bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2301: Myeloid cells promote fibroblast invasion and lead mammary adenocarcinoma cell invasion.
Authors: Shaw Aubie K. , Novitskiy Sergey , Coussens Lisa M. , Moses Harold L. 
Published: August 2014

Abstract
Myeloid cells localize to invasive edges of solid tumors where they promote invasive tumor growth, intravasation into vasculature and metastasis of malignant cells1,2. Fibroblasts, on the other hand, lead collective cell migration3 of carcinoma cells via fostering extracellular matrix (ECM) remodeling and generating tracks of collagen fibers that act as “highways” for cell migration4,5. To identify soluble molecules mediating these juxtacrine communication mechanisms between myeloid cells and fibroblasts in potentiating metastasis, we conducted pilot studies with subsets of spleen- or tumor-derived myeloid cells, tumor-derived fibroblasts, and mammary adenocarcinoma cells. Whereas spleen-derived CD11b+Ly6ChiLy6G− monocytes promote fibroblast migration ex vivo, two populations of tumor-derived myeloid cells, e.g., CD11b+Gr1+ and CD11b+Gr1− cells possessed this capability. In ex vivo migration assays, fibroblast migration was dependent on myeloid cell-derived factors, e.g., CXCL11, CXCL15, FGF2, IGF-1 and Shh, as well as fibroblast Akt and ERK1/2 phosphorylation. Inhibition of fibroblast MEK reduced myeloid cell-induced fibroblast migration, whereas FGF-RI inhibition completely abolished this capability. These studies indicate a role for myeloid cell-fibroblast communication in fostering migration (and potentially activation) of fibroblasts that lead collective cell migration properties of mammary carcinoma cells. Ongoing studies are identifying specific subpopulations of tumor-associated myeloid cells possessing these activities, as well as the role of FGF receptor signaling pathways in facilitating metastasis.
1.
Wyckoff, J.B., et al. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 67, 2649-2656 (2007).
2.
Qian, B.Z. & Pollard, J.W. Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39-51 (2010).
3.
Friedl, P., Locker, J., Sahai, E. & Segall, J.E. Classifying collective cancer cell invasion. Nat Cell Biol 14, 777-783 (2012).
4.
Khalil, A.A. & Friedl, P. Determinants of leader cells in collective cell migration. Integr Biol (Camb) 2, 568-574 (2010).
5.
Gritsenko, P.G., Ilina, O. & Friedl, P. Interstitial guidance of cancer invasion. J Pathol 226, 185-199 (2012).
The authors acknowledge generous support from the NIH/NCI, a Dept of Defense (DoD) Breast Cancer Research Program Postdoctoral Fellowship, a DoD Era of Hope Scholar Expansion Award, Susan G. Komen Fndt, and the Breast Cancer Research Fndt.
Citation Format: Aubie K. Shaw, Sergey Novitskiy, Lisa M. Coussens, Harold L. Moses. Myeloid cells promote fibroblast invasion and lead mammary adenocarcinoma cell invasion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2301. doi:10.1158/1538-7445.AM2013-2301
Abstract 2410: Circulating tumor cells to guide the choice between chemotherapy and hormone therapy as first line treatment for metastatic breast cancer patients: the STIC CTC METABREAST trial.
Authors: Pierga Jean-Yves , Baffert Sandrine , Hajage David , Brain Etienne , Armanet Sebastien , Simondi Cécile , Mignot Laurent , Asselain Bernard , Tresca Patricia , Bidard François-Clément 
Published: August 2014

Abstract
Background
Baseline CTC count already demonstrated its very good performance as an independent prognostic marker in metastatic breast cancer (MBC), before the start of any treatment (Cristofanilli, NEJM 2004; Pierga Ann Oncol 2011). Multivariate analyses performed in both a pooled analysis (Liu, ASCO 2011) and in the IC 2006-04 study showed that the other independent prognostic factors were the performance status and hormone-receptor (HR) status. Oppositely, the other criteria that are frequently used to choose between hormone therapy and chemotherapy for the treatment of first line hormone receptor-positive MBC patients (e.g. metastatic sites, metastasis-free interval…) were not independent prognostic factors. On the basis that CTC count may be a better criterion for this important choice than the currently used empiric criteria, we designed a large pivotal phase III trial.
Methods
N=996 HR+ M+ breast cancer patients will be randomized between the clinician choice and CTC count-driven choice. Main inclusion criteria include hormone receptor-positive MBC patients with no previous treatment for the metastatic disease, and who can receive either hormone therapy or chemotherapy as first line treatment. In the CTC arm, patients with ≥5 CTC/7.5ml will receive chemotherapy whereas patients with &lt;5 CTC/7.5ml will receive endocrine therapy as first line treatment. As every patient will receive a treatment, this pivotal trial has been designed to show a non-inferiority of the CTC arm for PFS (primary clinical endpoint) and a superiority of the CTC arm for the medico-economics study (co-primary endpoint). The STIC CTC METABREAST trial has been funded by the French Ministry of Health (STIC program) and Veridex. The promoter is the Institut Curie (Paris).
Results
This trial began in February 2012 and more than 15 French cancer centers participate to this study. The accrual should be completed in 2 to 3 years.
Conclusion
This large pivotal phase III trial is intended to demonstrate the clinical relevance of baseline CTC count.
Citation Format: Jean-Yves Pierga, Sandrine Baffert, David Hajage, Etienne Brain, Sebastien Armanet, Cécile Simondi, Laurent Mignot, Bernard Asselain, Patricia Tresca, François-Clément Bidard. Circulating tumor cells to guide the choice between chemotherapy and hormone therapy as first line treatment for metastatic breast cancer patients: the STIC CTC METABREAST trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2410. doi:10.1158/1538-7445.AM2013-2410
Abstract 2794: Ex vivo chemoresponse assay using patient-derived tumor xenografts in combination with high content imaging platform as models for oncology drug development.
Authors: Garg Mansi , Vo Martin , Ricono Jill , Broudy Thomas , Mirsaidi Cyrus , Praveen Kesavan Nair 
Published: August 2014

