bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2749: Liquid biopsy testing allows highly-sensitive detection of plasma cfDNA mutations in 87 breast cancer-related genes
Authors: Lira Maruja E. , Xie Tao , Deng Shibing , Kinong Jennifer , Gao Jingjin , Zhu Zhou , Lee Nathan , Rejto Paul , Bienkowska Jadwiga , Hardwick James , Wang Kai , Huang Stephen 
Published: July 2017

Abstract
Liquid biopsies have the potential to revolutionize the way physicians select personalized anti-cancer therapies, monitor patient responses to treatment, and characterize acquired resistance to cancer drugs. New tests that use a simple peripheral blood draw offer snapshots of a patient‘s total tumor DNA mutation profile and are attractive because of their minimally-invasive modality and because they integrate information from both primary and metastatic disease. Currently, most plasma cell-free DNA (cfDNA) mutation detection tests used in clinical research detect known hotspot mutations in a limited number of genes. Technologies that interrogate multi-gene panels in cfDNA are advancing, but commercially-available options suitable for clinical use are limited, come at a high cost, and are not customizable. We designed and developed a customized, next generation sequencing-based, liquid biopsy assay capable of detecting somatic mutations in 87 breast cancer genes involved in cell cycle and estrogen receptor signaling. Targeted regions (147 Kb) were enriched using hybrid capture resulting in an average capture specificity and uniformity of 65.93% and 96.38%, respectively. When tested on cfDNA from healthy donors (n=14), we demonstrated a level of specificity &gt;99.99%. Analytical sensitivity of 0.1% was established on HapMap and reference mutant cell line DNA. Using a pool of HapMap genomic DNA (n=10), 96% (48/50) of SNPs with expected allele frequency of 0.1% were detected. In reference mutant cell line DNA with 1% or 0.1% mutant allele frequencies, we were able to reliably detect all mutations present at 1% and mutations at 0.1% in 50% of the cases. Assay validation on plasma cfDNA with matching tumor from ER+, HER2- breast cancer patients will be presented. In conclusion, we developed a highly sensitive and specific liquid biopsy assay to interrogate 87 breast cancer-related genes. The high level of specificity and sensitivity makes the test ideal not only for detecting known cancer gene hotspot mutations but also for detection of novel gene mutations that may arise during treatment as a result of acquired drug resistance.
Citation Format: Maruja E. Lira, Tao Xie, Shibing Deng, Jennifer Kinong, Jingjin Gao, Zhou Zhu, Nathan Lee, Paul Rejto, Jadwiga Bienkowska, James Hardwick, Kai Wang, Stephen Huang. Liquid biopsy testing allows highly-sensitive detection of plasma cfDNA mutations in 87 breast cancer-related genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2749. doi:10.1158/1538-7445.AM2017-2749
Abstract 2762: The comparison of allogeneic stem cell transplantation outcomes between haploidentical donor and international donor: A retrospective multi-institutional study in Korea
Authors: Park Hyunkyung , Lee Yoo Jin , Shin Sang-Jin , Lee Jayoun , Kim Inho , Yoon Sung-Soo , Park Silvia , Lee Hyewon , Moon Joonho , Jang Jun Ho , Koh Youngil 
Published: July 2017

Abstract
Introduction: The successful rate of hematopoietic stem cell transplantation (HSCT) from HLA-mismatched donor has been increased according to the development in management of complications including graft versus host disease (GVHD) and infections. Especially, haploidentical HSCT provides an opportunity for all patients who do not have HLA-matched sibling donor.
Methods: In this study, we compared HSCT outcomes between haploidentical familiar donor and international donor (donors from Japan, China, Germany, Unites States of America and Taiwan) in acute leukemia patients. We reviewed the overall survival (OS), relapse free survival (RFS) and complications.
Results: Total 142 acute leukemia patients performed HSCT from 2000 to 2016; 98 patients underwent haploidentical donor transplantation and 44 patients underwent international donor transplantation. Major variables such as age, sex, disease status and the number of CD34 stem cells were not statistically different between two groups. In survival analysis, there was no significant difference according to the donor-type. 1-year OS rate for haploidentical transplantation group was 44.1% and 52.3% for international transplantation group (p=0.345). 1-year RFS rate was 36.6% versus 40.9%, respectively (p=0.362). In addition, the incidence of complication events was similar between two groups. The acute GVHD in haploidentical group and international group were 42.9% and 43.2% (P=0.97), and the infection event within 30days after transplantation were 49.5% in haploidentical group and 34.1% in international group (p=0.09). The cumulative incidence of chronic GVHD was no significantly different (P=0.34), respectively.
