bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-01-18: The relationship between components of tumour inflammatory cell infiltration and hematogenous metastasis in patients with primary breast cancer
Authors: Wu Naping , Wang Jue , Xia Tiansong , Zhou Wenbin , Liu Zhao , Zhao Yi , Liu Xiaoan , Zha Xiaoming , Wang Shui 
Published: May 2015

Abstract
Background: Tumors are infiltrated by inflammatory cells (e.g. macrophages, B and T lymphocytes), which may promote tumor growth and invasion. However, the clinical correlation between hematogenous metastasis and relative amount of inflammatory cells is still unknown.
Methods: The prevalence of circulating tumor cells (CTC) in peripheral blood of 133 breast cancer patients was detected by a multimarker comprised of cytokeratin 19 (CK19), small breast epithelial mucin (SBEM) and human mammaglobin (hMAM) real time quantitative RT-PCR (QPCR) platform. Meanwhile, CD68+macrophages, CD20+B lymphocytes and CD3+T lymphocytes at the peritumor and intratumor were also counted by immunohistochemical examination, in corresponding primary invasive breast carcinomas. The relationship between CTC in peripheral blood and inflammatory cell infiltration was analyzed.
Results: The positive rate of CTC was 39.8% (53 out of 133). The prevalence of CTC in peripheral blood was only observed in invasive breast carcinomas. There were more inflammatory cells at the peritumor than the tumor center (P &lt; 0.001).In addition, higher total numbers of infiltrating both CD68+macrophages and CD3+T lymphocytes were associated with significantly the prevalence of CTC in peripheral blood (P &lt; 0.05).
Conclusion: Our data support a hypothesis that CD68+macrophage and CD3+T lymphocyte infiltrating in the breast cancer microenvironment may promote tumor cells disseminating through circulation system.
Citation Format: Naping Wu, Jue Wang, Tiansong Xia, Wenbin Zhou, Zhao Liu, Yi Zhao, Xiaoan Liu, Xiaoming Zha, Shui Wang. The relationship between components of tumour inflammatory cell infiltration and hematogenous metastasis in patients with primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-18.
Abstract P4-01-19: The combined detection of CTC and serum HER2 ECD predict PFS for HER2-positive advanced breast cancer patients
Authors: Jiang Zefei , Zhou Jinmei , Wang Tao , Liu Yi , Li Lei , Zhang Huiqiang , Zhang Shaohua , Bian Li , Song Santai 
Published: May 2015

Abstract
Background: Circulating tumor cell (CTC) and serum HER2 ECD can all reflect an aggressive tumor behavior. We performed this prospective, monocenter, double-blinded study to investigate the potential clinical significance of combined detection of CTC and serum HER2 ECD for advanced breast cancer patients with histological HER2-positivity.
Methods: A total of 88 eligible patients were enrolled in the present study from April 2012 to October 2013. We used Cell search system and ADVIA Centaur System to detect CTC and serum HER2 ECD respectively. Patients received systemic treatment according to national and international guidelines.
Results: Twenty nine (33%) patients had ≥5 CTC, seventy three (83%) patients had serum HER2 ECD values of at least 15ng/ml, twenty seven (30.7%) patients had both elevated CTC and ECD values and fourteen (15.9%) patients had both normal CTC and ECD values. Patients with both normal CTC and serum HER2 ECD values exhibited a significantly longer median PFS than patients with both elevated values (9.0 months versus 2.8 months, p=0.023) and exhibited a trend toward longer PFS compared with patients with elevated CTC or ECD values (9.0 months versus 4.2 months, p=0.065), patients with both or one elevated values showed similar median PFS (2.8 months versus 4.2 months, p=0.211) (Figure1).
Conclusions: The combined detection of CTC and serum HER2 ECD showed prognostic significance for HER-2 positive advanced breast cancer patients, patients with both normal values exhibited longer median PFS than others.
Citation Format: Zefei Jiang, Jinmei Zhou, Tao Wang, Yi Liu, Lei Li, Huiqiang Zhang, Shaohua Zhang, Li Bian, Santai Song. The combined detection of CTC and serum HER2 ECD predict PFS for HER2-positive advanced breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-19.
Abstract P4-04-05: Contributions of STAT3 to pro-tumorigenic alterations within the microenvironment during mammary tumorigenesis
Authors: Chuntova Pavlina , Bohrer Laura R , Schwertfeger Kaylee 
Published: May 2015

