bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA41: Emerging Issues in Cancer Screening for Racial and Ethnic Minorities
Authors: Halbert Chanita Hughes 
Published: March 2017

Abstract
Cancer screening plays an important role in early detection; detecting cancer in an early stage has important implications for cancer health disparities. Considerable efforts have been made to increase access to early detection services among racial and ethnic minorities in order to improve cancer outcomes in these populations. However, our recent work has shown that racial disparities in cancer screening continue to exist. For instance, about 40% of women in our national random survey of cultural considerations in cancer screening were not up-to-date with mammography guidelines. Our other work with a community-based sample of African American men demonstrated that informed decision-making about PSA testing may be low. Fifty-seven percent of men reported having a PSA test during the past year, but none of the variables that are important to informed decision-making were associated with having annual screening. With respect to lung cancer screening, our recent qualitative research demonstrated that patients have limited discussions with providers about the benefits and limitations of lung cancer screening and had difficulty recalling receipt of information about screening, even though many decided to have low dose computed tomography (LDCT). This may be because of limited knowledge about screening guidelines and low enthusiasm and commitment to LCDT among providers. Providers relied on clinical reminders from the electronic health system to remind them to assess patients for eligibility for LDCT and offer screening. Provider referral to smoking cessation programs was also limited. Provider referral to smoking cessation programs, and delivery of this service, is especially important among high-risk smokers who are candidates for LCDT. Using data from the National Lung Screening Trial (NLST), our research demonstrated that current smokers have an increased risk of lung cancer and all-cause mortality compared to former smokers regardless of randomization to LCDT or the control condition. In addition, smoking abstinence for seven years was associated with a 20% reduction in lung cancer mortality among those screened with chest radiograph. Screening with LCDT and smoking abstinence for 15 years had the greatest mortality risk reduction. African Americans were under-represented in the NLST; therefore, greater efforts are needed to disseminate and implement lung cancer screening in more diverse health care facilities.
Citation Format: Chanita Hughes Halbert. Emerging Issues in Cancer Screening for Racial and Ethnic Minorities. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr IA41.
Abstract A16: Establishment and characterization of CCGL007, a novel human chronic lymphocytic leukemia cell line
Authors: Kuo Ching-Chuan , Chen Chih-Cheng , Huang Chih-Hsiang , Li-Mei Lin 
Published: March 2017

Abstract
Chronic lymphocytic leukemia (CLL) is a monoclonal disorder characterized by a progressive accumulation of functionally incompetent lymphocytes. However, lack of immortalized cell line representative of the CLL disease has hampered a full understanding of disease pathogenesis and development of novel therapeutic agents for treatment. There were very few representative CLL cell lines are available now. To this end, we have tested different culture condition with addition of growth factor supplements to generate CLL cell lines from highly purified peripheral blood B cells of CLL patients. Recently, we have successfully established a new CLL cell line, named CCGL007. CCGL007 cells grow as suspension in liquid culture. Surface marker analysis with a panel of monoclonal antibodies revealed that CCGL007 cell line expresses B cell markers. The chromosomal, immunophenotypic, molecular biologic characteristics, and in vivo tumorigenesis potential of CCGL007 is under investigation. We have used this cell model to test the efficacy of selected standard chemotherapy drugs and new therapeutic agents, such as ibrutinib and several novel in-house BTK inhibitors, against CLL cell growth, and CCGL007 represents as a suitable preclinical model for testing pharmacological agents.
Citation Format: Ching-Chuan Kuo, Chih-Cheng Chen, Chih-Hsiang Huang, Lin Li-Mei. Establishment and characterization of CCGL007, a novel human chronic lymphocytic leukemia cell line. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A16.
Abstract A29: Evaluating the dynamics of epigenetic changes conferring targeted cancer drugs resistance in tumor xenograft propagation model
Authors: YOU REN-IN , CHEN CHUN-SHAN , CHEN CHUN-YI , Agustina Simarmata 
Published: March 2017

