bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-05-04: NEAT1 enhances drug sensitivity by inhibiting cancer stem-like cells in triple-negative breast cancer
Authors: Kwong A , Chen J , Siu J , Chuek I , Shin V 
Published: May 2019

Abstract
Background: Accumulating evidence showed that long non-coding RNAs (lncRNAs) dysregulation is the hallmark of cancer. Nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to overexpress in many cancers, and promote cell growth and disease progression. However, the role of NEAT1 on drug sensitivity and stem-cell like property in triple-negative breast cancer is largely unknown.
Methods: LncRNA expression profile were compared between breast cancer patients and healthy individuals using lncRNA array. Large scale validation of NEAT1 expression in blood samples were performed by real-time PCR. Triple-negative breast cancer (TNBC) cells, MDA-MB-231 and its cisplatin resistance subline (MDA-MB-231/cis) were used. Stable transfection of cells with NEAT1 knockdown by shRNA, and evaluated single cell clonogenic assay, aldehyde dehydrogenase (ALDH) activity, CD44+/CD24- and other cancer stem cell (CSC) markers. Drug sensitivity assay, flow cytometry analysis, immunofluorescence staining and xenograft model were used to assess the functional role of NEAT1.
Results: Array data showed that NEAT1 was the top upregulated lncRNAs in the plasma of breast cancer patients. Consistent with the array data, validation of larger cohort of patients and healthy individuals (n=369) also demonstrated a higher expression of NEAT1 in breast cancer patients, in particular TNBC subtype. Knockdown of NEAT1 by shRNA sensitized breast cancer cells to cisplatin and taxol treatment. Cell proliferation and colony formation abilities were reduced with S-phase cell cycle arrest in shNEAT1 cells. Flow cytometry analysis revealed an induction of apoptosis with increased cleaved caspase-3. Cells expressing shNEAT1 abrogated ALDH activity, CD44+/CD24- subpopulation and expression of CSC markers (SOX2, NANOG and OCT4). More importantly, shNEAT1 cells retarded tumor growth in xenograft mice model and reduced CSC markers.
Conclusion: Taken together, NEAT1 expression is differentially expressed in breast cancer patients, and particularly higher in patients with TNBC. These findings suggest a potent therapeutic target to improve drug sensitivity in patients with TNBC.
Citation Format: Kwong A, Chen J, Siu J, Chuek I, Shin V. NEAT1 enhances drug sensitivity by inhibiting cancer stem-like cells in triple-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-05-04.
Abstract P6-05-09: Exosome microRNA contents are altered during breast cancer progression
Authors: Hannafon BN , Gin AL , Behbod F , Ding W-Q 
Published: May 2019

Abstract
Background: The progression of breast cancer involves the transformation of normal mammary epithelial cells to ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). This process is initiated by genetic alterations and characterized by changes to gene expression programs and microenvironmental alterations. However, the specific drivers of DCIS progression to IBC are not well understood nor has an indicator of progression been identified. Exosomes are small secretory vesicles that can contribute to cancer progression by transferring oncogenic factors, such as microRNAs (miRNAs), to surrounding cells in the tumor microenvironment, and enter the circulation to act at distant sites. miRNAs are short noncoding RNAs that regulate the expression of a target messenger RNA (mRNA). Altered regulation by miRNAs is implicated in cancer progression. In this study, we sought to characterize the exosome miRNAs in the MCF10 isogenic model of breast cancer progression in order to identify potential drivers of breast cancer.
Methods: Exosomes were isolated from the conditioned media of the MCF10 isogenic cell line model of breast cancer progression representing the following stages: normal, benign proliferative, carcinoma in situ, and invasive carcinoma. RNA was extracted from the exosomes and next generation RNA sequencing was performed. Exosome miRNA expression was validated in breast cancer cell lines and in plasma exosomes collected from a mouse-intraductal transplantation (MIND) model implanted with MCF10DCIS.com (DCIS) cells that can mimic human DCIS progression in vivo.
