bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5752: Susceptibility of cells from cervical transformation zone to HPV-16 induced immortalization and dysplastic differentiation
Authors: Deng Han , Hillpot Eric , Yeboah Philomina , Mondal Sumona , Woodworth Craig D. 
Published: July 2017

Abstract
Persistent infection of high-risk human papillomavirus (HPV) is a major risk factor for cervical cancer. Greater than 90% of these cancers originate in the cervical transformation zone (CTZ), a narrow band of squamous metaplastic epithelium between ectocervix and endocervix. It is unclear why the CTZ has high susceptibility to malignant transformation and few studies have specifically examined cells from this region. We hypothesized cells cultured from human CTZ are uniquely susceptible to cellular immortalization and dysplastic differentiation, two alterations that contribute to malignant development. Primary epithelial cells were cultured from each region of human cervix (ectocervix, endocervix and CTZ) and characterized for expression of differentiation markers to assess their origin. We examined susceptibility of cells from each region to immortalization after transfection with the complete HPV-16 genome or infection of HPV-16 E6/E7 retroviruses. In addition, we evaluated the extent of dysplastic epithelial differentiation in organotypic cultures of HPV16-immortalized cell lines derived from each region of cervix. Our results showed that cells from the CTZ express specific keratin markers (keratin 14 and 18) that confirm their origin. Primary cell cultures from CTZ and ectocervix are more susceptible to immortalization by the HPV16 complete genome or E6/E7 retroviruses. In contrast, preliminary results indicate that HPV-immortalized CTZ and endocervical cells are more susceptible to dysplastic differentiation when maintained in organotypic culture. Our results may help to identify important signal pathways or biomarkers that are unique to cells from CTZ and that can be targeted for improved screening, prevention or therapy.
Citation Format: Han Deng, Eric Hillpot, Philomina Yeboah, Sumona Mondal, Craig D. Woodworth. Susceptibility of cells from cervical transformation zone to HPV-16 induced immortalization and dysplastic differentiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5752. doi:10.1158/1538-7445.AM2017-5752
Abstract 5753: Inhibition of CCAR1, a coactivator of β-catenin, suppresses the proliferation and migration of gastric cancer cells
Authors: Chang Te-Sheng , Lu Chung-Kuang , Wei Kuo-Liang , Chen Yi-Hsing , Cheng Ying-Tung , Tung Shui-Yi , Wu Cheng-Shyong , Chiang Ming-Ko 
Published: July 2017

Abstract
Given a current hypothesis that cancer arises from cancer stem cells (CSCs), targeting key signaling pathways that support CSC self-renewal appears to be a useful approach to cancer therapy. Derranged expression of Wnt signaling is among the major pathways implicated in regulating the stenmess properties of a variety of human cancers, including gastric cancer. Cell cycle and apoptosis regulator 1 (CCAR1) is a transcriptional coactivator which has been shown to be a component of Wnt/β-catenin signaling, and plays an important role in transcriptional regulation by β-catenin. However, the function and clinical significance of CCAR1 in gastric cancer have not been elucidated. Here we show the elevated CCAR1 nuclear expression correlates with the occurrence of gastric cancer. In addition, RNAi-mediated CCAR1 reduction not only suppressed the cell growth and increased apoptosis in gastric cell lines AGS and MKN28, but also reduced the migration and invasion ability of these cells. Furthermore, In vivo xenograft assay revealed that the expression level of CCAR1 was critical for tumorigenesis. Our data demonstrates that CCAR1 contributes to carcinogenesis in gastric cancer and is required for the survival of gastric cancer cells. Moreover, CCAR1 may serve as a diagnostic marker and a potential therapeutic target.
Citation Format: Te-Sheng Chang, Chung-Kuang Lu, Kuo-Liang Wei, Yi-Hsing Chen, Ying-Tung Cheng, Shui-Yi Tung, Cheng-Shyong Wu, Ming-Ko Chiang. Inhibition of CCAR1, a coactivator of β-catenin, suppresses the proliferation and migration of gastric cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5753. doi:10.1158/1538-7445.AM2017-5753
Abstract 5757: Study of human mammary tumor virus (HMTV) in human breast cancer by NanoString nCounter and FISH analysis
Authors: Melana Stella M. , Tripodi Joseph , Nosike Digna , Shabnam Jaffer , Etkind Polly , Pogo Beatriz GT , Holland James F. 
Published: July 2017

