bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2731: Receptor for Hyaluronan Mediated Motility (RHAMM) promotes breast cancer progression
Authors: Daughters Claire Elizabeth , Knutson Todd P. , Forster Colleen , McCarthy James , Schwertfeger Kaylee , Nelson Andrew 
Published: September 2020

Abstract
Breast cancer remains one of the leading causes of cancer-related death in women in the U.S. with over 40,000 deaths annually. Understanding mechanisms of breast cancer progression holds great clinical utility to individualize patient therapy and to increase our portfolio of effective treatments for the different subtypes of breast cancer. We performed a focused gene expression analysis of 120 patients across all relevant hormone receptor (HR) subtypes at our institution. Increased expression of hyaluronan mediated motility receptor (HMMR, aka RHAMM) was associated with higher Nottingham grade, lymph node metastasis, and higher stage (all p&lt;0.01). RHAMM expression was higher in more aggressive HR subtypes (triple negative and HER2+). Unsupervised hierarchical clustering of the cohort with a 29 gene signature related to RHAMM biologic activity further supported these associations with breast cancer progression/aggressiveness. Using CRISPR/Cas9, stable RHAMM -/- MCF10DCIS cell lines were created; RHAMM deletion does not affect cell proliferation, but significantly reduces in vitro Matrigel invasion and soft agar colony formation. RHAMM knockout also diminishes invasive progression of the MCF10DCIS cells in vivo, using the mouse intraductal (MIND) xenograft model; 83% of control xenografts demonstrate tissue invasion by 6 weeks, while only 50% of RHAMM-/- xenografts show any invasive component (p=0.03). Our human and model system data indicate a role for RHAMM function in breast cancer invasion. On-going work will investigate the dependency of the invasive phenotype specifically on RHAMM-hyaluronan binding; this interaction can be pharmacologically disrupted and may represent a specific intervention to limit breast cancer invasion and potentially metastasis.
Citation Format: Claire Elizabeth Daughters, Todd P. Knutson, Colleen Forster, James McCarthy, Kaylee Schwertfeger, Andrew Nelson. Receptor for Hyaluronan Mediated Motility (RHAMM) promotes breast cancer progression [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 2731.
Abstract 2746: PET-CT/FACS platform to detect the biodistribution of radioisotope 89Zr PD-1 inhibitor in syngeneic tumor models
Authors: Tang Xuzhen , Wang Fuyang , Chen Junyi , Zeng Xuanming , Liu Zhibo , Ji Qunsheng 
Published: September 2020

Abstract
Cancer treatment has been revolutionized by targeting the interaction between tumors and immune system. For instance, PD-1/PD-L1 mono- or combo-therapy has achieved great success in clinics, and patient responsiveness is closed associated with PD-L1 expression in cancer cells, tumor infiltration leukocytes, and drug bio-distribution in the tumor microenvironment. We established a method to label PD-1 inhibitor with radioisotope 89Zr for in-life imaging (PET-CT). Anti-PD-1 sensitive mouse colorectal cell line MC38 and resistant mouse melanoma cell line B16F10 were implanted to C57BL/6 mice, which were then treated with 89Zr PD-1 inhibitor. PET imaging was performed at multiple time points to detect the bio-distribution of anti-PD-1, while the infiltrated immune cells were identified by FCM and PD-L1 expression measured by IHC. Notable tumor uptake of 89Zr PD-1 inhibitor was observed in mouse liver and tumor grafts. The uptake in tumor increased over time and plateaued 24 hours post-injection. MC38 and B16F10 tumor grafts showed difference in uptake levels. Blood and tumor at both flanks were removed for leucocyte phenotyping, and compared with B16F10, MC-38 tumors exhibited higher percentage of total lymphocytes and cytotoxic T lymphocytes, equivalent number of dendritic cells and less myeloid cells. Further phenotyping indicates that compared to MC-38, B16F10 tumors contain higher percentage of MDSC, most of which are monocytic myeloid derived suppressor cells. With our PET-CT/FACS platform, we can evaluate immunotherapy response and microenvironment changes in different tumors in “one-mouse” system. The unique immune microenvironment (high TIL, high CD8+ T and low MDSC) may contribute to the notable and sustainable uptake of PD-1 inhibitor and the corresponding efficacy. This system can act as a good translational platform to monitor the PK-PD readout of immune therapy.
Citation Format: Xuzhen Tang, Fuyang Wang, Junyi Chen, Xuanming Zeng, Zhibo Liu, Qunsheng Ji. PET-CT/FACS platform to detect the biodistribution of radioisotope 89Zr PD-1 inhibitor in syngeneic tumor models [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 2746.
Abstract 2757: Analysis of stromal myofibroblasts identifies secreted proteins that promote pancreatic ductal adenocarcinoma
Authors: Martin Kelly A. , Sebastian Aimy , Hum Nicholas R. , Byers Stephen , Wheeler Elizabeth K. , Coleman Matthew A. , Loots Gabriela G. 
Published: September 2020

