bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3832: Characterizing breast cancer CTCs for brain metastasis competence
Authors: Marchetti Dario 
Published: May 2015

Abstract
Mechanisms causing fatal breast cancer brain metastasis (BCBM) remain largely unknown as well as functionalities of brain-colonizing circulating tumor cells (CTCs) in BCBM disease.We have characterized CTCs isolated from peripheral blood mononuclear cells of patients with breast cancer by multi-parametric flow cytometry. In epithelial cell adhesion molecule (EpCAM)-negative CTCs, we identified a “brain metastasis selected marker” (BMSM) profile or HER2+/EGFR+, HPSE+ and Notch1+ CTCs. These CTCs, which are not captured by the CellSearchTM (Veridex, LLC)platform because of their EpCAM negativity, were analyzed for cell invasiveness and metastatic competency in vivo. CTCs expressing the BMSM profile were highly invasive and capable of generating metastases when xenografted in nude mice. Notably, increased brain metastatic capabilities, frequency and quantitation were detected in EpCAM− CTCs overexpressing the BMSM profile. The presence of proteins of this profile was also verified in the metastatic lesions of animals. Further, investigations of viable BMSM CTCs were carried out using the DEPArrayTM, a dielectrophoresis-based platform able to detect and sort pure CTCs which were investigated by whole genome amplification and proteomic content. CTC subsets were derived possessing combinatorial levels of the BMSM profile and distinct abilities to generate BCBM.Collectively, we provide evidence of isolation, culture and characterization of human breast cancer CTCs leading to the description of a BMSM protein profile that is considered necessary for CTC metastatic competency to brain. Studies are presently undergoing to capture multiple CTC subsets and validate the presence of the BMSM profile in longitudinal studies of populations of breast cancer patients with the objective to not only better understand BCBM onset but also to predict disease course for improved and informed clinical treatment.
Citation Format: Dario Marchetti. Characterizing breast cancer CTCs for brain metastasis competence. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3832. doi:10.1158/1538-7445.AM2014-3832
Abstract 3834: The National Biomarkers Development Alliance (NBDA): A comprehensive solution
Authors: Compton Carolyn C. , Team The NBDA 
Published: May 2015

Abstract
The development of effective and robust biomarkers is essential to the realization of the vision of precision medicine. Despite huge investments in biomarker discovery and development over decades, less than 100 biomarkers are used routinely in clinical medicine; and approximately 1.3 new protein biomarkers are approved per year by FDA - extremely few new biomarkers are approved by the FDA each year. At present, the high costs and failure rates in biomarker development represent one of the most significant roadblocks to medical progress. The biomarker development process itself requires re-engineering to reduce the massive inefficiencies, fragmentation, and failure rates that now characterize the system.
The NBDA is a nonprofit organization of academic, industry and government partners which aims to create a standards-based, comprehensive end-to-end approach to the development of biomarkers of different categories within a given context of use, guided throughout the development pipeline by regulatory and clinical implementation requirements. The NBDA will work with multi-sector stakeholders across the biomarker development continuum to identify where in the process standards matter, determine the status of existing standards and identify gaps, aggregate information referable to specific biomarkers and biomarker classes, and reproduce the work. NBDA will publish the recommendations it develops by consensus and science, building on the best of current practices. It will act in consultation with the FDA and professional standards organizations in order to meet the levels of evidence for biomarker qualification by regulators and validation in clinical use. Through standards and quality management approaches, it will link and integrate discovery, pre-clinical development, assay development and performance, clinical testing, regulatory approval, and post-market applications. Pilot projects in development are focused on newer classes of biomarkers: e.g., genomic biomarkers such as allelic variance as determined by next generation sequencing technologies; proteomics biomarkers generated by mass spectroscopy; volumetric and functional imaging; and complex biomarkers defined as combinations of different classes of biomarkers, the useful value of which is determined computationally. The ever more rapid development of assay technologies dictates that standards that allow them to be applied successfully to biomarker development keep pace. This can only be accomplished through broad coordination of effort and consensus, which is the goal of the NBDA.
Citation Format: Carolyn C. Compton, The NBDA Team. The National Biomarkers Development Alliance (NBDA): A comprehensive solution. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3834. doi:10.1158/1538-7445.AM2014-3834
Abstract 3838: Differential expression of Notch1 in lung, ovarian and breast cancers
Authors: Nguyen Dat , Rubinstein Larry , Sherman Mark E. , Tomaszewski Joseph E. , Takebe Naoko , Ivy Percy , Doroshow James H. , Yang Sherry X. 
Published: May 2015