Abstract
Interactions between tumor cells and their surrounding microenvironment are critical for the development and progression of breast cancer. Specifically, oncogenic alterations such as aberrant activation of growth factor receptors in epithelial cells lead to a pro-tumorigenic inflammatory response characterized by increased production of inflammatory factors and increased macrophage infiltration. Our studies focus on identifying novel mechanisms through which tumor-derived cytokines act in an autocrine manner to regulate tumor cells and in a paracrine manner to regulate infiltrating inflammatory cells. In recent studies, we have shown that following activation of the fibroblast growth factor receptor 1 (FGFR1) oncogene, mammary epithelial cells produce high levels of interleukin 6 (IL-6) family members. These cytokines activate signal transducer and activator of transcription 3 (STAT3) in both epithelial cells and macrophages. STAT3 is constitutively activated in up to 70% of primary breast tumors, and has been shown to enhance proliferation and angiogenesis as well as aid in immune suppression. Using a novel mouse model of FGFR1-driven tumor growth, we demonstrated that inhibition of STAT3 led to decreased tumor growth. Histological examination revealed high levels of STAT3 activation in both tumor cells and macrophages. Thus, further studies focused on identifying mechanisms through which STAT3 activation in different cellular compartments contributes to mammary tumor growth. Initial studies focused on the consequences of STAT3 activation in epithelial/tumor cells. We found that epithelial cell STAT3 activation resulted in accumulation of the extracellular matrix component hyaluronan, which contributed to epithelial cell proliferation, survival and migration. Meanwhile, STAT3 activation in macrophages led to expression changes within a variety of molecules which are known to enhance tumor cell survival, tumor invasion and regulation of the anti-tumor immune response. Thus, it becomes evident that systemic inhibition of STAT3 function can potentially inhibit tumor growth and progression by acting on both tumor cells and on the surrounding stroma. As STAT3 is being considered as a viable target for breast cancer therapy, understanding the mechanisms through which STAT3 promotes tumor growth and progression will be critical for developing optimal therapeutic strategies.
Citation Format: Pavlina Chuntova, Laura R Bohrer, Kaylee Schwertfeger. Contributions of STAT3 to pro-tumorigenic alterations within the microenvironment during mammary tumorigenesis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-05.
Abstract P4-04-13: Cancer-derived miR-105 promotes tumor invasion and destroys the natural barriers against metastasis
Authors: Wang Shizhen Emily , Zhou Weiying , Fong Miranda Y , Min Yongfen , Lin Pengnian Charles 
Published: May 2015

Abstract
Cancer-secreted miRNAs are emerging mediators of cancer–host crosstalk. In this study, we set out to identify cancer-derived miRNAs that participate in cancer metastasis by adapting the niche cells. We show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In epithelial and endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in non-metastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas intervention of miR-105 in highly metastatic tumors alleviates this effect. By testing clinical specimens from breast cancer patients, we further show that miR-105 can be detected in the circulation at the pre-metastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer. Our results demonstrate for the first time the dual roles of miR-105 in inducing the migratory potential of cancer cells as well as destroying the epithelial and endothelial barriers in the cancer niche by targeting the cellular tight junctions. In breast cancer patients, increased levels of miR-105 in the circulation can be detected at the pre-metastatic stage and predict the occurrence of metastasis. Anti-miR-105 treatment suppresses metastasis and abolishes the systemic effect of tumor-derived miR-105 on niche adaptation. Therefore, these pre-clinical observations strongly suggest clinical applications of miR-105 as a predictive or early-diagnostic blood-borne marker as well as a therapeutic target for breast cancer metastasis.
Citation Format: Shizhen Emily Wang, Weiying Zhou, Miranda Y Fong, Yongfen Min, Pengnian Charles Lin. Cancer-derived miR-105 promotes tumor invasion and destroys the natural barriers against metastasis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-13.
Abstract P4-04-16: Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production
Authors: Bowers Laura W , Brenner Andrew J , Hursting Stephen D , Tekmal Rajeshwar R , deGraffenried Linda A 
Published: May 2015

