bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4067: Cell phone use is associated with an inflammatory cytokine profile of parotid gland saliva
Authors: Gomez Ricardo S. , Siqueira Elisa C. , Souza Fabrício Tinôco A. , Ferreira Efigênia F. , Souza Renan P. , Friedman Eitan , Gomez Marcus V. , Gomes Carolina C. 
Published: July 2016

Abstract
There is controversy on the effects of the non-ionizing radiation emitted by cell phones on cellular processes and the impact of such radiation exposure on health. Conflicting results were reported on the association between cell phone use and parotid tumor development. Chronic inflammation is associated with an increased risk for cancer, such as seen in ulcerative colitis. To evaluate the effect that cell phone use has on the parotid gland, cytokine expression profile was determined in the saliva produced by the parotid glands in healthy volunteers, and correlated with self-reported cell phone use and laterality. The following parameters were determined, in 83 Brazilian individuals in saliva produced by the parotid glands comparing the saliva from the gland exposed to cell phone radiation (ipsilateral) to that from the contralateral parotid: salivary flow, total protein concentration, IL-1β, IL-6, IL-10, IFN-γ and TNF-α by ELISA. After multiple testing correction, decreased IL-10 and increased IL-1β salivary levels in the ipsilateral side compared with the contralateral side (p&lt;0.05) were detected. Subjects who used cell phones for more than 10 years presented higher differences between IL-10 levels in ipsilateral versus contralateral parotids (p = 0.0012). No difference was observed in any of the tested parameters in correlation with cell phone monthly usage in minutes. We conclude that exposure of parotid glands to cell phones can alter salivary IL-10 and IL-1β levels. These findings suggest a pro-inflammatory profile on parotid naturally exposed to cell phones, which can be associated not only to the radiation emitted by the device but with the warming caused by radiation and the battery of the cell during use.
Supported by: FAPEMIG (Fundação de Amparo à Pesquisa de Minas Gerais), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), Brazil
Citation Format: Ricardo S. Gomez, Elisa C. Siqueira, Fabrício Tinôco A. Souza, Efigênia F. Ferreira, Renan P. Souza, Eitan Friedman, Marcus V. Gomez, Carolina C. Gomes. Cell phone use is associated with an inflammatory cytokine profile of parotid gland saliva. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4067.
Abstract 4069: The carcinogenic effects of electronic cigarettes in oral cancer
Authors: Korrapati Avinaash , Yu Vicky , Saad Maarouf A. , Rahimy Mehran , Xuan Yinan , Zou Angela , Krishnan Aswini , Brumund Kevin , Ongkeko Weg M. 
Published: July 2016

Abstract
Alcohol consumption, tobacco use, and human papillomavirus infection have been well-established as the primary risk factors for head and neck squamous cell carcinoma (HNSCC). However, the surge in popularity of e-cigarettes (e-cigs) has prompted speculation of e-cig use potentially emerging as a new risk factor. With previous research on the safety of e-cigs still collectively inconclusive, a comprehensive study of the carcinogenicity of these devices remains urgently necessary. We therefore investigated the potential genotoxic, cytotoxic, and invasive and migratory effects of e-cig vapor exposure on human epithelial cells. A panel of normal epithelial and head and neck cancer cell lines was treated with 0.5%, 1.0%, and 2.0% by volume e-cig vapor from two popular e-cig brands, over periods ranging from 24 hours to 4 weeks. Neutral comet assay and immunostaining for γ-H2AX foci revealed significant induction of DNA double-stranded breaks (up to 3-fold increase, p &lt; 0.05) in cell lines incubated with both nicotinized and nicotine-free e-cig vapor. To evaluate the cytotoxicity of e-cigarettes, trypan blue exclusion and clonogenic assays were performed following short-term e-vapor exposure. Our results indicate that in epithelial cells, short-term treatment induces up to a 5-fold increase in cell death without nicotine, and up to a 10-fold increase with nicotine as compared to untreated controls (p &lt; 0.001). We subsequently assessed the effects of e-cigarettes on HNSCC progression and metastatic potential through exposure of established HNSCC cell lines to e-cigarette vapor. Wound healing assays revealed increased migration of HNSCC cells following e-cigarette treatment, with significant upregulation of key EMT-promoting genes observed via qRT-PCR. We will next examine the effects of long-term (6-9 months) e-cig vapor exposure in vivo using mouse models. Mouse oral epithelium will be harvested for histologic analysis and sequenced to determine the mutagenic potential of long-term e-cig vapor exposure. Nevertheless, our present findings based on short-term e-vapor exposure alone already pose alarming implications for the carcinogenic effects of e-cigarette use.