Abstract
Human Mammary Tumor Virus (HMTV), a retrovirus 90-98% homologous to Mouse Mammary tumor Virus (MMTV), the etiological agent of murine mammary cancer, has been detected by PCR in 40% of American women’s breast cancers, but not in healthy tissues of the same breast (Cancer Research 1995, 55:5173-79; Clin. Cancer Research 2001, 7-283-4). A complete 9.9 kb HMTV proviral sequence has been detected in breast cancer genomic DNA (Cancer Res 2001,61:1754-9). HMTV viral particles with betaretrovirus characteristics have been isolated from metastatic breast cancer cells in effusions (MSSM cells). Expression of HMTV proteins has been detected in MSSM cells by western blot, fluorescence-activated cell sorting analysis, and immunofluorescence assays but not in normal mammary epithelial cells (J Virol Methods 2010, 163(1): 157-61). PCR is a sensitive technique susceptible of contamination, which due to amplification, could result in false positive detection. Although murine DNA was not found by PCR, the possibility still exists that HMTV in human DNA could be a result of laboratory contamination. Despite the substantial evidence supporting the presence of HMTV in breast cancer the controversy continues because the chance of contamination has led to doubt that murine-like viruses are human pathogens. We now report additional analyses of breast cancer specimens employing other methods for HMTV detection that reinforce previous findings. NanoString nCounter, a new technology using specific 100 mer oligonucleotides as probes bound to reporter molecules that can detect HMTV gag, env and LTR sequences as well as two murine specific probes in a single reaction without amplification. Flourescence in situ hybridization (FISH) assays with a HMTV probe is a technology that permits visualization of HMTV proviral DNA in the nuclei of surgical samples of breast cancer as well as in MSSM cells. Results from Nanostring nCounter, and FISH analysis show the presence of HMTV DNA in surgical cancer specimens and in MSSM cells. The data exclude contamination and confirm the authenticity of HMTV in human breast cancer. Next-generation sequencing and other studies are in progress to determine the role of HMTV in the pathogenesis of breast carcinoma.
Citation Format: Stella M. Melana, Joseph Tripodi, Digna Nosike, Jaffer Shabnam, Polly Etkind, Beatriz GT Pogo, James F. Holland. Study of human mammary tumor virus (HMTV) in human breast cancer by NanoString nCounter and FISH analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5757. doi:10.1158/1538-7445.AM2017-5757
Abstract 5764: Oncogenic role of GAEC1 and its potential modulation with p53 in pathogenesis of colon cancer
Authors: Wahab Riajul , Islam Farhadul , Gopalan Vinod , Lam Alfred King-Yin 
Published: July 2017

Abstract
Introduction: GAEC1 (Gene amplified in esophageal cancer 1), is frequently amplified and overexpressed in colon cancer tissues. In the present study, we aimed to unveil the oncogenic potential of GAEC1 in carcinogenesis of colon cancer by studying the underlying cellular functions and molecular interactions by in vitro and in vivo experiments.
Method: Transient overexpression of GAEC1 with pcDNA3.1-GAEC1 and silencing with GAEC1-siRNA was performed and several downstream assays were done such as migration, clonogenic and apoptotic assay. Analysis of cell kinetics was done using flow cytometry and cell counting kit-8 was used for cell proliferation assay. Immunofluorescence and Western blot assay were used to determine the expression of different target proteins. Co-immunoprecipitation was used to confirm the protein-protein interaction. For xenotransplantation the severely combined immunodeficient (SCID) mice (4 groups, 6 in each group) were injected subcutaneously with GAEC1 shRNA and control shRNA transfected (stable) SW480 and SW48 colon cancer cells.
Result: The overexpression of GAEC1 increased cell proliferation, migration, reduced apoptosis in colon cancer cells. Also, these cells showed cell cycle arrest at the synthetic phase, activation of Bcl-2, K-ras, pAKT proteins as well as inhibition of p53, PUMA, p21 and BAX proteins. Conversely, knockdown of GAEC1 reduced cell proliferation, migration, decreased the phosphorylation of AKT, and induced apoptosis, G2/M phase arrest and cleavage of poly (ADP-ribose) polymerase (PARP). Co-immunoprecipitation revealed GAEC1’s interaction with p53. In addition ectopic over expression and silencing of GAEC1 lead to reciprocal effects of p53 protein expression. Moreover, knockdown of GAEC1 reduced the nuclear translocation of murine double minute 2 protein (mdm2) indicating that GAEC1 is responsible for the degradation of p53 through the direct interaction between mdm2-p53 in nucleus. Furthermore, our in vivo data demonstrate that the loss of GAEC1 inhibits the tumor formation in xenograft model.
Conclusion: Collectively our study demonstrates that GAEC1 exhibits the oncogenic role in colon cancer by reducing expression of p53 through protein-protein interaction which leads to the inhibition of PUMA, p21, BAX, and activation of Bcl-2, K-ras and pAKT protein expression.
Note: This abstract was not presented at the meeting.
Citation Format: Riajul Wahab, Farhadul Islam, Vinod Gopalan, Alfred King-Yin Lam. Oncogenic role of GAEC1 and its potential modulation with p53 in pathogenesis of colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5764. doi:10.1158/1538-7445.AM2017-5764
Abstract 5772: Developing a patient derived 3D co-culture model of prostate organoids to examine biological mechanisms involved in prostate cancer disparities
Authors: Marsili Joseph , Richards Zachary , Garcia Jason , Voisine Cindy , Nonn Larisa 
Published: July 2017

