bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2315: Perceived barriers to early diagnosis of breast cancer in south and southwestern Ethiopia: Qualitative study
Authors: Getachew Sefonias , Addissie Adamu , Tesfaw Aragaw , Taylor Lesley , Kantelhardt Eva 
Published: September 2020

Abstract
Background: Early diagnosis is a key determinant of breast cancer prognosis and survival. However, advanced stage presentation and delays in diagnosis are common problems in Ethiopia. More than half of the cases are diagnosed at advanced stages and the barriers to early diagnosis are not well studied in the country. Hence, this study aims to explore perceived barriers to early diagnosis of breast cancer in South and Southwestern Ethiopia.
Methods: A qualitative study was conducted from March to April 2018 in six selected public hospitals located both in urban and rural settings. Twenty five purposefully selected breast cancer patients and health care providers from these public hospitals were interviewed. An in-depth interview was conducted using a topic guide by qualitative research experts. A thematic analysis was performed using Open Code software version 4.02.
Results: Patient and health system related barriers are two main themes identified for barriers to early diagnosis of breast cancer. Patient related barriers included lack of awareness and knowledge of the disease, beliefs in traditional and religious means of treatments, lack of social and financial support to seek medical care. Health system related barriers included misdiagnosis of cases, long distance referrals due to service inaccessibility, high diagnostic costs, long waiting time, unavailability of screening and diagnostic tests.
Conclusion: Early diagnosis of breast cancer is affected by a multitude of barriers in South and Southwestern Ethiopia. Hence, to increase early diagnosis of breast cancer, awareness campaigns and education about the disease, its prevention, and early detection are needed. Opportunities exist to improve early diagnosis and timely treatment by strengthening referral linkages of health care facilities in rural areas. Efforts are needed to decentralize the tertiary level oncology care and improve capacity in local health facilities.
Citation Format: Sefonias Getachew, Adamu Addissie, Aragaw Tesfaw, Lesley Taylor, Eva Kantelhardt. Perceived barriers to early diagnosis of breast cancer in south and southwestern Ethiopia: Qualitative study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2315.
Abstract 2328: Polyethnic-1000: Advancing cancer genomics by studying ethnically diverse, underserved patient populations in New York
Authors: Robine Nicolas , Froeling Fieke , Hubert Benjamin , Chu Timothy , Chandler Ashlea , Zody Michael C. , Oschwald Dayna M. , Varmus Harold E. , Sawyers Charles , Tuveson David 
Published: September 2020

Abstract
Advances in sequencing technologies have revolutionized our approaches in medicine. However, our current knowledge about the molecular attributes of cancer has primarily been derived from patients of European descent. The overall aims of Polyethnic-1000 are to study the variability of somatic profiles and the effects of genetic ancestry on cancer biology and to bring genomic innovation to under-represented ethnic groups in the diverse patient population of New York City.A dynamic research platform is being created, involving the New York Genome Center, academic centers and partnering hospitals in the New York City region. In an initial retrospective study, the infrastructure, sample workflow, analysis and data sharing policies within the consortium have been developed. Whole-exome and RNA sequencing has been performed on 146 samples from self-identified non-white cancer patients treated at 14 different centers. Genetic ancestry estimation was performed at the super-population and population level using the 1000Genomes references. Data from over 24 tumor types were shared with our collaborators and the somatic variants were made available through our local installation of cBioPortal. Using the knowledge gained during the first stage, we are designing a prospective study to demonstrate our capacity to obtain samples from patients of varied ethnicities and to allow the formation of cohorts of interest for particular cancer types and particular ethnicities, with uniform consent for germline and somatic sequencing and return of results for potentially actionable mutations.By establishing a collaborative network, Polyethnic-1000 will deepen our understanding of the contributions that ethnicities make to the incidence and biology of cancers, potentially improving outcomes for patients who currently lack access to the most recent advances in medical science.
Citation Format: Nicolas Robine, Fieke Froeling, Benjamin Hubert, Timothy Chu, Ashlea Chandler, Michael C. Zody, Dayna M. Oschwald, Harold E. Varmus, Charles Sawyers, David Tuveson. Polyethnic-1000: Advancing cancer genomics by studying ethnically diverse, underserved patient populations in New York [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2328.
Abstract 2343: The incidence of BRAF mutation in non-small cell lung cancers is low in Korean patients
Authors: Kim Ahrong , Ahn Hyo Yeong , Lee Chang Hun , Kim Young Dae , Lee Min Ki , Jeong Yeon Joo , Lee So Jeong 
Published: September 2020

