bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3125: Upregulation of gap junctions with substituted quinolines in colon cancer cells
Authors: Bigelow Kristina M. , Nguyen Thu Annelise 
Published: June 2012

Abstract
Colon cancer is one of the most common cancers in the United States with a high predisposition to metastasize. Furthermore, 30-40% of patients have metastatic disease at the initial diagnosis. Cancer cells exhibit many deficiencies in cell-to-cell communication, particularly gap junctional intercellular communication (GJIC). GJIC has been reported to diminish as cancer cells progress. Gap junctions are intercellular channels composed of connexin proteins, which mediate the direct passage of small molecules from one cell to the next. They are involved in the regulation of cell cycle, cell differentiation, and cell signaling. Previous work demonstrated that connexin proteins such as Cx43, Cx32 and Cx26 have a distinct pattern in SW480, SW620, HT29 and Caco-2 human colon cancer cell lines. The findings suggest that the lack of GJIC, in part due to low level of connexin, may contribute to facilitate colon cancer progression. Since the regulation of gap junction is lost in colon cancer cells, the goal of this study is to restore GJIC in colon cancer cells. Recently, substituted quinolines (PQs), gap junction enhancers, have been shown to increase gap junction activity in breast cancer cells. The level of Cx43 is low in SW620 and SW480 human colon cancer cells. Transfected Cx43 cells have a 6-fold increase of gap junction activity compared to control using scrape load/dye transfer assay. Western blot analysis confirmed that a significant level of Cx43 was expressed in transfected Cx43 cells compared to control. This suggests that overexpressing Cx43 can restore GJIC. Interestingly, 200 nM PQ1 causes a 4-fold increase of gap junction activity as well and subsequently causes a decrease in cell proliferation by 15%. However, TPA, GJIC inhibitor, can reverse the gap junction activity of transfected Cx43 or treated PQ1 cells. Further analysis of Cx43, survivin, and cyclin D1 in treated cells was observed. Overall, the results show that substituted quinolines can directly enhance gap junction activity and attenuate cell proliferation in colon cancer cells. The findings provide an important implication in which restoration of gap junction activity can be targeted for drug development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3125. doi:10.1158/1538-7445.AM2011-3125
Abstract 3134: Neoadjuvant chemotherapy in ER+HER2- breast cancer: Response prediction based on immunohistochemical and molecular characteristics
Authors: Lips Esther H. , Mulder Lennart , De Ronde Jorma J. , Mandjes Ingrid A.M. , Vincent Andrew A. , Vrancken-Peeters Marie-Jeanne T.F.D , Nederlof Petra M. , Wesseling Jelle , Rodenhuis Sjoerd 
Published: June 2012

Abstract
Introduction: A pathological complete remission (pCR) is rarely achieved by neoadjuvant chemotherapy (NAC) in ER+HER2- tumors. Therefore, its use might be questionable in specific groups of this tumor type. To select which patients benefit and which could be withheld from NAC, we tested standard pathology and molecular markers in ER+HER2- breast tumors.
Methods: Pre-treatment biopsies were available from 211 ER+HER2- tumors, which had been treated with NAC. mRNA expression and aCGH data were available for 132 tumors. We determined progesterone receptor (PR)expression, endocrine responsiveness, histology, proliferation, molecular subtypes and BRCAness aCGH profiles. We correlated these data with chemotherapy response using pCR rates and the neoadjuvant response index (NRI).
Results: PR-negative tumors (n = 65, 30.8%) and Luminal B type tumors (n=43, 20.4%) responded significantly better to NAC than other tumors, for both pCR breast and the NRI as outcome measure (table 1). The associations remained significant in multivariate analysis. However, even in the subgroup of patients with the lowest response rate (tumors with both a positive PR and of the Luminal A type (n=58, 44 %)), the majority showed downstaging (median NRI=0.25)(table 1). For endocrine responsiveness and the BRCAness aCGH profile only an association with pCR breast was observed. Histology (lobular versus ductal) and proliferation did not show an association with chemotherapy response (table 1).
Discussion: PR expression and molecular subtype are associated with a better response to NAC. However, both markers had only weak predictive power and it was not possible to identify a subgroup with no or only minimal chemotherapy benefit. Therefore, the decision to refrain patients from NAC in ER+HER2- breast tumors should not be based on predictive markers, but exclusively on estimates of prognosis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3134. doi:10.1158/1538-7445.AM2011-3134
Abstract 3137: E-cadherin is a useful surrogate maker to predict chemosensitivity of neoadjuvant chemotherapy for breast cancer
Authors: Aomatsu Naoki , Yashiro Masakazu , Kashiwagi Shinichiro , Takashima Tsutomu , Kawajiri Hidemi , Onoda Naoyoshi , Ishikawa Tetsuro , Hirakawa Kosei 
Published: June 2012

