bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5986: Inverse relationship between Giant Axonal Neuropathy gene expression and EMT in human tumors
Authors: Veena Mysore S. , Shin Daniel Sanghoon , Jeong Chan , Chatoff Jenna R. , Venkatesan Natarajan , Basak Saroj K. , Gray David , Wilczynski Sharon P. , Wilczynski Sharon P. , Gray Steven J. , Kohn Donald B. , Wang Marilene B. , Srivatsan Eri S. 
Published: September 2020

Abstract
Gigaxonin, the protein product of the Giant axonal neuropathy (GAN) gene, is a E3 ubiquitin ligase involved in neural cell and fibroblast intermediate filament processing. We have previously shown that Gigaxonin interacts with p16 in cisplatin-mediated ubiquitination of NF-κB. We analyzed cervical and head and neck cancer cell lines and primary tumors and have found exon 8 c.1293C&gt;T single nucleotide polymorphism (SNP) to occur in both HPV positive and negative tumor cells lines and primary tumors. The prevalence of this SNP in the tumor samples was double that of the normal population (47.25% vs. 22%) and there was no relationship to HPV status. Cell lines containing the SNP showed higher expression of gigaxonin, and an inverse relationship to in vitro tumor cell line growth and cisplatin sensitivity. There was a direct relationship between the expression of gigaxonin and e-cadherin and inverse relationship to the expression of twist, snail and n-cadherin. CRISPR-Cas9 mediated conversion of T to C allele in gigaxonin overexpressing cervical cancer cell line ME 180 resulted in decreased gigaxonin expression accompanied by increased expression of twist, and snail and increased in vitro cell growth. Re-expression of gigaxonin in the CRISPR-Cas9 clone with a plasmid gigaxonin cDNA construct resulted in decreased expression of twist pointing to gigaxonin mediated downregulation of the EMT marker. We therefore hypothesize that GAN, associated with the neurodegenerative disease, is also a human tumor cell growth suppressor gene.
Citation Format: Mysore S. Veena, Daniel Sanghoon Shin, Chan Jeong, Jenna R. Chatoff, Natarajan Venkatesan, Saroj K. Basak, David Gray, Sharon P. Wilczynski, Sharon P. Wilczynski, Steven J. Gray, Donald B. Kohn, Marilene B. Wang, Eri S. Srivatsan. Inverse relationship between Giant Axonal Neuropathy gene expression and EMT in human tumors [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 5986.
Abstract 5999: The Warburg Effect suggests a palliative care approach to cancer therapy
Authors: Meade-Tollin Linda C. , Tsang Tom C. 
Published: September 2020

Abstract
Introduction: Otto Warburg discovered in 1924 that cancer cells needed a lot more glucose than normal cells. Today, the “Warburg Effect” is not only recognized as a “hallmark of cancer” but also served as the scientific basis for cancer detection using fluorodeoxyglucose (FDG) Positron emission tomography (PET-scans). Warburg suggested in 1927 that treating cancer patients with insulin can deprive glucose to the cancer cells by lowering the blood glucose levels and may inhibit tumor growth. Although at least six peer-reviewed publications so far have provided support for the feasibility of this approach, no clinical trial has ever been done. We have previously presented an analysis of the data from hospitals in China suggesting that insulin can be safely administered for patients receiving a small dosage of standard chemotherapy drugs as palliative treatments for late-stage cancer patients. Here, we report additional data from more patients and medical facilities.
Experimental procedures: Patients diagnosed with multiple types of late-stage solid tumors were treated with regular insulin (Humulin R) administered intravenously, and small doses of standard chemotherapy drugs (approximately 10% of the standard dosages). Blood glucose levels were monitored throughout the course of treatment. Hypoglycemia was reversed by ingestion of food and drink or injection of glucose solution. Depending on how well the patients tolerated the treatments, 5-30 units of insulin were used. No permanent side effects were observed or reported.
Summary of data: Over 400 treatments have been performed on over 30 patients ranging from 30 to 76 years old, and diagnosed with 14 types of cancer. The average age of the patients was 56.2 years old. Symptoms of hypoglycemia were observed in all 30+ patients, and readily reversed by intravenous infusions of glucose or ingestion of food and drink. The insulin treatments were well tolerated and no longer -term side effects were observed.
Conclusions: Our analysis supports the feasibility of using regular insulin as a reproducibly safe method to achieve glucose deprivation in patients with advanced stages of multiple types of cancer receiving palliative and hospice care. These and additional future studies could form the basis for eventually conducting a clinical trial testing whether regular insulin, which is inexpensive and available over the counter, can be an alternative therapeutic option for palliative and hospice care in some patients.
Citation Format: Linda C. Meade-Tollin, Tom C. Tsang. The Warburg Effect suggests a palliative care approach to cancer therapy [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 5999.
Abstract 6000: eIF3A regulate the Warburg effect via ENO1 in cervical cancer cells
Authors: Xu Pengfei , Li Dake 
Published: September 2020