Conclusion: These data suggest that HSCT from haploidentital donor shows similar outcomes including survival outcomes and complications with international donor transplantation. Therefore, haploidentitial donor transplantation can be good choice for acute leukemia patients who have no HLA_matched sibling donor.
Citation Format: Hyunkyung Park, Yoo Jin Lee, Sang-Jin Shin, Jayoun Lee, Inho Kim, Sung-Soo Yoon, Silvia Park, Hyewon Lee, Joonho Moon, Jun Ho Jang, Youngil Koh. The comparison of allogeneic stem cell transplantation outcomes between haploidentical donor and international donor: A retrospective multi-institutional study in Korea [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2762. doi:10.1158/1538-7445.AM2017-2762
Abstract 2766: Esophageal stenting in resource-limited settings
Authors: Mwachiro Michael M. , Parker Robert K. , Burgert Stephen , Lando Justus , Rankeeti Sinkeet , Chepkwony Robert , Kiniga Emmanuel , Dawsey Sanford , Topazian Mark , White Russell E. 
Published: July 2017

Abstract
Background: Esophageal cancer is the 6th leading cause of cancer death globally, with geographical high-risk areas in Asia, the Middle East, and eastern and southern Africa. Esophageal squamous cell carcinoma (ESCC) is the more common variant in Africa. In Kenya, its incidence is 2nd in men after prostate cancer and 3rd in women after breast and cervix-uteri cancers. Late presentation is a common occurrence in developing countries and is multifactorial due to challenges in access to health care, low socioeconomic status and delayed or missed diagnosis. A large percentage of these tumors are thus unresectable and are only eligible for palliative care via stenting. Our hospital is a 300-bed referral center in southwestern Kenya, which is a hotspot for ESCC, and we see over 400 cases of ESCC annually.
Methods: We have developed a technique for placement of esophageal self-expanding metallic stents (SEMS) without fluoroscopy that is safe and easily reproducible. This is an outpatient procedure, with the majority done under conscious sedation, and routine followup is not necessary. The tumor margins are noted at time of video endoscopy, a guidewire is placed, and dilation done with Savary dilators as required. The SEMS are then loaded on the stent delivery device and deployed into the proper position based on measurements, and placement is subsequently confirmed via endoscopic visualization.
Results: A total of 3000 SEMS have been placed to date at our hospital, without using fluoroscopy. The male: female ratio has been 1.5:1, and the average age has been 60.4 years. The distribution of tumor locations was 67% in the middle and distal third. The most common complications were tumor overgrowth with obstruction and stent migration. Procedure related mortality was 0.3%. Post-procedure improvement in dysphagia score was seen in over 80% , and patient satisfaction was high. Initial data puts our post stent survival time around 8 months/ 250 days
Conclusions: Placement of SEMS for ESCC, without fluoroscopy, is a safe and reproducible procedure which has a low rate of adverse events. This procedure results in effective palliation of a difficult disease and can easily be done in resource-limited settings which have endoscopy capabilities. Current efforts are ongoing to increase opportunities for training endoscopists in this procedure and for provision of affordable stents in Africa.
Citation Format: Michael M. Mwachiro, Robert K. Parker, Stephen Burgert, Justus Lando, Sinkeet Rankeeti, Robert Chepkwony, Emmanuel Kiniga, Sanford Dawsey, Mark Topazian, Russell E. White. Esophageal stenting in resource-limited settings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2766. doi:10.1158/1538-7445.AM2017-2766
Abstract 2768: Treosulfan induces differential gonadal toxicity profile compared with Busulfan
Authors: Levi Mattan , Stemmer Salomon , Stein Jerry , Shalgi Ruth , Ben-Aharon Irit 
Published: July 2017

Abstract
Background: Treosulfan (L-treitol-1,4-bis-methanesulfonate), an alkylating agent with myeloablative and immunosuppressive traits, has been increasingly incorporated as a main conditioning protocol for hematopoietic stem cell transplantation (HSCT) in pediatric malignant and non-malignant diseases. Treosulfan has been shown to present lower toxicity profile compared with conventional myeloablative regimens such as busulfan. Yet, while busulfan is considered highly gonadotoxic, the gonadal toxicity profile of treosulfan remains to be elucidated. Our aim was to study the short and long term gonadal effect of treosulfan in comparison to busulfan.
