bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4930: Ki-67 serves as a prognostic marker in early gastric cancer, but not in advanced gastric cancer
Authors: Lee Won Sup , Ko Gyung Hyuck , Go Se-Il , Lee Jeong-Hee , Jeong Sang-Ho , Lee Young-Joon , Hong Soon Chan , Ha Woo Song 
Published: July 2016

Abstract
Ki-67 protein is a cellular marker for proliferation. The role of Ki-67 as a prognostic factor has not been established in gastric cancer. We previously demonstrated that CD44v plays an important role in EThe present study was performed toinvestigate the significance of Ki-67 expression as a biomarker in early gastric cancer (EGC), but not advanced gastric cancer (AGC). With the study, we foundthat there is correlation between CD44v and Ki67. Here, evaluated the clinical significance with tissue microarray of gastric cancer by performing immunohistochemical staining for Ki-67. Its clinical significance was analyzed with adjustment via the propensity score-matching. The median follow-up duration was 72 months (range: 3 - 120 months). Ki-67 positive group showed worse prognosis than Ki-67-negative group in EGC (5-YSR, 78.9% vs. 92.0%, p = 0.018), but not in advanced gastric cancer (AGC) (5-YSR, 58.5% vs. 59.2%, p = 0.951). Interestingly, in the patients with well-differentiated histology, prognosis for Ki-67-positive group was considerably worse than that for Ki-67-negative group (5-YSR, 67.0% vs. 94.4%, p = 0.012), but not in those with moderately differentiated (p = 0.504) and poorly-differentiated histology (p = 0.905). In this cohort, there was a strong correlation between the proportion of EGC and well-differentiated histology (r = 0.215, p = 0.002). Multivariate analysis also revealed that the positive-Ki- 67 expression serve as a poor prognostic factor in EGC (HR 4.346, 95% CI 1.397 - 13.515, p = 0.011), but not in all the patients (p = 0.171). With bootstrap resampling, we internally validated these results (p = 0.011). In conclusion, this study suggests that Ki-67 expression may be a good biomarker for prognosis prediction for EGC, but not for AGC. [This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare & Family Affairs, Republic of Korea.(0820050).]
Citation Format: Won Sup Lee, Gyung Hyuck Ko, Se-Il Go, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong, Woo Song Ha. Ki-67 serves as a prognostic marker in early gastric cancer, but not in advanced gastric 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 4930.
Abstract 4936: The function role of Brf1 in alcohol-induced human and mouse hepatocellular carcinoma*
Authors: Zhong Shuping 
Published: July 2016

Abstract
Brf1 (TFIIB-related factor 1) specifically regulates the transcription of Pol III genes (RNA polymerase III-dependent genes), including tRNAs and 5S rRNAs, which are elevated in both transformed and tumor cells, suggesting that they play a crucial role in tumorigenesis. Our recent studies have demonstrated that alcohol consumption increases Brf1 expression and Pol III gene transcription to promote tumor development. However, it remains to be investigated that Brf1 is expressed in human cancers. At the present studies, we have determined the significance of Brf1 overexpression in human hepatocellular carcinoma (HCC) and the impaction of repressing Brf1 expression in alcohol-promoted cell transformation. Biopsies of human HCC, liver tumor samples of mice and cell lines of normal and tumor liver were utilized to determine alteration of Brf1 expression using cytological and molecular biological approaches. The result indicates that Brf1 expression is increased in human cases of HCC. High expression of Brf1 displays shorter overall survival period. Levels of Brf1 and Pol III gene transcription in HCC patients with alcohol consumption show an additional increase, compared with the cases of non-HCC with or without alcohol intake. Induction of Brf1 and Pol III genes by ethanol in hepatoma cells is higher than in non-tumor cells. Ethanol increases the rate of cell transformation. Repression of Brf1 inhibits alcohol-promoted cell transformation. Together, these studies demonstrate that Brf1 is overexpressed in HCC cases and liver tumor cell lines. High level of Brf1 in human HCC is correlated with short survival time. Alcohol consumption enhances Brf1 expression to promote cell transformation. Brf1 is a new biomarker of diagnosis and prognosis of HCC.
*: The project is supported by NIH grants: AA017288, AA021114 and AA02324 to Shuping Zhong
Citation Format: Shuping Zhong. The function role of Brf1 in alcohol-induced human and mouse hepatocellular carcinoma*. [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 4936.
Abstract 4939: Evaluating a novel biomarkers set for postoperative outcome in patients with gastrointestinal cancer
Authors: Masaki Kunizaki , Hidaka Shigekazu , Tominaga Tetsurou , Furukawa Yoichi , Nagayasu Takeshi 
Published: July 2016

