bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3373: TGF-β1 signaling mediated lymphangiogenesis in gastric cancer
Authors: Pak Kyung Ho , Cheong Jae-Ho , Park Ki Chung 
Published: July 2016

Abstract
Background
Recent evidence showed that Transforming growth factor (TGF)-β1 could have important role for gastric cancer progression and metastasis. However, the role of TGF- β1 for lymph node metastasis and lymphangiogenesis, the important steps of gastric cancer progression, is largely unknown. To investigate the role of TGF-β1 on lymphangiogenesis and its molecular mechanisms is the main purpose of this study.
Methods
We selected two gastric cancer cell-line models, MKN45 and KATOIII, which hold appropriate characteristics for the current study. We checked the possibility of the autocrine function of TGF-β1 for lymphangiogenesis in these gastric cancer cell-lines. We investigated the changes of TGF-β1 signaling molecules and VEGF-C expression in responding to TGF-β1 and its inhibitor. To examine the binding of Smad3 to the promoter region of VEGF-C, we performed electrophoretic mobility shift assay (EMSA). Both Smad-dependent and Smad-independent pathways were also examined to elucidate which pathways were involved in lymphangiogenesis. Finally, tube forming assay was performed to validate phenotypical effect of TGF-β1 on lymphangiogenesis.
Results
Two gastric cancer cell-line models, MKN45 and KATOIII, showed autocrine regulation of TGF-β1. TGF-β1 signaling was transduced to VEGF-C, mediated by Smad3. Smad3 was bound to the promoter of VEGF-C which was confirmed with EMSA. Based on EMSA results, KATOIII showed stronger reaction between Smad3 and VEGF-C promoter than MKN45 did. In MKN45, TGF-β1 also transduced its signal to VEGF-C through PI3k-Akt pathway, one of the Smad-independent pathway. Lymphatic endothelial cells cultured in the condition media of MKN45 and KATOIII underwent tubule structure formation. The growth of HLEC was accelerated with TGF-β1 mixed conditioned media, while failed to induce tubular structure in the presence of TGF-β1 inhibitor. The expression level of secreted VEGF-C was as same in responding to TGF-β1 and its inhibitor as the lymphatic tube forming results in gastric cancer cells.
Conclusion
TGF-β1 could promote lymphangiogenesis through VEGF-C expression in gastric
cancer cell line models. TGF-β1 signaling could be transduced through either
Smad-mediated or non- Smad-mediated depending on gastric cancer cell-line
characteristics.
Citation Format: Kyung Ho Pak, Jae-Ho Cheong, Ki Chung Park. TGF-β1 signaling mediated lymphangiogenesis in 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 3373.
Abstract 3384: IGFBP5-derived peptide as a novel angiogenesis inhibitor for treatment of ovarian cancer
Authors: Lee Jeong-Won , Hwang Jae Ryoung , Cho Young-Jae , Lee Yoo-Young , Choi Chel Hun , Bae Duk-Soo , Kim Byoung-Gie 
Published: July 2016

Abstract
Insulin-like growth factor-binding protein 5 (IGFBP5) plays a role in cell growth, differentiation, and apoptosis. We found that IGFBP5 was markedly downregulated in ovarian cancer tissue, and that its overexpression in cancer cells induced cell death. In this study, we undertook to evaluate the functional significance of each region of IGFBP5 as a tumor suppressor of ovarian cancer. We found that the C-terminal region of IGFBP5 inhibited tumor growth in a 2774 cell xenograft mouse model, and that expression of VEGF, IL-6, and TNF-α were inhibited in 2774 cells stably expressing the C-terminus of IGFBP5. In order to evaluate its effects on tumor suppression, a peptide derived from the C-terminus of IGFBP5 (BP5-C) was synthesized. As a control, a peptide mutated in the IGF-binding site of BP5-C (BP5-Cmut), as well as peptides derived from the IGFBP2 C-terminus and heparin-binding site were also synthesized. Of these peptides, BP5-C and BP5-Cmut inhibited VEGF expression and NF-kB activity. Furthermore, BP5-C inhibited angiogenesis in an in vitro and an ex vivo system, consisting of HUVEC tube formation and rat aortic ring blood vessel sprouting, respectively. The in vivo effect of BP5-C on tumor growth was studied using i.p. injection of ovarian cancer 2774 cells into mice, as well as with a patient-derived xenograft mouse model. BP5-C peptide significantly inhibited tumor growth, angiogenesis, and VEGF expression in both xenograft models. These results suggest that the C-terminus of IGFBP5 exerts an anti-cancer activity by inhibiting angiogenesis via downregulation of VEGF in an IGF-independent manner, and may be considered as a novel angiogenesis inhibitor for the treatment of ovarian cancer.
Citation Format: Jeong-Won Lee, Jae Ryoung Hwang, Young-Jae Cho, Yoo-Young Lee, Chel Hun Choi, Duk-Soo Bae, Byoung-Gie Kim. IGFBP5-derived peptide as a novel angiogenesis inhibitor for treatment of ovarian 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 3384.
Abstract 3390: CTHRC1 promotes angiogenesis by recruiting Tie2-expressing monocytes to pancreatic tumors
Authors: Jo Seongyea , Lee Jaemin , song. jinhoi 
Published: July 2016