Abstract
Introduction: BRAF mutation is present in about 8% of all cancer. Oncogenic activity of BRAF V600E mutation was established in lung cancers. Dabrafenib and trametinib combination therapy is preferred first line therapy for advanced or metastatic lung cancer with BRAF V600E mutation. However, there is only little basic knowledge of BRAF mutational status among Korean population. In this study, BRAF mutation, particularly BRAF V600E mutational status was explored among Korean non-small cell lung cancer patients. The clinical and pathologic characteristics of BRAF V600E mutation in non-small cell lung cancers were also investigated.
Materials and Methods: The final cohort was 378 cases of primary non-small cell lung cancers. Fromalin-fixed paraffin embedded (FFPE) tissue blocks were used. PNA-mediated clamping PCR for BRAF V600, BRAF V600E real-time PCR and immunohistochemistry for mutation specific monoclonal antibody of Ventana VE1 were performed on all 378 cases of non-small cell lung cancers. For positive cases, direct sequencing was performed for validation.
Results: BRAF V600 mutation was detected in five cases using PNA clamping method among 378 non-small cell carcinoma cases. By using BRAF real-time PCR, a BRAF V600E mutation was detected in 3 patients among total 378 cohort. There were 2 discordant cases between PNA clamping and real-time PCR. On immunohistochemistry, 3 patients showed positive staining for tumor cytoplasm and all positive cases also had positive results in real-time PCR. Direct Sanger sequencing was done in 5 cases that had any positive results for 3 methods. The results of Sanger sequencing was the same with those of real-time PCR and immunohistochemistry. Direct sequencing using PAN PCR product was performed on 2 negative cases for validation. On sequencing using PNA clamping PCR product, all cases showed mutation for BRAF gene other than V600E genotype. Finally, there were 3 cases (0.8%) of BRAF V600E mutation and 2 cases of BRAF mutation (0.5%) other than V600E genotype. Among BRAF mutated patients, there were 2 never smokers and 3 ever smokers. All patients harboring BRAF mutation had no concomitant EGFR or ALK aberrations.
Conclusion: BRAF mutation incidence is relatively lower than that of Western data set and similar to that of Japanese report. Immunohistochemistry for Ventana VE1 antibody can be a useful screening method to detect BRAF V600E mutation.
Citation Format: Ahrong Kim, Hyo Yeong Ahn, Chang Hun Lee, Young Dae Kim, Min Ki Lee, Yeon Joo Jeong, So Jeong Lee. The incidence of BRAF mutation in non-small cell lung cancers is low in Korean patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2343.
Abstract 2361: Mendelian randomization study: The association between metabolic pathways and colorectal cancer risk
Authors: Jung Su Yon , Papp Jeanette , Sobel Eric , Zhang Zuo-Feng 
Published: September 2020

Abstract
Purpose: The roles of obesity-related biomarkers and their molecular pathways in the development of postmenopausal colorectal cancer (CRC) have been inconclusive. We examined insulin resistance (IR) as a major hormonal pathway mediating the association between obesity and CRC risk in a Mendelian randomization (MR) framework.
Methods: We performed MR analysis using individual-level data of 11,078 non-Hispanic white postmenopausal women from our earlier genome-wide association study. We identified four independent single-nucleotide polymorphisms associated with fasting glucose (FG), three with fasting insulin (FI), and six with homeostatic model assessment-IR (HOMA-IR), which were not associated with obesity. We estimated hazard ratios (HRs) for CRC by adjusting for potential confounding factors plus genetic principal components.
Results: Overall, we observed no direct association between the combined 13 IR genetic instruments and CRC risk (HR = 0.96, 95% confidence interval [CI]: 0.78 - 1.17). In phenotypic analysis, genetically raised HOMA-IR exhibited its effects on the increased risk while FG and FI on the reduced risk for CRC, but with a lack of statistical power. Subgroup analyses by physical activity level and dietary fat intake with combined phenotypes showed that genetically determined IR was associated with reduced CRC risk in both physical activity-stratified (single contributor: MTRR rs722025; HR = 0.12, 95% CI: 0.02 - 0.62) and high-fat diet subgroups (main contributor: G6PC2 rs560887; HR = 0.59, 95% CI: 0.37 - 0.94).
Conclusions: Complex evidence was observed for a potential causal association between IR and CRC risk, which may contribute to an additional value of intervention trials to lower IR and reduce CRC risk.
Citation Format: Su Yon Jung, Jeanette Papp, Eric Sobel, Zuo-Feng Zhang. Mendelian randomization study: The association between metabolic pathways and colorectal cancer risk [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2361.
Abstract 2368: Risk factors of pancreatic cancer in Vietnam: A matched case-control hospital-based study
Authors: Dao Tu V. , Tran Thuan V. , Nguyen Dung K. , Bui Oanh T. , Nguyen Quang T. , Tran Huong T. 
Published: September 2020

