bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5123: Changes of oral microbiome profiles associated with oral squamous cell carcinoma
Authors: Hashimoto Kengo , Nomoto Shuji , Hirabayashi Sho , Ueda Sei , Oh-iwa Ichiro , Nagao Toru , Shimozato Kazuo 
Published: August 2018

Abstract
[Background] Oral squamous cell carcinoma (OSCC) is the most frequently occurring cancer among the head and neck SCCs worldwide. Despite significant efforts in OSCC research and advanced surgical treatments, radiotherapy, and chemotherapy, the 5-year overall survival rate has remained &lt; 50% for the last few decades. OSCC prognosis remains poor due to late diagnosis. Therefore, clinically effective biomarkers for the early detection of OSCC can greatly improve the survival rate and prognosis. Approximately 15% of oral cancers cannot be explained by major risk factors, such as tobacco and alcohol use. A growing body of evidence supports an association between specific microorganisms, including those in the oral cavity, and various types of cancers. Because the role of bacteria in OSCC development has not been completely described, we investigated the changes in abundance of oral microbiota associated with OSCC. [AIMS] To identify the association between the oral microbiome and OSCC for the early detection and prevention. [Materials and methods] Unstimulated saliva samples were collected from 4 OSCC-free, 6 leukoplakia, and 6 OSCC subjects. Total bacterial genomic DNA from saliva was isolated, and 16S rRNA gene survey was performed by next-generation sequencing of the V4 region. The sequences were analyzed against reference sequences from the Human Oral Microbiome Database, and the relative abundance distribution for phylogenetic groups in 3 different libraries was compared. [Results] In total, 448 bacterial species from combined (OSCC-free, leukoplakia, and OSCC) libraries were detected, which were classified into 133 genera, 69 families, 41 orders, 26 classes, and 12 phyla. The frequency of phylum Bacteroidetes was more notably abundant in OSCC subjects compared with leukoplakia and OSCC-free subjects. In contrast, the abundances of genera Streptococcus and Rothia were significantly lower in OSCC subjects compared with leukoplakia and OSCC-free subjects using the Mann-Whitney U test. [Conclusion] This study revealed some OSCC-associated shifts in oral microbial communities. Salivary screening is suitable for the primary screening procedure because of its noninvasiveness and easy accessibility. Therefore, these changes in the saliva microbiome may have potential application as a useful diagnostic tool for the early detection of OSCC and malignant transformation of pre-cancerous regions.
Citation Format: Kengo Hashimoto, Shuji Nomoto, Sho Hirabayashi, Sei Ueda, Ichiro Oh-iwa, Toru Nagao, Kazuo Shimozato. Changes of oral microbiome profiles associated with oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5123.
Abstract 5125: The relationship between microbiome Fusobacterium nucleatum and autophagy in esophageal cancer
Authors: Liu Yang , Baba Yoshifumi , Nakagawa Shigeki , Sawayama Hiroshi , Ishimoto Takatsugu , Iwatsuki Masaaki , Yamashita Yoichi , Miyamoto Yuji , Yoshida Naoya , Baba Hideo 
Published: August 2018

Abstract
Background: Research into the microbiome is a rapidly advancing field in human cancers. The gut microbiome has recently been shown to play an important role in health, as well as in diseases such as obesity, inflammatory bowel disease, diabetes, non-alcoholic fatty liver disease, and several types of cancers. Fusobacterium nucleatum is a component of the human microbiome that primarily inhabits the oral cavity. It causes periodontal disease and has also been implicated in the development of human cancers. We have recently reported that Fusobacterium nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. In addition, It has been revealed that Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Nonetheless, the relationship between Fusobacterium nucleatum and autophagy in esophageal cancers have been still unknown. We constructed this study to examine the relationship between Fusobacterium nucleatum and autophagy.
Methods: Using 284 esophageal cancers, we detected ATG-7 and ULK -1 expression by IHC staining in tumors.
Results: 21% cases showed ATG-7 positive and 25% cases showed ULK-1 positive. ATG-7 and ULK-1 expression in Fusobacterium nucleatum-positive tumors were significantly higher compared with that of Fusobacterium nucleatum-negative tumors (P=0.026 and P=0.0077). In addition, ATG-7 expression was associated with cancer-specific survival rate in esophageal cancer patients (P=0.0496). There was no relationship of ULK-1 expression and prognosis.
Conclusion: Fusobacterium nucleatum was related with ATG-7 and ULK-1. Our findings may shed lights on understanding the mechanism by which Fusobacterium nucleatum affects chemoresistance in esophageal cancer.
Citation Format: Yang Liu, Yoshifumi Baba, Shigeki Nakagawa, Hiroshi Sawayama, Takatsugu Ishimoto, Masaaki Iwatsuki, Yoichi Yamashita, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. The relationship between microbiome Fusobacterium nucleatum and autophagy in esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5125.
Abstract 5142: Elevated glycolysis in pre-malignant ovarian cancer
Authors: Lokshin Anna E. , Azher Mounia Alaoui El , Velikokhatnaya Liudmila , Prosser Denise 
Published: August 2018