Abstract
CTHRC1 (collagen triple helix repeat-containing 1), a protein secreted during the tissue repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 plays an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here, we demonstrate a novel role of CTHRC1 as a potent endothelial activator, promoting angiogenesis by recruiting bone marrow-derived cells into the tumor microenvironment during tumorigenesis. Recombinant CTHRC1 (rCTHRC1) enhanced endothelial cell (EC) proliferation, migration and capillary-like tube formation, consistent with observed increases in neovascularization in vivo. Moreover, rCTHRC1 induced upregulation of angiopoietin-2 (Ang-2), a Tie2 receptor ligand, through ERK-dependent activation of AP-1 in ECs, resulting in recruitment of Tie2-expressing monocytes (TEMs) to CTHRC1-overexpressing tumor tissues. Treatment with a CTHRC1-neutralizing antibody abrogated Ang-2 expression in ECs in vitro. Moreover, CTHRC1-neutralizing antibody treatment in a xenograft mouse model reduced tumor burden and infiltration of TEMs in tumor tissues, indicating that blocking the CTHRC1/Ang-2/TEM axis during angiogenesis inhibits tumorigenesis. Collectively, our findings support the conclusion that CTHRC1 induction of the Ang-2/Tie2 axis mediates the recruitment of TEMs, which are important for tumorigenesis and can be targeted to achieve effective antitumor responses in pancreatic cancers.
Citation Format: Seongyea Jo, Jaemin Lee, jinhoi song. CTHRC1 promotes angiogenesis by recruiting Tie2-expressing monocytes to pancreatic tumors. [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 3390.
Abstract 3392: Lung cancer cell derived extracellular vesicles carrying DNAs, RNAs and proteins that may trigger oncogenic signals and promote angiogenesis
Authors: Lin Chien-Chung , Huang Wei-Lun , Su Wu-Chou 
Published: July 2016

Abstract
Extracellular vesicles (EVs) secreted from tumor cells have been implicated in modulating the tumor microenvironment changes. In this study, we demonstrated that EVs secreted by lung cancer cell are loaded with several cargos, such as DNA, RNA, cytokines, and growth factors. After the EVs had been taken up by recipient cells, the cargos might activate oncogenic pathways. We firstly isolated EVs from cell-free medium of lung cancer cells lines (AS2, PC9) and malignant pleural effusion (MPE) from patients with lung cancer. Isolated EVs were confirmed by the morphology and size in transmission electron microscopy (TEM) and the presentation of specific EV markers (Alix, CD63, and Tsg101). We found that several RNA species with enrichment of small RNAs and mutated EGFR DNA in the EVs of PC9 cells. After labeling with the green fluorescent dye Cellvue, the uptake of EVs by AS2 cells was imaged by the fluorescent microscopy. With these data, we further investigated the role of EVs in regulating the tumor microenvironment. We found the content of IL-6 in EVs, secreted from AS2 and CL1-5 cells, increased gradually after changing culture medium. And after uptake of EVs by recipient cells the cargos induced higher phsophorylation of Stat3 and AKT compared to the treatment with serum-free medium. Previously, we have shown that IL-6/Stat3/tissue factor (TF)/VEGF pathway enhances lung cancer angiogenesis, metastasis and the generation of MPE. In the current study, we demonstrated that EVs from lung cancer cells and in the MPE contain high level of VEGF and TF. And treatment with the EVs, containing high VEGF and TF, induced more prominent extravasation than cell free medium did in Miles assays. In conclusion, we successfully isolated EVs not only from culture supernatants but also from MPE of lung cancer patients. The EVs contain many biologically active molecules that may modulate behaviors of cancer cells and cells in tumor microenvironment.
Citation Format: Chien-Chung Lin, Wei-Lun Huang, Wu-Chou Su. Lung cancer cell derived extracellular vesicles carrying DNAs, RNAs and proteins that may trigger oncogenic signals and promote angiogenesis. [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 3392.
Abstract 3403: Amphiregulin promotes vascular endothelial growth factor-dependent angiogenesis in human chondrosarcoma cells
Authors: Huang Yu-Wen , Tsai Hsiao-Chi , Tang Chih-Hsin 
Published: July 2016