Abstract
Background: Data about the risk factors and cancer types in developing countries remains limited. We investigate for the first time the role of a number of risk factors (family cancer history, smoking, alcohol consumption, diabetes, hypertension) associated with pancreatic cancer among Vietnamese patients.
Methods: Patients hospitalized at 4 hospitals (K, Bach Mai, Viet Duc, Thai Nguyen) and diagnosed with pancreatic cancer (confirmed by histopathology and/or MRI/CT scan) in the period from January 2017 to May 2019 were included in the study. Some risk factors of the patients were collected and compared with a healthy age- and gender-matched (1:1) control group.
Results: We have identified 196 patients with diagnosis of pancreatic cancer of which 114 males and 82 females. The average age of the patient at the time of diagnosis was 58.28 years (standard deviation of 12.94, ranging from 25 to 87). A positive family history, smoking and hypertension disease of pancreatic cancer significantly reduced the risk (OR and 95% CI were 0.06 [0.02 - 0.18], 0.53 [0.27 - 1.00], 0.1 [0.04 - 0.25], respectively). A past or present history of diabetes significantly increased the cancer risk (OR = 2.76 [1.34 - 6.05]), especially in female (OR = 5.68 [1.49 - 28.69]). Current alcohol drinkers showed a significantly increased risk of pancreatic cancer (OR = 2.23 [1.20 - 4.25]).
Conclusions: Our finding showed that diabetes significantly increased the risk of pancreatic cancer in Vietnam, especially in women. An alcohol intake habit also increased the risk of pancreatic cancer. Further studies are required for fully understood the other risk factors related to this type of cancer.
Citation Format: Tu V. Dao, Thuan V. Tran, Dung K. Nguyen, Oanh T. Bui, Quang T. Nguyen, Huong T. Tran. Risk factors of pancreatic cancer in Vietnam: A matched case-control hospital-based study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2368.
Abstract 2371: FBXL12 modulates Fanconi anaemia-BRCA signaling under conditions of oncogene-induced replication stress
Authors: Brunner Andrä , Johansson Henrik , Kourtesakis Alexandros , Rantala Juha , Spruck Charles , Wohlschlegel James , Lehtiö Janne , Sangfelt Olle 
Published: September 2020

