bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3716: The origin of metastatic ovarian tumors: A national population-based analysis
Authors: Simons Michiel , Bruls Jolien , Overbeek Lucy , Bulten Johan , Massuger Leon , Nagtegaal Iris 
Published: August 2015

Abstract
Objective: A significant part of ovarian malignancies are metastatic tumors with a wide variety in site of origin. Differentiating between a primary and metastatic malignancy of the ovaries can be difficult, especially in case of mucinous carcinomas, and misdiagnosis might have considerable impact on both treatment and prognosis. To further examine the origin of metastatic tumors in the ovary, we performed a large scale, nationwide search for metastatic ovarian malignancies in the Dutch Pathology Registry (PALGA).
Materials and methods: All pathology reports concerning metastatic ovarian carcinomas and associated primary tumors in the Netherlands from 2000-2010 were collected. Age, year of diagnosis, tumor type, location of the primary tumor and laterality of the ovarian tumor were extracted from the database. Tumors without a proven primary tumor were excluded. The Chi-square test was used to compare multiple nominal variables.
Results: 2,312 patients were identified. The most common primary sites were colon (33.2%), endometrium (17.1%), breast (14.3%), appendix (7.3%) and stomach (4.5%). Bilateral tumors were the most frequent mode of presentation (46.3%) followed by right (26.7%) and left side metastases (19.8%). In 7.2% of cases, laterality was unknown. Mucinous carcinomas were the most common histological type (46.7%), followed by signet-ring cell carcinomas (7.9%) and endometrioid carcinomas (7.7%). Of colorectal tumors, only 40.2% metastasized bilaterally, compared to 64% of breast, 63% of gastric and 59% of appendix tumors. Left sided ovarian tumors originated more often from the left colon than the right colon (69.4%, p&lt;0.0001). Right sided ovarian tumors did not originate more often from the right side of the colon than from the left side. Appendiceal primary tumors did give rise to more right sided ovarian metastases (71.6%, p = 0.016).
Conclusion: The most common histological tumor type in metastatic ovarian carcinomas is mucinous carcinoma. The colon is the most frequent primary site of metastatic malignancies to the ovaries, followed by endometrium, breast, appendix and stomach. Breast, stomach and appendix tumors metastasized mostly bilateral, whereas colorectal tumors metastasized mostly unilateral and ipsilateral. The mechanisms underlying these preferred sites for metastasis or laterality are still unclear.
Citation Format: Michiel Simons, Jolien Bruls, Lucy Overbeek, Johan Bulten, Leon Massuger, Iris Nagtegaal. The origin of metastatic ovarian tumors: A national population-based analysis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3716. doi:10.1158/1538-7445.AM2015-3716
Abstract 3730: Feasibility of office hysteroscopy for evaluation of women with postmenopausal bleeding and association with improved pathological diagnosis
Authors: Shaw Jacquelyn M. , Mehta Sukrant , Chudnoff Scott , Levie Mark , Einstein Mark H. , Goldberg Gary L. , Nevadunsky Nicole S. 
Published: August 2015

Abstract
Objectives: Endometrial sampling is critical in the evaluation of women for cancers of the uterine corpus. Hysteroscopy in the operating room is associated with monetary and time expense to the patient and health care system. The purpose of this study was to compare histopathological diagnoses of endometrial biopsies obtained by office hysteroscopy (OH) versus endometrial pipelle (EP).
Methods: After IRB approval, records of all women with ICD-9 diagnosis (627.1) for postmenopausal bleeding who had OH attempted in the last 5 years at a single medical institution were evaluated. Demographic data collected included age, BMI, medical comorbidities, and histopathologic diagnosis. “Inadequate tissue” for pathologic evaluation was defined as stated in the pathology report or absence of endometrial tissue on biopsy specimen. Statistical analysis was performed using chi-square and Fisher's exact testing with SPSS software.
Results: 85 OHs were attempted and 50 had prior attempted EPs. 98% of OHs and 94% of EPs were successfully performed. However, adequate pathology was obtained in 93% of OHs verses 38% of EPs (p&lt;0.01). Median age was 61 years (range 48-85) and median BMI was 32 kg/m2 (range 19-71). 5% had a BMI&lt;25. The prevalence of diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease were 32%, 74%, 44%, and 21% respectively. There was a significant difference in pathologic diagnoses between OH and EP (p &lt;0.01). Six patients were diagnosed with endometrial hyperplasia, and 3 with endometrial cancers by OH that were not identified by EP.
Conclusions: OH is a feasible procedure that may enhance clinicians’ ability to diagnose benign, pre-malignant and malignant causes of post-menopausal bleeding. Further research is needed to understand the association of cost and quality of life with OH versus hysteroscopy in the operating room.
Table 1.Pathology findings from OH vs. EPPathologyOffice Hysteroscopy (OH)%Endometrial Pipelle Biopsy (EP)%n = 79n = 19Endometrial Cancer34%00%Endometrial Hyperplasia68%00%Benign Endometrium1924%1053%Atrophic Endometrium45%421%Benign Endometrial Polyp4759%526%
Citation Format: Jacquelyn M. Shaw, Sukrant Mehta, Scott Chudnoff, Mark Levie, Mark H. Einstein, Gary L. Goldberg, Nicole S. Nevadunsky. Feasibility of office hysteroscopy for evaluation of women with postmenopausal bleeding and association with improved pathological diagnosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3730. doi:10.1158/1538-7445.AM2015-3730
Abstract 3731: The course of fatigue and its correlates in colorectal cancer survivors: A prospective cohort study of the PROFILES registry
Authors: Husson Olga , Mols Floortje , van de Poll-Franse Lonneke , Thong Melissa 
Published: August 2015