Abstract
Background: Current studies have demonstrated that neoadjuvant chemotherapy (NAC) improves the prognosis of patients with breast cancer, however, no reliable maker to predict chemosensitivity of NAC is not available. Although E-cadherin is one of the markers for chemosensitivity in several types of carcinomas, the significance of E-cadherin for chemosensitivity of NAC remains unclear. The aim of this study was to evaluate the value of E-cadherin as a surrogate maker of NAC for breast cancer.
Experimental Design: A total of 104 patients with breast cancer of stage II and III, as evaluated by core needle biopsy and ultrasonography, was treated with NAC, including FEC (5-fluorouracil + epirubicin + cyclophosphamide) followed by weekly paclitaxel. Expressions of E-cadherin, estrogen receptor, progesterone receptor, and HER2 were assessed by immunohistochemistry. Clinical responses and pathological responses were classified according to WHO criteria or The General Rules for Breast Cancer.
Results: A clinical response (responder; complete response + partial response) was observed in 93 (89%) of 104 patients. The pathological complete response rate (pCR) was 29% (30/104). E-cadherin was positive in 60 (57%) of 104 breast cancer. Fifty-eight (96%) of 60 E-cadherin-positive tumors were responders, while 35 (80%) of 44 E-cadherin-negative tumors were non-responders (p=0.005). The pCR rate (37%; 22/60) of E-cadherin-positive tumors also was significantly (p=0.04) higher than that (18%; 8/44) of E-cadherin-negative tumors. Among the 104 breast cancer cases, 32 (31%) revealed a triple-negative phenotype (estrogen receptor-negative, progesterone receptor-negative, and HER2-negative). The pCR of triple-negative breast cancer was 34% (11/32). In the 32 triple-negative breast cancers, the pCR rate (64%; 7/11) of E-cadherin-positive tumors was significantly (p=0.004) higher than that (19%; 4/21) of E-cadherin-negative tumors.Conclusion: E-cadherin might be a clinically useful maker to predicting the response to NAC in breast cancer, especially in triple-negative breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3137. doi:10.1158/1538-7445.AM2011-3137
Abstract 3138: FOXC1 represses estrogen receptor-α expression via increasing NF-κB activity in breast cancer: A novel mechanism to explain antiestrogen resistance
Authors: Wang Jinhua , Li Guifa , Ray Partha , Sim Myung-Shin , Walter Michael A. , Giuliano Armando E. , Cui Xiaojiang 
Published: June 2012