Abstract
Chondrosarcoma is the second most common sarcoma in bone malignancy and is characterized by a high metastatic potential. Angiogenesis has been considered an important role in the cancer metastasis. Therefore, a better understanding of angiogenic and metastatic pathways are needed. Amphiregulin (AR) has been implicated in tumor metastasis and angiogenesis. However, the relationship of amphiregulin with vascular endothelial growth factor A (VEGF-A) expression and angiogenesis in human chondrosarcoma cells is mostly unknown. In this study, we found that the expression of amphiregulin and VEGF-A were correlated with tumor stage and were significantly higher than that in the normal cartilage. VEGF-A expression increased which depend on time and dose dependent of amphiregulin. Exogenous amphiregulin with chondrosarcoma cells promoted VEGF-A expression and subsequently increased migration, proliferation and tube formation in endothelial progenitor cells (EPCs) and human umbilical vein endothelial cells (HUVECs). We also found that amphiregulin increased VEGF-A expression and angiogenesis through focal adhesion kinase (FAK), Src and protein kinase C (PKC) signaling pathway. Knockdown of amphiregulin decreased VEGF-A expression in chondrosarcoma cells. The angiogenesis effects in Matrigel plug nude mice model in vivo was also abolished in amphiregulin-knockdown cells. Taken together, these results indicate that amphiregulin occurs through FAK, Src, and PKC pathway, resulting in the activation of VEGF-A expression and contributing to the angiogenesis of human chondrosarcoma cells.
Citation Format: Yu-Wen Huang, Hsiao-Chi Tsai, Chih-Hsin Tang. Amphiregulin promotes vascular endothelial growth factor-dependent angiogenesis in human chondrosarcoma 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 3403.
Abstract 3405: The analysis of TRPV6 expression in lymphoid tumours
Authors: DiPasquale Ashley M. , Rahmeh Tarek , Andrew Lauren , Agar Jane , Miller Kim , Finniss Matthew , Murugesan Alli , Reiman Anthony 
Published: July 2016

Abstract
Introduction:
TRPV6 is a calcium channel that is found overexpressed in various malignancies and is correlated with the prognosis of patients with prostate cancer. TRPV6 targeted anticancer therapies are in development. We are interested in the potential of TRPV6 as a potential biomarker and therapeutic target in lymphoma. This retrospective study examines the expression levels of TRPV6 in various lymphoid tumour types, and correlates expression levels with grade, prognostic scores, and survival rates.
Methods:
A clinical-pathological database was constructed using the health records and lymphoid tumor samples of patients diagnosed with diffuse large B-cell lymphoma (DLBCL), Follicular lymphoma (FL), small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), and Hodgkin's lymphoma (HL). Immunohistochemical studies were performed on lymphoid tumor samples to analyze the level of TRPV6 expression. Tumor samples were graded on a 3-point scale. A score of +3 indicated dense staining with high expression levels, and a score of +1 indicated minimal staining with low expression levels. TRPV6 expression levels were correlated with prognostic scores (IPI, FLIPI) and survival rates using Chi-squared, Mantel-Cox, and Kaplan-Meier survival curves. Descriptive statistics were used to describe patient demographics.
Results:
We found high TRPV6 expression levels in DLBCL and HL tumor samples with &gt; 40% of samples scoring +3. We found low TRPV6 expression levels in FL and SLL/CLL with &gt; 40% of samples scoring +1. We found no significant correlation between the level of TRPV6 expression and prognostic scores or survival rates in any of the lymphoma subtypes studied. In follicular lymphoma tumor samples, it was noted on observation that the large tumor cells generally stained +3 while the small tumor cells generally stained +1.
Conclusion:
This retrospective study showed DLBCL and HL tumors have high levels of TRPV6 expression. It also showed that TRPV6 is found highly expressed in the large transformed cells (centroblasts) in follicular lymphoma. These results demonstrate a need to further assess the role of TRPV6 in the aggressiveness of follicular lymphoma, as well as the prognosis and survival in DLBCL and HL with a larger sample size. Further studies of the potential of TRPV6 as a therapeutic target in lymphoma will focus on DLBCL, high grade/transformed FL, and HL.
Citation Format: Ashley M. DiPasquale, Tarek Rahmeh, Lauren Andrew, Jane Agar, Kim Miller, Matthew Finniss, Alli Murugesan, Anthony Reiman. The analysis of TRPV6 expression in lymphoid tumours. [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 3405.
Abstract 3412: Prognostic significance of plasma ghrelin in patients with gastric cancer
Authors: Soleyman-Jahi Saeed , Zendehdel Kazem , Abdirad Afshin , Fallah Amir Afraz , Ghasemi Sevil , Sadeghi Fatemeh 
Published: July 2016