Abstract
Objective: Cancer survivors who remain fatigued during long-term follow-up are at risk for worse health outcomes. To achieve personalized management of cancer-related fatigue, insight into its correlates among long-term survivors is needed to identify survivors at risk of remaining fatigued and also the correlates for intervention.
Methods: Colorectal cancer (CRC) survivors diagnosed between 2000-2009, as registered in the population-based Eindhoven Cancer Registry, completed three annual surveys that included the Fatigue Assessment Scale, the EORTC Quality of Life (EORTC-QLQ-C30) questionnaire, Hospital Anxiety and Depression Scale, and physical activity levels. Linear mixed-model were used to assess the course of fatigue and identify its correlates.
Results: 1734 (66%) CRC survivors completed at least 2 surveys. Fatigue levels were relatively stable over time. Being female, young (≤65 years old), single, low education, chemotherapy treatment, or having ≥1 comorbid condition was associated with higher fatigue scores. Years since diagnosis, radiotherapy treatment and disease stage were not related to fatigue scores. Significant between- and within-subjects effects were found for well-being factors (social, emotional, and cognitive function, and global quality of life), symptoms (anxiety, depression, pain, and insomnia) and functional status (physical and role function, and physical activity levels) in relation to fatigue. Differences in fatigue could be largely attributed to behavior/well-being (59%) and functional status (37%), and to some extent to sociodemographic (4%) and clinical (8%) factors.
Conclusion: This study showed that behavior/well-being and functional status explained more variance in fatigue levels among CRC survivors than sociodemographic and clinical factors.
Citation Format: Olga Husson, Floortje Mols, Lonneke van de Poll-Franse, Melissa Thong. The course of fatigue and its correlates in colorectal cancer survivors: A prospective cohort study of the PROFILES registry. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3731. doi:10.1158/1538-7445.AM2015-3731
Abstract 3744: Single-cell analysis of adaptive resistance and fractional responses of melanoma cells to RAF/MEK inhibition
Authors: Fallahi-Sichani Mohammad , Moerke Nathan J. , Niepel Mario , Zhang Tnghu , Gray Nathanael S. , Sorger Peter K. 
Published: August 2015

Abstract
Treatment of BRAFV600E melanomas with drugs, such as vemurafenib, that inhibit RAF/MEK signaling is effective in the short term, but remission is not durable. Acquired drug resistance is thought to involve short-term adaptive responses that compensate for RAF/MEK inhibition via up-regulation of other pro-growth mechanisms. Thus, understanding and ultimately preventing adaptive responses is a key to durable therapy. Systematic data comparing BRAFV600E tumor cells is generally lacking and it is not known whether adaptation is fundamentally similar across cell types or among individual cells within a cell population.
We apply a systematic approach to studying the responses of human melanoma cell lines to five drugs, RAF and MEK inhibitors, with the overall goal of (i) characterizing variability in adaptation with time, dose, cell type and across individual cells, (ii) discovering new or poorly characterized adaptive mechanisms, and (iii) demonstrating the effectiveness of a high-throughput approach involving multiplex measurement, single-cell analysis and computational modeling. The data involves time-course measurement of total level and activity of signaling proteins and cell state markers using array-based methods and single-cell immunofluorescence assays as well as measurement of apoptosis and cell viability under the same conditions. Statistical modeling using partial least squares regression (PLSR) revealed which of the changes in the ∼200,000 point dataset were phenotypically consequential.
We found that responses to RAF inhibitors are remarkably diverse and involve multiple pathways that can be up or down-regulated over time, with significant variability across cell types and individual cells. We identified a role for JNK/c-Jun signaling in altering the cell-cycle distribution of melanoma cells, causing apoptosis-resistant cells to accumulate and drug maximal effect (Emax) to fall; co-drugging with RAF and JNK inhibitors or JUN knockdown reverse this effect. The primary effect of JNK inhibitors is to minimize the cell-to-cell variability in pS6 suppression, promoting the induction of apoptosis.
Our study shows that a systems-level approach (combining high density time-dependent measurements, quantitative modeling and single-cell analysis) may provide a general framework for evaluating new drugs with adaptive and paradoxical response, and identifying potentially useful combination therapies.
Citation Format: Mohammad Fallahi-Sichani, Nathan J. Moerke, Mario Niepel, Tnghu Zhang, Nathanael S. Gray, Peter K. Sorger. Single-cell analysis of adaptive resistance and fractional responses of melanoma cells to RAF/MEK inhibition. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3744. doi:10.1158/1538-7445.AM2015-3744
Abstract 3748: Transcriptome landscape of brain tumor progression at single-cell resolution
Authors: Kim Kyu-Tae , Lee Jin-Ku , Park Dong-Hyun , Nam Do-Hyun , Lee Hae-Ock , Park Woong-Yang 
Published: August 2015