Abstract
The Forkhead-box transcription factor FOXC1 has recently been identified as a critical marker for human basal-like breast cancer, which lacks or under-expresses estrogen receptor-α (ERα). Here we show a consistent inverse correlation between FOXC1 expression and ERα expression in multiple cDNA microarray data sets of human breast cancer. Overexpression of FOXC1 in ERα-positive breast cancer cells induces cell growth, migration, and invasion, but downregulates ERα mRNA and protein levels and consequently reduces cellular responses to estradiol and tamoxifen. This could explain why tamoxifen-refractory breast cancer cells exhibit higher FOXC1 levels as compared with tamoxifen-sensitive parental cells. We also found that FOXC1 induces NF-κB activation, which is known to be associated with ER-negative breast cancer, by increasing Pin1-mediated p65 protein stability and thus p65 protein levels. NF-κB mediates, at least in part, the regulation of ERα by FOXC1, because inhibition of NF-κB by an IκBα super-repressor and small-molecule inhibitors attenuated the suppression of ERα expression by FOXC1. Furthermore, the importance of the NF-κB pathway in FOXC1-stimulated cell growth was demonstrated by increased cell sensitivity to pharmacologic inhibition of NF-κB. Taken together, these results reveal a novel ERα-regulating mechanism that may explain the loss or low expression of ERα in basal-like breast cancer and also may provide new insight into mechanisms for antiestrogen resistance in breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3138. doi:10.1158/1538-7445.AM2011-3138
Abstract 3151: Navitoclax enhances the activity of chemo-therapeutic and targeted agents across a large panel of epithelial cancer cell lines
Authors: Wong Maureen , Tan Nguyen , Kassees Robert , Berry Megan , Nannini Michelle , Sampath Deepak , Belmont Lisa 
Published: June 2012

Abstract
Navitoclax (formerly ABT-263), a potent inhibitor of Bcl-2, Bcl-xL, and Bcl-w, has shown promising activity in CLL, a disease in which Bcl-2 is highly expressed. In this study, we wished to explore its potential as a Bcl-xL inhibitor. Bcl-xL is thought to contribute to resistance to cancer therapy in epithelial cancers. Navitoclax and the related molecule, ABT-737, potentiate the activity of chemotherapy and targeted agents in cell lines and mouse models. In order to identify predictive biomarkers of synergy and identify combinations most likely to translate to the clinical setting, we performed combination studies on a panel of 100 cell lines derived from breast, lung, ovarian and pancreatic cancer. We evaluated the combination of navitoclax with gemcitabine, paclitaxel, as well as targeted agents that inhibit EGFR, phosphatidylinositol-3-kinase and MAP kinase pathways. These studies demonstrate that navitoclax is broadly synergistic with these agents as evaluated by a Bliss independence model. The majority of cell lines and combinations exhibited Bliss scores that exceeded the values predicted for two independent agents. Correlative marker analysis revealed that levels of proteins within the Bcl-2 family correlated with synergy scores for chemotherapy combinations, while activation of the EGFR/Ras/Raf pathway was a better predictor for the combinations of navitoclax with targeted agents. Combination studies in xenograft models demonstrate that navitoclax can enhance the activity of chemotherapy and targeted agents in vivo. Furthermore, biomarker expression correlated with response in vivo. These studies suggest distinct strategies for patient selection that are dependent upon the combination agent.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3151. doi:10.1158/1538-7445.AM2011-3151
Abstract 3158: Stathmin expression predicts response to taxanes in metastatic endometrial cancer
Authors: Werner Henrica MJ , Trovik Jone , Wik Elisabeth , Akslen Lars A. , Salvesen Helga B. 
Published: June 2012

