bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1393: Fine mapping and characterization of Emca8.2, a genetic determinant of susceptibility to estrogen-induced mammary cancer on chromosome 5 in the rat.
Authors: Colletti John A. , Seiler Nicole L. , Hickman Maureen P. , Samanas Nyssa B. , Warren Chrsitopher L. , Shull James D. 
Published: August 2014

Abstract
Although estrogens have long been implicated in the etiology of breast cancer, the mechanisms through which estrogens contribute to breast cancer development remain poorly defined. Furthermore, many of the genes that influence the risk of developing breast cancer also remain to be determined. The ACI rat model of 17β-estradiol (E2)-induced mammary cancer is being used to elucidate the mechanisms through which estrogens contribute to breast cancer development and to identify novel genetic determinants of breast cancer susceptibility. Female ACI rats develop mammary cancer at an incidence nearing 100% when treated with physiological levels of E2. In contrast, the Brown Norway (BN) rat strain is resistant to E2-induced mammary cancer. A total of seven quantitative trait loci (QTL), designated Emca3 (Estrogen-induced mammary cancer) through Emca9, have been mapped in reciprocal intercrosses between ACI and BN rats. The purpose of the current study is to fine map the Emca8 genetic determinants of mammary cancer susceptibility, which was mapped to rat chromosome 5 (RNO5). ACI alleles at this QTL act to increase the number of mammary cancers per rat and to decrease the latency to the appearance of the first palpable mammary cancer. A series of congenic rat strains have been generated by introgressing defined segments of RNO5 from the resistant BN rat strain onto the genetic background of the susceptible ACI strain. By defining the susceptibility of these congenic rat strains relative to that of the parental ACI strain, a locus determining susceptibility to E2-induced mammary cancer, designated Emca8.2, has now been localized to a 1.1 megabase (Mb) region of distal RNO5 containing approximately 1200 genetic sequence variants. To help identify the mechanisms through which Emca8.2 determines susceptibility to mammary cancer, the expression levels of the candidate genes within the fine-mapped region have been investigated. The mapping and expression data that define the genomic architecture of Emca8.2 will be presented and discussed.
Citation Format: John A. Colletti, Nicole L. Seiler, Maureen P. Hickman, Nyssa B. Samanas, Chrsitopher L. Warren, James D. Shull. Fine mapping and characterization of Emca8.2, a genetic determinant of susceptibility to estrogen-induced mammary cancer on chromosome 5 in the rat. [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 1393. doi:10.1158/1538-7445.AM2013-1393
Abstract 1401: Overexpression of HER4 isoforms in transgenic mice reveal isoform-specific role in mammary gland development and carcinogenesis.
Authors: Wali Vikram B. , Gilmore-Hebert Maureen , Elenius Klaus , Stern David F. 
Published: August 2014

Abstract
Human epidermal growth factor receptor 4 (HER4/ERBB4) belongs to the family of four receptor tyrosine kinases (HER1-4). While HER1, HER2 and HER3 are often overexpressed in breast cancer and predict poor prognosis, the role of HER4 in cancer is still unclear. Some studies suggest a tumor suppressor role of HER4, while contradictory reports suggest its oncogenic potential. HER4 gene produces multiple isoforms as a result of alternative splicing, in contrast to other members of this receptor family. We have used a gain-of-function MMTV-HER4 model isoforms, to evaluate potential developmental and carcinogenic roles of HER4-CYT1 and CYT2. Mammary gland ductal morphogenesis was significantly suppressed by expressing one of the transgene isoforms, strongly suggesting a role of HER4 in normal mammary ductal morphogenesis in addition to its role in lactation described previously. Interestingly, sustained expression of one HER4 transgene isoform resulted in formation of mammary tumor lesions, whereas no significant findings were observed in the control group. Formation of tumor lesions in these transgenic mice strongly suggests an oncogenic function of a HER4 isoform. These novel findings may help improve the rational design of targeted breast cancer therapy. Supported by NIH grant RO1 CA80065.
Citation Format: Vikram B. Wali, Maureen Gilmore-Hebert, Klaus Elenius, David F. Stern. Overexpression of HER4 isoforms in transgenic mice reveal isoform-specific role in mammary gland development and carcinogenesis. [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 1401. doi:10.1158/1538-7445.AM2013-1401
Abstract 143: Breast cancer incidence rate in american women started to increase: Trend analysis from 2000 to 2009.
Authors: Hou Ningqi , Huo Dezheng 
Published: August 2014