Abstract
Introduction: Obesity is associated with a worse breast cancer prognosis, particularly in estrogen receptor alpha (ERα) positive, postmenopausal patients. Resistance to aromatase inhibitor treatment may be one mechanism mediating this effect, as obese patients have a lower response rate to this class of drugs and higher breast tissue aromatase expression. We hypothesized that obesity-associated circulating factors promote breast cancer cell cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production, resulting in an elevation in pre-adipocyte aromatase expression that enhances breast cancer cell estrogen receptor activity and proliferation.
Methods: We utilized an in vitro model of the obese patient’s tumor microenvironment in which cultured MCF-7 breast cancer cells and pre-adipocytes were exposed to pooled serum from obese (OB; BMI≥30.0 kg/m2) or normal weight (N; BMI 18.5-24.9 kg/m2) postmenopausal women.
Results: Exposure to OB versus N patient sera significantly increased MCF-7 cell COX-2 expression and PGE2 production. This was coupled with 89% greater pre-adipocyte aromatase expression following culture in conditioned media (CM) from MCF-7 cells exposed to OB versus N patient sera, a difference nullified by treatment of the MCF-7 cells with the COX-2 inhibitor celecoxib during CM generation. Previous analysis of the sera revealed significantly higher interleukin 6 (IL-6) concentrations in the OB versus N patient samples. Depletion of IL-6 from the sera resulted in neutralization of the difference between OB and N CM-stimulated aromatase expression. N CM generated with the addition of IL-6 treatment at the time of N patient sera exposure also induced pre-adipocyte aromatase expression that was statistically equivalent to the OB CM condition. Finally, CM from pre-adipocyte/MCF-7 cell co-cultures exposed to OB patient sera stimulated greater MCF-7 and T47D breast cancer cell ERα activity and proliferation in comparison to N.
Conclusions: This study indicates that obesity-associated systemic IL-6 indirectly enhances pre-adipocyte aromatase expression via increased breast cancer cell PGE2 production, thereby promoting greater cancer cell ERα activity and proliferation. Investigation regarding the efficacy of a COX-2 inhibitor/aromatase inhibitor combination therapy in the obese postmenopausal patient population is warranted.
Citation Format: Laura W Bowers, Andrew J Brenner, Stephen D Hursting, Rajeshwar R Tekmal, Linda A deGraffenried. Obesity-associated systemic interleukin-6 promotes pre-adipocyte aromatase expression via increased breast cancer cell prostaglandin E2 production [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-16.
Abstract P4-04-26: Down-regulation of p16INK4a inhibits miR-146b-5p and modulates IL-6 in breast stromal fibroblasts
Authors: Al-Ansari Mysoon M , Aboussekhra Abdelilah 
Published: May 2015

Abstract
Breast cancer is a major health problem that threatens millions of women’s lives each year worldwide. Cancer-associated fibroblasts (CAFs), which constitute the major component of the tumor stroma, have been reported to actively contribute to tumor cells proliferation and invasion. Recently, we have shown down-regulation of the tumor suppressor p16INK4a protein in breast cancer-associated fibroblasts. Moreover, p16INK4a deficiency led to the activation of the stromal fibroblasts, which express/secrete elevated levels of IL-6, a major player in breast carcinogenesis. We have shown here that p16INK4a negatively regulates the IL-6 expression and secretion in breast stromal fibroblasts. Furthermore, we have shown that IL-6 is playing a major role in mediating the paracrine pro-carcinogenic effect of p16-deficient fibroblasts. We have also shown that p16INK4a inhibits the IL-6 expression in a miRNA-146b-5p-dependent manner. Importantly, we present clear evidence that miR-146b-5p inhibition activates breast stromal fibroblast. Indeed, miR-146b-5p inhibition increased the migration/invasion abilities of breast stromal fibroblasts, and the paracrine effect of these cells on the migration/invasion of breast cancer cells. Furthermore, miR-146b-5p-deficient stromal fibroblasts triggered epithelial to mesenchymal transition in breast cancer cells in a paracrine manner. In addition, we have shown that miR-146b-5p is down-regulated in CAFs as compared to their adjacent counterpart fibroblasts. These results indicate that p16INK4a negatively regulates IL-6 through the activation of miR-146b-5p, which plays a major role in repressing breast stromal fibroblasts and inhibiting their pro-carcinogenic effects. This indicates that miR-146b-5p has cell-non-autonomous tumor suppressor function. Therefore, this miRNA could be of great therapeutic value.
Citation Format: Mysoon M Al-Ansari, Abdelilah Aboussekhra. Down-regulation of p16INK4a inhibits miR-146b-5p and modulates IL-6 in breast stromal fibroblasts [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-26.
Abstract P4-04-27: Chemokines released by breast cancer-associated fibroblasts induce epithelial to mesenchymal transition in MCF7 breast cancer cells
Authors: Soon Patsy S , Kim Edward , Benn Diana E , Baxter Robert 
Published: May 2015