Abstract
Current strategies for developing new anticancer drugs rely heavily on preclinical testing in cancer cell lines and their derived in vivo cell line xenograft models. The value of a predictive assay is heavily dependent on the extent to which it can recapitulate the biology of disease. It has been reported that heterogeneity of cell populations within the tumor microenvironment has significant correlation with the efficacy of any treatment regimen. Cell line models fail to recapitulate the heterogeneous nature of tumor. The purpose of this study was to investigate whether the use of patient-derived primary tumor cells (PTC) could be expanded as xenografts for in vitro chemosensitivity assays to predict clinical outcomes in anticancer drug testing. We have developed preclinical cancer models using PTCs grown in 3D cultures that better mimic in vivo conditions. One of the disadvantages of using patient derived cells is the limited number of cells available from biopsy samples. We utilized patient-derived xenografts (PDX) as a strategy to expand the human tumor cells in mice, while taking efforts to retain the actual tumor biology of the patient. We used high content imaging to evaluate colony segmentation, morphological features, proliferative and apoptotic endpoints to determine efficacy of oncology drug candidates. We conducted a retrospective study using PTCs from solid tumor indications including endometrial and lung to evaluate the correlation between various models and usefulness in predicting the outcome of a specific drug candidate. Our results indicate that PDX models in combination with 3D PTC models have predictive value and enable secondary interrogation beyond single agent anti-proliferative activity to better profile the antitumor activity of targeted agents. Improved preclinical models are required to advance our understanding of the molecular aberrations that underpin cancer and are critical for developing and deploying targeted therapies that will improve patients’ lives.
Citation Format: Mansi Garg, Martin Vo, Jill Ricono, Thomas Broudy, Cyrus Mirsaidi, Kesavan Nair Praveen. Ex vivo chemoresponse assay using patient-derived tumor xenografts in combination with high content imaging platform as models for oncology drug development. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2794. doi:10.1158/1538-7445.AM2013-2794
Abstract 2811: A prostate stroma-derived profile is predictive of early relapse and reflects potential mechanisms of aggressive disease.
Authors: Jia Zhenyu , Rahmatpanah Farahnaz , Chen Xin , McClelland Michael , Mercola Dan 
Published: August 2014

Abstract
The microenvironment of prostate cancer plays a major role in tumor initiation, growth, and metastatic spread. Using RNA expression data from fresh frozen human prostatectomies for which the clinical outcome was followed for over 5 years, we have developed a general approach to identify gene expression changes of the tumor-adjacent stroma that distinguishes aggressive prostate cancer cases from indolent cases. Highly significant gene associations were defined by correlating expression with Disease-free Survival (DFS) and also, separately, by comparing RNA expression between cases that remained disease free for at least 4 years following surgery with those cases that exhibited relapse within 1 year of surgery. A total of 193 highly significant genes were identified, of which 15 were common to the two approaches. These 15 genes were used to develop a PAM (Prediction Analysis for Microarrays)-based algorithm to classify new cases as indolent or aggressive and to provide a probability for each classification. The algorithm was tested on stroma-enriched samples from 47 new cases with known outcome with an accuracy of 87% [1]. A potential functional basis for some the genes associated with aggressive disease was suggested by the observation that p53 expression is decreased in aggressive disease whereas p53-target genes and cell cycle inhibitors including p21, GADD45A, and GADD45B are increased, which is a pattern others have noted as suggestive of senescence [2]. Increased IGFBP6, Tubulin alpha 1a, and Lamin A/C further suggest a senescence-associated secretory phenotype [3]. A potential secretory factor of known significance in the growth of prostate cancer (IGF-1/Somatomedin-C) has elevated RNA levels in the stroma of the same cases. These features argue that an accurate and general prediction of aggressiveness may be derived from the tumor microenvironment and may be composed of genes that have functional roles in bringing about aggressive disease.
[1] Jia et al. 2012 PLoS ONE, 7(8):e41371
[2] Liebermann and Hoffman 2008 Journal of Molecular Signaling, 3:15
[3] Coppe et al. 2008 PLoS Biology, 6(12):e301
Citation Format: Zhenyu Jia, Farahnaz Rahmatpanah, Xin Chen, Michael McClelland, Dan Mercola. A prostate stroma-derived profile is predictive of early relapse and reflects potential mechanisms of aggressive disease. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2811. doi:10.1158/1538-7445.AM2013-2811
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2825: Using SHG to study breast cancer tumor progression.
Authors: Burke Kathleen A. , Brown Edward 
Published: August 2014