Abstract
Background: Different prognosis observed for patients of the same clinical stage in gastric cancer, emphasizes the fact that new biological prognostic factors are needed to complement clinical staging. We aimed to investigate the prognostic significance of plasma ghrelin in gastric cancer patients.
Methods: In this prospective study, we included 83 gastric cancer patients from Cancer institute of Tehran, Iran. All the patients were candidates for gastrectomy with or without preoperative neoadjuvant chemotherapy (PNC). The patients were followed for three years. Demographic, clinical and para clinical data were registered. Using an ELISA based assay plasma levels of total and active ghrelin were assessed prior to and one week after the operation. Univariate and multivariate COX analyses were used to investigate the independent predictors of patients overall survival.
Results: The mean (±SD) age of the patients was 60.3±13.6. Sixty-five (78.3%) patients were male. Majority of the patients had gastric adenocarcinoma (95.2%). Thirty-seven (44.6%) patients had TNM stage II or I. Poorly differentiated grade was detected in 29 (34.9%) of the patients. Forty-eight (57.8%) patients received PNC before the operation. Mean (±SD) survival was 529 ± 373 days. Mean level of the plasma total ghrelin was 269.8±268.7 and 108.7±91.2 (pg/ml) before and after the operation, respectively (P&lt;0.001). Mean level of the plasma active ghrelin was 68.0 ± 63.8 and 44.0± 29.6 (pg/ml) before and after the operation, respectively (P&lt;0.001). Patients in the upper half or highest quartile of postoperative total ghrelin had better survival compared to the corresponding subgroups (Log rank test P = 0.02 and P&lt;0.001, respectively). Multivariate COX model revealed that late TNM stage (HR = 2.93, 95% CI: 1.37-6.27), no PNC (HR = 2.18, 95% CI: 1.08-4.37), history of significant weight-loss (HR = 2.32, 95% CI: 1.04-5.00) and lower quartile (≤38 pg/ml) of postoperative plasma total ghrelin (HR = 3.74, 95% CI: 1.45-9.63) predicted poor survival of patients. The level of other ghrelins did not show independent prediction of survival.
Conclusion: Our findings showed that low level of plasma total ghrelin after the gastrectomy could independently predict poor survival in gastric cancer patients. This emphasizes both prognostic and therapeutic significance of this biomarker in gastric cancer.
Citation Format: Saeed Soleyman-Jahi, Kazem Zendehdel, Afshin Abdirad, Amir Afraz Fallah, Sevil Ghasemi, Fatemeh Sadeghi. Prognostic significance of plasma ghrelin in patients with 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 3412.
Abstract 3414: Ethnic disparities in breast cancer survival in Sarawak, Malaysia
Authors: Sung Hyuna , Devi C.R. Beena , Guida Jennifer , Tang Tieng Swee , Anderson William F. , Yang Xiaohong R. 
Published: July 2016