Abstract
Ovarian cancer is the fifth leading cause of cancer death in women and the most lethal gynecologic malignancy. High-grade serous ovarian carcinoma (HGSC) originates mainly from the fallopian tube epithelium, and is characterized by TP53 mutation identified in all HGSCs as well as the fallopian tubal precursor of serous tubal intraepithelial carcinomas (STICs). The loss of a functional TP53 is an early event in the malignant transformation of fallopian tube epithelium. We have established 4 primary cell cultures of normal fallopian tube epithelial (FTE) cells, and further generated immortalized FTE cells using SV40 large plus small T antigens (FTE-TAg) to disrupt TP53 function. This model mimics the primary lesions of ovarian cancer and is suitable to identify biomarkers and molecular targets of ovarian cancer. Therefore, we compared the secretomes of primary FTE cells with that of their parental isogenic pairs FTE-TAg cells using mass spectrometry analysis. We identified 813 proteins, 228 of which were differentially expressed. Ingenuity Pathway Analysis (IPA) core analysis revealed glycolysis as a major canonical pathway. Overexpression of key enzymes of glycolytic pathway was confirmed by IHC in human STIC lesions. Molecular mechanisms of glycolysis regulation in premalignant lesion of ovarian cancer were determined. Role of glycolysis in the establishment of premalignant ovarian cancer microenvironment (PME) was characterized. Prevention approaches targeting glycolysis were tested in transgenic animal model of ovarian cancer.
Citation Format: Anna E. Lokshin, Mounia Alaoui El Azher, Liudmila Velikokhatnaya, Denise Prosser. Elevated glycolysis in pre-malignant ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5142.
Abstract 5144: Cooperative effects of mushroom polysaccharides and herbal saponins on tumor growth and gut microenvironment in ApcMin/+mice
Authors: Li Xiao-ang , Huang Guoxin Huang , Khan Imran , Xia Wen-rui , Leong Wai kit , Hsiao W.L. Wendy 
Published: August 2018

Abstract
Prebiotics are considered as non-digestible food ingredients that stimulate the growth of beneficial gut bacteria, thus contribute to the health of the host. Recent evidences have suggested that prebiotics treatment may become one of the key therapeutic strategies for many diseases, especially for cancer. In our previous studies, both Gynostemma pentaphyllum saponin (GpS) and Ganoderma lucidum polysaccharides (GlP) demonstrated significant prebiotic effects in mouse models. In addition, GpS alone exerted significant anti-tumor effect by restoring the dysbiosis of the gut microbiota and microenvironment of the ApcMin/+mice. Thus, we hypothesized that supplement with GlP might enhance the anti-cancer effect of GpS through the modulation of the gut microbiota. To test the hypothesis, we treated ApcMin/+mice with four different treatments, i.e. GlP (750mg/kg), GpS (300mg/kg), GlP (750mg/kg) + GpS (300mg/kg) and the drinking water control. The results showed that GlP+GpS was more effective in suppressing the polyp growth compared to the GpS or GlP groups. GlP+GpS also improved the health of gut barriers by inducing Paneth cells and goblet cells, and reinstating the E-cadherin and N-cadherin expressions in a greater extend compared to the other groups. All treatments facilitated the polarization of M1 macrophage to M2 macrophage, and increased the anti-inflammatory cytokines (IL-4 and IL-10). Interestingly, expressions the SCFA receptors, GPR 43, 49 and 119 were markedly elevated in all treatment groups, with the most prominent expression observed in the GlP+GpS group. 16S rRNA sequencing data were analyzed by using alpha diversity analysis and weighted UniFrac distance analysis. Differential alterations of the composition of gut microbiota were observed in all treatment groups. Certain bacteria (Anoerodtipe, Bacteroides, Clostridium, Citribacter, Subdoligranulum, C.
leptum) associated colitis and colorectal carcinoma were significant decreased, while some SCFA-producing bacteria (Blautia sp., Eubacterium saphenum, Clostridium aminobutyricum) were enhanced in the treated groups. We concluded that the anti-tumor effects of GpS and GlP might be in part through the modulation of the gut microbiota and the improvement of epithelial microenvironment, and the stronger effects were produced by the GpS+ GlP combined treatment.
[This study was supported by Macau FDCT 015/2014/A1 and 103/2016/A3]
Citation Format: Xiao-ang Li, Guoxin Huang Huang, Imran Khan, Wen-rui Xia, Wai kit Leong, W.L. Wendy Hsiao. Cooperative effects of mushroom polysaccharides and herbal saponins on tumor growth and gut microenvironment in ApcMin/+mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5144.
Abstract 5149: CMTM6 is a potential metastasis regulator of EWS cells
Authors: Nishiyama Yuko , Asano Naofumi , Fujiwara Yuko , Kondou Tadashi , Tsuchiya Naoto 
Published: August 2018