Methods: Mature 2 months old male and 3 months old female mice (“pubertal cohort”) were injected with treosulfan 2000 mg/kg or busulfan 40 mg/kg and were sacrificed one week, one month or six months post drug administration. Immature male and female mice (“prepubertal cohort”) were injected with treosulfan 750 mg/kg or busulfan 15 mg/kg and were sacrificed one week or three months post drug administration. Testicular function was assessed by measurements of sperm count and motility, testes and epididymides weight, serum anti-Mullerian Hormone (AMH) and testicular ID4 or GFRA1 mRNA (markers for stem spermatogonia). Immunohistochemistry was performed to evaluate testicular proliferation (Ki-67), apoptosis (TUNEL) and meiotic-active spermatocytes (DAZL-PCNA). Ovarian function was assessed by measurements of ovary weight, serum AMH, follicles count and ovarian SOHLH2, NOBOX of FIGLA mRNA (markers for primordial follicles). Immunohistochemistry was performed to evaluate ovarian proliferation (Ki-67), apoptosis (TUNEL) and growing follicles (AMH-PCNA).
Results: Treosulfan testicular toxicity was milder compared to busulfan toxicity, in both mature and immature male mice, while stem spermatogonia were spared. However, ovarian toxicity of both treosulfan and busulfan was severe and permanent in both mature and immature female mice; possibly by a short term irreversible reduction of reserve primordial follicles in the ovaries.
Conclusion: Our results indicate that treosulfan exerts a differential gonadal toxicity profile compared with busulfan, manifested by mild testicular toxicity and severe ovarian toxicity.
Citation Format: Mattan Levi, Salomon Stemmer, Jerry Stein, Ruth Shalgi, Irit Ben-Aharon. Treosulfan induces differential gonadal toxicity profile compared with Busulfan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2768. doi:10.1158/1538-7445.AM2017-2768
Abstract 2769: Project Survival: Prospective clinical study utilizing multiomics and artificial intelligence to discover novel molecular markers for detection, stratification, and outcome in pancreatic cancer
Authors: Sarangarajan Rangaprasad , Crowley John , Stoll-D'Astice Amy , Bussberg Valerie , Nguyen Cindy , Rodrigues Leonardo O. , Chen Emily , Grund Eric Michael , Vishnudas Vivek K. , Kiebish Michael , Akmaev Viatcheslav R. , Hidalgo Manuel , Narain Niven R. , Moser A. James 
Published: July 2017

Abstract
Pancreatic adenocarcinoma is the third leading cause of cancer death and has an extremely poor response to first line therapies. There is a critical unmet need to discover and implement effective diagnostic panels to stratify this disease and personalize treatment. Project Survival is a prospective study designed to discover biomarkers for patient diagnosis, stratification, and prognostics for pancreatic cancer. The multisite study is in year 2 of enrolling subjects within 6 categories: healthy volunteers with a relative with pancreatic cancer (N=50), pancreatitis (N=50), pancreatic cystic neoplasm (N=50), suspicious pancreatic masses with pathology other than pancreatic cancer (N=50), early stage (N=200) and metastatic pancreatic cancer (N=200). The study analyzes matched subject sera, plasma, buffy coat, saliva, urine, and tumor/adjacent normal tissues and integrates them with full clinical annotation. Multiple time points per subject per year are taken longitudinally over the course of the six year timeline enabling dynamic modeling. Samples are analyzed by Mass Spectrometry for the proteome, signaling lipidome, structural lipidome, and metabolome. The BERG Interrogative Biology® platform utilizes Artificial Intelligence to integrate multiomic profiles with medical annotation and clinical endpoints. Utilizing the power of the Bayesian Network learner, bAIcis™ (BERG Artificial Intelligence Clinical Information System), multiomic profiles were aligned to the longitudinal clinical information and subjected to the AI-algorithms that inferred probabilistic cause-and-effect relationships among molecular and clinical variables inferring markers of pancreatic cancer status and defining the interconnectivity of molecular features with clinical phenotype. Network features linking clinical endpoints and key network pressure points will be identified as molecular drivers. The drivers of clinical endpoints will be analyzed to rank potential biomarkers.
