whether miRNAs regulation involves in FTH1 mediating PYCR1 expression. Taken together, our study provides a novel function of FTH1 and its cross-talk with PYCR1 may be a novel target for pancreatic cancer research and thus these findings will help us to find metabolite-based therapeutic strategies to improve KRAS-mutated PDAC. Citation Format: Ji Min Park, Ching-Feng Chiu. The cross-talk between FTH1 and PYCR1 drives pancreatic cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6378.
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Acuna, Nicholas, Song-Yi Park, Anna H. Wu, Lynne R. Wilkens, and V. Wendy Setiawan. "Abstract 737: Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort." Cancer Research 82, no. 12_Supplement (June 15, 2022): 737. http://dx.doi.org/10.1158/1538-7445.am2022-737.
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Abstract Background: Certain diet components (i.e. low intake of fruit/vegetables and high intake of salt and processed meats) have been associated with risk of gastric cancer. However, it is unclear whether overall diet quality assessed by pre-defined indices, that take into account the complexity of dietary intake, is associated with gastric cardia and distal adenocarcinoma particularly in a racially and ethnically diverse population. Our objectives are to 1) examine the association of a variety of diet quality indices with risk of gastric cardia and distal adenocarcinoma and 2) assess if there are any subgroups that may benefit from better diets to reduce risk of gastric adenocarcinoma. Methods: The analysis included 176,752 men and women aged 45-75 from the Multiethnic Cohort (MEC), who were African American, Japanese American, Latino, Native Hawaiian, or White, and completed a quantitative food frequency questionnaire (QFFQ) at cohort entry. Incident cases of gastric cancer (cardia ICD-O-3 C16.0 and non-cardia adenocarcinoma C16.1-C16.6) were identified by linkages with the Surveillance, Epidemiology, and End Results (SEER) cancer registries. Dietary indices, Alternative Healthy Index-2010 (AHEI-2010), Healthy Eating Index-2015 (HEI-2015), Dietary Approach to Stop Hypertension (DASH) score, alternate Mediterranean Diet (aMED) score, and Dietary Inflammatory Index (DII®), were calculated from the QFFQ and categorized into quintiles. Multivariable Cox models were used to estimate the association between dietary indices and gastric cancer risk by anatomic site. Effect modification was assessed for distal cancer by sex, smoking status, and aspirin use. Results: A total of 207 incident cases of gastric cardia and 836 incident cases of gastric non-cardia were identified during an average follow up of 19.2 years. We did not observe any significant associations between any of the dietary indices and gastric cancer for both cardia and non-cardia tumors. However, we observed effect modification by aspirin use for aMED (P for heterogeneity = 0.01) as well as for DII (P for heterogeneity = 0.02). Among ever aspirin users, we observed an inverse association between aMED (HRQ5 vs Q1: 0.82, 95% CI: 0.53-1.26, Ptrend = 0.03) with non-cardia cancer, and the association with DII® was borderline statistically significant for the trend test (HRQ5 vs Q1: 0.86, 95% CI: 0.57-1.29, Ptrend = 0.07). Conclusion: In a multiethnic population, we did not observe overall significant associations between these dietary quality indices and risk of gastric cancer. However, among ever aspirin users there could be a reduction of gastric non-cardia adenocarcinoma risk with a higher adherence to a Mediterranean diet. Citation Format: Nicholas Acuna, Song-Yi Park, Anna H. Wu, Lynne R. Wilkens, V. Wendy Setiawan. Diet quality and risk of gastric adenocarcinoma: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 737.
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Lee, Kyung-Sik, Hye-Seong Park, Guk-Yeol Park, Gi-Chan Lee, Eun-Ji Choi, Jae-in Yu, Seung-Joo Yang, et al. "Abstract 6189: Development of an anti hepatocellular carcinoma CAR T strategy targeting PDL1." Cancer Research 82, no. 12_Supplement (June 15, 2022): 6189. http://dx.doi.org/10.1158/1538-7445.am2022-6189.
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Abstract [Purpose] Immunosuppressive tumor microenvironment (TME) is the major hurdle to cancer immunotherapy. Advanced hepatocellular carcinoma (aHCC) is one of the representative cold tumors with immunosuppressive TME and presents obvious correlation between immune check point expression, such as programmed cell death ligand 1 (PD-L1), and poorer prognosis. In aHCC patients, cancer cells and stellate cells in TME appeared to express high level of PD-L1, which should suppress activities of antitumor immune cells. In this context, the combination of PD-1/PD-L1 inhibitors and other therapeutic modalities are tried to treat aHCC. The chimeric antigen receptor (CAR) T cell therapy is a potent way of eradicating cells expressing targetable antigens. Removal of PD-L1 expressing cells in the aHCC TME will improve the clinical outcomes of current therapies against aHCC. In the present study, we developed an autologous anti-PD-L1 CAR T strategy and show high efficacy of tumor suppression using an HCC xenograft model. [Result] We constructed second generation CAR lentiviral vector expressing an unique anti-PD-L1 scFv manifesting moderated affinity. The scFv was specifically generated by phage display technique using human B cell-derived naïve cDNA library, which targets PD-L1 with intermediate affinity in solid tumor TME. As the secondary signaling motif, CD28 was chosen and tested along with CD3 zeta chain. The effector CAR T, named VPC1, cells specifically recognized PD-L1 expressing HCC cells and exhibited rapid and robust cytotoxic activity in 2D and 3D culture experiments. In an HCC xenograft NSG mouse model, VPC1 CAR T cells significantly suppressed the tumor growth. More importantly, VPC-1-treated animals have well tolerated the CAR T therapy with no significant adverse manifestations during one month observation period and exhibited gradual weight gains since 3 days after CAR T cell injection. [Conclusion] We hereby report that a new autologous PD-L1 CAR-T therapeutic is capable of eradicating solid tumors expressing PD-L1, which would significantly potentiate efficacies of current conventional and immunotherapeutic strategies. Citation Format: Kyung-Sik Lee, Hye-Seong Park, Guk-Yeol Park, Gi-Chan Lee, Eun-Ji Choi, Jae-in Yu, Seung-Joo Yang, Mihwa Kim, Yoonjoo Choi, Je-Jung Lee, Joon Haeng Rhee, Bum Chan Park, Jae Eun Park. Development of an anti hepatocellular carcinoma CAR T strategy targeting PDL1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6189.