Abstract
Ewing's sarcoma (EWS) is a highly aggressive and metastatic malignant tumor of bone and soft tissues, whose incidence is highest in children and young adulthood. Control of metastasis based on the molecular targeting contributes to improve patient prognosis. To this end, we screened expression of microRNAs in clinical samples to identify target molecules, which regulate malignant properties of EWS cells. Microarray analysis indicated that miR-451a is significantly downregulated in the cases with poor prognosis. Although miR-451a did not affect cell proliferation, it strongly repressed migration of EWS cells. Gene expression analysis revealed that miR-451a targeted CMTM6, a chemokine-like membrane protein with unknown function. Depletion of CMTM6 by siRNAs strongly inhibited migration of EWS cells. Our data suggest that at least the expression of miR-451a and CMTM6 is involved in metastasis onset.
Citation Format: Yuko Nishiyama, Naofumi Asano, Yuko Fujiwara, Tadashi Kondou, Naoto Tsuchiya. CMTM6 is a potential metastasis regulator of EWS cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5149.
Abstract 5155: The modulation of actin dynamics via atypical protein kinase-C activated cofilin regulates migration of colorectal cancer cells
Authors: Islam S M Anisul , Khalid Khandker Mohammad , Bommareddy Raja Reddy , Patel Rekha , Acevedo-Duncan Mildred 
Published: August 2018

Abstract
Colorectal cancer (CRC) is the second most common cancer in both men and women in the United States. The exact mechanism of CRC cells migration is poorly understood. Actin polymerization is thought to be an initial step in cancer cells motility cycle which drives the formation of cell protrusions that defines the direction of migration and initiate cell crawling. Cofilin is a significant actin regulating molecule that can regulate the migration of cancer cells by the formation of lamellipodia and filopodia. In this study, the effect of atypical Protein Kinase C (aPKC) on cofilin in CRC was studied by using two inhibitors of aPKC: 1) ICA-I (5-amino-1-(2,3-dihydroxy-4-hydroxymethyl) cyclopentyl)-1H-imidazole-4-carboxamide) is a specific inhibitor of PKC-ι and 2) ζ-Stat (8-hydroxy-1, 3, 6-naphthalenetrisulfonic acid) is a specific inhibitor of PKC-ζ. The cell lines tested were CCD18CO normal colon fibroblast and LOVO & RKO metastatic CRC cells. The inhibition of aPKC did not bring any significant toxicity in CCD18CO colon fibroblasts cells. However, our data showed that the inhibition of aPKC blocks the migration of CRC cells migration by increasing the level of cofilin phosphorylation at serine-3. Additionally, the aPKCs inhibition brought a significant reduction of CRC cells proliferation along with the reduction of survival markers. Our findings suggest that the PKC-ι and/or PKC-ζ may be responsible for the migration of CRC cells as well as carcinogenesis. These results suggest the possibility of utilizing aPKCs as the potential therapeutic targets for the CRC cells metastasis.
Citation Format: S M Anisul Islam, Khandker Mohammad Khalid, Raja Reddy Bommareddy, Rekha Patel, Mildred Acevedo-Duncan. The modulation of actin dynamics via atypical protein kinase-C activated cofilin regulates migration of colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5155.
Abstract 5167: Rab27a promotes melanoma cell invasion and metastasis via the regulation of exosome secretion
Authors: GUO DAJIANG , Lui Goldie Y. , Sharp Danae M. , Lai Siew Li , Tikoo Shweta , Kwan Rain , Geldermalsen Michelle van , Holst Jeff , Haass Nikolas K. , Weninger Wolfgang , Beaumont Kimberley A. 
Published: August 2018