Abstract
Deregulation of protein kinase activity has been shown to play a central role in the pathogenesis of human cancers. Although selective targeted therapy by kinase inhibitors have been emerged as important therapeutic agents in the treatment of a variety of human malignancies. Cancer cells become resistant to targeted cancer drugs are a major obstacle to successful cancer treatment. A major mechanism of resistance is the presence of a small sub-population of cancer cells have genetic changes, aberrant epigenetic modifications and activation of alternative signaling pathways by modifying the expression of several downstream effectors contribute to the acquisition of cancer target drug resistance. To dissect the alternate pathways exist to confer targeted cancer drugs resistance, the kinase inhibitors resistant cancer cells were established by continuous culture in increasing doses. Furthermore, the resistant cancer cells were inoculated into SCID mice and then tumors were excised and serially transplanted into additional mice for propagation. By in vivo serial dilution tumor-propagating assay, the established resistant cancer cell lines and xenografts were characterized using cell growth kinetics, targeted drug sensitivity and tumorigenicity. The gene overexpression and shRNA knockdown approaches were employed to investigate the mechanism of bypassing target gene effects from propagating cells in vitro. Confirmation of target drug sensitivity of drug resistant transfectants may allow for the identification of new therapeutic targets or prognostic biomarkers of cancer drugs response. The resistance-related genes having measurable effects in vitro and in vivo demonstrate that the established model in this study is appropriate for validation of genes that responsible for targeted drug resistance.
Citation Format: REN-IN YOU, CHUN-SHAN CHEN, CHUN-YI CHEN, Simarmata Agustina. Evaluating the dynamics of epigenetic changes conferring targeted cancer drugs resistance in tumor xenograft propagation model. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A29.
Abstract A31: Proteomic characterization of stromal contribution to tumor using patient-derived xenografts
Authors: McDermott Jason E. , Liu Tao , Petyuk Vladislav , Smith Richard , Rodland Karin 
Published: March 2017

Abstract
Patient-derived xenografts (PDXs) are an important and powerful tool to study many types of cancer and provide valuable insight into potential drug response and development of resistance. Due to the differences in tissue lineage PDXs also allow the dissection of stromal contribution to the tumor that is not easily obtainable from examination of the original tumor itself. We have applied mass-spectrometry enabled proteomics, phosphoproteomics, and RNAseq to compare primary metastasis, and PDXs derived from several metastatic sites from the same original tumor which was a colorectal adenocarcinoma.
Comparing our results with a large-scale proteomic characterization of tumors performed under the clinical tumor analysis consortium (CPTAC) shows that the original metastasis, and PDXs from different sites, are significantly similar, regardless of metastasis site. Proteomic profiles of these samples are enriched in proteins expressed in the tissue of origin, rather than the site of metastasis. Pathway analysis from proteomics revealed enrichment in complement cascade, extracellular matrix receptors, and focal adhesion. These were different than the pathways indicated by the transcriptomics, which included cell cycle, focal adhesion, and MAP signaling, but not complement or extracellular matrix.
We found in the case of complement and focal adhesion the original metastasis sample was very different from the PDX samples, if we only considered human protein contributions. Considering mouse proteins we found that the mouse stromal contribution complemented the human tumor contribution in the PDXs, aligning the functional analysis in both types of samples. Combining these results with subsequent analysis of driver mutations revealed that the proteomic contribution of stroma was as high as 40%. We have extended these observations to additional pairs of clinical tumor specimens and paired PDXs, including different tumor types. In all cases, there is greater similarity among the same sample type (resected tumor, metastatic lesion, or PDX) than between different sample types from the same patient.
Citation Format: Jason E. McDermott, Tao Liu, Vladislav Petyuk, Richard Smith, Karin Rodland. Proteomic characterization of stromal contribution to tumor using patient-derived xenografts. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A31.
Abstract B07: Screening of patient-derived carcinoma cells and animal models identifies transcription as target in pancreatic cancer.
Authors: Khazak Vladimir , Skobeleva Natalia , Beglyarova Natalia , Bobrov Egor , Zhou Yan , Jablonski Sandra A. , Weiner Louis M. , Paz Keren , Astsaturov Igor 
Published: March 2017

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy that affects 44,000 individuals yearly in the US. With almost 90% lethality even when diagnosed prior to metastasis, there is an urgent unmet medical need for new therapies or better matching of existing therapies to patients. To address this emergency, we first had developed a panel of new physiological models for study of PDAC, rapidly expanding surgical PDAC tumor samples in culture with the Rho kinase inhibitor Y-27632, and creating matched patient-derived xenografts (PDX). Using this panel, we evaluated sensitivity to a large panel of existing drugs. Only a small minority of agents were cytotoxic in vitro in a significant number of independent PDAC models. Among these, transcriptional repressors were predominated. From a short list of drugs not previously used in PDAC, triptolide, a covalent inhibitor of the ERCC3, a bifunctional regulator of transcription and DNA repair, was most consistently effective in vitro and highly effective in vivo, causing prolonged complete regression in multiple PDX models. Triptolide is a natural product compound from Chinese medicinal plant Tripterygium wilfordii, and it was found to be the most active agent in the screen. Importantly, triptolide showed superior activity in MYC-amplified PDX models, suggesting a critical role for ERCC3 in this subset. Triptolide elicited rapid and profound depletion of MYC oncoprotein, a transcriptional co-factor for ERCC3. Expression of ERCC3 was MYC-dependent, while resistance to triptolide was associated with elevated ERCC3 and MYC expression. These findings provide preclinical evidences for transcriptional vulnerability in PDAC via ERCC3 targeting and a new mechanistic approach for disruption of MYC-dependent pancreatic cancers.
Citation Format: Vladimir Khazak, Natalia Skobeleva, Natalia Beglyarova, Egor Bobrov, Yan Zhou, Sandra A. Jablonski, Louis M. Weiner, Keren Paz, Igor Astsaturov. Screening of patient-derived carcinoma cells and animal models identifies transcription as target in pancreatic cancer.. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B07.
Abstract B20: Development of metastatic patient-derived xenografts (PDXs) for accurate assessment of anti-metastatic therapeutics in pre-clinical settings
Authors: Ice Ryan , Kiseleva Anna , Loskutov Yuriy , Smolkin Matthew , Salkeni Adham , Hazard Hannah , Layne Ginger , Pugacheva Elena 
Published: March 2017