Abstract
The majority of cancer mortality is a result of metastatic events, making it increasingly important to uncover prognostic markers that can predict the metastatic potential of a primary tumor to aid in determining the best course of patient treatment. Stromal extracellular matrix restructuring increases efficiency of cell migration away from the primary tumor into surrounding tissues and vasculature, thereby enhancing metastatic potential. We have determined that the ratio of the forward propagating to backward propagating Second Harmonic Generation (SHG) signals from type I collagen can be used as a quantitative method of differentiating healthy and tumor breast tissue, and tracking stromal changes throughout tumor progression. Tumors were graded and staged according to standard pathological qualifications, incorporating morphological changes in the tissue as well as extent of tumor growth and invasion. As the tumor cells initiate development in the ducts of the breast tissue the F/B ratio of the fibrillar collagen does not change. Upon progression from an in situ to an invasive carcinoma the F/B ratio of ductal tumors significantly decreases. Taking a closer look at this phenomenon, to examine whether the invasion through the basement membrane into the surrounding tissue causes an immediate change in the F/B ratio, tumors of varying grade and stage were analyzed showing significant trends throughout development. Increased tumor grade was associated with a gradual decrease in the F/B ratio, whereas size of the tumor had no significant effect on the F/B but all sizes were significantly lower than healthy tissue. Interestingly, there was a significant increase in the F/B ratio associated with the furthest progression of lymph-node involvement. Invasive Lobular Carcinoma analysis revealed a similar decrease in F/B, but was not affected by lymph node involvement. On the other hand F/B of these tumors was significantly affected by an interaction with the chest or skin. These results provide insight into the different development processes undergone by two related breast carcinomas, which could differ due to their alternative methods of invasion and stromal components. F/B ratio measurements can be used alongside pathological analysis to provide information about the metastatic potential of the primary tumor, as demonstrated by the relationship between F/B ratio of IDC and lymph node metastasis. Enhanced scientific understanding of stromal development could be applied to the development of improved biomarkers and metastatic treatment methods.
Citation Format: Kathleen A. Burke, Edward Brown. Using SHG to study breast cancer tumor progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2825. doi:10.1158/1538-7445.AM2013-2825
Abstract 2844: ATATESTM activated the same patient's immune system to eliminate hundreds of melanoma tumors for cure of cancer.
Authors: Qian Yong 
Published: August 2014

Abstract
A 26 year old male melanoma cancer patient had over 1000 solid tumors originated from a laser treatment of a mold on his back. Mutated cancer cells metastasized to his lymph nodes first then spread to the skin all around the body. He had symptoms of vomitting, poor apetide, loosing weight and lack of strength for several months before seeking BioMedicure's help. ATATESTMproducts, with antigenic material information from millions of tumor cells preserving in spheres, were made out of his melanoma tumors for immunotherapy over one month. His symptoms have been reversed after a couple of months’ ATATESTM immunotherapy. Over 95% of his melanoma tumors have been under control and disappearing over time. Multiple death pathways elicited by ATATESTM have been observed and investigated. The detailed mechanisms of action for ATATESTM will be presented.
Citation Format: Yong Qian. ATATESTM activated the same patient's immune system to eliminate hundreds of melanoma tumors for cure of cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2844. doi:10.1158/1538-7445.AM2013-2844
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 288: TGF-beta induced epithelial-to-mesenchymal transition is attenuated when the MNK/eIF4E pathway is functionally impaired.
Authors: del Rincon Sonia V. , Huor Bonnie , Ngan Elaine , Petruccelli Luca , Siegel Peter , Miller Wilson H. 
Published: August 2014