Abstract
Eukaryotic translation initiation factor 3A (eIF3A) is one of the core subunits of the translation initiation complex eIF3. eIF3A is critical for ribosomal subunit joining and recruiting mRNA to the ribosome, as well as for the regulation of various gene products. However, the function of eif3A have not been reported in cervical cancer (CC). Here we reported that Eif3A protein was overexpressed in CC tissues and the higher expression of Eif3A predicted a worse prognosis. Further experiments showed that eIF3A knockdown inhibited CC cells' proliferation and migration and promoted apoptosis in vitro and in vivo. eIF3A silencing accelerated acidification of the culture medium of CC cells. Seahorse results showed that the decreased expression of eIF3A significantly reduced glycolysis flux in CC cells. Mass spectrometry suggested that eIF3A knockdown could significantly repressed the expression of ENO1, which is a famous glycolytic protein. Western blot assay indicated that eIF3A silencing significant decreased the expression of ENO1. Therefore, our results indicated that eIF3A could enhance the warburg effect in cervical cancer by regulating ENO1.
Citation Format: Pengfei Xu, Dake Li. eIF3A regulate the Warburg effect via ENO1 in cervical cancer cells [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 6000.
Abstract 6006: Total body irradiation and graft-versus-host disease: A meta-analysis
Authors: Poonsombudlert Kittika , Prueksapraopong Chattip , Kewcharoen Jakrin , Limpruttidham Nath 
Published: September 2020

Abstract
Objective: Total Body Irradiation (TBI) has been one of the standard conditioning regimens since the early development of allogeneic hematopoietic stem cell transplant (HSCT). Some studies have suggested a correlation between the use of TBI and the development of acute and chronic graft-versus-host disease (aGVHD and cGVHD) but there is currently no meta-analysis to confirm the association. Therefore, we conducted a meta-analysis to evaluate the association between TBI and GVHD.
Method: We performed a comprehensive literature search in MEDLINE, Cochrane Library and EMBASE database from inception to February 2019 for studies that evaluated the association between TBI and aGVHD or cGVHD. We calculated pooled odd ratios (OR) with 95% confidence interval (CI) and I2 statistic using the random-effects model (Odd Ratio) of aGVHD and cGVHD in the TBI group versus the non-TBI group.
Result: Thirteen studies were included involving a total of 19,303 participants (TBI=10,222, non-TBI 9,081).There was a significant association between TBI use and development of aGVHD (pooled OR 1.32, 95% CI 1.09-1.60, I2=76.7 %) and cGVHD (pooled OR 1.32, 95% CI 1.12-1.54, I2=46.2%)
Conclusion: The results of our meta-analysis suggested that the use of TBI is significantly associated with aGVHD and cGVHD in the setting of allogeneic hematopoietic stem cell transplant.
Citation Format: Kittika Poonsombudlert, Chattip Prueksapraopong, Jakrin Kewcharoen, Nath Limpruttidham. Total body irradiation and graft-versus-host disease: A meta-analysis [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 6006.
Abstract 6010: Tumor mhicroenvironment effects on hematopoietic stem cell induced tumor growth following radiation therapy
Authors: Parsons Tyler M. , Buelow Katie , Hanna Alaa , Galoforo Sandra , Wilson George , Madlambayan Gerard 
Published: September 2020