Abstract
Introduction: Endometrial cancer is the most frequent gynecological cancer in industrialized countries. Although the majority have a good prognosis, up to 20% recurs. To date there are few markers available to predict response to treatment of metastatic endometrial cancer. Patients with tumors expressing estrogen- and progesterone receptors have the best response to antihormonal treatment. Still, more markers are needed to predict response to other therapy modalities in patients with metastatic endometrial cancer. Stathmin is known to have a role in microtubule dynamics. In ovarian cancer it was recently shown that high stathmin expression predicted unfavorable prognosis in patients treated with paclitaxel/platinum chemotherapy. We therefore hypothesize that level of stathmin expression may predict response to microtubule-stabilizing chemotherapy in endometrial cancer.
Material and methods: Between 2001 and 2010, 603 patients treated for endometrial cancer were recruited prospectively in a population based setting. Stathmin expression in primary tumors was measured by immunohistochemistry and linked to treatment response to taxanes in patients with metastatic disease. Response was evaluated by the RECIST criteria and analyzed as partial-/complete response versus stable disease/progression.
Results: Of the 603 patients, a total of 117 either relapsed (n=80) or progressed (n=37) after their first line of treatment. Of these, 87 were treated; with chemotherapy (n=34), radiation (n=38) or hormonal therapy (n=15). The remainder did not receive any further treatment or underwent surgery. Complete information regarding response to therapy according to the RECIST criteria was available in 57 patients. Stathmin expression in primary tumors predicted response to microtubule-stabilising chemotherapy (p=0.02, Fisher Exact test): Amongst patients with low expression of stathmin 11 of 12 (92%) had partial-/complete response, whereas only 2 of 6 (33%) patients with a high level of stathmin had partial-/complete response. Stathmin expression was not associated with response to other treatment modalities.
Conclusion: Stathmin expression in primary tumors predicts response to microtubule-stabilizing chemotherapy in metastatic endometrial cancer. Biologically, this is plausible due to the known function for stathmin in microtubule dynamics. A larger cohort is needed to confirm these data and the usefulness of stathmin expression as a marker for treatment of metastatic endometrial cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3158. doi:10.1158/1538-7445.AM2011-3158
Abstract 3168: An antioxidant and DNA repair gene expression pattern associated with lung cancer risk is also associated with COPD risk
Authors: Willey James C. 
Published: June 2012

Abstract
Lung cancer and Chronic Obstructive Pulmonary Disease (COPD) are leading causes of morbidity and mortality both in the United States and worldwide. Inhalation of cigarette smoke is the primary known and preventable cause but only 10-15% of heavy smokers develop these diseases. This suggests that cigarette smoke exposure interacts with inherited susceptibility factors to determine risk. While some susceptibility genes are known, they account for less than 5% of risk for either disease. There is urgent need to identify additional heritable susceptibility factors for these diseases that explain the majority of COPD and lung cancer risk. For example, the National Lung Screening Trial (NLST) recently reported a 20% reduction in mortality from lung cancer. Because there are over 50 million individuals in the US who meet the criteria for the NLST, at a cost of $400/CT scan, the yearly cost of screening could be $20 billion. The objective in this study is to determine the role of inter-individual variation in antioxidant and DNA repair gene transcript regulation in conferring risk for both COPD and lung cancer. The central hypothesis is that inherited DNA variants are associated with increased risk for both COPD and lung cancer and that many of these manifest as increased transcript abundance dispersion in key antioxidant, DNA repair, and transcription factor genes. In support of our hypothesis, we recently identified a lung cancer risk test (LCRT) that comprises transcript abundance values of 14 genes, including nine anti-oxidant, three DNA repair, and two transcription factor genes. For each of these genes, transcript abundance values were dispersed over a greater range in lung cancer compared to matched controls (Blomquist et al, 2009). In addition, inherited DNA variation causes variation in transcript regulation of genes comprised by the LCRT (Crawford et al, 2007;Blomquist et al, 2010). Here we report that in a small number of non-lung cancer cases studied thus far N=13), a subject with positive LCRT value has a 6.7-fold increased likelihood of having COPD (defined by FEV1/FVC&lt;0.7). Development of biomarkers for lung cancer and/or COPD risk will enable prioritization for screening and/or chemoprevention trials and provide drug targets for development of chemo-preventative and therapeutic pharmaceuticals. These developments are expected to reduce mortality and health care costs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3168. doi:10.1158/1538-7445.AM2011-3168
Abstract 3170: Early detection and follow up of head and neck squamous cell carcinoma – A longitudinal serum based biomarker study
Authors: Soudry Ethan , Brait Mariana , Adam Bao-Ling , Gourin Christine , Sidransky David 
Published: June 2012