Abstract
Background: Although advances in treating early stage breast cancers have increased the overall survival rate, once the disease has metastasized treatment options subside to palliative care. The limited access to metastatic biopsies and disease-relevant pre-clinical models to test new therapeutics targeted against advanced metastatic cancers limits progress and translation of investigational therapeutics to the clinic.
Methods: To address this deficiency we developed a collection of metastatic patient derived xenograft models via direct transplantation of metastatic biopsy or residual surgical material in immunocompromised mice. We successfully collected and established triple negative as well as ER/PR positive patient xenografts which are available for collaborative research. We further characterized and utilized the PDXs to assess the efficacy of new combination therapy to treat distant metastases.
Results: The efficacy of Aurora A kinase inhibition by small molecule inhibitor MLN8237 (Alisertib) as monotherapy and in combination with microtubule targeting drug, eribulin, on different stages of metastasis and potential mechanisms of its action was defined. Our work using PDX models indicates that Alisertib does not limit growth of the primary tumor. These findings are similar to the results of clinical trials with Alisertib in breast cancer. Importantly, we found that Alisertib dramatically decreases growth of the established metastases and prevents further dissemination via inactivation of AKT and activation of cytotoxic autophagy. Combination of Alisertib with eribulin led to a synergistic decrease in metastases to distant organs and provided additional local control of mammary tumor growth.
Conclusion: Metastatic PDX models provide new, accurate assessment of anti-metastatic regiment's efficacy. MLN8237 plus eribulin combination shows synergistic inhibition of metastatic spread, growth of established metastases and prolongs overall survival. Future clinical trials are needed to further test this regiment in clinic to improve survival of metastatic cancer patients.
Citation Format: Ryan Ice, Anna Kiseleva, Yuriy Loskutov, Matthew Smolkin, Adham Salkeni, Hannah Hazard, Ginger Layne, Elena Pugacheva{Authors}. Development of metastatic patient-derived xenografts (PDXs) for accurate assessment of anti-metastatic therapeutics in pre-clinical settings. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B20.
Abstract B46: Inhibition of STAT3 enhances the radiosensitizing effect of Temozolomide in vitro and in vivo: Validation using patient-derived glioblastoma model
Authors: Han Tae Jin , Choi Eun Jung , Cho Bong Jun , Song Sang Hyuk , Paek Sun Ha , Kim In Ah 
Published: March 2017

Abstract
Background and purpose: Despite aggressive treatment with radiation therapy plus temozolomide (TMZ), the prognosis for glioblastoma remains poor. We investigated the potential of targeting signal transducer and activator of transcription-3 (STAT3) to improve the therapeutic outcome of glioblastoma.
Material and methods: We evaluated the preclinical potential of a STAT3 inhibitor, Cpd188 combined with temozolomide and radiation in vitro assays using two established glioblastoma cell lines (U251, U87) and two patients-derived glioblastoma cell lines (GBL12, GBL28) and in vivo studies using nude mice bearing intracranial U251 xenografts.
Results: Cpd188 potentiated the radiosensitizing effect of TMZ in U251 cell which has high levels of p-STAT3 expression. Increased radiosensitizing effects of TMZ were associated with impaired DNA damage repair, apoptosis and the reversion of epithelial-mesenchymal transition (EMT). Cpd188 delayed in vivo tumor growth both alone and in combination with radiation and TMZ. We also confirmed the radiosensitizing effect of Cpd188 of GBL28 cell which was originated from a patient with high level of STAT3 expression and unmethylated MGMT.
Conclusion: Targeting STAT3 using Cpd188 could be a viable therapeutic approach to improve the outcome of current standard therapy for glioblastoma patients having high p-STAT3 expression regardless of MGMT methylation status.
*Work supported by the grant (#2013R1A1A2074531) from the Ministry of Science, ICT & Future Planning to In Ah Kim
Citation Format: Tae Jin Han, Eun Jung Choi, Bong Jun Cho, Sang Hyuk Song, Sun Ha Paek, In Ah Kim{Authors}. Inhibition of STAT3 enhances the radiosensitizing effect of Temozolomide in vitro and in vivo: Validation using patient-derived glioblastoma model. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr B46.
Abstract IA01: The proteogenomics of breast cancer patient-derived xenografts
Authors: Ellis Matthew J. 
Published: March 2017