Abstract
Targeting the Notch signaling pathway for cancer treatment is currently the subject of early clinical trials. However, treatment-related toxicities, particularly gastrointestinal adverse events, have limited clinical development of this class of agents. The development of efficacy biomarkers to gamma-secretase inhibitors and antibodies to Notch ligands and receptors could speed clinical testing. Mutations in Notch1, a dominant Notch receptor, are rare in human solid tumors, and clinical activity has not been observed in patients with tumors bearing Notch1 activating mutations, including T-cell acute lymphoblastic leukemia from available clinical data. Identification of tumors with abundant target expression and/or active Notch signaling status characteristic of Notch intracellular domain (NICD) expression by immunohistochemistry may have clinical utility. All levels of tumor Notch1 expression comprised of low, moderate and high detected by immunohistochemistry and quantitated by digital imaging technology were observed in 52% (34/66) of lung cancers, 51% (35/68) of ovarian cancers, and 11% (7/63) of breast cancers (lung or ovary vs. breast, P&lt;0.0001 by 2-sided Fisher Exact Test). Notch1 was expressed at high levels in 20% of lung cancers including sarcoma, neuroendocrine, small cell and undifferentiated carcinomas, as well as adenocarcinoma and squamous cell carcinomas. High expression of Notch1 was observed in 9% of ovarian tumors including undifferentiated carcinoma, serous adenocarcinoma, and endometrioid adenocarcinoma. In breast cancer, it was noted in one case of infiltrating ductal carcinoma with triple-negative phenotype. Expression of high-level Notch1 varies in lung cancer vs. ovarian cancer vs. breast cancer (P=0.002 by Chi-square statistic), and was frequently associated with NICD expression. Notch1 was not significantly associated with estrogen receptor, progesterone receptor or HER2 status in breast cancer. These data suggest that the frequency of all levels of Notch1 expression is significantly higher in lung cancer and ovarian cancer than breast cancer; and high-level Notch1 is more frequent in lung cancer than in ovarian cancer, and, likewise, more frequent in ovarian cancer than in breast cancer. For the first time, expression of Notch1/NICD has been identified in undifferentiated carcinomas. The findings may provide useful information for the rational design of Notch inhibitor clinical trials.
Citation Format: Dat Nguyen, Larry Rubinstein, Mark E. Sherman, Joseph E. Tomaszewski, Naoko Takebe, Percy Ivy, James H. Doroshow, Sherry X. Yang. Differential expression of Notch1 in lung, ovarian and breast cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3838. doi:10.1158/1538-7445.AM2014-3838
Abstract 3842: Relationship between weight change and response to trastuzumab-based neoadjuvant chemotherapy among women with operable HER2 overexpressing breast cancer
Authors: Hajjaji Nawale , Chocteau Dorothee , Gerard Sylvie , Orgerie Marie Brigitte 
Published: May 2015

Abstract
Purpose
Weight change (gain or loss) in early breast cancer patients is associated with worse survival. However, limited research investigates the impact of weight change in the neoadjuvant setting in women with HER2 overexpressing breast cancer. The goals of this study were to examine i) the relationship between weight change during trastuzumab-based neoadjuvant chemotherapy and pathologic response, and ii) determine whether weight change during post-operative trastuzumab was associated with outcome.
Patients and methods
From March 2004 to March 2013, 52 patients diagnosed with invasive non-metastatic HER2 overexpressing breast cancer were recruited from H.S. Kaplan Cancer center, France. They received trastuzumab-based neoadjuvant chemotherapy (NAC) before surgery, followed by adjuvant trastuzumab. Patients were distributed in the “weight loss” or “weight gain/stable” categories according to their relative weight change after NAC, and after adjuvant trastuzumab. Logistic regression was used to examine associations between weight change and pathologic response. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to evaluate the relationship between weight change and progression free survival (PFS).
Results
Median age was 50 years (range 21 to 71 years); 25% of women experienced body weight loss during NAC, 40% had stable body weight, and 35% gained weight. In multivariate analysis, weight loss was significantly associated with worse pathologic complete response (pCR) in tumor compared with the weight gain/stable group (OR = 0.18; 95% CI, 0.04 to 0.84). There was no difference in pCR in nodes according to weight change (OR = 0.34; 95% CI, 0.06 to 1.76). Body mass index was not associated with pCR. At a median follow up time of 3 years, PFS was not associated with weight change during NAC but with weight change during adjuvant trastuzumab. PFS was worse in patients loosing weight during adjuvant trastuzumab (OR = 0.05; 95% CI, 0.01 to 0.34).
Conclusion
Weight loss was associated with worse pCR to trastuzumab-based neoadjuvant chemotherapy. In addition, weight loss during adjuvant trastuzumab was associated with worse PFS. These results suggest that weight control and promotion of weight maintenance in women with HER2 overexpressing breast cancer should be integrated within cancer treatment to optimize patient outcomes.
Citation Format: Nawale Hajjaji, Dorothee Chocteau, Sylvie Gerard, Marie Brigitte Orgerie. Relationship between weight change and response to trastuzumab-based neoadjuvant chemotherapy among women with operable HER2 overexpressing breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3842. doi:10.1158/1538-7445.AM2014-3842
Abstract 3845: Symptoms burden in subjects with cervical cancer and supportive care:A view from a developing country
Authors: Olagunju Andrew T. , Aina Olatunji F. , Sarimiye Foluke O. , Olagunju Tinuke O. 
Published: May 2015