Results: Comparisons were made between differentially expressed miRNAs among each condition (fold change &gt;1.5; Kruskal-Wallis p&lt;0.05,). Twenty-nine miRNAs were differentially expressed among invasive and DCIS exosomes. The expression of 5 oncogenic miRNAs (miR-30c-5p, -210, -182-5p, -200c-3p, and -200b-3p) were consistently increased, while 2 tumor suppressive miRNAs (miR-423-5p and -92b-3p) were consistently decreased with invasive progression. Exosome miRNA expression was confirmed in breast cancer cell lines and mouse plasma exosomes.
Conclusion: This work demonstrates that the microRNA contents of exosomes change upon malignant transformation to invasive breast cancer and indicate that certain exosome microRNAs are consistently up- or down-regulated and may contribute to breast cancer progression.
Citation Format: Hannafon BN, Gin AL, Behbod F, Ding W-Q. Exosome microRNA contents are altered during breast cancer progression [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-05-09.
Abstract P6-08-01: Not presented
Authors: Guimarães I , Gimba E , Castelo-Branco M , Sternberg C , Silva I , Rangel L 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Guimarães I, Gimba E, Castelo-Branco M, Sternberg C, Silva I, Rangel L. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-08-01.
Abstract P6-09-03: Association of Caspase 8 polymorphisms with TILs and disease-free survival in primary breast cancer patients
Authors: Wimberger P , Bachmann HS , Kuhlmann JD , Link T , Kröber E , Thomssen C , Malle B , Vetter M , Kantelhardt EJ 
Published: May 2019

Abstract
BACKGROUND: The minor allele of two caspase-8 polymorphisms, namely CASP8 -652 6N InsDel and CASP8 Asp302His, were shown to promote survival of T-lymphocytes and were repeatedly associated with reduced breast cancer susceptibility. However, besides some preliminary findings, clinical relevance of these polymorphisms in patients with already existing primary breast cancer has not yet been established. Considering an immunomodulatory and potentially tumor-protective role of these caspase-8 variants, we genotyped 785 primary breast cancer patients and correlated caspase-8 variants with i) disease-free survival (DFS) and ii) the presence of tumor infiltrating lymphocytes (TILs).
METHODS: Primary breast cancer samples were collected at the Martin-Luther University, Halle-Wittenberg between 2009 and 2011 as part of the multicenter prospective PiA trial (NCT 01592825). The majority of patients had luminal-like tumors (75.9%), followed by triple negative (10.1%), luminal-Her2-like (9.6%) and Her2-enriched tumors (4.5%). Genotyping was performed by pyrosequencing, TILs status was assessed by hematoxylin and eosin staining.
RESULTS: The CASP8 -652 deletion was significantly associated with improved DFS in an allele-dose dependent manner (p=0.027). Homozygosity for the -652 6N Del variant was an independent predictor for improved DFS (p=0.005). In patients with a 302His/His genotype, there was no event of recurrence during the entire observation time. Combined analysis of diplotypes revealed that both polymorphisms had an influence on DFS (p=0.029). Interestingly, patients with the 302His/His variant among the unstratified patient cohort and among the luminal-like subtype alone had tumors with very low lymphocyte infiltration (0-10% TILs in 65% of cases compared to 31% of cases for other genotypes, p=0.025).
CONCLUSION: In line with previous epidemiological findings, we propose a prognostically favorable role of the CASP8 -652 6N Del and the Asp302His variant in primary breast cancer patients. Moreover, we suggest for the first time a role of the Asp302His variant in immunosurveillance and lymphocyte infiltration of breast cancer. Our findings strongly encourage further analyze of these genetic variants as a biomarker for prognostic and immunotherapeutic considerations.
Citation Format: Wimberger P, Bachmann HS, Kuhlmann JD, Link T, Kröber E, Thomssen C, Malle B, Vetter M, Kantelhardt EJ. Association of Caspase 8 polymorphisms with TILs and disease-free survival in primary breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-09-03.