Abstract
Next generation DNA sequencing (NGS) has provided vast quantities of data on the genomic landscape of common solid malignancies yet the discovery yield in terms of new treatment approaches has been modest. At the most fundamental level this is because we still lack a deep understanding of how complex somatic changes in the cancer genome drive the cellular phenotypes associated with cancer lethality. Our recent work in breast cancer has demonstrated that discovery mass spectrometry-based proteomics of genome annotated clinical and PDX samples (“proteogenomics”) elucidates functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies potential therapeutic targets. The advantages of patient-derived xenografts (PDX) as a source of material for proteogenomics are readily evident. Larger amounts of tumor protein required for mass spectrometry can be obtained, sample ischemia can be controlled and drug perturbation studies to study drug resistance can be easily conducted. However we still have to firmly establish that the proteome of the progenitor human tumor strongly correlates with the proteomic characteristics of the tumor that eventually emerges after engrafting into immunocompromised mice. This is critical as from the genomic perspective, engraftment does represent an evolutionary bottle neck that, at least in some cases, alters tumor clonality. The discovery potential as well as limitations of PDX for the emerging area of proteogenomics will therefore be discussed.
Citation Format: Matthew J. Ellis. The proteogenomics of breast cancer patient-derived xenografts. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA01.
Abstract IA06: Patient-derived orthotopic xenografts (PDOX): Better mimic the patient than subcutaneous xenografts
Authors: Hoffman Robert M. 
Published: March 2017

Abstract
The majority of human solid tumors do not metastasize when grown subcutaneously in immunocompromised mice; this includes patient-derived xenograft (PDX) models. However, orthotopic implantation of intact tumor tissue can lead to primary tumor growth and metastasis that mimics that seen in patients. These patient-derived orthotopic xenograft (PDOX) models have a long history and better recapitulate human cancer than PDX models.
Citation Format: Robert M. Hoffman. Patient-derived orthotopic xenografts (PDOX): Better mimic the patient than subcutaneous xenografts. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA06.
Abstract IA07: Patient-derived tumor xenografts for genotype-drug response correlations in colorectal cancer
Authors: Trusolino Livio 
Published: March 2017

Abstract
Ten years after completion of the Human Genome Project, genetic alterations with causative roles in cancer have been identified. Inhibitors that target “druggable” mutant gene products have been developed. Finally, a number of these drugs have entered the clinic and are now used in patients.
Some fundamental issues need to be addressed before the informative potential of genome- wide molecular surveys is translated into clinical benefit. First, given the heavy mutational load accrued during neoplastic progression, driver alterations are difficult to distinguish from passenger events. Second, next-generation approaches are likely to identify previously neglected small subsets of very rare variants, which requires population-scale studies for statistically solid genotype/response correlations. Third, not always does the presence of an oncogenic driver predict response. Therefore, treatment paradigm may not be decided on the sole basis of the mutational status of a single gene with potential cancer-causing function, but rather on the basis of the heterogeneous context in which that mutation is found (“precision medicine”).
All these challenges also apply to metastatic colorectal cancer (mCRC). Less than 20% of mCRC patients respond to anti-EGFR antibodies “the gold standard targeted therapy”, which calls for the identification of novel predictive biomarkers and suggests that uncharacterized drivers other than EGFR can sustain the growth of different CRC subsets. The categorization of tumor subpopulations featuring specific driver lesions, the validation of such lesions as targets, and the need for discrimination between “actionable” opportunities and those with weak clinical transferability require reliable preclinical models. The scope of our research is to refine genetic, mechanistic and therapeutic annotation of mCRC subsets using predictive in vivo models – namely, large collections of molecularly annotated patient-derived tumorgrafts as a means to systematically increase the success rate of rationally based clinical trials that emanate from preclinical findings.
Citation Format: Livio Trusolino. Patient-derived tumor xenografts for genotype-drug response correlations in colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA07.