Abstract
The prostate is composed of a fibro-muscular stromal and glandular epithelial cells. Cross-talk between these cell populations is essential for normal prostate development and is involved in carcinogenesis. In the past year, an estimated 220,800 new cases of prostate cancer (PCa) were diagnosed and 27,540 died of PCa. PCa in African American men occurs more frequently, develops at a much earlier age, and is more aggressive and lethal compared to men of European descent. Both biological and socioeconomic factors likely contribute to this disparity. There is currently a paucity of relevant preclinical models in which to examine biological mechanisms in African American PCa. Patient-derived organoids are a recently developed in vitro preclinical model which facilitate examination of underlying mechanisms of disease etiology. However, current models of epithelial organoid growth lack the prostate stroma. To address this unmet need, we began development of a 3D organoid model that incorporated both primary human prostatic epithelial (PrE) and stromal (PrS) cells to better mimic the microenvironment of the organ. Prostate organoids were derived from cells collected from radical prostatectomy tissues from patients (UIC IRBs: 2006-0679 (PI Behm), (2013-0341(PI Nonn). Mixtures of single PrE-derived and single PrS-derived cells were seeded in 3D in matrigel. Bright-field microscopy of live organoids and histological examination of fixed organoids showed that the addition of PrS cells to the culture altered the shape of the organoids compared to the spherical phenotype observed in PrE only cultures. Immunofluorescent analysis of the basal cell marker p63 showed increased epithelial differentiation in the co-culture organoids. In summary, these data suggest that inclusion of prostate stroma in co-culture organoid models influences prostatic epithelial organoid development in vitro. Ongoing studies are focused on molecular analysis or organoid phenotypes and comparison of AA and EA-derived organoids.
Citation Format: Joseph Marsili, Zachary Richards, Jason Garcia, Cindy Voisine, Larisa Nonn. Developing a patient derived 3D co-culture model of prostate organoids to examine biological mechanisms involved in prostate cancer disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5772. doi:10.1158/1538-7445.AM2017-5772
Abstract 5777: Translation of HPV mediated immortalization to cancer precision medicine
Authors: Dakic Aleksandra , Palechor-Ceron Nancy , Krawczyk Ewa , Yuan Hang , Suprynowicz Frank , Agarwal Seema , Schlegel Richard , Simic Vera , Sripadhan Praathibha , Chen Chen , Lu Jie , Hou Tung-Wei , Choudhury Sujata , Liu Xuefeng 
Published: July 2017