Abstract
The tumor microenvironment (TME), comprised of tumor tissue, stromal cells, extracellular matrix (ECM), bone marrow (BM)-derived immune cells, and various signaling molecules, rarely remains static. These components continuously respond to internal and external stimuli to promote tumor progression as well as regrowth after therapy. Recently, we reported that functional BM-derived hematopoietic stem and progenitor cells (HSPCs) take up residence within growing lung tumors. Interestingly, when tumors were
exposed to radiation therapy (RT) there was a significant increase in HSPC numbers within tumors (p&lt;0.003). These HSPCs seemed to positively affect tumor regrowth as their numbers directly correlated with regrowth rates (R2=.4875). To determine the role of HSPCs in tumor growth we proposed a mechanism wherein tumor-associated HSPCs are maintained within tumors but following exposure to RT can differentiate into tumor-supportive macrophage populations, thus aiding in tumor regrowth. To test this hypothesis, Lewis Lung Carcinoma tumors were subcutaneously generated in mice and exposed to either RT or no radiation treatment (NRT). Analysis using RT-PCR and immunohistochemistry demonstrated that RT produces TME conditions that favor the differentiation of HSPCs into tumor-supportive M2-macrophages through the increased production of colony stimulating factor 1 (CSF-1) (p&lt;0.005). In addition, we show that inhibition of CSF-1R phosphorylation using a pharmacologic inhibitor (GW2580) had no effect on HSPCs numbers but resulted in significantly decreased M2 macrophage numbers resulting in decreased tumor growth and regrowth (p&lt;0.005). Furthermore, we found that the interaction of HSPC-bound integrin α6 with Laminin 5-1-1 is associated with HSPC maintenance within tumors. Interestingly, Laminin 5-1-1 levels were decreased in RT treated tumors compared to NRT controls (p&lt;0.005) further indicating that the RT-derived microenvironments supported HSPC differentiation into M2 macrophages. Overall, these studies define a new understanding of tumor biology in which tumor-associated HSPCs are an essential component of tumor progression and survival and identify new treatment strategies to overcome these effects and achieve more optimal clinical outcomes.
Citation Format: Tyler M. Parsons, Katie Buelow, Alaa Hanna, Sandra Galoforo, George Wilson, Gerard Madlambayan. Tumor mhicroenvironment effects on hematopoietic stem cell induced tumor growth following radiation therapy [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 6010.
Abstract 6012: Cancer stem cells could be responsible for the chimeras of hematopoietic cells in the cancer microenvironment
Authors: Hassan Ghmkin , Afify Said M , Kumon Kazuki , Osman Amira , Zahra Maram H , Seno Akimasa , Seno Masaharu 
Published: September 2020