Abstract
Oncogene-induced replication stress (OIRS) constitutes an early obstacle to cancer progression. De-regulation of cell death or senescence programs contribute to overcoming this barrier. However, even after escaping these fail-safe mechanisms, cancer cells need to handle elevated levels of DNA damage and ensuing genomic instability in order to continue proliferating. How this is achieved is only partially understood.
To advance our understanding of this response and to identify potentially druggable regulators, we screened the family of human F-box proteins (FBP) for effects on replication re-start under conditions of OIRS. FBPs function as interchangeable substrate recognition sub-units of the SKP1-Cullin1-FBP ubiquitin ligase complex. They are required for conferring substrate specificity to the complex and some FBPs have been attributed roles as oncogenes or tumor suppressors while the majority remain largely uncharacterized.
Our screen revealed the relatively unknown FBP FBXL12 as crucial regulator for sustained proliferation and genomic integrity under conditions of cyclin E-induced replication stress. FBXL12-depleted cells exhibit excessive replication fork stalling, high levels of DNA damage signaling and spontaneous senescence in OIRS breast cancer model cell lines. Interestingly, the same effects are not manifest in untransformed cell lines.
Furthermore, we found that FBXL12 interacts with central chromatin-associated components of the Fanconi anemia (FA)-BRCA signaling pathway, ubiquitylating and targeting them for proteasomal degradation, and thereby exerting its effects on stalled replication forks.
The specific nature of FA-BRCA signaling regulation by FBXL12 as well as potential clinical implications for basal-like breast cancers will be discussed.
Citation Format: Andrä Brunner, Henrik Johansson, Alexandros Kourtesakis, Juha Rantala, Charles Spruck, James Wohlschlegel, Janne Lehtiö, Olle Sangfelt. FBXL12 modulates Fanconi anaemia-BRCA signaling under conditions of oncogene-induced replication stress [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2371.
Abstract 2377: Atm-dependent recruitment of brd7 is required for transcriptional repression and repair at dna breaks flanking transcriptional active regions
Authors: Hu Kaishun 
Published: September 2020

Abstract
DNA double-strand break (DSB) is highly cytotoxic and deleterious lesions, causing gross chromosomal rearrangements, genomic instability and tumorigenesis (Meisenberg et al., 2019). In mammalian cells, such damages are mainly repaired through two pathways: non-homologous end joining (NHEJ) and homologous recombination (HR) (San Filippo et al., 2008). To avoid conflicts between ongoing transcription and repair activities, the DNA damage response (DDR) must coordinate the processes of repair signaling and local transcriptional capacity (Adam and Polo, 2014). Cells have evolved the ability of switching off transcription for DSB repair in ATM, DNA-PK and PARP1-dependent manner which is a critical step for maintaining genome-epigenome integrity (Iannelli et al., 2017; Shanbhag et al., 2010; Uckelmann and Sixma, 2017). The mono-ubiquitylation of H2A on K119 is one of the key determinants of transcriptional repression at sites of DNA damage (Kakarougkas et al., 2015; Rona et al., 2018; Shanbhag et al., 2010). However, depletion of these factors did not alleviate completely DSB-induced transcriptional repression, suggesting that additional yet unidentified factors or complexes are involved in the process. Here, we identified that BRD7, another specific subunit of PBAF complex, participated in DNA damage response (DDR) and was recruited to the damaged chromatin via ATM signaling. Mechanistically, BRD7 joined the polycomb repressive complex 2 (PRC2), the nucleosome remodeling and histone deacetylation (NuRD) complex at the damaged DNA and recruited E3 ubiquitin ligase RNF168 to the DSBs. Furthermore, ATM-mediated BRD7 phosphorylation is required for recruitment of the PRC2 complex, DSB sensor complex MRE11-RAD50-NBS1 (MRN) and RNF168 to the active transcription sites at DSBs, resulting in transcriptional repression and DNA repair. Moreover, BRD7 deficiency sensitized cancer cells to PARP inhibition. Collectively, BRD7 is crucial for DNA repair and DDR-mediated transcription repression, which may serve as a therapeutic target. Moreover, our findings have identified the missing link between DNA repair and transcription regulation that maintains genome integrity, as well as highlight the important role of PBAF complex in maintaining genomic integrity.
Citation Format: Kaishun Hu. Atm-dependent recruitment of brd7 is required for transcriptional repression and repair at dna breaks flanking transcriptional active regions [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2377.
Abstract 242: Identification of biomarkers predicting sensitivity to GLS1 inhibition using a CRISPR screen
Authors: Henry Christophe , Berthelot Karine , Lanneau Christophe , Orsini Cécile , Gorge-Bernat Dimitri , Meaux Isabelle , Chassin Dorine , Moll Jürgen , Thiers Berangere , Machnik David , Debussche Laurent 
Published: September 2020