Abstract
The E6/E7 oncogenes of the high-risk HPVs are both necessary and sufficient to immortalize HFKs and their presence and expression is required for the continued proliferation of HPV-positive cervical cancer cells. We and others have shown previously that hTERT induced by E6 and cytoskeleton alteration by E7 are critical. Both E6 and feeder cells activate telomerase, while both E7 and Rock inhibitor (Y-27632) disrupt the actin cytoskeleton and inactivate Rho. Feeders and Y-27632 to induce unlimited cell proliferation of human keratinocytes. Unexpectedly, we observed that feeders and Y-27632 could be used to establish both normal and tumor cell cultures from non-keratinocyte tissues. This culture has been termed as “conditional reprogramming”, since CR cultures stop proliferating or terminally differentiate after its removal, depending on culture conditions. The Combination of CR and Organoids ( (Matrigel, air-liquid interface (ALI)) cultures represents next generation human cancer models and functional diagnostics for cancer precision medicine as described in August 2015 in the NCI precision medicine initiative and three nature review articles (Nat Rev Cancer. 2015 Dec; Nat Rev Genet. 2015 Jul; Nat Rev Clin Oncol. 2014 Nov.). The technique is relatively simple and has been reproduced in more than 50 laboratories (including an original and independent article in Science from Massachusetts General Hospital) (Science. 2014, 346(6216):1480-6.). Importantly, the CR technology can generate 2x10&lt;6cells in a week from small biopsies, and can generate cultures from cryopreserved tissue and small biopsies. We therefore initiated studies to examine whether CR cultures reflected the biology and genotype of the original tumor and whether cultures might be used to predict clinical responses. Moreover, the epithelial cells can be propagated indefinitely in vitro, yet retain the capacity to become fully differentiated when placed into conditions that mimic their natural environment. Thus, the CR method significantly advances applications for regenerative medicine.
Citation Format: Aleksandra Dakic, Nancy Palechor-Ceron, Ewa Krawczyk, Hang Yuan, Frank Suprynowicz, Seema Agarwal, Richard Schlegel, Vera Simic, Praathibha Sripadhan, Chen Chen, Jie Lu, Tung-Wei Hou, Sujata Choudhury, Xuefeng Liu. Translation of HPV mediated immortalization to cancer precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5777. doi:10.1158/1538-7445.AM2017-5777
Abstract 5796: Heparan sulfate proteoglycans mediate tumor cell invasion and metastasis
Authors: Qazi Henry , Shi Zhong-Dong , Song Jonathan W. , Cancel Limary M. , Munn Lance L. , Tarbell John M. 
Published: July 2017

Abstract
The surface proteoglycan/glycoprotein layer (glycocalyx) on tumor cells has been associated with cellular functions that can potentially enable invasion and metastasis. In addition, aggressive tumor cells with high metastatic potential have enhanced invasion rates in response to interstitial flow stimuli in vitro. Our previous studies suggest that heparan sulfate (HS) in the glycocalyx plays an important role in this flow mediated mechanostransduction and upregulation of invasive and metastatic potential. In this study, highly metastatic renal cell carcinoma cells were genetically modified to suppress HS production by knocking down its synthetic enzyme NDST1. Using modified Boyden chamber and microfluidic assays, we show that flow-enhanced invasion is suppressed in HS deficient cells. To assess the ability of these cells to metastasize in vivo, parental or knockdown cells expressing fluorescence reporters were injected into kidney capsules in SCID mice. Histological analysis confirmed that there was a large reduction (95%) in metastasis to distant organs by tumors formed from the NDST1 knockdown cells compared to control cells with intact HS. The ability of these cells to invade surrounding tissue was also impaired. The substantial inhibition of metastasis and invasion upon reduction of HS suggests an active role for the tumor cell glycocalyx in tumor progression.
Citation Format: Henry Qazi, Zhong-Dong Shi, Jonathan W. Song, Limary M. Cancel, Lance L. Munn, John M. Tarbell. Heparan sulfate proteoglycans mediate tumor cell invasion and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5796. doi:10.1158/1538-7445.AM2017-5796
Abstract 580: Nivolumab treatment of metastatic renal cancer patients impairs Tregs and potentiates NK function: The role of CXCR4 inhibition (“REVOLUTION Trial”)
Authors: Santagata Sara , Trotta Anna Maria , Napolitano Maria , Portella Luigi , Rossetti Sabrina , Perdona Sisto , Pignata Sandro , Scala Stefania 
Published: July 2017