Citation Format: Avinaash Korrapati, Vicky Yu, Maarouf A. Saad, Mehran Rahimy, Yinan Xuan, Angela Zou, Aswini Krishnan, Kevin Brumund, Weg M. Ongkeko. The carcinogenic effects of electronic cigarettes in oral cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4069.
Abstract 4072: Molecular cytogenetic characterization of HPV types 16 and 18 cervical cancers: Acquired genomic instability by E6 and E7 oncoproteins
Authors: Tate Karen , Tran Lucy , Baker Melanie , Evans Kamilah , Rouse Mechelle , Chung Seyung , Nguyen Duy , Kim Juri , Smith-Joe Enijah , Vadgama Jay , Li Mengtao , Lin Yu-Ling , Patillo Roland , McGhee Eva 
Published: July 2016

Abstract
Human Papillomavirus (HPV) high-risk types 16 and 18 are directly associated with approximately 90% incidence of invasive cervical carcinoma. Epithelial cells infected with HPV become transformed and acquire genomic instability. As a result of this transformation, E6 and E7 oncogenes are perpetually expressed. E6 degrades the tumor suppressor p53; E7 inhibits tumor suppressor pRB, leading to disproportionate target cell growth and proliferation. While there have been studies exploring genomic instability induced by HPV oncoproteins E6/E7, the full scope of the genomic damage has not been clearly characterized. Three HPV positive cervical cancer cell lines, HeLa (HPV18), SiHa (HPV16) and CaSki (HPV16), were studied using Spectral Karyotyping (SKY) and Giemsa banding (G-banding). Our results using SKY and G-banding analysis showed HeLa cells exhibited frequent translocations on chromosomes 4 and 11, and deletions on chromosomes 11 and 20. The SiHa cells exhibited translocations primarily on chromosomes 9 and 20, with deletions on chromosome 10. CaSki revealed translocations on chromosomes 10 and 4, with deletions on chromosome 21. All three cell lines gained copies on chromosome 5. The aforementioned aneuploidy is demonstrative of the induced genomic instability acquired from HPV infection, which include tumor suppressor genes; p53 and pRB disruptions caused by E6 and E7 oncoproteins. HeLa cells showed extensive genomic instability on chromosome 11q22-23, where the ATM gene is located. Acquired genomic instability to the ATM chromosome region may further increase the rate of cervical cancer.
Citation Format: Karen Tate, Lucy Tran, Melanie Baker, Kamilah Evans, Mechelle Rouse, Seyung Chung, Duy Nguyen, Juri Kim, Enijah Smith-Joe, Jay Vadgama, Mengtao Li, Yu-Ling Lin, Roland Patillo, Eva McGhee. Molecular cytogenetic characterization of HPV types 16 and 18 cervical cancers: Acquired genomic instability by E6 and E7 oncoproteins. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4072.