Citation Format: Rangaprasad Sarangarajan, John Crowley, Amy Stoll-D'Astice, Valerie Bussberg, Cindy Nguyen, Leonardo O. Rodrigues, Emily Chen, Eric Michael Grund, Vivek K. Vishnudas, Michael Kiebish, Viatcheslav R. Akmaev, Manuel Hidalgo, Niven R. Narain, A. James Moser. Project Survival: Prospective clinical study utilizing multiomics and artificial intelligence to discover novel molecular markers for detection, stratification, and outcome in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2769. doi:10.1158/1538-7445.AM2017-2769
Abstract 2788: High ALDH1, S phase fraction, p16INK4A in esophageal squamous cell carcinoma could predict response to neoadjuvant chemotherapy
Authors: Kumar Rajeev , Kannan R. Ravi , Verma Akalesh Kumar , Talukdar Anuradha , Deka Monoj Kumar , Tapkire Ritesh , Vermani Litika , Ghosh Sankar Kumar 
Published: July 2017

Abstract
Background: The prevalence of locally advanced esophageal squamous cell carcinoma (ESCC) remains high despite technological advancements in its diagnosis. This leads to prolonged multimodality treatment often resulting in poor response eventually leading to poor prognosis. Currently, there are no biomarkers available to predict response to neoadjuvant chemotherpy. Aldehyde dehydrogenase 1 (ALDH1), human epidermal growth factor receptor-2 (HER2), p16INK4A, ploidy and S phase fraction are considered significant biomarkers in various solid malignancies. However, there is paucity of data on their clinical significance in ESCC. In the present study, we investigated their significance in predicting the response to neoadjuvant chemotherapy (NACT) in ESCC patients.
Methods: Immunohistochemisty of ALDH1, HER2, p16INK4A and propidium iodide based cell cycle analysis through flow cytometer was performed in pre treatment biopsy sample collected from 108 ESCC patients who were presented at a comprehensive cancer centre in northeast India and all of them subsequently received neo adjuvant chemotherapy. Results: ALDH 1, HER2 and p16INK4A were found positive in 65.7%, 7.4% and 22% of pre treatment ESCC specimens respectively. ALDH1 expression correlates with poor response to neo adjuvant chemotherapy (P&lt;0.001). A significant proportion of poor responders were found to be smokers (P=0.004). Poor responders also tends to correlate with increased mortality (P=0.009). HER2 couldn’t predict response to NACT. However, all HER2 positive cases were associated with high ALDH1 expression (P=0.034). 50% of those with pathologically complete response were p16 positive on the contrary only 15% non responders were positive for p16 (P&lt;0.001). 84% of the ESCC patients reported aneuploid tumor status and responder's were found having high S phase fraction (P=0.041). Conclusion: High ALDH1 expression can predict poor response whereas high p16 and S phase fraction can indicate good response to neoadjuvant chemotherapy in ESCC patients. HER2 seems having no clinical significance in the response assessment of neo adjuvant chemotherapy in ESCC.
Citation Format: Rajeev Kumar, R. Ravi Kannan, Akalesh Kumar Verma, Anuradha Talukdar, Monoj Kumar Deka, Ritesh Tapkire, Litika Vermani, Sankar Kumar Ghosh. High ALDH1, S phase fraction, p16INK4A in esophageal squamous cell carcinoma could predict response to neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2788. doi:10.1158/1538-7445.AM2017-2788
Abstract 2799: Development of a mouse model of KRAS mutated colorectal cancer tumorigenesis
Authors: Maitra Radhashree , Venkatesh Madhu Kumar , Augustine Titto Alby , Chandy Carol , Liu Qiang , Goel Sanjay 
Published: July 2017

Abstract
Introduction Development of a preclinical animal model that mimics KRAS mutated colorectal cancer disease etiology is essential for validation of new therapeutic interventions. Colorectal cancer patients with tumors harboring KRAS mutation are excluded from receiving anti EGFR monoclonal antibodies, and currently have no alternate FDA approved treatment options available. Ongoing research requires validations of different modalities on a robust preclinical study platform that will resemble the disease phenotype and genetic profile. In this context we have developed viable animal mouse model of colorectal cancer bearing KRAS mutation that authentically serves as a model for the disease.