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most incurable types of cancer. Cancer that develops in the acinar cells of the pancreas is typically not diagnosed until later stages, such as stage 3 or 4. As such, this form of cancer is particularly lethal with only 9% of patients reaching 5-year survival. PDAC is known to have a particularly dense extracellular matrix composed of fibroblasts, which have been previously shown to play an important role in promoting resistance to drug therapy. Characterization of the stromal networks involved in PDAC tumor development as well as protein markers of fibroblast subpopulations within the tumor stroma are critical to developing new fibroblast-targeted therapeutic approaches as well as understanding key signaling molecules that ultimately promote tumor progression and drug resistance. Single-cell RNA sequencing (scRNAseq) was utilized to analyze cancer-associated fibroblasts (CAFs) from KPC mouse-derived, MT3 subcutaneous murine allografts along with two fibroblast lines derived from human PDAC tumors: CRC-811 and IA-1340. Single cell gene expression profiling and subsequent analysis of MT3-derived CAFs resulted in the identification of three CAF subpopulations including a myofibroblast subpopulation that expressed high levels of smooth muscle actin (Acta2), which was also observed in both human samples. Fibroblast subpopulations enriched in Acta2 expression, expressed high levels of Wnt5a along with several other secreted factors including Tgfb1, Tgfb2 and Ctgf. Wnt5a is a secreted protein that activates non-canonical Wnt signaling pathways and is known to regulate normal developmental processes, including proliferation, differentiation, migration, adhesion and polarity. However Wnt5a is not natively expressed in MT3 cancer cells derived from syngeneic tumors, but potentially in the stroma. We hypothesize it is exclusively derived from fibroblasts. Previously it has been shown that Wnt5a inhibition suppressed gastric cancer metastasis, therefore further validation of the role of myofibroblast-derived Wnt5a on PDAC disease progression is warranted. This study received funding by LDRD 19-SI-003. This work was conducted under the auspices of the USDOE by LLNL (DE-AC52-07NA27344). IM Release Number: LLNL-ABS-798442.
Citation Format: Kelly A. Martin, Aimy Sebastian, Nicholas R. Hum, Stephen Byers, Elizabeth K. Wheeler, Matthew A. Coleman, Gabriela G. Loots. Analysis of stromal myofibroblasts identifies secreted proteins that promote pancreatic ductal adenocarcinoma [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 2757.
Abstract 2809: Pancreatic cancer patient-derived organoids as a tool for personalized medicine
Authors: Tiriac Herve 
Published: September 2020

Abstract
Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we find that PDO therapeutic profiles paralleled patient outcomes and that PDOs enable longitudinal assessment of chemo-sensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemo-sensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemo-refractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.
Citation Format: Herve Tiriac. Pancreatic cancer patient-derived organoids as a tool for personalized medicine [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 2809.
Abstract 2845: Role of neutrophil associated a2 isoform of V-ATPase in cancer
Authors: Ibrahim Safaa A. , Riehl Valerie , Schneiderman Sylvia , Beaman Kenneth D. 
Published: September 2020

