tbuckley/cabot-search huggingface dataset:
Abstract 1866: Ultrahigh resolution optical coherence microscopy for label-free imaging of human cervical lesions <i>ex vivo</i>
Authors: Xianxu Zeng, Canyu Li, Xiaofang Wang, Jason Jerwick, Tao Xu, Yuan Ning, Linlin Zhang, Yutao Ma, Xiaoan Zhang, Chao Zhou
Journal: Cancer Research (2017)

Abstract Cervical cancer remains the fourth most common cause of cancer and the fourth leading cause of cancer death in women worldwide. In contrast to the decreasing prevalence in developed countries, incidence of cervical cancer remains high in developing countries, such as China, India and Chile. Effective screening of cervical cancer is crucial for early diagnosis of the disease. Ultrahigh resolution optical coherence microscopy (UHR OCM) is an emerging label free imaging technique that can be used to obtain three dimensional (3D) “optical biopsy” of biological samples with cellular resolution up to 2 mm beneath the tissue surface. The goal of this study is to assess the diagnostic value of UHR OCM for human cervical precancer and cancer screening and identify characteristic features in UHR OCM images that correlate with the gold standard histopathology. Six hundred and fifty eight (658) fresh cervical tissues from cervical biopsy, conization and panhysterectomy were obtained from 254 consenting volunteers. Multiple 3D UHR OCM images were obtained from each specimen before the sample was processed for standard histopathology evaluation. Of the 658 samples imaged, 474 had normal cervix or benign lesions, 110 had low grade squamous intraepithelial lesion (LSIL), 57 had high grade squamous intraepithelial lesions (HSIL) and 17 had invasive cancer. UHR OCM images were compared to histopathology slides obtained from the same specimens in order to identify diagnostic image features. Distinctive patterns for squamous epithelium, columnar epithelium, basement membrane, cervical inflammation and erosion, koilocytic cells, low grade and high grade squamous intraepithelial lesions and cervical cancer were clearly observed. Our results lay the foundation for future non-invasive optical evaluation of cervical tissue in vivo. This could lead to a less invasive and more effective screening strategy for cervical cancer based on OCM guided biopsies. Citation Format: Xianxu Zeng, Canyu Li, Xiaofang Wang, Jason Jerwick, Tao Xu, Yuan Ning, Linlin Zhang, Yutao Ma, Xiaoan Zhang, Chao Zhou. Ultrahigh resolution optical coherence microscopy for label-free imaging of human cervical lesions ex vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1866. doi:10.1158/1538-7445.AM2017-1866
Abstract 4348: Methylation analysis of uveal melanoma reveals definitive patterns in tumors harboring BAP1 mutations
Authors: Michael Durante, Matthew Field, Stefan Kurtenbach, Parker Bussies, Christina Decatur, J. William Harbour
Journal: Cancer Research (2017)

Abstract Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy and can be classified by gene expression profiling into two distinct molecular classes that correspond to metastatic risk: Class 1 (low risk) and Class 2 (high risk). The less aggressive Class 1 UMs express a more differentiated phenotype and exhibit numerous characteristics of normal uveal melanocytes, while the metastasizing Class 2 UMs display loss of melanocytic differentiation and have acquired a primitive, stem-like phenotype. The majority of Class 2 UMs harbor loss of chromosome 3 in addition to inactivating mutations of the tumor suppressor BAP1, which also catalyzes ubiquitin removal from histone H2A and modulates gene expression. Histone modifications have been shown to be associated with DNA methylation and this study investigates the global methylation and gene expression changes in BAP1 mutant tumors. Methods: RNA-Sequencing data and Illumina Human Methyl 450K BeadChip Array data obtained from 92 primary uveal melanoma tumors was analyzed using optimized pipelines. Results: This analysis revealed that the more aggressive Class 2 tumors exhibit a distinct pattern of hypermethylation and silencing of developmental genes involved in neural crest migration and differentiation. Chromosomal regions that were significantly enriched for hypermethylated genes with decreased gene expression in Class 2 tumors included chromosome 3p14-26, 3q12-29 and 8p12-22, whereas the only significantly enriched region for genes that were hypomethylated with increased gene expression in Class 2 tumors was chromosome 8q22-24. Additionally, BAP1 itself was differentially hypermethylated in Class 2 UMs, suggesting that it may regulate its own transcription. Conclusions: Class 2 UMs harboring BAP1 mutations displayed distinct regions of differential hypermethylation in comparison to Class 1 UMs. In these tumors, the most significantly hypermethylated regions occurred on chromosome 3 and in regions that were enriched for genes encoding neural crest guidance cue proteins that regulate homing, migration and invasion. These findings suggest that BAP1 mutations are associated with marked reorganization of the DNA methylome, providing new insights into the pathophysiology of UM and suggesting that methylation may serve as a diagnostic to further stratify metastatic risk. Furthermore, these findings may open new opportunities for targeted therapy of Class 2 UMs. Citation Format: Michael Durante, Matthew Field, Stefan Kurtenbach, Parker Bussies, Christina Decatur, J. William Harbour. Methylation analysis of uveal melanoma reveals definitive patterns in tumors harboring BAP1 mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4348. doi:10.1158/1538-7445.AM2017-4348
Abstract 111: Targeting STAT3 and telomerase for the treatment of colorectal cancer
Authors: Seyung Chung, Quincy Okobi, Debbie Adekoya, Jaydutt Vadgama
Journal: Cancer Research (2017)