Abstract P6-09-08: High circulating levels of Periostin are associated with a poor survival in primary, non-metastatic breast cancer patients
Authors: Hoffmann O , Goebel A , Bittner A-K , Rauner M , Hofbauer LC , Kimmig R , Kasimir-Bauer S , Rachner TD 
Published: May 2019

Abstract
Background: Periostin, also known as osteoblast-specific factor OSF-2, functions as a ligand for integrins to support adhesion and migration of tumor cells which leads to increased cell survival, invasion, angiogenesis and metastasis in different cancer types including breast cancer (BC). Assuming that metastasis requires a dissemination of tumor cells, associated with worse outcome in BC, the aim of this study was to determine the expression of Periostin in blood samples of patients with primary, non-metastatic BC and to correlate the results with clinical parameters including the presence of disseminated tumor cells (DTCs) in the bone marrow (BM), survival and the risk of developing metastatic disease.
Patients and Methods: BM and blood sampling were performed before surgery in an adjuvant setting in 509 patients with first diagnosis of BC between Aug 2006 and Dec 2009. Two BM aspirates were analyzed for DTCs using density centrifugation followed by immunocytochemistry applying the pan-cytokeratin antibody A45-B/B3. Blood was collected from each patient and Periostin serum levels were measured by ELISA (Biomedica, Vienna, Austria).
Results: Periostin levels were detectable (504.8 ± 178.7 pmol/l) in all BC patients. There were no significant differences between serum Periostin levels when stratifying according to tumor stage, lymph node involvement or grading. Periostin levels were significantly increased in women above the age of 60 (468.6±166.6 pmol/l vs. 540.1±184.2 pmol/l; p&lt;0.0001) and significantly enhanced in postmenopausal compared to peri- or premenopausal women (p&lt;0.05 and p&lt;0.001, respectively). No differences were observed between DTC-positive and DTC-negative patients. When separating patients according to high (top 50%) or low (low 50%) Periostin levels, patients with low Periostin levels had a significantly shorter BC specific survival (HR 0.61; 95%CI 0.39-0.96; p=0.03).
Conclusion: In summary, while Periostin levels were unchanged in patients with and without DTCs, high levels of Periostin were associated with a poorer BC specific survival. These results warrant further studies on the role of Periostin in BC.
Citation Format: Hoffmann O, Goebel A, Bittner A-K, Rauner M, Hofbauer LC, Kimmig R, Kasimir-Bauer S, Rachner TD. High circulating levels of Periostin are associated with a poor survival in primary, non-metastatic breast cancer patients [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-09-08.
Abstract P6-10-01: Consumption of sugar-containing beverages and cancer risk: Results from the NutriNet-Santé prospective cohort
Authors: Chazelas E , Srour B , Desmetz E , Kesse-Guyot E , Julia C , Druesne-Pecollo N , Galan P , Zelek L , Hercberg S , Latino-Martel P , Deschasaux M , Touvier M 
Published: May 2019

Abstract
OBJECTIVE
To assess the associations between the consumption of sugar-containing and artificially sweetened beverages and cancer risk.
DESIGN
Population based prospective cohort study.
SETTING AND PARTICIPANTS
Overall, 101 257 participants aged ≥18y (mean age: 42.2±14.4y) from the French NutriNet-Santé cohort (2009-2017) were included. Consumptions of sugar-containing and artificially sweetened beverages were assessed using repeated 24h-dietary records, designed to register participants' usual consumption for 3300 different food and beverage items.
MAIN OUTCOME MEASURES
Associations between beverage consumption and overall, breast, prostate and colorectal cancer risk were assessed by multivariable Cox Proportional Hazard models adjusted for known risk factors.
RESULTS
A 100mL increase in the consumption of sugar-containing beverages was significantly associated with an increased risk of overall cancer (HR=1.08, 95% confidence interval 1.04 to 1.12, P&lt;.0001) and breast cancer (HR=1.11, 95% confidence interval 1.04 to 1.19, P&lt;0.002). The consumption of artificially sweetened beverages was not associated with cancer risk. In sub-analyses, a 100 mL increase in the consumption of 100% fruit juice was significantly associated with an increased risk of overall cancers (HR=1.08, 95% confidence interval 1.02 to 1.15, P=0.01). These associations were strongly mediated by the sugar contained in these beverages. In contrast, weight gain during follow-up did not appear as a strong mediator. Besides, results were similar in overweight and non-overweight participants.