Abstract
Tumors associated neutrophils (TAN) regulate the tumor microenvironment by directly promoting tumor progression and represent a potential therapeutic target for cancer treatment. Identifying neutrophil associated proteins that promotes neutrophil pro-tumorigenic properties will provide new specific targets for cancer therapy. The a2 isoform of V-ATPase (a2V) is multisubunit enzyme that is expressed on the intravesicular membranes as well as the plasma membrane of activated immune cells. Immuno-histochemical analysis shows that TAN in human cancer tissues express a2V. Isolated neutrophils from healthy donors were primed with tumor conditioned media collected from MDA MB-231 and MCF-7. Primed neutrophils showed increased gene expression of a2V while a1 and a3 isoform expression were not changed. Increased a2V in neutrophils was confirmed in the protein level by western blot and immunofluorescence staining. Flow cytometric analysis showed increased a2V surface staining on live primed neutrophils. Multiplex Luminex assay showed increased secreted protein levels of multiple pro-, anti-inflammatory cytokines and protumorigenic factors such as IL-8, VEGF and MMP-9 from primed neutrophils. Currently we are characterizing a method to knock down the a2V in human neutrophils isolated from peripheral blood and investigating its effect on neutrophil phenotypes. Together these data suggest that neutrophil associated a2V can play an important role in regulating the neutrophil phenotype. This makes it a potential candidate to target for cancer therapy.
Citation Format: Safaa A. Ibrahim, Valerie Riehl, Sylvia Schneiderman, Kenneth D. Beaman. Role of neutrophil associated a2 isoform of V-ATPase in cancer [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 2845.
Abstract 2861: Targeting cancer with antibody-drug conjugates: Promises and challenges
Authors: Dean Alexis , Twomey Julianne , Zhang Baolin 
Published: September 2020

Abstract
Chemotherapy is inherently associated with side effects due to its poor selectivity towards tumor cells/tissues. Antibody-drug conjugate (ADC) technology promises to overcome barriers of classical chemotherapy by utilizing monoclonal antibodies to deliver potent payloads to selected target cancer cells. The antibody and cytotoxic payload are joined by a chemical linker resulting in an agent with the prospect of increased selectivity, anti-cancer activity, and improved systemic circulation. As of 2019, the US Food and Drug Administration (FDA) has approved five ADCs with cancer indications, including brentuximab vedotin for treatment of CD30-expressing lymphomas, trastuzumab emtansine for Her2-positive breast cancer, inotuzumab ozogamicin for CD22-positive acute lymphoblastic leukemia (ALL), gemtuzumab ozogamicin for CD33-positive acute myeloid leukemia (AML), and polatuzumab vedotin for diffuse large B-cell lymphoma (DLBCL). Currently, there are about 80 ADCs under clinical development in nearly 130 clinical trials. Despite initial success, there are still many challenges in the development of ADCs with respect to their safety and efficacy profiles. In this study, we aim to survey the recent efforts in the design and development of ADCs. We have focused on site-specific conjugation methods for producing homogenous ADCs with consistent drug-antibody ratio (DAR) - a challenge often observed in conventional conjugation methods. This information is further discussed with respect to the ADC interaction with target cells to elicit cytotoxicity. The survey results will be presented, giving perspective on technical considerations for ADC design towards better correlation between preclinical and clinical results and overall safer and more efficacious products.
Citation Format: Alexis Dean, Julianne Twomey, Baolin Zhang. Targeting cancer with antibody-drug conjugates: Promises and challenges [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 2861.
Abstract 2878: Granzyme B functionalized nanocarriers targeting membrane-bound Hsp70 for multimodal cancer therapies
Authors: Shevtsov Maxim , Kaesler Susanne , Stangl Stefan , Yakovleva Luidmila , Tagaeva Ruslana , Marchenko Yaroslav , Nikolaev Boris , Khachatryan William , Galibin Oleg , Pitkin Emil , Multhoff Gabriele 
Published: September 2020