Abstract
Introduction: The Rab GTPase family has been increasingly related to carcinogenesis and cancer biology during the past decade. In melanoma, Rab27a has been identified as a tumor dependency gene. Rab27a is thought to regulate exosome secretion in several cell types, however the exact role of Rab27a in melanoma biology and the underlying mechanisms are not well investigated.
Experimental Procedures: To investigate the influence of Rab27a on melanoma biology and exosome secretion, Rab27a shRNA knockdown (KD) or CRISPR knockout (KO) was performed in human and murine melanoma cell lines. The effect of Rab27a loss on melanoma cell invasion and motility was analyzed by in vitro 3D spheroid invasion and live cell imaging. Rab27a function on melanoma metastasis was investigated using a mouse melanoma spontaneous metastasis model. Exosomes secreted by melanoma cell lines with/without Rab27a KD/KO were purified and characterized by electron microscopy, NanoSight analysis, BCA assay, western blotting and mass spectrometry.
Results: Our results indicate that Rab27a loss in Rab27a high metastatic melanoma cell lines reduced 3D spheroid invasion and cell motility and Rab27a loss also reduced spontaneous melanoma metastasis in vivo. Rab27a KD invasion phenotype can be partially rescued by addition of exosomes from Rab27a replete cell conditioned media, but not exosomes derived from Rab27a KD cells. Loss of Rab27a does not alter the number of exosomes secreted from melanoma cells, but does alter exosome protein composition and morphology. Mass spectrometry analysis has shown that Rab27a replete cell secreted exosomes are more involved in regulating cell invasion and motility than the exosomes from Rab27a KD cells.
Conclusion: In summary, Rab27a promotes the invasion and metastasis of a subset of melanoma cells via the regulation of pro-invasive exosomes, which indicates Rab27a as a potential therapeutic target for preventing melanoma progression.
Citation Format: DAJIANG GUO, Goldie Y. Lui, Danae M. Sharp, Siew Li Lai, Shweta Tikoo, Rain Kwan, Michelle van Geldermalsen, Jeff Holst, Nikolas K. Haass, Wolfgang Weninger, Kimberley A. Beaumont. Rab27a promotes melanoma cell invasion and metastasis via the regulation of exosome secretion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5167.
Abstract 517: LncRNA expression at the different site of high-grades serous carcinoma
Authors: Filippov-Levy Natalie , Smith Yoav , Trope Claes Gøran , Davidson Ben , Reich Reuven 
Published: August 2018

Abstract
Background: High-grades serous carcinoma (HGSC) is the most aggressive subtype of ovary cancer. The disease appears at three anatomic sites: ovary tumor, solid metastasis and effusions. Not much is known about the regulatory pathways involved in cancer progression. Long non coding RNA (lncRNA) is non protein coding RNA with size &gt;200bp. Exosomes are 30-100nm endosomal-derived vesicles containing mRNA, miRNA, lncRNA, transcription factors, proteins and lipids. They are secreted from various cells and their substance and amount alter between healthy and diseases state.
Objective: Identification of lncRNA effecting cancer progression and patient survival.
Methods: Custom made lncRNA microarray (composed off˜17,000 lncRNAs and˜22,000 mRNAs) followed by validation series of 180 specimens from three anatomic sites, including 77 effusions, 40 ovarian HGSC specimens, 21 solid metastases and exosomes from 42 effusion supernatants. 10 selected lncRNA were subjected to clinicopathologic parameters and survival association analysis.
Results: out of 10 lncRNA chosen for validation, 5 lncRNA- ESRG, Link-A, MEG3, GATS and PVT1 - were differently expressed between the anatomic sites and exosomes (all p&lt;0.001). In univariate survival analysis, higher ESRG levels were significantly related to longer overall survival (OS) in the entire cohort (p=0.023), Higher Link-A levels in post-chemotherapy specimens was significantly associated with longer OS (p=0.015). MEG3 levels were significantly higher in pre-chemotherapy effusions tapped at diagnosis (n=40) compared to post-chemotherapy specimens (p=37; p=0.017). Higher GATS expression was seen in specimens from patients who were sub-optimally debulked (p=0.046). Moreover, H19 which did not change significantly between the anatomic sites, was higher in effusions from patients whose tumors showed primary resistance to chemotherapy (PFS≤6 months).
Conclusion: lncRNAs are differently express at different anatomic site and exosomes in HGSC and can provide new therapeutic targets. Furthermore, their level in effusion fluids can serve as a prognostic marker.
Citation Format: Natalie Filippov-Levy, Yoav Smith, Claes Gøran Trope, Ben Davidson, Reuven Reich. LncRNA expression at the different site of high-grades serous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 517.
Abstract 5203: Bitter melon extract modulates immune signaling in prevention of tobacco associated carcinogen induced oral carcinogenesis
Authors: Sur Subhayan , Steele Robert , Ray Ratna B. 
Published: August 2018