CONCLUSIONS
In this large prospective study, a 100mL increase in the consumption of sugar-containing beverages in the diet was associated with an 8% significant increase in overall cancer risk and an 11% significant increase in breast cancer risk. 100% fruit juices were also associated with an 8% increased risk of overall cancers. Given the massive consumption of sugar-containing beverages in Western countries, these results suggest that they may represent a key modifiable risk factor for cancer prevention.
Citation Format: Chazelas E, Srour B, Desmetz E, Kesse-Guyot E, Julia C, Druesne-Pecollo N, Galan P, Zelek L, Hercberg S, Latino-Martel P, Deschasaux M, Touvier M. Consumption of sugar-containing beverages and cancer risk: Results from the NutriNet-Santé prospective cohort [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-10-01.
Abstract P6-10-02: Not presented
Authors: McDonnell SL , Baggerly CA , French CB , Baggerly LL , Garland CF , Gorham ED , Lappe JM 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: McDonnell SL, Baggerly CA, French CB, Baggerly LL, Garland CF, Gorham ED, Lappe JM. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-10-02.
Abstract P6-14-02: Withdrawn
Authors: Esser MR , Rowe JJ , McCann ML , Nicholas-Alexander M , Helck EP , Lewis SM 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Esser MR, Rowe JJ, McCann ML, Nicholas-Alexander M, Helck EP, Lewis SM. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-14-02.
Abstract P6-17-34: Not presented
Authors: Yang F , Yin Y , Jiang Z 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Yang F, Yin Y, Jiang Z. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-34.
Abstract P6-18-27: Withdrawn
Authors: Odom D , Mitra D , Hollis K , Richardson D , Kaye JA , McRoy L 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Odom D, Mitra D, Hollis K, Richardson D, Kaye JA, McRoy L. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-27.
Abstract P6-21-04: Targeting PI3Kβ alone and in combination with chemotherapy or immunotherapy in tumors with PTEN loss
Authors: Owusu-Brackett N , Zhao M , Akcakanat A , Evans KW , Yuca E , Tapia C , Ileana-Dumbrava E , Janku F , Meric-Bernstam F 
Published: May 2019

Abstract
Background: PTEN functions as a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway to promote balanced cell proliferation, survival and differentiation. PTEN loss occurs across a variety of cancer subtypes; PTEN-deficient tumors are dependent on PI3Kβ activity, making PI3Kβ a compelling target. We evaluated the efficacy of PI3Kβ inhibitor AZD8186 as a single agent and in combination with standard chemotherapy and immune checkpoint inhibitors focused on tumors with loss of PTEN function.
Methods: In vitro, cell proliferation assays were performed to determine the half maximal inhibitory concentration (IC50) after 3 days of treatment and to test the effects in combination with standard chemotherapy. Colony formation assays were performed to confirm efficacy of AZD8186 in PTEN-deficient cell lines. Western blot analysis was performed to assess PTEN protein expression and to evaluate effects of AZD8186 on PI3K signaling. In vivo, antitumor efficacy of AZD8186 as a single agent as well as in combination with paclitaxel and anti-PD1 was evaluated.
Results: AZD8186 inhibited the cell proliferation of three of ten TNBC cell lines in vitro; PTEN loss was significantly correlated with AZD8186 sensitivity (p= 0.008). Colony formation assay confirmed sensitivity of PTEN-deficient cell lines to AZD8186. AZD8186 inhibited PI3K signaling with decreased expression of pAKT, pGSK3β, pPRAS40 and pS6. AZD8186 treatment of PTEN-deficient cell lines, MDA-MB-436 and MDA-MB-468, resulted in increased apoptosis. Cell proliferation assays demonstrated additive effect of the combination of paclitaxel with AZD8186. AZD8186 significantly enhanced antitumor activity of paclitaxel in MDA-MB-436 and MDA-MB-468 cell-line-derived xenografts, with disease stabilization in the latter. In syngeneic models, AZD8186 enhanced antitumor efficacy of anti-PD1 antibodies in PTEN-deficient BP murine melanoma xenograft (p=0.0073), but not in PTEN-wildtype colon carcinoma, CT26.