Methodology: The C57 BL/6 mice with truncated APC floxed allele was crossed with heterozygous KRAS floxed outbred mice to generate APC f/f KRAS +/f mouse colony. In another set of breeding APC floxed mice were crossed with CDX2-Cre-ERT2 mice and selected for APCf/f CDX2-Cre-ERT2 after second round of inbreeding. The final model of the disease was generated by the cross of the two aforementioned colonies when viable APC f/f KRAS +/f CDX2-Cre-ERT2 were genotyped and characterized. The model animals were tamoxifen induced to generate tumors. Micro-PET scan was used to detect and measure tumor volume. H & E staining was done to establish neoplasm and immunohistochemistry was performed to determine histological similarities with human FFPE biopsies. The MSI/MSS status was also determined.
Results Ø The newly developed animal model develops colonic tumors upon induction with Tamoxifen. Ø The tumors were malignant as confirmed by H and E staining. Ø The tumors showed a higher radioactive FDG uptake (SUV) in micro-PET scan Ø The tumors resembled human colorectal cancer tissue Ø Once tumor is generated the animals died of cachexia and rectal bleeding
Conclusion: Heterozygous mutation of KRAS oncogene along with deletion mutation of Adenomatous polyposis coli (APC) gene is embryonically lethal in animal models. We have successfully developed a viable animal model of KRAS mutated colorectal cancer with tamoxifen inducible tumors harboring KRAS and APC mutations. The tumors mimic the human disease type both genetically and immunohistochemically. This model can serve as a robust preclinical platform for understanding the disease mechanism at the molecular level as well for evaluation of various therapeutic interventions.
Citation Format: Radhashree Maitra, Madhu Kumar Venkatesh, Titto Alby Augustine, Carol Chandy, Qiang Liu, Sanjay Goel. Development of a mouse model of KRAS mutated colorectal cancer tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2799. doi:10.1158/1538-7445.AM2017-2799
Abstract 2810: Using CRISPR/Cas9 to generate primary soft tissue sarcoma in genetically engineered and wild-type mice
Authors: Huang Jianguo , Chen Mark , Whitley Melodi J. , Kuo Hsuan-Cheng , Walens Andrea , Mowery Yvonne M. , Mater David V. , Eward William , Cardona Diana M. , Luo Lixia , Ma Yan , Nelson Christopher E. , Robinson-Hamm Jacqueline N. , Gersbach Charles A. , Dodd Rebecca D. , Kirsch David G. 
Published: July 2017

Abstract
Genetically engineered mouse models (GEMMs) that employ site-specific recombinase (SSR) technology are important tools for pre-clinical studies, but this approach is costly and time-consuming. Here, we show that the CRISPR/Cas9 system can be used to efficiently complement existing GEMMs of sarcoma and generate primary sarcomas in wild type mice. Mice with the genotype KrasLSL-G12D/+; Rosa26LSL-Cas9-EGFP/+ received intramuscular delivery of an adenovirus expressing Cre recombinase and a single guide RNA (sgRNA) targeting Trp53. Cre-mediated expression of oncogenic Kras and Cas9, in combination with CRISPR/Cas9-mediated knockout of Trp53, was sufficient to generate primary soft tissue sarcomas. These tumors arose with kinetics similar to those generated using the Cre-loxP system to activate oncogenic Kras and delete Trp53 alleles. Additionally, we injected an adenovirus containing Cas9 and sgRNAs targeting Nf1 and Trp53 into the sciatic nerve of wild type mice. These mice formed malignant peripheral nerve sheath tumors (MPNSTs) in the same timeframe as MPNSTs generated using the Cre-loxP system to delete Nf1 and Ink4a/Arf alleles in GEMMs. These data demonstrate that CRISPR/Cas9 can be used to generate soft tissue sarcomas in wild type mice. Moreover, these results suggest that this technology can complement existing GEMMs for rapid assessment of tumor-modifying genes. These tools should decrease the time and expense associated with employing autochthonous mouse models of sarcoma for preclinical research.
Citation Format: Jianguo Huang, Mark Chen, Melodi J. Whitley, Hsuan-Cheng Kuo, Andrea Walens, Yvonne M. Mowery, David V. Mater, William Eward, Diana M. Cardona, Lixia Luo, Yan Ma, Christopher E. Nelson, Jacqueline N. Robinson-Hamm, Charles A. Gersbach, Rebecca D. Dodd, David G. Kirsch. Using CRISPR/Cas9 to generate primary soft tissue sarcoma in genetically engineered and wild-type mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2810. doi:10.1158/1538-7445.AM2017-2810