Abstract There is an increasing evidence of pro-inflammatory cytokines involvement in cancer development. Here, we found that two cytokines, IL-6 and TNF-α, induced colorectal cancer cells more active and invasive. Combined treatments of IL-6 and TNF-α phosphorylated transcription factors STAT3 in a synergistic manner. STAT3 and NF-κB physically interacted upon cytokine stimulation. Similarly, STAT1 hetero-dimerized with STAT3 and the binding affinity was enhanced with cytokine treatments. STAT3 bound the promoter region of human telomerase reverse transcriptase (hTERT), and IL-6 and TNF-α stimulation further enhanced this STAT3 binding affinity. Withaferin A, an anti-inflammatory steroidal lactone, inhibited the IL-6 and TNF-α induced cancer cell invasiveness and decreased colonosphere formation. Notably, withaferin A inhibited STAT3 phosphorylation and abolished the STAT3 and NF-κB interactions. STAT3 binding to hTERT promoter was inhibited and telomerase activity was decreased with the withaferin A treatments. Taken together, pro-inflammatory cytokines induced-cancer cell invasiveness is mediated by STAT3 regulated mechanism in colorectal cancer cells. Our study suggests the novel natural compound therapy for the metastatic colorectal cancer in clinical settings. Citation Format: Seyung Chung, Quincy Okobi, Debbie Adekoya, Jaydutt Vadgama. Targeting STAT3 and telomerase for the treatment of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 111. doi:10.1158/1538-7445.AM2017-111
Evolution of the MDA-MB-175 breast cancer cell line from a low to a high HER2 expressing tumor line
Authors: Lisa M. Crocker, Gail Phillips, Brian Reardon, Hartmut Koeppen, Mark X. Sliwkowski, Ralph H. Schwall, Sarajane Ross
Journal: Cancer Research (2005)

1086  HER2/ErbB2 overexpression is known to play a key role in tumorigenesis and metastasis of breast adenocarcinomas. Breast cancer patients whose tumors overexpress HER2 are candidates for treatment with Herceptin®. The breast adenocarcinoma line, MDA-MB-175, expresses HER2 at the 1+ level (∼ 100,000 HER2 receptors/cell) in vitro. Previous studies with this cell line indicate that gamma-heregulin functions as an autocrine growth factor signaling through the HER3-HER2 complex. In vitro treatment of MDA-MB-175 cells with the anti-HER2 antibody, pertuzumab (2C4/OmnitargTM), significantly disrupts proliferation due to the fact that this antibody interrupts ligand-dependent formation of HER2-HER3 heterodimer complexes. Attempts to establish a tumor model with this line have proven difficult, since tumors do not grow when cells are inoculated subcutaneously or into the mammary fat pad (MamFP). Through a series of technical approaches, we established a robust xenograft model by surgically inoculating these cells into the gonadal fat pad (GonFP) of beige nude mice bearing supplemental estrogen. To refine this model, we then began transplanting the GonFP tumors into the MamFP, with and without exogenous estrogen supplementation, and showed a consistent and reliable tumor take rate. Histologically, the tumors from the GonFP and the MamFP are not morphologically different. Surprisingly, HER2 expression was quantitatively different for these two tumor cell lines. Immunohistochemistry analysis revealed that the GonFP tumors increased slightly in HER2 expression to 2+, whereas tumors from the MamFP were now 3+ for HER2 expression. These tumors were characterized further with respect to HER receptors and ligands as well as establishing the estrogen receptor (ER) status of the xenografts compared to the original cell line. Both tumors are strongly ER positive in a very small percentage of tumor cells (
Abstract 1309: Association between insulin resistance and breast cancer risk: A Mendelian randomization analysis of data from 228,000 women of European descent
Authors: Xiang Shu, Lang Wu, Nikhil K. Khankari, Kyriaki Michailidou, Manjeet K. Bolla, Jean Wang, Joe Dennis, Xiao-ou Shu, Jacques Simard, Douglas F. Easton, Wei Zheng
Journal: Cancer Research (2017)