Abstract
Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as potential clinical tools for cancer theranostics. Membrane-bound 70 kDa heat shock protein (mHsp70) is ubiquitously expressed on the cell membrane of various tumor types but not on normal cells and therefore provides a tumor-specific target. The serine protease granzyme B (GrB) that is produced as an effector molecule by activated T and NK cells has been shown to specifically target mHsp70 on tumor cells. Following binding to Hsp70, GrB is rapidly internalized into tumor cells inducing the process of cellular apoptosis. Decoration of the nanoparticles surface with GrB increased the targeting properties of the nanocarriers as was shown by confocal and electron microscopies. In series of in vivo studies it was demonstrated that GrB functionalized SPIONs act simultaneously as a contrast enhancement agent when being intravenously administered for magnetic resonance imaging and induce specific tumor cell apoptosis (human U87 glioblastoma in NMRI nu/nu mice, rat C6 glioma in Wistar rats, B16 melanoma in C57/Bl6 mice). Continuous prolonged administration of GrB-SPIONs via programmable subcutaneously implanted mini-pump system iPrecio further enhanced the therapeutic benefit of magnetic conjugates. Moreover, significant therapeutic response was achieved in immunocompromised mice models (advanced U87 brain tumor, small lung cancer H1339 with brain metastasis) with a high tumor burden. Combinatorial regimens employing stereotactic radiotherapy and/or magnetic targeting with immune checkpoint inhibitors (anti-CTLA-4 monoclonal antibodies) are found to further enhance the therapeutic efficacy of GrB-SPIONs in different tumor mouse models. The study was funded by RFBR, project № 19-08-00024; DFG grant SFB824/3, Germany, TaGoNaX DFG project № 336532926, STA1520/1-1.
Citation Format: Maxim Shevtsov, Susanne Kaesler, Stefan Stangl, Luidmila Yakovleva, Ruslana Tagaeva, Yaroslav Marchenko, Boris Nikolaev, William Khachatryan, Oleg Galibin, Emil Pitkin, Gabriele Multhoff. Granzyme B functionalized nanocarriers targeting membrane-bound Hsp70 for multimodal cancer therapies [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 2878.
Abstract 2933: KLF5 and its association with HIF-1α promotes PTC progression and metastatic potential through AKT activation
Authors: Poyil Pratheeshkumar , Siraj Abdul K , Padmaja Divya , Parvathareddy Sandeep Kumar , Thangavel Saravanan , Melosantos Roxanne , Victoria Ingrid G. , Begum Rafia , Al-Dayel Fouad , Al-Kuraya Khawla S. 
Published: September 2020

Abstract
Thyroid cancer is the second most common malignancy among females in Saudi Arabia, with Papillary thyroid carcinoma (PTC) accounting for 80-90%. Kruppel-like factor 5 (Klf5) is a transcription factor that plays a critical role in cell transformation, proliferation, and oncogenesis. Immunohistochemical analysis of KLF5 was performed in 1219 PTC cases. KLF5 over-expression was noted in 65.1% (793/1219) of PTCs, and was significantly associated with tall-cell variant (p &lt;0.0001), extrathyroidal extension (p = 0.0003), lymph node metastasis (p &lt; 0.0001) and stage IV tumors (p &lt; 0.0001). A significant association was also noted with HIF-1α over-expression (p = 0.0492). Interestingly, KLF5 over-expressing tumors showed poor disease-free survival (p = 0.0066). Functional studies in PTC cell lines showed that KLF5 co-immunoprecipitated with HIF-1α. Knockdown of KLF5 decreased the expression of HIF-1α while KLF5 was not affected by HIF-1α inhibition, suggesting that KLF5 is a functional upstream of HIF-1α. Down-regulation of KLF5 using a specific inhibitor, ML264 or siRNA inhibited cell migration, invasion, and angiogenesis. Also, the treatment of PTC cell lines with ML264 resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner. Furthermore, the silencing of KLF5 significantly decreased the self-renewal ability of spheroids generated from PTC cells. Our findings confer that KLF5 may be a potential therapeutic target for the treatment of papillary thyroid cancer.
Citation Format: Pratheeshkumar Poyil, Abdul K Siraj, Divya Padmaja, Sandeep Kumar Parvathareddy, Saravanan Thangavel, Roxanne Melosantos, Ingrid G. Victoria, Rafia Begum, Fouad Al-Dayel, Khawla S. Al-Kuraya. KLF5 and its association with HIF-1α promotes PTC progression and metastatic potential through AKT activation [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 2933.
Abstract 295: Protein phosphatase, Mg2+/Mn2+ dependent 1G promotes proliferation via modulating phosphorylation of retinoblastoma protein and associates with poor outcome in hepatocellular carcinoma
Authors: Hu Wen , Guan Xin Yuan , Li Lei , Zhu Yinghui , Li Yan , Zeng Ting Ting , Wen Yun Fei 
Published: September 2020