Abstract
Despite encouraging results, Nivolumab response is not as wide as expected in renal cancer ( RCC). Among mechanisms of immunoresistance T-regulatory cells(Tregs) activity plays a central role. We previously showed that tumoral Tregs in RCC patients are more suppressive than healthy donors Tregs. Since tumoral Tregs express high level of CXCR4, the receptor antagonism was evaluated on patients Tregs revealing that CXCR4 antagonism reverted Treg suppressive activity( Santagata et al, submitted manuscript). To identify biomarkers informative and predictive of nivolumab efficacy Treg function, tumoral access and NK interactions was determined in nivolumab treated mRCC patients (“ Revolution” trial). At today eleven patients were analyzed for Tregs and NKs function at time 0-2-4 weeks-3-6 months of treatment. 2 patients died for unrelated causes, 5 Patients showed PR, 4 SD and 1 PD at six months. At time 0 Tregs function, evaluated as inhibition of T-effector (Teff) proliferation, varied among patients; two patients showed anergy reversed by Nivolumab treatment. Overall, increase in Teff proliferation, compatible with a decreased Tregs activity, was revealed during nivolumab treatment and, while the total peripheral Tregs was unaffected, a decrease in CD4+CD25+127lowFOXp3 highCD45RA - (suppressive Tregs) was detected. NK activity, evaluated as CD107a exposure, increased with nivolumab treatment with a concomitant reduction in the inhibitory receptors CD158a, PD-1 and CXCR4. Moreover patients Tregs and NKs were evaluated in vitro for the efficacy of CXCR4 inhibition in affecting cell function. CXCR4 antagonists suppressed the Treg mediated inhibition of Teff proliferation. In conclusion the evaluation of 11 patients enrolled in the REVOLUTION study revealed detectable variations on Tregs and NKs function relatively to Nivolumab treatment to be correlated with clinical outcome. Tregs suppressive function was impaired by inhibition of CXCR4 receptor.
Citation Format: Sara Santagata, Anna Maria Trotta, Maria Napolitano, Luigi Portella, Sabrina Rossetti, Sisto Perdona, Sandro Pignata, Stefania Scala. Nivolumab treatment of metastatic renal cancer patients impairs Tregs and potentiates NK function: The role of CXCR4 inhibition (“REVOLUTION Trial”) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 580. doi:10.1158/1538-7445.AM2017-580
Abstract 5807: Disseminated tumor cell clearance by the immune system
Authors: Piranlioglu Raziye , Lee Eun Mi , Ouzunova Maria , Arbab Ali S. , Rodriguez Paulo C. , Iskander Asm L. , Korkaya Hasan 
Published: July 2017

Abstract
The classical model of metastasis suggests that the tumor cell dissemination occurs late in tumor development, however accumulating evidence coming from mouse studies and clinical data provide striking evidence that tumor cells start to disseminate during the initial steps of tumor development. However, the dissemination from the primary area does not always result in metastasis. Due to the non-permissive nature of microenvironment in distant sites, these early disseminated tumor cells might be cleared or maintained in a non-proliferative/dormant state. The mechanism by which some early disseminated tumor cells colonize and generate metastatic growth while some remain dormant is not well known. In order to understand the underlying factors that may contribute to the metastatic growth, we performed time course experiments by utilizing murine mammary tumors (4T1 as metastatic and EMT6 as less metastatic) in a syngeneic mouse model. Luciferase expressing 4T1 or EMT6 tumor cells were orthotopically implanted into the fat pads and tumor cell dissemination was analyzed over 3-week time points. We determined that both 4T1 and EMT tumors disseminated as early as one to two-week post implantation, however only 4T1 tumor develop metastasis in distant organs. Moreover, we also resected primary tumors 1, 2 and 3-week post implantation of EMT6-Luci or 4T1-Luci tumors and observed distant metastasis via optical imaging of luciferase expression in live animals. Although the majority of 4T1 tumor-bearing mice (&gt;80%) develop pulmonary metastasis when 4T1 tumors resected 2 and 3 weeks post-implantation only 10% of mice develop metastasis when primary tumor resected one-week post implantation. In contrast, EMT6 tumors following resection only relapsed in the primary tumor site but failed to develop metastasis. Furthermore, EMT6 tumor-bearing mice efficiently cleared tail vein injected EMT6-luci cells in the lungs. We investigated the possible mechanism by which EMT6 tumor-bearing mice clears disseminated tumor cells in the lung. We provide evidence that pulmonary infiltrated mMDSCs mediate tumor cell killing via secretion of high levels of cytotoxic granules, granzyme A, granzyme B, perforin. This was confirmed by mouse transcriptome and qPCR analyses as well as biochemistry using in vivo samples and in vitro co-culture samples. Our studies provide a new paradigm in the understanding of the fate of disseminated tumor cells in secondary organs and the role of the immune system in this process.
Citation Format: Raziye Piranlioglu, Eun Mi Lee, Maria Ouzunova, Ali S. Arbab, Paulo C. Rodriguez, Asm L. Iskander, Hasan Korkaya. Disseminated tumor cell clearance by the immune system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5807. doi:10.1158/1538-7445.AM2017-5807