Abstract
Background: Recent report showed that breast cancer incidence rate in the US stabilized after a sharp reduction in 2002 and 2003. It is important to continue monitoring breast cancer incidence rates according to age group, race/ethnicity, estrogen receptor (ER), and tumor stage.
Methods: Age-standardized breast cancer incidence rates were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries from 2000 to 2009, among 677,774 female breast cancer patients aged 20 and above. Jointpoint regression models were used to fit a series of joined straight lines on a log scale to the trends of annual age-standardized rates.
Results: The overall breast cancer incidence significantly increased for non-Hispanic black from 2005 to 2009 (annual percentage change, APC =2.0%, p=0.01) and Asian/Pacific Islanders from 2000 to 2009 (APC 1.2%, p=0.02). Since 2004, incidence rates in women age 40-49 significantly increased for all racial/ethnic groups (overall APC = 1.1%, p=0.001). Incidence rate of carcinoma in situ significantly increased in all racial/ethnic groups (APC ranges from 2.3%-3.0%, p&lt;0.005) and localized breast cancer incidence significantly increased in non-Hispanic blacks (APC=1.3%, p=0.004) and Asian (APC=1.2%, p=0.03). ER positive breast cancer significantly increased in almost all age/race sub-groups after 2005 (APC by race: non-Hispanic white 1.5%, non-Hispanic black 4.3%, Asian/Pacific Islander 1.7%, and Hispanic 1.8%, p-values&lt;0.05), while ER negative breast cancer decreased in most sub-groups (APC by race: non-Hispanic white -3.9%, non-Hispanic black -3.7%, Asian/Pacific Islander -1.5%, and Hispanic -4.3%, p-values&lt;0.05).
Conclusions: Recent incidence of breast cancer appears to be increasing in certain subgroups, including non-Hispanic black, Asian/Pacific Islanders, women 40-49 years old, low-stage breast cancer, and estrogen-receptor positive breast cancer. These changes are unlikely due to mammography screening rate that has remained stable in recent years, but may be partially explained by the transition from film to digital mammography, which has higher sensitivity to detect breast cancer, especially young-onset breast cancer. It deserves further investigation on why the rate of estrogen receptor negative breast cancer declined.
Citation Format: Ningqi Hou, Dezheng Huo. Breast cancer incidence rate in american women started to increase: Trend analysis from 2000 to 2009. [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 143. doi:10.1158/1538-7445.AM2013-143
Abstract 1463: Detection of cancer before distant metastasis.
Authors: Coumans Frank AW , Siesling Sabine , Terstappen Leon WMM 
Published: August 2014

Abstract
Introduction: The majority of deaths from cancer are due to disseminated disease rather than the primary tumor. As metastases are often discovered years after surgical removal of the primary tumor, probably at least one metastasis was already present at the time of surgery. To establish a distant metastasis cells must disseminate from the primary tumor and overcome a series of obstacles, the metastatic cascade. In this study we develop a mathematical model for this cascade to estimate the technology requirements for detection of a primary tumor before the first metastasis has been formed.
Methods: The metastatic cascade is described in discrete steps: 1. local tumor growth; 2. dissemination into circulation; 3. survival in circulation; 4. extravasation into tissue; and 5. growth into a metastasis. The model was built using data and relationships described in the literature to predict the relationship between tumor size and probability of distant metastasis for 38715 patients with surgically removed TxNxM0 primary breast cancer from the Netherlands Cancer Registry. The model was calibrated using primary tumor size, probability of distant metastasis and time to distant metastasis for 1489 patients with stage T1bNxM0 (25% of total patients with T1bNxM0). Validation of the model was done with data for all patients.
Results: From the time to distant metastasis of these 38715 breast cancer patients, we determined a tumor doubling time of 1.7 ± 0.9 months. Fitting the data for 25% of T1b patients estimates a metastatic efficiency of 1 metastasis formed per 60 million disseminated tumor cells. Validation of the model to data of patients in all T-stages shows good agreement between model and epidemiological data. To reduce the 5-year risk of distant metastasis for TxNxM0 from 9.2% to 1.0%, the primary tumor needs to be detected and removed before it reaches a diameter of 2.7 ± 1.6 mm. At this size, the model predicts that there will be 9 ± 6 CTC/L blood.
Conclusions: To reduce the rate of distant metastasis in surgically treated TxNxM0 breast cancer to 1%, imaging technology will need to be able to detect lesions of 2.7 mm in diameter or smaller. Before CTC detection can be applied in the early disease setting, sensitivity will need to be improved by at least 15-fold and combined with technology that minimizes false positives.
Citation Format: Frank AW Coumans, Sabine Siesling, Leon WMM Terstappen. Detection of cancer before distant metastasis. [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 1463. doi:10.1158/1538-7445.AM2013-1463
Abstract 1464: In vitro culturing of CTCs/DTCs in personalized cancer management.
Authors: Bobek Vladimir 
Published: August 2014