Abstract
BACKGROUND: Tumor progression within a brain is the process of acquiring malignant genetic mutations from glial progenitor cells, dodging their original developmental fate and deteriorating functional connectivity of CNS. In order to devise effective targeted therapeutic strategies, understanding distinct molecular and phenotypic evolutionary features of cancer clones is eminent.
METHODS: To examine molecular signatures associated with malignant glioma progression, we analyzed transcriptome dynamics of 311 single-cells derived from 3 patients showing distinct disease patterns. Combined with single-cell level signatures, clonal architecture of tumors was reconstructed based on Bayesian-model clustering with integrated information of SSNVs and SCNAs identified from bulk population-level using aCGH and WES.
RESULTS: We found evidence of branched evolutionary patterns within and across two histopathological separated tumor regions. Both tumors have high clonal probable somatic mutations, and evolutionary inference showed clonal lineage between two tumor regions was divided at early time during tumor progression. For all patients, the gene expression signatures within a tumor were heterogeneous but converged towards mesenchymal phenotype in the aggressive region. In the first case, the left tumor was self-limiting and showed mixed proneural and classical gene expression signatures whereas the right side tumor has expanded to the corpus callosum with EGFR overexpression and mesenchymal gene expression. In a case of a monocentric tumor with PDGFRA amplification, cancer cells disseminated from the core mass with massive immune cell infiltration underwent transcriptome switching from proneural to mesenchymal gene expression, with a concomitant FGFR1 copy number gain and mutation. Lastly, in a secondary glioblastoma with IDH1 mutation, GLIOLAN positive glioblastoma was surrounded by grade III oligodendroglioma. The two tumor areas showed intermingled heterogeneous gene expression signatures, with upregulation of astrocytic/mesenchymal genes in the GLIOLAN positive tumor cells.
CONCLUSIONS: Our results show distinct genetic patterns of clonal expansion across patients undergoing malignant glioma progression. We also provide the transcriptome-wide view of gene expression signatures directed by genomic alterations. Overall our study reveals heterogeneity of individual tumor but elucidates common genomic features of glioblastoma progression.
Citation Format: Kyu-Tae Kim, Jin-Ku Lee, Dong-Hyun Park, Do-Hyun Nam, Hae-Ock Lee, Woong-Yang Park. Transcriptome landscape of brain tumor progression at single-cell resolution. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3748. doi:10.1158/1538-7445.AM2015-3748
Abstract 3758: A combined machine learning and bioinformatic analysis approach identifies biological pathways that predict clinical stage and survival outcome in neuroblastoma patients
Authors: Carlisle Alex , Caceres Ivan , Mehta Sonali , Schindler Jay , Sharma Jonathan 
Published: August 2015

Abstract
Neuroblastoma is an aggressive pediatric cancer that displays tremendous clinical and biological heterogeneity. Approximately 40% of patients present with metastatic disease and have poor outcome; new biomarkers that improve risk classification and prognostication are desperately needed. Applying a machine learning-based approach to analyzing transcriptome-wide signals in multiple populations of neuroblastoma patients spanning clinical stage we identified a combined set of 14 clinical and molecular variables that predicted survival outcome and tumor stage with over 87% accuracy. A systems biology-based analysis of the molecular variables from our predictive set identified 5 major networks with hubs defining 3 major ontological processes: apoptosis, nucleotide biosynthesis, and RNA metabolism.
Citation Format: Alex Carlisle, Ivan Caceres, Sonali Mehta, Jay Schindler, Jonathan Sharma. A combined machine learning and bioinformatic analysis approach identifies biological pathways that predict clinical stage and survival outcome in neuroblastoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3758. doi:10.1158/1538-7445.AM2015-3758
Abstract 3768: Identification of new alternative lengthening of telomeres (ALT)-positive cancer cell lines using the C-circle assay
Authors: Malykh Andrei G. , Doyle Jonathan R. , Tian Fang , Lee Joyce HY , Henson Jeremy D. , Reddel Roger R. 
Published: August 2015