Abstract
Development of cancer stem cells (CSCs) model from iPSCs for different types of cancers will help to investigate the tumorigenesis and designing new therapies applicable to CSCs. In this context, our lab has developed a novel method to generate CSCs from iPSCs under cancer microenvironment using conditioned medium from different cancer cell lines. In our previous study, BT549 cell line conditioned media was used to convert iPSCs to CSCs (miPSCs-BTcscs). Here, we investigated the potential of adherent CSCs converted from iPSCs to give hematopoietic like cells. Cancer stem cells, miPSCs-BTcscs, were obtained by conversion of miPSCs (iPS MEF-Ng-20D-17) cells in the presence of conditioned medium from breast cancer cell line BT549 cells followed by the primary culture of the tumor formed in Balb/c nude mice. The stemness and tumorigenicity of miPSCs-BTcscs cells had previously been confirmed. miPSCs-BTcscs cells were cultured on gelatin coated dish in absence of Leukemia Inhibitory Factor (LIF) and select undifferentiated cells was done using puromycin. Non-adherent cells (NACs) arising from adherent CSCs collected and their viability, the morphology and the expression of hematopoietic cells markers were investigated using Giemsa staining, flow cytometry, immunofluorescence staining, and RT-PCR. Moreover, to assess the potential of clonogenicity in vivo and the engraftment of NACs, NACs were injected into the tail vein of busulfan conditioned Balb/c nude mice. The round nucleated NACs were found to be viable, positive for Lin markers and CD34 and expressed hematopoietic markers just like homing to the bone marrow. When NACs were injected into a mouse, Wright-Giemsa staining showed that the number of white blood cells got higher than those in the control mice after 4 weeks. As conclusion, CSCs were demonstrated to have the potential to provide progenies with hematopoietic markers, morphology and homing ability to bone marrow, which could give a new insight into tumor microenvironment according to the plasticity of CSCs.
Citation Format: Ghmkin Hassan, Said M Afify, Kazuki Kumon, Amira Osman, Maram H Zahra, Akimasa Seno, Masaharu Seno. Cancer stem cells could be responsible for the chimeras of hematopoietic cells in the cancer microenvironment [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 6012.
Abstract 6016: The impact of cancer stem cell markers in the tissues of pancreatic ductal adenocarcinoma for prognosis after surgical resections
Authors: Inokawa Yoshikuni , Yamada Suguru , Hayashi Masamichi , Sunagawa Yuki , Sonohara Fuminori , Takami Hideki , Hattori Norifumi , Kanda Mitsuro , Kobayashi Daisuke , Tanaka Chie , Nakayama Goro , Koike Masahiko , Kodera Yasuhiro 
Published: September 2020

Abstract
Introductions: The prognosis after resection of pancreatic ductal adenocarcinoma (PDAC) is still limited though the survival benefit is recently reported by neo-adjuvant chemotherapy (NAC). The existence of cancer stem cells (CSCs) is known as one of the important mechanisms for cancer cells to survive against chemotherapy. We hypothesized that the population of CSCs among cancer cells after chemotherapy could contribute recurrence after surgical resections, and could be detected by some CSC markers.
Methods: We checked elevation of CSC markers in resected cases after pre-operative therapy (NAC with gemcitabine plus nab-paclitaxel, n=3; NAC with FOLFIRINOX, n=3; and neo-adjuvant chemo-radiotherapy (NACRT) with S1+Radiation, n=3) compared to surgery alone (n=3) with RT2 Profiler PCR Array. As CSC models, we performed sphere formation assay with PDAC cell lines (Panc1 and BXPC3) and evaluated the expression of CSC markers with qRT-PCR. Then, we performed qRT-PCR with 48 PDAC resected cases including 26 cases with pre-operative therapy (54%).
Results: RT2 Profiler PCR Array showed higher expression of some CSC markers with pre-operative treatment (n=9) than without them (n=3). Spheroid assay showed elevation of CSC markers in spheroid compared to parental cells (Panc1: 10 among 16 markers, BXPC3 14 among 16 markers). In the cohort of 48 resected PDAC patients, ALDH1, Nanog, SOX2, MYC CXCR4 and DCLK1 showed significantly higher expression in pre-operative therapy than in surgery alone (P&lt;0.05). About prognosis, higher expression of YAP1 in tumor tissues showed worse outcomes of recurrence free survival (RFS) (P=0.06), and higher CXCR4 in adjacent parenchyma of pancreas showed worse RFS among patients with NAC and NACRT (P=0.08).
Conclusions: Our findings indicated that CSCs are more in resected tissues after NAC and NACRT than in without pre-operative therapy. YAP1 expression in tumors or CXCR4 in adjacent parenchyma of pancreas can be prognosis markers after surgical resection for PDAC.
Citation Format: Yoshikuni Inokawa, Suguru Yamada, Masamichi Hayashi, Yuki Sunagawa, Fuminori Sonohara, Hideki Takami, Norifumi Hattori, Mitsuro Kanda, Daisuke Kobayashi, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera. The impact of cancer stem cell markers in the tissues of pancreatic ductal adenocarcinoma for prognosis after surgical resections [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 6016.
Abstract 6018: The perfused 3DKUBE™ rare tumor assay models in vivo drug response
Authors: Millard Melissa , Appleton Kathryn M. , Elrod Ashley , Bateman Nicholas W. , Abulez Tamara , Conrads Kelly , Hood Brian , Conrads Thomas P. , Holmes Lillia M. , DesRochers Teresa M. 
Published: September 2020