Abstract
Subsequent detection, quantification and molecular characterization of CTCs has an enormous potential in numerous of oncology areas. But detection and isolation of CTCs is technically quite challenging. The whole dissemination process encompasses also individual tumor cells which are found in relatively big quantities in peritoneal washings (PW) and pleural effusions (PE), so called disseminated tumor cells (DTCs).
Thanks in vitro cultures of separated CTCs/DTCs we were able to introduce additional chemosensitivity testing for the purpose of individualized cancer treatment. We present an isolation and cultivation of CTC/DTC of non-small cell lung cancer and gastrointestinal cancers (esophageal cancer, colorectal cancer, gastric cancer, pancreatic cancer) describing cultivation methodology on patients case studies.
The cancer cells were separated from body fluids (PW, PE, blood) using the differences in size of cancer cells if compared to other nucleated cells detected in body cavities. After reaching the confluence the chemosensitivity of cell cultures has been tested by xCELLigence system (RTCA, Roche) for different concentrations of single cis-platinum, gemcitabine and fluorouracyl (incubation time 24-72 hours) or their combinations. The dynamic real-time cell growth monitoring enables parallel or sequential combinations of administered drugs with a direct outcome for patients care.
Conclusions: We assume that developing cultivation strategies for CTCs/DTCs could bring us closer to the definition of the CTC/DTC-function within the dissemination process with a perspective to use this knowledge in personalized cancer treatment.
Citation Format: Vladimir Bobek. In vitro culturing of CTCs/DTCs in personalized cancer management. [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 1464. doi:10.1158/1538-7445.AM2013-1464
Abstract 1480: The effect of Metformin on microtentacle formation and stabilization in breast cancer cells.
Authors: Chakrabarti Kristi , Whipple Rebecca A. , Boggs Amanda E. , Charpentier Monica S. , Slovic Jana , Vitolo Michele I. , Martin Stuart S. 
Published: August 2014

Abstract
Metastasis is one of the main causes of mortality in women with breast cancer. Epithelial-to-mesenchymal transition (EMT) has emerged to be a key mediator of breast cancer metastasis. It has previously been shown that EMT can stabilize and increase microtentacles (McTNs) in breast cancer cell lines and enhance their metastatic potential. McTNs are dynamic, microtubule-enriched plasma membrane extensions that are stabilized with the exposure of a carboxy-terminal glutamic acid residue in alpha-tubulin (Glu-tubulin). McTN stabilization has been shown to promote tumor cell aggregation and reattachment in vitro. In this study, we investigated the effect of EMT suppression on McTN formation and stabilization in breast cancer cells by the dimethyl biguanide, Metformin. While it is widely used to treat type 2 diabetes, Metformin has more recently been shown to inhibit EMT in multiple breast cancer cell lines. We show here that Metformin decreased mesenchymal markers, such as N-cadherin and vimentin, in a dose-dependent manner in MDA-MB-231 breast cancer cells. Confocal and fluorescent microscopy was used to visualize and quantify McTN formation in these cells. There was a significant decrease in McTNs in MDA-MB-231 cells treated with 5mM Metformin for 24 hours. We correlated the decrease in the number of McTNs with a decrease in Glu-tubulin protein levels, which suggests that Metformin also inhibits McTN stabilization. The decrease in McTN formation and stabilization was also associated with diminished tumor cell reattachment in vitro. In addition, Metformin was able to protect MDA-MB-231 cells from increased McTN formation induced by the microtubule stabilizing agent, Taxol. Metformin's mechanism of action on breast cancer cells to elicit these cytoskeletal modifications has yet to be elucidated. However, these results suggest a role for Metformin at multiple stages of tumor progression to protect breast cancer patients from clinical spread of disease.
Citation Format: Kristi Chakrabarti, Rebecca A. Whipple, Amanda E. Boggs, Monica S. Charpentier, Jana Slovic, Michele I. Vitolo, Stuart S. Martin. The effect of Metformin on microtentacle formation and stabilization in breast cancer cells. [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 1480. doi:10.1158/1538-7445.AM2013-1480
Abstract 1488: Metastatic analysis of clonal epithelial and mesenchymal-like murine mammary tumor cells.
Authors: Palen Katie A. , Johnson Bryon D. , Gershan Jill A. 
Published: August 2014