Abstract
The conditional essential amino acid glutamine is utilized by tumors to sustain bioenergetic requirements in a nutrient-poor microenvironment. Based on this specific tumor need, efforts have been made to target the glutamine metabolism using glutaminase inhibitors. This approach has demonstrated activity in preclinical models and in a range of phase I studies. It was shown that a subset of models/patients are benefiting from glutaminase inhibition, however, biomarkers predicting sensitivity to GLS1 inhibitors are lacking. The objective of this study is to identify molecular predictors of the sensitivity towards GLS1 inhibition. Using the cBioportal, we analyzed the most prevalent genetic deficiencies in Triple Negative Breast cancers, Kidney cancers, Acute Myeloid Leukemia and Multiple Myeloma. From this analysis, a library of CRISPR gRNA including the most disease relevant LOF linked-genes was created. Individual cell lines stably expressing Cas9 were used for a focused CRISPR screen in the presence of suboptimal doses of GLS1 inhibitor. The sgRNA library mimicking the major genetic deficiencies identified from the cBioportal datamining was delivered in pool lentiviral particles. Genes deficiencies associated with increased GLS1 sensitivity were identified with sgRNA targeted NGS sequencing of the remaining cell population at treatment completion. We present the setup and validation of an innovative experimental design for the identification of biomarkers predictive to GLS1 inhibition with the aim to identify gene deficiencies associated with increased sensitivity to GLS1 inhibitors that could be used as predictive biomarkers in the clinic.
Citation Format: Christophe Henry, Karine Berthelot, Christophe Lanneau, Cécile Orsini, Dimitri Gorge-Bernat, Isabelle Meaux, Dorine Chassin, Jürgen Moll, Berangere Thiers, David Machnik, Laurent Debussche. Identification of biomarkers predicting sensitivity to GLS1 inhibition using a CRISPR screen [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 242.
Abstract 2428: Emodin enhances efficacy of Oxaliplatin and 5 Fluorouracil in colon cancer by promoting cell cycle arrest
Authors: Saunders Ian T. , Ezeagwu Dexter , Kumar Naresh , Mir Hina , Singh Shailesh 
Published: September 2020

Abstract
Dysregulation of cellular proliferation and evasion of apoptosis are key contributors to colon cancer (CoCa) development. Chemotherapeutic agents such as 5-Fluorouracil (5FU) and Oxaliplatin (OxT) which are frequently offered to treat CoCa are known to target cells in S and G2 phase of cell cycle. Cancer cells often overcome the effects of 5FU and OxT by deregulating cell cycle in response to these drugs. Therefore, to improve the cytotoxic effect of these chemotherapeutic agents it is important to keep CoCa cells in S and G2 phase. Hence, understanding the molecular mechanisms involved in CoCa cell-cycle progression and chemotherapeutic response could provide strategies for developing effective treatment options. Hence, in this study, we determined the effect of natural agent “Emodin” on CoCa cell-cycle regulation and its ability to increase the efficacy of 5FU and OxT by cell cycle regulation. The effects of Emodin, 5FU, and OxT as a single agent or in combination on CoCa (DLD-1, COLO-201, HCT116 p53WT, and HCT116 p53-/-) cell viability were determined by MTT assays. Combination index of Emodin, 5FU, and OxT were evaluated using Calcusyn. Emodin-induced changes in molecules involved in cell-cycle regulation and proliferation were analyzed via RT-PCR and confirmed by western blot (WB) analysis. Cell-cycle distribution with Emodin treatment alone and in combination with 5FU and OxT were assessed via flow cytometry and WB. Collectively, our data shows that Emodin alone was able to decrease cell survival and induced apoptosis in CoCa cells. Furthermore, cytotoxic ability of 5FU and OxT was increased when combined with Emodin as compared to when these chemotherapeutic drugs were given as single agents Emodin-induced cell-cycle regulation resulted in increased expression of tumor suppressor genes such as p21, p27 and p53, modulated cyclin/cyclin-dependent kinase expression, and induced cell-cycle arrest. Emodin also negatively impacted several signaling pathways associated with cell growth and differentiation. Overall, this study demonstrates that Emodin could be a promising adjuvant to either 5-Fluorouracil or Oxaliplatin in the treatment of CoCa.
Citation Format: Ian T. Saunders, Dexter Ezeagwu, Naresh Kumar, Hina Mir, Shailesh Singh. Emodin enhances efficacy of Oxaliplatin and 5 Fluorouracil in colon cancer by promoting cell cycle arrest [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2428.