Conclusion: AZD8186 has single agent efficacy in PTEN-deficient triple negative breast cancer cell lines in vitro, with modest single agent efficacy in vivo. AZD8186 enhanced the antitumor efficacy of paclitaxel and of Anti-PD1 antibodies in vivo. Further study is needed to determine optimal combination therapies for PTEN-deficient solid tumors.
Citation Format: Owusu-Brackett N, Zhao M, Akcakanat A, Evans KW, Yuca E, Tapia C, Ileana-Dumbrava E, Janku F, Meric-Bernstam F. Targeting PI3Kβ alone and in combination with chemotherapy or immunotherapy in tumors with PTEN loss [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-04.
Abstract P6-21-10: Not presented
Authors: Pacaud R , Thomas S , Roche E , Pawlowska N , Munster P 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Pacaud R, Thomas S, Roche E, Pawlowska N, Munster P. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-10.
Abstract PD1-02: Withdrawn
Authors: Cortes J , Martin M , Pernas S , Gomez Pardo P , Lopez-Tarruella S , Gil-Martin M , Manso L , Ciruelos E , Perez-Fidalgo JA , Hernando C , Ademuyiwa FO , Weilbaecher K , Mayer I , Pluard TJ , Martinez Garcia M , Vahdat L , Wach A , Barker D , Romagnoli B , Kaufman PA 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Cortes J, Martin M, Pernas S, Gomez Pardo P, Lopez-Tarruella S, Gil-Martin M, Manso L, Ciruelos E, Perez-Fidalgo JA, Hernando C, Ademuyiwa FO, Weilbaecher K, Mayer I, Pluard TJ, Martinez Garcia M, Vahdat L, Wach A, Barker D, Romagnoli B, Kaufman PA. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD1-02.
Abstract PD1-12: Omics profiling of CDK4/6 inhibitors reveals functionally important secondary targets of abemaciclib
Authors: Mills CE , Hafner M , Subramanian K , Chen C , Chung M , Boswell SA , Everley RA , Walmsley CS , Juric D , Sorger PK 
Published: May 2019

Abstract
The recent introduction of small molecule inhibitors of cyclin-dependent kinases (CDK) 4/6 to the clinic has improved the treatment of hormone receptor positive breast cancer, and shown promise in other malignancies. The three clinically used CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, are reported to be broadly similar although recent data suggest that abemaciclib has distinct single-agent activity in patients and a unique adverse effects profile. Key questions are: How do these drugs differ at the molecular level? Should such differences inform their use in the clinic? Can these three agents be used interchangeably or should patient stratification differ between them? We use molecular and functional profiling by mRNA sequencing, mass spectrometry-based proteomics, and GR-based dose-response assays to obtain complementary views of the mechanisms of action of CDK4/6 inhibitors. We show that abemaciclib, but not ribociclib or palbociclib, is a potent inhibitor of kinases other than CDK4/6, including CDK1/Cyclin B, which appears to cause arrest in the G2 phase of the cell cycle, and CDK2/Cyclin E/A, which is implicated in resistance to palbociclib. We show that inhibition of these additional targets is accessible in a xenograft model. Whereas ribociclib and palbociclib induce cytostasis, and cells adapt to these drugs within 2-3 days of exposure, abemaciclib induces cell death and durably blocks cell proliferation. Abemaciclib is active even in retinoblastoma protein (pRb)-deficient cells in which CDK4/6 inhibition by palbociclib or ribociclib is completely ineffective. The degree of polypharmacology of small molecule drugs is increasingly viewed as an important consideration in their design, with implications for efficacy, toxicity, and acquired resistance. In the case of CDK4/6 inhibitors, we propose that abemaciclib polypharmacology elicits unique molecular responses. More generally, we propose that multi-omic approaches are required to fully elucidate the spectrum of targets relevant to drug action in tumor cells. We expect such understanding to assist in stratifying patient populations and ordering sequential therapies when resistance arises.
Citation Format: Mills CE, Hafner M, Subramanian K, Chen C, Chung M, Boswell SA, Everley RA, Walmsley CS, Juric D, Sorger PK. Omics profiling of CDK4/6 inhibitors reveals functionally important secondary targets of abemaciclib [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD1-12.