Abstract
Tumor metastasis is the most common cause of cancer mortality, and yet it is among the most poorly understood processes in tumor progression. While carcinomas are composed primarily of epithelial cells, tumors contain a continuum of cells with epithelial and mesenchymal-like properties. This tumor cell heterogeneity is attributed to differentiation plasticity, which is characterized by epithelial to mesenchymal (EMT) or mesenchymal to epithelial transitions (MET). It has been proposed that tumor cells undergo EMT in order to disseminate from the primary tumor and MET in order to seed at secondary sites. The invasive mesenchymal carcinoma cell phenotype is thought to be a state required for tumor dissemination, but to date, pathologists have not found conclusive evidence of mesenchymal cells in human metastatic tumor samples. An alternative theory suggests that both mesenchymal and epithelial cells are required for metastasis to occur. According to this theory, detachment from the primary tumor and invasion by mesenchymal cells facilitates the movement of epithelial tumor cells that are able to seed at distant sites. We hypothesize that the presence of mesenchymal-like mammary tumor cells facilitate the metastasis of epithelial tumor cells and that only epithelial cells are able to seed at distant sites. To test this hypothesis, we cloned epithelial and mesenchymal-like primary cell lines from spontaneous mammary tumors produced in FVB MMTV/Neu mice. Epithelial cells have been stably transfected to express firefly luciferase and GFP, and we are in the process of cloning mesenchymal-like cells expressing Renilla luciferase and mCherry. We have preliminary data that shows that when clonal epithelial cells are administered into the mammary fat pad of FVB MMTV/Neu mice, tumors grow, but do not form metastatic lesions. In contrast, when stably transfected clonal epithelial cells are administered with non-transfected clonal mesenchymal-like tumor cells, luciferase+ metastatic lesions in the spleen, liver and lung are detected biophotonically, and GFP + cells are detected in the spleen and liver. These data indicate that epithelial cells are present (but does not rule out the presence of mesenchymal cells) at the metastatic site. Whether epithelial cells undergo EMT, and how metastasis is facilitated by the presence of mesenchymal cells remains to be determined.
Citation Format: Katie A. Palen, Bryon D. Johnson, Jill A. Gershan. Metastatic analysis of clonal epithelial and mesenchymal-like murine mammary tumor cells. [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 1488. doi:10.1158/1538-7445.AM2013-1488
Abstract 1491: Downregulation of KLF5 contributes to TGF-β- and EGF-induced EMT by reducing miR-200s.
Authors: Zhang Baotong , Dong Jin-tang 
Published: August 2014