Abstract 4074: Macrophages promote the progression of premalignant mammary gland lesions through activation of the Axl signaling cascade
Authors: Carron Emily C. , Machado Heather L. , Homra Samuel 
Published: July 2016

Abstract
Infiltrating inflammatory cells, including tumor-associated macrophages (TAMs), have been shown to promote breast cancer cell invasion and have been correlated with metastasis and poor prognosis. While it is well-established that macrophages are recruited to the invasive fronts of established tumors to exert pro-tumor signals, their role in premalignancy remains poorly understood. Using a novel p53−/− syngeneic transplantable model of premalignancy, we show that inflammatory cells, including macrophages, are indeed recruited to early lesions prior to invasion. Microarray analysis was performed on two different pre-invasive lines, termed PN1a, (high tumor-forming potential) and PN1b (low tumor-forming potential). Interestingly, several pro-inflammatory chemokines, macrophages markers, and the pro-inflammatory cytokine growth arrest specific 6 (Gas6) were increased in PN1a lesions as compared to PN1bs. In a 3-D co-culture system, macrophages were recruited to PN1a acini and induced invasion, while PN1b cells remained non-invasive, supporting our in vivo data. Depletion of macrophages in vivo with clodronate containing liposomes significantly delayed progression of PN1a lesions to invasive cancer, indicating a critical role for macrophages in early progression. Gas6 and its receptor tyrosine kinase, Axl, were highly expressed in PN1a preinvasive lesions, but decline in invasive tumors, suggesting that this pathway is a key driver of the transition from pre-invasive to invasive cancer. Further studies using our 3-D co-culture system with Gas6−/− macrophages demonstrated that macrophages promote the formation of non-polar disorganized structures by activating Axl. Finally, transplantation of PN1a cells into Gas6 +/− mice resulted in a delay in tumor formation, indicating that stromal-derived Gas6 (and potentially macrophage derived) may promote the progression of early stage lesions through the paracrine activation of Axl. As a plethora of Axl inhibitors have been developed and are currently in clinical trial, these studies have critical implications for the prevention and treatment of invasive breast cancer.
Citation Format: Emily C. Carron, Heather L. Machado, Samuel Homra. Macrophages promote the progression of premalignant mammary gland lesions through activation of the Axl signaling cascade. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4074.
Abstract 4087: Mammary fibroblasts exert divergent effects on the survival of invasive breast cancer cells
Authors: Hagel Kimberly , Weigel Kelsey , Boyd Meaghan , McCormack Luke , Champion Matthew , Schafer Zachary 
Published: July 2016

Abstract
Cancer development and progression are inherently inefficient processes riddled with anti-tumorigenic obstacles. Anoikis, or apoptosis induced by detachment from the extracellular matrix (ECM), represents one prominent hindrance to cancer progression that transformed cells must overcome in order to survive, particularly during the ECM-bereft metastatic cascade. Far from acting in isolation, we report that one mechanisms of anoikis evasion by invasive breast cancer cells involves the exploitation of carcinoma-associated fibroblasts (CAFs) from the surrounding tumor microenvironment. CAFs secrete insulin-like growth factor-binding proteins (IGFBPs) that facilitate non-canonical activation of integrin-linked kinase (ILK), activation of ERK/MAPK, and ultimately stabilization of the anti-apoptotic protein Mcl-1 to promote cancer cell survival during ECM detachment. Further investigation into the influence of the tumor microenvironment on cancer cell survival revealed that, contrary to the role of CAFs, normal mammary fibroblasts (NMFs) appear to exert anti-tumorigenic effects on ECM attached cancer cells. Utilizing conditioned media from NMFs, we have found that NMFs secrete factors that increase caspase activation in multiple cancer cell lines, suggestive of NMF-mediated cancer cell death. Because cancer progression necessitates the intermingling of cancer cells with normal stromal cells, particularly at early time points in primary tumor and metastases formation, we hypothesize that this NMFs pose yet another obstacle to disease progression that may compliment the process of anoikis by capping the metastatic cascade with environments that are inhospitable to cancer cell survival. Similar to anoikis evasion, our data suggests that cancer cells must evade NMF-induced death stimuli in order to survive, possibly through the accrual of CAFs in the tumor microenvironment to combat or replace the pro-apoptotic NMFs. Using traditional and 3D mammalian cell culture in combination with in vivo studies, we aim to delineate the roles of both CAFs and NMFs on cancer cell survival under conditions of differential ECM availability. A more complete understanding of the nuances dictating cancer cell-fibroblast interactions could yield informative data relevant to chemotherapeutic research and development.
Citation Format: Kimberly Hagel, Kelsey Weigel, Meaghan Boyd, Luke McCormack, Matthew Champion, Zachary Schafer. Mammary fibroblasts exert divergent effects on the survival of invasive breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4087.