Abstract
Objectives: Cervical cancer is not only a leading gynecologic cancer in the developing countries but disproportionately accounts for the burden due to cancer. In spite of the need for holistic care of cervical cancer, little is known about the experience of the affected populations beyond their cancer treatment. This study aims to investigate the pattern and distribution of symptoms burden in subjects with cervical cancer in a developing context.
Methods: This cross sectional study was carried out among 122 consenting participants with cervical cancer using a designed questionnaire to elicit socio-demographic with clinical profile and symptoms burden. Subsequently, Centre for Epidemiological Studies Depression Scale Revised (CESD-R) was used to ascertain presence of depressive symptoms in participants. Data analyses were done using SPSS-15.
Results: Majority of the subjects, 50(41.0%) and 68(55.7%) were in their fifth decade of life and unmarried respectively. Six (4.9%) participants presented with early stage cancer, while close to two-thirds of the participants made up of 76(62.3%) subjects had advanced stage cancer. The largest proportion, consisting of about 7 in every 10 participants had pain, 70(57.4%) participants reported sexual dysfunction, and common sexual problems that were reported include loss of libido, dyspareunia and anorganism among others. In addition, physical complications like ulcer, weight loss and multiple complaints were seen in 56(45.9%) participants. Significant depressive symptoms based on CESD-R cut-off score of 16 and above was elicited among close to half of the participants, 58(47.5%).
Conclusions: Late presentation and significant burden of diverse symptoms including pain, sexual, physical and depressive were prevalent among individuals with cervical cancer. Health education with proactive health interventions to promote early presentation and supportive care to ensure qualitative overall care are implied.
Citation Format: Andrew T. Olagunju, Olatunji F. Aina, Foluke O. Sarimiye, Tinuke O. Olagunju. Symptoms burden in subjects with cervical cancer and supportive care:A view from a developing country. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3845. doi:10.1158/1538-7445.AM2014-3845
Abstract 3850: Genetic and intermediate phenotypic susceptibility markers of gastric cancer in Hispanic-Americans: A case control study
Authors: Sun Yuhui , Stroehlein John , Ajani Jaffer , Chang David , Wu Xifeng , Gu Jian 
Published: May 2015

Abstract
Background: Hispanics are the largest non-white ethnic group in the U.S. and account for approximately 17% of U.S. population. Hispanics have higher incidence and mortality rates for gastric cancer than whites or Asians. Association studies have identified several genetic susceptibility loci and intermediate phenotypic biomarkers for gastric cancer in whites and Asians. However, no studies have evaluated genetic susceptibility and intermediate phenotypic biomarkers in Hispanics. Methods: In a case-control study of 132 Hispanic gastric cancer patients and 125 Hispanic controls, we evaluated the association of 5 previously identified, single nucleotide polymorphisms (SNPs) predisposing to gastric cancer in whites and/or Asians. In addition, two intermediate phenotypic markers in peripheral blood leukocytes, i.e., telomere length and mitochondrial DNA (mtDNA) copy number, were examined with respect to risk for gastric cancer.
Results: The variant C allele of the SNP rs2294008 in PSCA gene was associated with a significantly reduced risk of gastric cancer (per allele OR=0.60, 95%CI, 0.41-0.88; P=0.009) after adjusting for age, gender, and smoking status. Low mtDNA copy number was associated with a significantly increased risk of gastric cancer (OR=6.83; 95%CI, 3.33-14.00; P &lt;0.01). Telomere length was not significantly associated with the risk of gastric cancer (OR=1.25, 95% CI, 0.70-2.24; P=0.450).
Conclusion: Hispanics share certain genetic susceptibility loci and intermediate phenotypic biomarkers with whites and Asians, but may also have distinct genetic susceptibility factors related to risk for gastric cancer
Citation Format: Yuhui Sun, John Stroehlein, Jaffer Ajani, David Chang, Xifeng Wu, Jian Gu. Genetic and intermediate phenotypic susceptibility markers of gastric cancer in Hispanic-Americans: A case control study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3850. doi:10.1158/1538-7445.AM2014-3850
Abstract 3857: Induction of ALDH1A2 expression is critical for cancer stem cell properties in neuroblastoma
Authors: Nishimura Noriyuki , Hartomo Tri Budi , Pham Thi Van Huyen , Yamamoto Nobuyuki , Hrase Satoshi , Hayakawa Akira , Hasegawa Daiichiro , Kawasaki Keiichiro , Kosaka Yoshiyuki , Matsuo Masafumi , Takeshima Yasuhiro , Iijima Kazumoto , Nishio Hisahide 
Published: May 2015