Abstract
Head and neck squamous cell carcinoma (HNSCC) accounts for more than 37,000 new cases in the US each year. More than half of the patients present in an advanced stage, which confers a poor prognosis. However if detected early this cancer maybe highly curable. Currently there is no biomarker in clinical practice for early detection or prognosis prediction. Many studies are attempting to discover potential biomarkers in tissue, saliva and serum. Promoter methylation suppresses gene expression in cancer and several candidates have been demonstrated to be cancer specific biomarkers. Increased mitochondrial content is another feature that has been demonstrated related to cancer. Our goal is to validate potential biomarkers previously described by our group and others to be linked to HNSCC, in serum samples from a cohort of patients with longitudinal follow up and a subset of normal subjects’ samples. We assessed mitochondrial DNA content (Cox I and Cox II) and methylation status of EDNRB and KIF1a by quantitative PCR in an evaluation set of samples consisting of 75 pre and post treatment serum samples from HNSCC patients and from 11 healthy cancer-free subjects. In tumors, the observed methylation frequencies were 17%, 22% for EDNRB and KIF1a, respectively. There was no observed methylation for EDNRB and KIF1a in normal samples. Increased mitochondrial DNA content was observed in 54% and 59% of the HNSCC samples, by COX1 and COX2, respectively. And no increased content was noted in the normal set. Combining all the markers and analyzing as a panel (at least one positive), we obtained a sensitivity of 83% with specificity of 100%. When we compared post treatment samples to pre treatment samples, we noticed a decreased mitochondrial DNA content in patients without recurrence, and an increase in patients that recurred, however, due to the small number of samples, these associations needs to be confirmed. Our findings indicate that a serum based panel that includes mitochondrial DNA content analysis and cancer specific methylation markers may serve as a high quality detection tool for HNSCC, as well as recurrence prediction. Validation of these preliminary data is ongoing in a larger independent cohort with comprehensive clinical and follow up data.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3170. doi:10.1158/1538-7445.AM2011-3170
Abstract 3175: Detection of hypermethylated vimentin gene in urine of colorectal cancer patients
Authors: Song Benjamin P. , Jain Surbhi , Lin Selena Y. , Block Timothy M. , Brenner Dean E. , Su Ying-Hsiu 
Published: June 2012

Abstract
Although the success of cancer treatment often depends on the early detection of cancer, colorectal cancer (CRC) screening is hindered by low compliance rates (40%) of inconvenient, invasive screening tests. Previous studies have demonstrated that urine contains circulation-derived low-molecular-weight (LMW) DNA (&lt;300 bp) and suggested that LMW urine DNA could be used to detect CRC associated genetic alterations. Aberrant hypermethylation of the vimentin gene (mVIM) has been shown to be a potential stool DNA marker for CRC screening. It was of interest to see whether mVIM could be detected in urine of patients with CRC. In this study, we developed a quantitative MethyLight assay targeting a 39 bp DNA template for mVIM. A locked nucleic acid was incorporated at the CpG sites of the reverse primer of the assay to increase the assay sensitivity and specificity for methylated templates. A blinded concordance study between urine and matched CRC tissue was performed. Twenty matched sets of urine and CRC tissue were collected and subjected to DNA isolation. Total urine DNA was further fractionated into both LMW DNA (&lt; 1 kb) and high-molecular-weight (HMW) DNA (&gt;1 kb) fractions. The MethyLight assay was used to quantify the amount of mVIM in each DNA sample. mVIM was detected in 75% (15/20) of the LMW urine DNA fraction, 0% (0/20) of the HMW urine DNA fraction and 85% (17/20) of the CRC tissue DNA. There was a 60% concordance in detecting mVIM between the CRC tissues and their corresponding urine samples. As negative controls, twenty LMW urine DNA fractions from subjects with no known neoplasia were also tested for mVIM and only 10% (2/20) of control samples contained detectable mVIM. mVIM may be a useful part of a urine based genetic biomarker panel for the early detection of CRC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3175. doi:10.1158/1538-7445.AM2011-3175