Abstract
Krüpple-like factor 5 (KLF5) is a basic transcriptional factor that has been well documented for its regulatory role in the proliferation and survival of epithelial cells. Recently, bioinformatic analysis suggests that KLF5 also regulates epithelial-to-mesenchymal transition (EMT), yet experimental evidence is still lacking regarding whether and how KLF5 regulates EMT. As a form of epithelial cell plasticity, EMT can be induced by many cytokines including TGF-β and EGF. Here we report a role of KLF5 in EMT. We found that KLF5 was significantly down-regulated during TGF-β- and EGF-induced EMT in epithelial cells including HaCaT cells, MCF-10A cells, and mouse primary keratinocytes; and that silencing KLF5 induced EMT as well, as indicated by altered cell morphology, enhanced migration, upregulation of CDH2, FN1 and ZEB1, dislocation of CDH1 from cell-cell junctions, and induction of actin fibers. To determine whether miRNAs mediate the role of KLF5 in EMT, a real-time qPCR assay was employed to search for miRNAs regulated by KLF5 during EMT. Five members of the miR-200 family, all of which have been implicated in EMT, were found to be down-regulated upon the downregulation of KLF5. KLF5 directly regulated the expression of miR-200s by binding to the GC boxes of their promoters, as demonstrated by functional and biochemical analyses including luciferase reporter assay, ChIP-PCR assay, and oligo pull-down assay. Functionally, overexpression of miR-200s inhibited EMT induced by KLF5 silencing or TGF-β and EGF treatment in HaCaT cells, and forced expression of KLF5 attenuated TGF-β- and EGF-induced EMT by rescuing miR-200s expression. To evaluate whether the KLF5-miR-200s axis modulates EMT in vivo, we determined the expression of Klf5, miR-200s and EMT markers in knockout mice and human breast cancer specimens. In mouse prostate neoplasms induced by Pten deletion, knockout of Klf5 repressed the expression of miR-200s and induced the downregulation of CDH1 and upregualtion of vimentin, which are indicative of EMT. Expression of KLF5 also correlated with miR-200s at the RNA level in human breast cancer specimens. These findings suggest that KLF5 directly regulates the transcription of miR-200s in epithelial cells, and that downregulation of the KLF5-miR-200 axis plays a causal role in TGF-β- and EGF-induced EMT, providing new insights into the regulation of EMT.
Citation Format: Baotong Zhang, Jin-tang Dong. Downregulation of KLF5 contributes to TGF-β- and EGF-induced EMT by reducing miR-200s. [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 1491. doi:10.1158/1538-7445.AM2013-1491
Abstract 1497: Inducing a mesenchymal-to-epithelial transition for the targeting of cancer stem cells.
Authors: Pattabiraman Diwakar R. , Reinhardt Ferenc , Bierie Brian , Weinberg Robert A. 
Published: August 2014

Abstract
The occurrence of metastasis and the persistence of chemotherapy-resistant carcinoma cells are the two leading factors that contribute to cancer-related deaths. Both these properties of tumors have been shown to arise from the epithelial-to-mesenchymal transition (EMT), a process that leads to the generation of cancer stem cells (CSCs). Hence, it is believed that eradication of these CSCs represents the most effective way to curb tumor progression and relapse. Recent studies from the Weinberg lab have implicated key signalling pathways in the induction and maintenance of the mesenchymal state, including TGFβ and Wnt. Through this project, we propose to use a number of small-molecule inhibitors of specific signaling pathways, including those mentioned above, to induce a mesenchymal-to-epithelial transition (MET) in human breast cancer cell lines. Upon inhibition of these essential pathways, the ability of these cells to form tumors, seed metastases, and exhibit resistant to doxorubicin and paclitaxel will be tested. Preliminary results show selective targeting of mesenchymal cells upon treatment with a combination of TGFβ and non-canonical Wnt inhibitors, which appear to induce their apoptosis as well as promote their differentiation back to an epithelial-like state. We hypothesize that upon inducing differentiation of the mesenchymal/stem-like population of the cancer cells using various combinations of small-molecule inhibitors, they will lose their ability to metastasize and will exhibit an increased susceptibility to apoptosis upon treatment with the above-mentioned chemotherapeutic agents. If successful, these inhibitors, or improved versions, will have the potential to be used in conjunction with chemotherapeutic drugs in the clinic to curb the relapse and progression of cancers. The significance of this work extends beyond breast cancers to a large number of carcinomas that have been shown to undergo an EMT, including prostate, colon and lung cancers.
Citation Format: Diwakar R. Pattabiraman, Ferenc Reinhardt, Brian Bierie, Robert A. Weinberg. Inducing a mesenchymal-to-epithelial transition for the targeting of cancer stem cells. [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 1497. doi:10.1158/1538-7445.AM2013-1497
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.