Abstract
Models that accurately reflect patient drug response are essential for the clinical design of personalized treatment plans and necessary for preclinical drug development. The advancement of predictive models for rare tumor types is impeded in part, by the relative scarcity of fresh tumor tissue available for study. To address the problem of tissue availability we have developed a label-free, combined functional and chemical selection method for the isolation of rare tumor cancer stem cells (CSC) and circulating tumor cells (CTC) from primary patient tissue and blood. Enriched cells were expanded as 3D microtumors under optimized conditions, validated as CSC through in vivo tumorigenesis studies, and characterized by correlative genomic, proteomic/phosphoproteomic, and phenomic analysis. We found isolation and expansion by this method yielded a source of primary cells suitable for live, cell-based predictive drug screening in multiple rare tumor derived models of neuroendocrine and mesenchymal origin, including locally or regionally advanced and metastatic SCLC, recurrent Merkel Cell Carcinoma, recurrent osteosarcoma and dermatofibrosarcoma protuberans. The 3DKUBE™ rare tumor assay was performed using validated CSCs cultured as perfused 3D microtumors (pMTs). Drug studies using the perfused, 3DKUBE™ rare tumor assay modeled individual patient response better than CSC-based or 3D static microtumor-based drug screens and thus demonstrate the effectiveness of this platform for predictive modeling of individual patient drug response. Taken together, this system provides a means of performing ex vivo drug response experiments on very small tissue samples, including core biopsies, with relevant results for patients.
Citation Format: Melissa Millard, Kathryn M. Appleton, Ashley Elrod, Nicholas W. Bateman, Tamara Abulez, Kelly Conrads, Brian Hood, Thomas P. Conrads, Lillia M. Holmes, Teresa M. DesRochers. The perfused 3DKUBE™ rare tumor assay models in vivo drug response [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 6018.
Abstract 6024: An integrin αvβ3+ stem-like tumor cell subset promotes breast cancer progression via c-Jun/AXL signaling
Authors: Sun Qi , Wang Yufen , Officer Adam , Harismendy Olivier , Desgrosellier Jay S. 
Published: September 2020

Abstract
Breast cancer cells bearing similarities to normal mammary stem cells play a key role in tumor progression. Here, we characterize a unique stem-like tumor cell population that expresses the integrin αvβ3 and is associated with aggressive patient disease. We now show that αvβ3+ cells that also express EpCAMLow represent a functionally and transcriptomically distinct breast cancer cell type. Rare αvβ3+ cells enrich for stemness properties such as anchorage-independent colony formation, self-renewal, differentiation and tumor initiation at limiting dilution. Unbiased whole transcriptome analysis by RNA-Seq identified several genes specifically upregulated in αvβ3+ cells that are also enriched in normal adult mammary stem cells. Phospho-array profiling of major signaling pathways revealed increased activation of the proto-oncogene c-Jun in αvβ3+ stem-like cells. Inhibition of JNK/c-Jun signaling further identified the receptor tyrosine kinase AXL as a critical downstream target gene necessary for tumorsphere formation. Our findings reveal a c-Jun/AXL signaling pathway required for stemness properties in αvβ3+ tumor cells important for breast cancer progression.
Citation Format: Qi Sun, Yufen Wang, Adam Officer, Olivier Harismendy, Jay S. Desgrosellier. An integrin αvβ3+ stem-like tumor cell subset promotes breast cancer progression via c-Jun/AXL 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 6024.