Abstract 4089: Thyroid tumor microenvironment: mutual interaction between cancer and inflammatory cells
Authors: Tuli Neha Yashpal , Bednarczyk Robert B. , Ben Rahoma Ghada M. , Moscatello Augustine , Geliebter Jan , Tiwari Raj K. 
Published: July 2016

Abstract
Thyroid cancer is the most prevalent endocrine malignancy in the United States with an unacceptably high recurrence rate of 20-30%. Tumor associated macrophages (TAMs), one of the most critical component of solid tumor microenvironments, promote cancer initiation, growth, progression, metastasis and angiogenesis. These TAMs release cytokines as well as other secretory components like exosomes in the tumor microenvironment. Previously, we found that M1 polarized TAMs modulate thyroid cancer phenotype by inducing epithelial-mesenchymal transition (EMT), facilitating tissue metastasis and dissemination. In our present study, we used an in vitro model system to assess the crosstalk between the secretory components of macrophages and the epithelial cells in the thyroid tumor microenvironment. We used THP-1 monocyte/macrophage cell line along with thyroid cancer cell lines: consisting of two papillary cancer cell lines (BCPAP and TPC-1), one anaplastic cancer cell line (8505C) and one follicular cancer cell line (CGTHW-1). We observed that activated THP-1 macrophages are polarized towards M1 phenotype, secreting pro-inflammatory cytokines such as TGF-β, IL6, TNF-α, IL-1β, amongst others. These cytokines are responsible for halt in proliferation and change in morphology to mesenchymal phenotype promoting EMT in thyroid cancer cells. Similar pattern in phenotypical changes were noted in thyroid cancer cells treated with activated THP-1 macrophage exosomes. We also observed that EMT markers, such as vimentin and NFκ-B, are modulated in response to activated macrophage secreted exosomes. Moreover, secretory components from anaplastic thyroid cancer cells led to enhanced activation of THP-1 cells. These findings support a mutual cooperation between thyroid cancer cells and inflammatory cells in tumor microenvironment in defining thyroid cancer phenotype. Such correlation can identify early markers and prevent thyroid cancer differentiation, and are putative targets for therapy.
Citation Format: Neha Yashpal Tuli, Robert B. Bednarczyk, Ghada M. Ben Rahoma, Augustine Moscatello, Jan Geliebter, Raj K. Tiwari. Thyroid tumor microenvironment: mutual interaction between cancer and inflammatory cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4089.
Abstract 409: Immunofluorescent digital slide technology to evaluate correlation between Glypican-3 expression and response to codrituzumab
Authors: Tanaka Takayoshi , Sugitani Yasuo , Abe Tokiya , Kawaida Miho , Yamazaki Ken , Hashiguchi Akinori , Sakamoto Michiie , Ohtomo Toshihiko 
Published: July 2016

Abstract
Background: Codrituzumab/GC33/RO5137382 is a recombinant humanized monoclonal antibody against Glypican-3 (GPC3) which is highly expressed in HCC cells. As part of phase I clinical trial, GC-002US study, evaluating escalating doses of codrituzumab plus sorafenib in HCC, immunofluorescent staining of GPC3 were applied in addition to GPC3 immunohistochemistry (IHC) with conventional DAB staining. The objectives of this work were to compare GPC3 expression levels by different staining methods and evaluate the correlation between these GPC3 scores and codrituzumab activities.
Methods: Biopsies specimens (n = 34) collected at baseline in the phase I trial were evaluated by GPC3-IHC and immunofluorescent quantification digital slide (IQD) methods. GPC3-IHC were conducted using mouse anti-human GPC3 antibody, mouse GC33 (Ventana Medical Systems) as reported previously (Ikeda M. et al., Cancer Sci. 2014: 105; 455-462) and H scores were derived by two pathologists. For IQD, biopsy specimens were stained with same primary antibody, and were incubated with Qdot 655-conjugated secondary antibody. Fluorescent images of whole slides were obtained with the Nano-Zoomer (Hamamatsu Photonics K. K.). The IQD intensity score (immunofluorescent intensity per pixel) and cell score (immunofluorescent intensity per cell) were calculated respectively using MatLab (MathWorks Inc.).