Abstract
Gastrointestinal cancer is the leading cause of cancer deaths in developed countries. The incidence of gastroinetestinal cancer has been increasing dramatically in Japan and has attracted worldwide attention. Despite the introduction of new postoperative chemotherapy regimens and the progress in endoscopic surgery techniques, overall survival is still poor for most advanced gastrointestinal cancer patients. The prognosis of gastrointestinal cancer patients is based on the presence of lymph node metastasis and the depth of tumour cell invasion. Usually, these parameters can be determined by microscopic examination of tissue sections from the primary neoplasm and lymph nodes. However, it is not always possible to establish a prognosis based only on the histopathological examination of cancer specimens. Therefore, there is continuing interest in prognostic factors that can permit more accurate patient stratification, improve clinical decision-making and possibly contribute to more rational study analysis. In the past few years, much progress has been made towards a better understanding of the molecular mechanisms of gastrointestinal cancer. Mutations and overexpression of p53 are common characteristics of various solid tumors. The overexpression of mutant p53 protein has been found to induce the formation of serum p53 IgG antibodies in gastrointestinal cancer patients. In addition, recent studies have revealed that the inflammation-based scoring is a useful tool for predicting postoperative outcome in gastrointestinal cancer patients. Therefore, in this study, we retrospectively reviewed a database of patients who had undergone elective surgery for gastrointestinal cancer at the Division of Surgical Oncology, Nagasaki University Hospital, and that was conducted to evaluate the usefulness of the combination of such biomarkers (CEA, CA19-9, GPS, s-p53ab etc.) for prediction of postoperative mortality in gastroinetestinal cancer patients.
Citation Format: Kunizaki Masaki, Shigekazu Hidaka, Tetsurou Tominaga, Yoichi Furukawa, Takeshi Nagayasu. Evaluating a novel biomarkers set for postoperative outcome in patients with gastrointestinal 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 4939.
Abstract 4950: Collagen, type I, alpha 1 (COL1A1): a potential urinary biomarker that can distinguish between benign prostate hyperplasia and localized prostate cancer
Authors: Jedinak Andrej , Vuichoud Camille , El-Hayek Andrew , Loughlin Kevin R. , Moses Marsha A. 
Published: July 2016