Abstract
Neuroblastoma is an aggressive tumor characterized by its heterogeneity ranging from spontaneous regression to malignant progression, and accounts for ∼15% of all cancer-related deaths in children. Despite current aggressive therapies, over 50% of high-risk neuroblastoma patients have experienced a tumor relapse. As in most cancers, recurrent neuroblastoma is primarily driven by chemoresistant cancer stem cells (CSCs), which are identified as a subpopulation of cancer cells with the multipotent ability to self-renew, generate differentiated progeny, and recapitulate a heterogeneous population of cancer cells in xenograft cancers. An increasing number of studies isolated CSCs as spheres, side population cells, and cell-surface marker-positive cells based on the markers associated with stem cell populations in a variety of cancers. Although high activity of aldehyde dehydrogenase (ALDH), which catalyzed the oxidation of aldehydes to carboxylates and comprised 19 isoforms in human cells, was used to identify and isolate CSCs from many types of cancers, it remained to be characterized in neuroblastoma. In the present study, we investigated the ALDH activity and the expression profile of 19 ALDH isoforms in spheres and parental cells of neuroblastoma. The ALDH activity was enriched in spheres compared to parental cells, while the expression profile was considerably varied among different neuroblastoma cells. Among ALDH isoforms consistently induced in spheres, ALDH1A2 knockdown most severely impaired the sphere and colony formation. Reciprocally, increased expression of ALDH1A2 enhanced these functions in neuroblastoma cells. ALDH1A2 expression was further correlated with the differentiation of neuroblastoma xenografts, the resistance to 13-cis-retinoic acid (13-cRA), and the overall survival of neuroblastoma patients. These results suggest that the induction of ALDH1A2 expression is critical for CSC properties in neuroblastoma.
Citation Format: Noriyuki Nishimura, Tri Budi Hartomo, Thi Van Huyen Pham, Nobuyuki Yamamoto, Satoshi Hrase, Akira Hayakawa, Daiichiro Hasegawa, Keiichiro Kawasaki, Yoshiyuki Kosaka, Masafumi Matsuo, Yasuhiro Takeshima, Kazumoto Iijima, Hisahide Nishio. Induction of ALDH1A2 expression is critical for cancer stem cell properties in neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3857. doi:10.1158/1538-7445.AM2014-3857
Abstract 3862: Isolation and nanoscale visualization of glioblastoma stem-like cells utilizing the Notch1 receptor
Authors: Pohlmann Elliot , Murphy Susan , Kelly Debbie , Sheng Zhi 
Published: May 2015

Abstract
Tumor eradication is an elusive goal in modern medicine. This unmet goal is in part due to the imprecise therapeutic targeting of a specific population of cells having “stem-like” properties. These stem-like tumor cells can remain almost senescent during chemotherapeutic interventions to evade treatment and produce genetically different secondary tumor lineages than their parental tumors. Here we develop a novel approach that utilizes the Notch1 receptor, found on the surface of glioma cells, to isolate a population of cells bearing stem-like properties. We identified this population to be Nestin+GFAP-, capable of serum differentiation into Nestin-GFAP+ cells, and self-regenerating. In addition, this unique population of cells has increased stem-like qualities compared to the CD133 marker. Utilizing affinity nanocapture grids, we were able to visualize Notch1+ stem-like cells and the perforation of their plasma membranes by unlabeled gold nanorods via electron microscopy. Previous studies have shown that tumor stem-like cells can exist within the larger tumor milieu, representing a potential threat to recurrence. We propose that 1) Notch1 may serve as a novel marker to define glioblastoma stem-like cells, capable of being used for targeting chemotherapeutic approaches in the future, and 2) affinity nanocapture grids represent a unique method for examining individual living cells at the nanoscale.
Citation Format: Elliot Pohlmann, Susan Murphy, Debbie Kelly, Zhi Sheng. Isolation and nanoscale visualization of glioblastoma stem-like cells utilizing the Notch1 receptor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3862. doi:10.1158/1538-7445.AM2014-3862