Abstract
Introduction: There are three distinct South-East Asian ethnic groups in Sarawak, Malaysia (Chinese, Malay, and natives) whose breast cancer incidence rates and the distribution of tumor subtypes were reported to be significantly different. It remains unclear whether survival varies among breast cancer cases in these ethnic groups. We aimed to evaluate the relationship between survival and ethnicity when taking into account tumor characteristics.
Methods: We analyzed incident breast cancer cases who were enrolled and treated in Sarawak General Hospital, Malaysia, between 1992 and 2014. The association of ethnicity with survival (relapse-free survival and overall survival) was evaluated using multivariate Cox-proportional hazard model. Subgroup analysis was conducted for each tumor subtype defined by hormone receptor (HR+, ER+ or PR+; HR-, ER- and PR-) and HER2 status (HR+/HER2-, HR+/HER2+, HR-/HER2-, and HR-/HER2+).
Results: Among 2,758 eligible cases (median follow-up years, 2.90 years), there were 636 deceased and 423 relapsed cases. While there was no significant difference in disease recurrence, overall survival varied significantly by ethnicity. Compared with Chinese women, Malay women had a higher proportion of mortality (HR = 1.50; 95% CI = 1.14-1.96; P = 0.0037). This disparity remained significant only among cases with HR+ tumors (HR = 1.91; 95% CI = 1.17-3.11; P = 0.0091 among HR+/HER2-; HR = 2.74; 95% CI = 1.30-5.77; P = 0.0079 among HR+/HER2+). There was no difference in survival between Chinese and native women overall or stratified by subtype.
Conclusions: Our results showed that Malay women experienced worse survival compared to Chinese women particularly among cases with HR+ tumors. Future studies are needed to clarify the underlying factors for this association in order to develop intervention strategies to reduce disparity.
Citation Format: Hyuna Sung, C.R. Beena Devi, Jennifer Guida, Tieng Swee Tang, William F. Anderson, Xiaohong R. Yang. Ethnic disparities in breast cancer survival in Sarawak, Malaysia. [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 3414.
Abstract 3440: Time and regional incidence trends of human papillomavirus-associated oropharyngeal cancer in Ontario, Canada
Authors: Shi Wei , Hall Stephen F. , Rey-McIntyre Katrina , Griffiths Rebecca , Xu Wei , Su Jie , Bruce Jeff , Huang Shaohui , O’Sullivan Brian , Yip Kenneth W , Liu Fei-Fei 
Published: July 2016

Abstract
Background: Despite the increasing incidence of human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) in the Western World, there are little data describing the change in HPV incidence within Ontario, Canada. We therefore assessed HPV-positivity in a retrospective study of 612 OPC patient samples.
Methods: Diagnostic formalin-fixed and paraffin embedded OPC patient samples belonging to two cohorts were retrieved from institutions across Ontario, Canada over two time periods: 1998-1999 (n = 245) and 2003-2004 (n = 367). In all samples, HPV status was assessed initially using p16 immunohistochemistry (IHC). For p16 negative and equivocal staining samples, HPV in situ hybridization (ISH; using an HPV subtype 16/18 probe) was performed as the final indicator for HPV positivity. HPV-positivity rate was then compared over time and geographic region.
Results: Overall, p16-positivity was observed in 52.3% (320 of 612) of the OPC patients. For the p16-negative (n = 246) and p16-equivocal (n = 46) samples, 25.3% (n = 74) were positive by HPV16/18 ISH. The HPV infection incidence for the 1998-1999 cohort was 54.3% (133 of 245 samples; 95% CI: 53.9(47.4-60.2)). The HPV infection incidence increased significantly in the 2003-2004 cohort to 71.1% (261 of 367 samples; 95% CI: 71.4(66.5-76.0)) (p&lt;0.0001). When divided based on geographical region, HPV incidence also increased significantly over time (Northern Ontario by 49%, p = 0.04; Eastern Ontario by 23%, p = 0.009; Southern Ontario by 17%, p = 0.009; Central Ontario by 12%, p = 0.05). There were no significant differences between urban and rural areas over the two cohort periods (urban p = 0.8; rural, p = 0.6).
Conclusions: HPV-associated OPC increased in incidence in Ontario, Canada, over a 6-year period from 1998 to 2004, which appeared to be applicable across the entire province, regardless of urban or rural regions. A composite HPV detection method using p16 in combination with HPV ISH identified an additional 25% of HPV-positive OPC cases.
Citation Format: Wei Shi, Stephen F. Hall, Katrina Rey-McIntyre, Rebecca Griffiths, Wei Xu, Jie Su, Jeff Bruce, Shaohui Huang, Brian O’Sullivan, Kenneth W Yip, Fei-Fei Liu. Time and regional incidence trends of human papillomavirus-associated oropharyngeal cancer in Ontario, Canada. [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 3440.