Abstract
Benign prostate hyperplasia (BPH) is the most frequent benign disease among men worldwide and its incidence increases with age. Prostate cancer (PCa) and BPH share similar symptoms and an elevated serum prostate-specific antigen (PSA) can be observed with either benign or malignant growth of the prostate. It is the demographic overlap of BPH and PCa, and the lack of discrimination between these two prostate diseases by PSA, that defines the diagnostic dilemma faced by clinicians when treating prostate disease. The goal of the current study was to identify novel non-invasive, biomarkers that can distinguish between BPH and PCa. We utilized iTRAQ (Isobaric Tags for Relative and Absolute Quantitation) mass spectrometry techniques to sensitively and accurately identify the urinary proteome of men with BPH vs. men with PCa. We then performed functional enrichment analysis and pathways enrichment analysis of these proteins using Ingenuity Pathway Analysis (IPA) tools to determine differentially expressed pathways and functions in PCa as compared to BPH. Network analysis identified differences in a number of signaling molecules including ERK1/2, TGFβ, PI3K, p38 MAPK and NFκB, with a high degree of interactivity. Protein expression was validated by immunoblot analyses using monospecific antibodies. Here, we focused on collagen, type I, alpha 1 (COL1A1), one of a number of extracellular matrix-associated proteins detected. We found that COL1A1 was significantly (P &lt; 0.001) elevated in the urine of patients diagnosed with early or localized PCa but not in the urine of men with BPH. Complementary studies were conducted on human BPH and PCa cells. Our data suggest that COL1A1 may represent a novel non-invasive biomarker that can discriminate between BPH and early PCa. (Supported by The Ellison Foundation)
Citation Format: Andrej Jedinak, Camille Vuichoud, Andrew El-Hayek, Kevin R. Loughlin, Marsha A. Moses. Collagen, type I, alpha 1 (COL1A1): a potential urinary biomarker that can distinguish between benign prostate hyperplasia and localized prostate 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 4950.
Abstract 4978: T cell mediated immunity after combination therapy with intralesional PV-10 and co-inhibitory blockade in a melanoma model
Authors: Weber Amy M. , Liu Hao , Kodumudi Krithika N. , Sarnaik Amod A. , Pilon-Thomas Shari 
Published: July 2016

Abstract
PV-10 is a 10% solution of Rose Bengal, a xanthene dye that was originally developed for ophthalmic use and later used in liver function studies. PV-10 was formulated for intralesional (IL) injection and is currently being investigated as a novel cancer therapeutic. In murine studies, we have previously shown that intralesional (IL) injection of PV-10 leads to a regression of both injected tumors and untreated bystander tumors. We have also shown that combination therapy of IL PV-10 with blockade of PD-1 and PDL-1 leads to increased anti-tumor immunity. In this study, we have examined the role played by specific immune cell populations in eliciting this response in a murine melanoma model. We first investigated the antigen specificity of CD8+ T cells in the spleens of mice treated with the combination therapy of IL PV-10 and systemic co-inhibitory blockade. We found that splenocytes from mice treated with the combination of IL PV-10 and anti PD-1 antibody have an increased mean percentage of OVA antigen-specific CD8+ T cells (5.77%) compared to single treatment with anti PD-1 antibody (3.8%) or IL PV-10 (3.60%) alone in OVA-expressing B16 tumor bearing mice. To investigate the role of T cell subsets in mediating an immune response, OVA-expressing B16 tumor bearing mice were treated with IL PV-10 followed by intraperitoneal injection of anti-PD-1 antibody. In addition, mice were given either 2.43 antibody to deplete CD8+ T cells, GK1.5 antibody to deplete CD4+ T cells, or PC61 to deplete regulatory T cells (Tregs). We found that depletion of CD4+ T cells in combination with IL PV-10 and anti-PD-1 antibody treatment resulted in an enhanced anti-tumor effect, with an average tumor size of 52.8 mm2 on day 25 compared to the control group (173.7 mm2), and depletion of Tregs resulted in an even greater anti-tumor effect, with an average tumor size of 1.2 mm2 on day 25 (p&lt;0.05). In contrast, mice treated with the CD8+ depleting antibody exhibited diminished anti-tumor immunity compared to the control group, with an average tumor size of 200 mm2 on day 25. Together, these studies indicate that the effect of combination therapy with IL PV-10 and co-inhibitory blockade is mediated by CD8+ T cells, and that depletion of both CD4+ T cells and CD25+ Tregs significantly enhances anti-tumor immunity in a melanoma model.
Citation Format: Amy M. Weber, Hao Liu, Krithika N. Kodumudi, Amod A. Sarnaik, Shari Pilon-Thomas. T cell mediated immunity after combination therapy with intralesional PV-10 and co-inhibitory blockade in a melanoma 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 4978.
Abstract 499: ESR1 methylation in circulating tumor cells of patients with breast cancer
Authors: Mastoraki Sofia , Strati Areti , Chimonidou Maria , Malamos Nikos S. , Georgoulias Vasilis , Lianidou Evi S. 
Published: July 2016