Abstract
Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism used by approximately 10% of human cancers, including poor prognosis childhood and adult cancers for which development of better treatments is a priority. Currently there are only about ten published ALT+ cancer cell lines available for research, only four of which are available from international repositories. The development of the C-Circle Assay has made it possible to accurately and conveniently test a large number of cell lines for ALT activity. We have tested a panel of 297 cancer cell lines from the American Type Culture Collection (ATCC) with the C-Circle Assay for ALT and identified 34 new ALT+ cell lines. Importantly, we have identified for the first time ALT+ cancer cell lines derived from breast carcinoma, hepatocellular carcinoma, melanoma and leukemia. The overall proportion of ALT+ cancer cell lines was 11.4% (n = 297), which included 19.5% of leukemia (n = 46), 19.0% of melanoma (n = 21), 12.7% of non-small cell lung carcinoma (n = 53) and 3.3% of breast carcinoma (n = 37) cell lines. These results identify additional cancer cell line resources for research into the ALT mechanism, including cell lines from cancer types where ALT has not previously been studied in detail.
Citation Format: Andrei G. Malykh, Jonathan R. Doyle, Fang Tian, Joyce HY Lee, Jeremy D. Henson, Roger R. Reddel. Identification of new alternative lengthening of telomeres (ALT)-positive cancer cell lines using the C-circle assay. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3768. doi:10.1158/1538-7445.AM2015-3768
Abstract 3784: Regulation of chromatin condensation by mitotic checkpoint protein MAD2
Authors: Shandilya Jayasha , Roberts Stefan GE 
Published: August 2015

Abstract
The process of cell division is stringently regulated by spindle and mitotic checkpoint components mainly MAD2, MAD1, CDC20, BUBR1, BUB3 and MAD3. These checkpoint proteins detect unattached or improperly attached kinetochore-microtubule binding sites and generate an anaphase-wait signal by inhibiting the anaphase-promoting complex (APC/C). Activation of checkpoint signaling arrests the cells at metaphase until the attachment errors are rectified and all the chromosomes are properly bi-oriented at the metaphase plate. Together with these checkpoint proteins, the expression of checkpoint-regulatory factors such as p31 (comet) and recently identified, WT1 can hypo- or hyper-activate the signaling pathway, respectively and regulate the timing of mitotic exit. Recently we found that WT1 can interact with MAD2 and regulate the mitotic checkpoint function. Furthermore our studies show that MAD2 and WT1 can also influence the chromatin condensation process required for mitotic progression. We analyzed the effect of MAD2 and WT1 perturbations on the epigenetic mark (phosphorylation of histone H3) associated with condensed chromatin state. Our results show that MAD2 regulates the recruitment of chromatin modifying enzyme Aurora kinase B during mitosis. We further show that MAD2 is an important factor required for synchronization of key events beyond the checkpoint signaling sites to ensure the fidelity of chromosome segregation.
Citation Format: Jayasha Shandilya, Stefan GE Roberts. Regulation of chromatin condensation by mitotic checkpoint protein MAD2. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3784. doi:10.1158/1538-7445.AM2015-3784
Abstract 3808: Targeting cholesterol for increased chemotherapy efficacy
Authors: Yamaguchi Ryuji 
Published: August 2015

Abstract
The PI3K-AKT pro-survival signal present in most cancer cells is the major obstacle to effective chemotherapies. However, most chemotherapeutics targeting the PI3K-AKT pathway have undesirable side effects. β-cyclodextrin (βCD) and its derivatives were found to diminish PI3K-AKT activities in cancer cells with limited side effects. Treatments of cultured cells with βCD depleted cholesterol from the plasma membrane abolishing their coated pits. Even though growth factors such as IGF1 and insulin activated their receptors, their signals were not transduced to downstream signals such as PI3K-AKT pro-survival pathway. The inhibitory effect lasted as long as βCD was present in the medium. Injected into a mouse, βCD attenuated IGF1-induced blood glucose drop for several hours.
In the absence of PI3K-AKT pro-survival signal, cells became sensitized to mitochondria dependent cell death such as Bcl2 antagonists ABT-263 in many epithelial cells and Fas and TRAIL in type II cells. In mice carrying human cancer cells, the addition of HPβCD (a derivative of βCD) to the 2-deoxyglucose & ABT-263 combination therapy, and to the TRAIL therapy improved their efficacies.
Citation Format: Ryuji Yamaguchi. Targeting cholesterol for increased chemotherapy efficacy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3808. doi:10.1158/1538-7445.AM2015-3808