Abstract
Purpose: The tumour microenvironment plays a critical role in tumour progression, with cancer-associated fibroblasts (CAFs) in particular being involved in this process (1). Treating breast cancer cells with conditioned media from CAFs has been shown to induce epithelial-mesenchymal transition (EMT) of the breast cancer cells compared to conditioned media from normal breast fibroblasts (NBFs) (2). This study aims to identify factors released by CAFs which induce EMT in breast cancer cells.
Methodology: Primary cultures of six pairs of CAFs and NBFs were established from breast cancer patient samples. Serum-free conditioned media from these cells were collected for chemokine array analysis. MCF7 breast cancer cells were treated with recombinant chemokines and their corresponding receptor antagonists. Vimentin levels, as determined by immunoblot, and cell invasiveness, as measured by transwell assay, were used as indicators of EMT.
Results: Chemokine array showed that CAFs secreted more CXCL1, CXCL8, CXCL12 and CCL2 compared to matched NBFs. Recombinant CXCL8, CXCL12 and CCL2, but not CXCL1, were able to induce vimentin and to increase invasiveness in MCF7 cells. Antagonists for receptors of CXCL8, CXCL12 and CCL2 counteracted the effect of EMT induction on MCF7 cells by recombinant chemokines.
Conclusion: CXCL8, CXCL12 and CCL2, which are secreted at higher levels by CAFs compared to NBFs, induced EMT and increased invasiveness in MCF7 cells. These results suggest that therapeutic targeting of these chemokines or their receptors may be inhibitory to metastasis in some breast cancers.
References:
1. Bhowmick, N A et al. (2004) Nature 432, 332-337
2. Soon, P S et al. (2013) Endocr Relat Cancer 20, 1-12.
Citation Format: Patsy S Soon, Edward Kim, Diana E Benn, Robert Baxter. Chemokines released by breast cancer-associated fibroblasts induce epithelial to mesenchymal transition in MCF7 breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-27.
Abstract P4-05-07: Functional genomics of TP53 mutations and its impact in breast cancer progression
Authors: Pal Anasuya , Gonzalez-Malerva Laura , Eaton Seron , Guzman Mayra , Chow Donald , Yin Hongwei , Park Jin , Anderson Karen , LaBaer Joshua 
Published: May 2015