Abstract
AIMS: DNA methylation is an epigenetic alteration which plays a decisive role in the regulation of signal translation processes. In our lab, we have demonstrated for the first time the epigenetic silencing of tumor and metastasis suppressor genes in CTCs through their promoter methylation. Estrogen receptor (ER) is an important prognostic biomarker and is predictive of response to endocrine therapy in breast cancer. In this study, we evaluated for the first time ESR1 methylation in CTCs of breast cancer patients.
METHODS: We developed and validated a novel highly sensitive and specific qMSP assay for ESR1 methylation using commercially available DNA methylation controls and the MDA-MB-231 cell line. We further examined its performance in EpCAM-positive immune-magnetically isolated CTC fractions, followed by DNA isolation and sodium bisulfite (SB) treatment from: a) 74 operable, b) 48 metastasis- verified breast cancer patients and c) 30 healthy donors (control group).
RESULTS: The developed assay is highly specific and sensitive since it can detect 0.1% methylated ESR1 sequences in the presence of 99.9% un-methylated. ESR1 was found to be methylated in 16/74 (21.6%) operable breast cancer patients, in 10/48 (20.8%) patients with verified metastasis, but only in 1/30 (3.3%) healthy donors (EpCAM-positive CTC fraction).
CONCLUSIONS: The EpCAM-positive CTC fraction was found to be methylated for ESR1 in about 20% of patients with breast cancer. We will further evaluate these findings in respect to the clinical outcome of these patients, since the epigenetic silencing of ESR1 could be of important clinical significance especially for its impact on the efficacy of treatment.
Citation Format: Sofia Mastoraki, Areti Strati, Maria Chimonidou, Nikos S. Malamos, Vasilis Georgoulias, Evi S. Lianidou. ESR1 methylation in circulating tumor cells of patients with breast 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 499.
Abstract 4991: Immunologic analyses of uveal melanoma patients treated with radiation therapy
Authors: Barker Christopher A. , Francis Jasmine H. , Kuriakose Robin K. , Lian Ming , Marr Brian P. , Abramson David H. 
Published: July 2016

Abstract
Early stage uveal melanoma is frequently treated by radiation therapy (RT) alone. Preclinical studies suggest the efficacy of RT in melanoma is dependent on the immune system. We studied the immune system of patients with uveal melanoma before and after RT, hypothesizing there would be associations between these parameters and clinical outcomes. With institutional review board permission, patient, tumor, peripheral blood count characteristics were extracted from medical records of 299 patients with clinically localized uveal melanoma undergoing RT. Similar data was collected for 16 patients who presented with metastatic uveal melanoma at initial diagnosis. A subset of 8 patients treated with RT for uveal melanoma underwent peripheral blood sampling before, one and three months after RT on a prospective biospecimen collection protocol. Flow cytometry was performed to characterize leukocyte populations before and after RT. Serum was analyzed for cytokines and antibody titers before and after RT. Associations between neutrophil-to-lymphocyte ratio (NLR), leukocyte subpopulations, cytokines and antibody titers with tumor response to RT and survival were investigated. NLR was significantly lower in patients presenting with clinically localized uveal melanoma (mean 2.7), compared to those presenting with metastatic uveal melanoma at initial diagnosis (mean 3.4, p&lt;0.05). Among patients with clinically localized uveal melanoma who underwent RT, a multivariable Cox regression model found that age, tumor stage, and NLR were all significantly associated with overall survival. Changes in several leukocyte populations were observed after RT, with the overall CD8 / regulatory T cell ratio increasing by 27% one month after RT. Increases in several cytokines were observed, with C reactive protein and granulocyte-macrophage colony stimulating factor increasing 2-3 fold in the first month after RT. One of eight patients seroconverted to a positive Melan-A antibody titer three months after RT; this was associated with one of the largest reductions in tumor size observed (&gt;60%). In conclusion, several immune system parameters of patients with uveal melanoma treated with RT appeared to change after treatment, and may be associated with tumor response and treatment outcome, including survival. Further study on the development of distant metastasis in an expanded cohort of patients is planned. Additional investigations into the capacity of RT to modulate the immune system of cancer patients are warranted.
Citation Format: Christopher A. Barker, Jasmine H. Francis, Robin K. Kuriakose, Ming Lian, Brian P. Marr, David H. Abramson. Immunologic analyses of uveal melanoma patients treated with radiation therapy. [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 4991.
Abstract 500: Prognostic impact of CTC detected using a novel fluidic cell microarray chip CTC detection system in patients with breast cancer
Authors: Sawada Takeshi , Araki Jungo , Yamashita Toshinari , Masubuchi Manami , Chiyoda Tsuneko , Yunokawa Mayu , Hoshi Kumiko , Tao Shoichi , Yamamura Shohei , Yatsushiro Shouki , Abe Kaori , Kataoka Masatoshi , Shimoyama Tatsu , Maeda Yoshiharu , Kuroi Katsumasa , Tamura Kenji , Sawazumi Tsuneo , Minami Hironobu , Suda Yoshihiko , Koizumi Fumiaki 
Published: July 2016