Abstract
The epithelial-mesenchymal-like transition (EMT) is a process enabling epithelial cells to gain the motile characteristics of mesenchymal cells, in a manner resembling metastasis. TGF-beta, via well-defined transcriptional mechanisms, is considered a master regulator of EMT. However, the idea that TGF-beta can regulate the translational machinery to drive EMT remains largely unexplored. The eukaryotic translation initiation factor eIF4E is known to be overexpressed in breast cancer, has been linked to increased invasiveness, and is a promising target for the treatment of breast cancer. Our hypothesis is that phosphorylation of eIF4E stimulated by TGF-beta is required for inducing EMT and metastasis in breast cancer. Our novel preliminary data show that TGF-beta can stimulate eIF4E phosphorylation as normal mammary epithelial cells become mesenchymal. Silencing of eIF4E attenuates molecular and behavioral changes associated with EMT. Moreover, decreasing eIF4E levels can impair TGF-beta induced migration and invasion of ErbB2-expressing breast cancer cells. In keeping with a role of phosphorylated eIF4E in driving the metastatic phenotype, we show that chemically and genetically inhibiting the eIF4E kinase MNK1 attenuates TGF-beta-stimulated EMT. We hypothesized that the expression of master regulators of EMT could be restricted when the eIF4E/MNK pathway is functionally impaired, which prompted us to look at the expression of Twist and Snail in TGF-beta treated eIF4E- and MNK- silenced cells. Our data shows that TGF-beta-induced Snail protein expression, but not mRNA level, is repressed when the MNK/eIF4E pathway is functionally impaired. Our results indicate that MNK and eIF4E are essential for EMT and suggest that therapeutic inhibition of MNK/eIF4E pathway may be a useful strategy for the control of tumor invasion and metastasis.
Citation Format: Sonia V. del Rincon, Bonnie Huor, Elaine Ngan, Luca Petruccelli, Peter Siegel, Wilson H. Miller, Jr. TGF-beta induced epithelial-to-mesenchymal transition is attenuated when the MNK/eIF4E pathway is functionally impaired. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 288. doi:10.1158/1538-7445.AM2013-288
Abstract 2880: A prospective study of 51 serum immune markers and risk of non-Hodgkin lymphoma.
Authors: Purdue Mark P. , Hofmann Jonathan N. , Kemp Troy J. , Chaturvedi Anil K. , Lan Qing , Park Ju-Hyun , Pfeiffer Ruth M. , Hildesheim Allan , Pinto Ligia A. , Rothman Nathaniel 
Published: August 2014

Abstract
Background: Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), the etiologic relevance of subclinical immunologic effects is unclear. Few prospective studies have investigated the relationship between circulating immune markers and NHL, and those conducted to date have been limited in sample size, the number of evaluated analytes, or in their ability to examine markers of risk many years preceding disease diagnosis. To better understand this question, we conducted a nested case-control study investigating pre-diagnostic serum levels of 51 immune markers within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.
Methods: Fifty-one immune markers (including cytokines, chemokines, extracellular matrix proteins, growth factors and soluble products of immune activation) were measured in baseline serum from 301 NHL cases diagnosed 5+ years after blood collection (median 8.0 years, range 5.0-13.9) and 301 individually matched controls using Luminex bead-based assay panels. Odds ratios (ORs) and 95% confidence intervals (CIs) relating marker levels with NHL risk were computed using conditional logistic regression modeling.
Results: We observed strong associations with NHL for elevated levels of several analytes: a pro-inflammatory marker, soluble tumor necrosis factor receptor 2 (sTNFRII; fourth quartile vs. first: OR 3.4, 95% CI 2.0-5.8; Ptrend = 5.9 x 10−6); a regulator of B-cell traffic, B-cell attracting chemokine 1 (BCA-1; 2.7, 1.7-4.2; Ptrend = 1.1 x 10−5); a regulator of angiogenesis, soluble vascular endothelial growth factor receptor 2 (sVEGFR2; 2.3, CI 1.4-3.9; Ptrend = 0.0005); and the pro-inflammation and apoptotic cytokine TNF-related apoptosis inducing ligand (TRAIL; 1.6, 1.0-2.5; Ptrend = 0.02). These associations remained significant in analyses of cases diagnosed 8-13 years after blood collection and, with the exception of TRAIL, following Bonferroni correction and simultaneous model adjustment.
Conclusions: Our findings suggest that elevated levels of sTNFRII, BCA-1, sVEGFR2, and, possibly, TRAIL may reflect biologic processes contributing to lymphomagenesis. Additional research is needed to replicate these findings, identify cell sources of these markers, and elucidate the underlying biologic mechanisms.
Citation Format: Mark P. Purdue, Jonathan N. Hofmann, Troy J. Kemp, Anil K. Chaturvedi, Qing Lan, Ju-Hyun Park, Ruth M. Pfeiffer, Allan Hildesheim, Ligia A. Pinto, Nathaniel Rothman. A prospective study of 51 serum immune markers and risk of non-Hodgkin lymphoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2880. doi:10.1158/1538-7445.AM2013-2880