Abstract
Somatic TP53 mutations are prevalent in basal-like breast cancer (BLBC) tumors. Patients with BLBC tumors have fewer treatment options and respond poorly to current therapies. The majority of TP53 point mutations occurs in the DNA binding domain and can be categorized as either DNA contact or structural mutations. TP53 mutation results in a dominant negative phenotype with neomorphic activity. We predicted that different p53 mutations may lead to different phenotypic characteristics. To investigate this, we generated MCF10A stable transduced cell lines over-expressing the ten most frequent TP53 point mutations associated with breast cancer located in the DNA binding domain of TP53. Ectopic expression of TP53 in these stable cells has been confirmed by qRT-PCR and immunoblot. To assess the impact of mutation on carcinogenesis, we developed a series of high-throughput quantitative assays that measure several hallmarks of cancer, including proliferation, escape from apoptosis, epithelial to mesenchymal transition (EMT), cell migration and invasion, anoikis and morphology in 3D. We observed that one DNA contact mutation with the substitution of a positively charged amino acid with hydrophobic side chains such as R248W, and two structural mutants Y234C and H179R are resistant to apoptosis in presence of doxorubicin, are the most invasive displaying a mesenchymal phenotype characterized by the presence of disrupted B-catenin and E-cadherin staining, with reported worst clinical outcome, suggesting that these are the most aggressive phenotypes. Interestingly, the DNA contact mutants (R248Q, R273H, R248W, and R273C) had a growth advantage in absence of growth factors while structural mutants (R175H, H179R, Y220C, Y234C and Y163C) were more resistant to apoptosis after the cells were challenged with doxorubicin. G245S is comparable to the MCF10Ap53wt and is less proliferative, sensitive to apoptosis, and neither migratory nor invasive. In comparison, R248W which is one of the most aggressive mutants, together with R273C, and H179R resist anoikis; but Y234C, requires matrix for attachment in order to be invasive. In conjunction, these results confirmed our hypothesis that different TP53 point mutants have distinct phenotypes and functional effects on hallmarks of cancer due to distinct underlying cellular programs.
Citation Format: Anasuya Pal, Laura Gonzalez-Malerva, Seron Eaton, Mayra Guzman, Donald Chow, Hongwei Yin, Jin Park, Karen Anderson, Joshua LaBaer. Functional genomics of TP53 mutations and its impact in breast cancer progression [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-07.
Abstract P4-05-09: Matrin 3: A novel micro-tubule associated RNA binding protein that acts as a potent tumor suppressor
Authors: Subbarayalu Panneerdoss , Rajamanickam Subapriya , Viswanadhapalli Suryavathi , Dybdal-Hargreaves Nicholas , Timilsina Santosh , Bansal Sanjay , Bansal Hima , Mohammad Tabrez , Chen Yidong , Herr John C , Mooberry Susan L , Rao Manjeet K 
Published: May 2015

Abstract
Microtubules are highly dynamic components of the cytoskeleton that play an important role in a wide range of cellular processes including cell division, cell motility and intracellular transport. Increasing evidence suggests that alterations in microtubule dynamics are critical for cancer growth and metastasis. Microtubule associated proteins (MAPs) regulate microtubule dynamics and consequently can affect sensitivity of cancer cells to microtubule targeting drugs. We discovered a novel microtubule associated protein "Matrin 3 (MATR3)" that is known to bind to RNA and play a critical role in RNA transport and RNA stabilization. Immunofluorescence analyses revealed that although MATR3 is predominantly a nuclear protein, it translocates to the cytoplasm and interacts with microtubules when breast cancer cells are treated with paclitaxel. We show that MATR3 associates with stabilized microtubules and it mediates microtubule polymerization in a taxol-dependent manner. Interestingly, our results reveal that MATR3 acts as a effective tumor suppressor as it inhibits breast cancer colony formation, migration and invasion of breast cancer cells in addition to suppressing breast tumor growth in vivo. Analysis of breast cancer samples showed a significantly lower expression of MATR3 when compared to normal adjacent tissues. Our results indicate the possibility that MATR3 mediates its tumor suppressor function by binding and regulating proteins that are known to affect microtubule dynamics. We believe that nuclear-cytoplasmic shuttling of MATR3 is critical for stability of key proteins that might regulate paclitaxel-dependent microtubule dynamics and subsequently cellular effects in cancer cells.
Citation Format: Panneerdoss Subbarayalu, Subapriya Rajamanickam, Suryavathi Viswanadhapalli, Nicholas Dybdal-Hargreaves, Santosh Timilsina, Sanjay Bansal, Hima Bansal, Tabrez Mohammad, Yidong Chen, John C Herr, Susan L Mooberry, Manjeet K Rao. Matrin 3: A novel micro-tubule associated RNA binding protein that acts as a potent tumor suppressor [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-09.