Results: There was a statistically significant correlation between GPC3 H scores and IQD scores. Among GPC3 scores, only the IQD cell score was correlated with serum GPC3 C-terminus increase by treatment (p = 0.032), whereas in the patients treated with higher dose of GC33 (≥ 10 mg/kg/week) the cytoplasmic H and the IQD intensity score were also correlated with serum GPC3 C-terminus increase by treatment. Interestingly, increasing cut-off values of IQD cell score levels led to lower HR and longer PFS. Best HR with lowest p value was observed at a cut-off value of 66,183 (HR = 0.24, p = 0.038).
Conclusion: This study suggested that higher GPC3 expression on HCC cells quantified by IQD method was superior to other scores to predict codrituzumab activity, though this analysis was conducted only with limited number of subjects assessed. Further assessment and validation in clinical study of codrituzumab would be necessary to make a final conclusion on the clinical application of GPC3 IQD.
Citation Format: Takayoshi Tanaka, Yasuo Sugitani, Tokiya Abe, Miho Kawaida, Ken Yamazaki, Akinori Hashiguchi, Michiie Sakamoto, Toshihiko Ohtomo. Immunofluorescent digital slide technology to evaluate correlation between Glypican-3 expression and response to codrituzumab. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 409.
Abstract 41: DCA bind to EGFR/EGFRvIII/PDK1 and affect the proliferation and growth in TMZ resistant glioblastoma model
Authors: Velpula Kiran Kumar , Sahu Kamlesh , Tuszynski Jack , Guda Maheedhara R. , Asuthkar Swapna , Martin Sarah E. , Lathia Justin D. , Tsung Andrew J. 
Published: July 2016

Abstract
Glioblastomas are characterized by amplification of epidermal growth factor receptor (EGFR).
Approximately half of the GBM tumors with EGFR over-expression also express a constitutively active ligand independent EGFR variant III (EGFRvIII). This phenotype represents a tumor specific target correlating with a high growth potential. Despite advances in treatment, whether surgery, chemotherapeutics or molecular targeted therapies, very few have shown promise. Temozolomide (TMZ), as standard of care alkylation therapy, demonstrates improved survival when administered with concomitant radiotherapy. Unfortunately, acquired TMZ chemo-resistance is observed in more than 90% of recurrent GBMs. To understand the mechanisms in the context of TMZ resistance, we generated an in vitro TMZ resistant model by continuous exposure of U373 cells constitutively expressing EGFRvIII (U373vIII) to 150uM TMZ for 6 months (U373vIIIR). Dicholoroacetate (DCA) is a known metabolic inhibitor of pyruvate dehydrogenase kinase 1 (PDK1). Its application to cancer has recently been revived in the realm of metabolic oncology, where reversal of the Warburg effect has resulted in decreased tumor growth. Treatment of U373, U373vIII, and U373vIIIR GBM cell lines with DCA was found to induce cytotoxicity and reduced cell survival across all cell lines. Further, micro array studies conducted on U373vIII or U373vIIIR and their subsequent treatment with DCA revealed that PDK1 is the sole target in TMZ resistant tumors expressing EGFRvIII. Additionally, we demonstrated that 1mM DCA induced mitochondrial membrane potential change as evidenced in JC-1 staining and electron microscopic studies confirming mitochondrial apoptosis. Consistent with our previous findings that EGFR interacts with PDK1, our computational analysis revealed that DCA aligns itself to the binding sites of both EGFR and EGFRvIII with strong binding affinity apart from its binding to PDK1. Clinically, expression of EGFRvIII correlated with PDK1 when compared to EGFR in GBM surgical specimens. Collectively, our studies demonstrate that principles of metabolic oncology and DCA are active in GBM treatment despite resistance providing new insight into the development of alternative treatment in TMZ failure.
Citation Format: Kiran Kumar Velpula, Kamlesh Sahu, Jack Tuszynski, Maheedhara R. Guda, Swapna Asuthkar, Sarah E. Martin, Justin D. Lathia, Andrew J. Tsung. DCA bind to EGFR/EGFRvIII/PDK1 and affect the proliferation and growth in TMZ resistant glioblastoma model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 41.