Abstract
Oral squamous cell carcinoma (OSCC) is a complex malignancy and tobacco habit is one of the main etiological factors. Our previous study showed potential chemopreventive effect of bitter melon (Momordica charantia) extract (BME) in different pre-clinical cancer models like head and neck, breast, prostate. The aim of this study is to understand the molecular mechanism of BME in prevention of carcinogen induced in-vivo oral carcinogenesis. For this purpose, we induced oral cancer in immunocompetent mice by using tobacco associated carcinogen 4-nitroquinoline 1-oxide (4-NQO), and treated with BME through their drinking water. We observed that BME feeding significantly reduced the incidence of 4-NQO induced oral cancer. Histological analysis showed moderate dysplasia to invasive squamous cell carcinoma in 4NQO treated mice tongue, whereas no remarkable changes were seen in the BME-fed mice. RNA-seq data showed differential expression of several genes during carcinogenesis and during prevention of the cancer. We previously showed that BME treatment decreases the infiltrating regulatory T (Treg) cells by inhibiting FoxP3+ populations in the tumors and in spleens, suggesting an immunomodulatory role of BME in prevention. Here, we observed elevated expression of pro-inflammatory genes s100a9, IL23a, IL-1β and immune check point gene PDCD1/PD1 of the pathway, during oral cancer development. Interestingly, BME treatment significantly reduced the expression of these molecules. Subsequently, we observed the enhancement of MMP9 during carcinogenesis, which was reduced in BME-fed mouse tongue tissues. Taken together, our observation strongly demonstrated a chemopreventive effect of BME on carcinogen induced oral cancer.
Citation Format: Subhayan Sur, Robert Steele, Ratna B. Ray. Bitter melon extract modulates immune signaling in prevention of tobacco associated carcinogen induced oral carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5203.
Abstract 5206: The biological significance of CCL 16 regulated by thyroid hormone in liver cancer cells
Authors: Wu Cheng-Heng , Lin Kwang-Huei 
Published: August 2018

Abstract
Thyroid hormones(THs) are multi-function mediators that modulate various physiological processes. Thyroid hormone receptors(TRs) are type II nuclear receptors, TRs binds to thyroid hormone response elements (TREs) of target promoter regions modulates target gene expression at the transcriptional level upon THs binding. Previous literatures illustrate an association between aberrant TR regulation and human hepatocellular carcinoma (HCC). We employed cDNA microarrays and SILAC secretome analysis to identify the T3-regulated secreted proteins after T3 treatment in TR-expressing hepatoma cell lines, Chemokine (C-C motif) ligand 16 (CCL16) expression is positively regulated by T3 treatment. The patients with higher expression of CCL16 have poor recurrence survival rate. Ectopic expression of CCL16 in HCC cell lines increased tumor growth rate in vivo but not in vitro. CCL16 induced chemotaxis of monocytes and macrophages via interacting with its receptors CCR1 and CCR5. Expression of proangiogenic genes in macrophages were increased while co-cultured with HCC cell lines. The motility of HUVECs were increased after treated with conditional medium of macrophages co-cultured with HCC cell lines. Our study revealed that CCL16 recruited macrophage and promoted tumor progression.
Citation Format: Cheng-Heng Wu, Kwang-Huei Lin. The biological significance of CCL 16 regulated by thyroid hormone in liver cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5206.