Abstract
The serine/threonine protein phosphatase family has been demonstrated involved in a variety of cellular processes. Here, we identified that protein phosphatase, Mg2+/Mn2+ -dependent 1G (PPM1G) is an oncogene-associated protein in hepatocellular carcinoma (HCC), and is associated with the progression of HCC. In this study, we carried out a series of in vitro (MTT, colony formation, immunoblot analysis, IHC, and Q-PCR) as well as in vivo (Hepatocellular carcinoma cell xenograft mouse model) experiments to determine the biological roles of PPM1G in HCC. Our results showed that PPM1G expression was significantly increased in HCC tissues, compared with the adjacent non-tumorous tissues. Further analysis revealed that high expression of PPM1G is associated with advanced clinical characters including advanced clinical stage and tumor recurrence. Kaplan-Meier analysis suggested that a high level of PPM1G is correlated to unfavorable overall survival (P &lt; 0.0001) as well as disease-free survival (P = 0.004) in patients with HCC. Furthermore, overexpression of PPM1G promoted cell proliferation while this effect can be attenuated by the knockdown of PPM1G in in vitro and in vivo studies. Notably, our findings showed that the tumor suppressor gene expression (e.g. pRb phosphorylation and p53 protein) was inhibited upon the silencing of PPM1G. Taken together, our study demonstrated that PPM1G plays an crucial role in HCC cell proliferation by modulating pRb phosphorylation as well as p53 expression. Furthermore, this study provides strong clinical implications of PPM1G in prognostic prediction in patients with HCC.
Citation Format: Wen Hu, Xin Yuan Guan, Lei Li, Yinghui Zhu, Yan Li, Ting Ting Zeng, Yun Fei Wen. Protein phosphatase, Mg2+/Mn2+ dependent 1G promotes proliferation via modulating phosphorylation of retinoblastoma protein and associates with poor outcome in hepatocellular carcinoma [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 295.
Abstract 2951: Knockdown of SCAMP3 suppresses the proliferation and emboli formation capacity of inflammatory breast cancer cells through EGFR signaling
Authors: Suarez-Arroyo Ivette J. , Reyes-Chea Jael , Martinez-Montemayor Michelle M. 
Published: September 2020

Abstract
Inflammatory Breast Cancer (IBC) is one of the most lethal forms of breast cancer (BC), where patients have a 43% increased risk of death compared to women with non-IBC advanced BC. Approximately 30% of triple-negative (TN) IBC cases overexpress the Epidermal Growth Factor Receptor (EGFR). EGFR amplification is associated with a poor overall survival rate compared with EGFR-negative IBC cases. We previously identified increased expression of the secretory carrier membrane protein 3 (SCAMP3) in EGFR overexpressing TN SUM149 IBC cells, tissues and in the IBC metastasis promoting structure, the tumor emboli. SCAMP3 is an endosome-associated protein known to regulate the degradation of EGFR. Thus, we aim to elucidate the role of SCAMP3 in the regulation of EGFR signaling and IBC progression. To investigate how SCAMP3 contributes to the IBC cellular response, we knocked out (KO) the expression of SCAMP3 in IBC SUM149 cells using the CRISPR/Cas9 technique. Wild type (WT) and KO IBC cells treated with EGF for 30 min in serum-starved conditions were used to assess cell viability after 24, 48, 72, and 96h, colony, and emboli formation capacity. Our results demonstrate a reduction in the proliferation, colony, and emboli formation capacity of SCAMP3 KO cells in comparison with the WT. Taken together our results show that SCAMP3 plays a promoting role in the progression of IBC through EGFR signaling modulation.
Citation Format: Ivette J. Suarez-Arroyo, Jael Reyes-Chea, Michelle M. Martinez-Montemayor. Knockdown of SCAMP3 suppresses the proliferation and emboli formation capacity of inflammatory breast cancer cells through EGFR signaling [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 2951.