Abstract
No current circulating tumor cell (CTC) enumeration system provides better prognostic value than CellSearch. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. This system was validated in preclinical studies and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p = 0.010) of MDA-MB-231 cells and an equivalent detection rate (p = 0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p = 0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by time-to-treatment-failure. The hazard ratio between CTC+ and CTC- was 4.043 in CellSearch (95% CI, 1.248 to 13.10; p = 0.01985); in contrast, it was 10.97 in FCMC (95% CI, 2.18 to 55.21; p = 0.003662). CTC detected using FCMC have the potential to be a better prognostic factor than CTC detected using CellSearch.
Citation Format: Takeshi Sawada, Jungo Araki, Toshinari Yamashita, Manami Masubuchi, Tsuneko Chiyoda, Mayu Yunokawa, Kumiko Hoshi, Shoichi Tao, Shohei Yamamura, Shouki Yatsushiro, Kaori Abe, Masatoshi Kataoka, Tatsu Shimoyama, Yoshiharu Maeda, Katsumasa Kuroi, Kenji Tamura, Tsuneo Sawazumi, Hironobu Minami, Yoshihiko Suda, Fumiaki Koizumi. Prognostic impact of CTC detected using a novel fluidic cell microarray chip CTC detection system in patients with breast 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 500.
Abstract 5007: Differential expression of neurogenes among breast cancer subtypes identifies high risk patients
Authors: Mancino Mario 
Published: July 2016

Abstract
The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes. Then we used bioinformatics tools to interrogate two published breast cancer databases SAGE and MicMa (n = 96) and generated a list of 7 neurogenes that are differentially express among breast cancer subtypes. The clinical potential was further investigated using the GOBO database (n = 1881). We identified 6 neurogenes that are differentially expressed among breast cancer subtypes and whose expression correlates with prognosis. Histamine receptor1 (HRH1), neuropilin2 (NRP2), ephrin-B1 (EFNB1), neural
growth factor receptor (NGFR) and amyloid precursor protein (APP) were differentially overexpressed in basal and HER2-enriched tumor samples and syntaxin 1A (STX1A) was overexpressed in HER2-enriched and luminal B tumors. Analysis of HRH1, NRP2, and STX1A expression using the GOBO database showed that their expression significantly correlated with a shorter overall survival (p&lt;0.0001) and distant metastasis-free survival (p&lt;0.0001). In contrast, elevated co-expression of NGFR, EFNB1 and APP was associated with longer overall (p&lt;0.0001) and metastasis-free survival (p&lt;0.0001). We propose that HRH1, NRP2, and STX1A can be used as prognostic biomarkers and therapeutic targets for basal and HER2-enriched breast cancer subtypes.
Citation Format: Mario Mancino. Differential expression of neurogenes among breast cancer subtypes identifies high risk patients. [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 5007.