Abstract Background: Epidemiologic studies suggest that insulin resistance may be associated with breast cancer risk. We conducted Mendelian randomization (MR) analyses to reduce the biases associated with previous studies and provide evidence for causal inference. Materials and Methods: We used genetic variants identified in genome-wide association studies for circulating fasting insulin (15 variants), early insulin secretion (16 variants), fasting proinsulin (8 variants), fasting glucose (35 variants), and 2-hour glucose (8 variants) as instruments in MR analyses. To reduce possible pleiotropic effects, variants associated with obesity were removed from the instruments. We first evaluated the association of these instruments with type 2 diabetes risk in 110,452 subjects to assess instrument validity. We then investigated the association of these instruments with breast cancer risk using data obtained from 122,977 cases and 105,974 controls of European descent included in the Breast Cancer Association Consortium (BCAC). Odds ratios (OR) were calculated to measure the associations of instrumental variables with risk of overall breast cancer and its subtypes defined by estrogen-receptor [ER] status. Results: All instrumental variables constructed for this study were strongly associated with type 2 diabetes risk with ORs of 3.01 (p=7.86x10-5), 0.22 (p=3.54x10-14), 1.90 (p=8.28x10-4), 6.11 (p=3.59x10-19), and 1.91 (p=6.8x10-16) for per unit increase of fasting insulin, early insulin secretion, fasting proinsulin, fasting glucose, and 2-hour glucose levels, respectively. Statistically significant associations with overall breast cancer risk were found for fasting insulin (OR=1.36 for per unit increase, 95% CI=1.09-1.70, p=0.011) and fasting proinsulin (OR=1.21, 95% CI=1.06- 1.38, p=0.011). These associations were observed only for ER-positive breast cancer. No statistically significant association at p&amp;lt;0.05 was found for early insulin secretion, fasting glucose, or 2-hour glucose levels. Conclusions: Our study provides strong support that certain insulin resistance traits may be causally associated with risk of breast cancer, particularly ER-positive breast cancer. Citation Format: Xiang Shu, Lang Wu, Nikhil K. Khankari, Kyriaki Michailidou, Manjeet K. Bolla, Jean Wang, Joe Dennis, Xiao-ou Shu, Jacques Simard, Douglas F. Easton, Wei Zheng. Association between insulin resistance and breast cancer risk: A Mendelian randomization analysis of data from 228,000 women of European descent [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1309. doi:10.1158/1538-7445.AM2017-1309
Genome-wide association study (GWAS) of chemotherapy-induced Raynaud's phenomenon (RP) to reveal shared pathways with cardiovascular disease (CVD).
Authors: Omar El Charif, Heather E. Wheeler, Matthew Trendowski, Eric R Gamazon, Shirin Ardeshirrouhanifard, Darren R. Feldman, Robert James Hamilton, David J. Vaughn, Clair Beard, Chunkit Fung, Jeri Kim, Sophie D. Fossa, Mohammad Issam Abu Zaid, Taisei Mushiroda, Michiaki Kubo, Lawrence H. Einhorn, Nancy Cox, Lois B. Travis, M. Eileen Dolan
Journal: Journal of Clinical Oncology (2017)

e18162 Background: RP is an adverse drug reaction characterized by reduced blood flow to the extremities causing pain and sensations of cold. Few studies have examined the genetic basis for RP, although family studies suggest a heritable component to primary RP. Methods: Eligible testicular cancer survivors (TCS) were &lt; 55 y at diagnosis, treated with first line cisplatin-based chemotherapy, and completed questionnaires. Genotyping with standard quality control and imputation were performed. A case-control RP phenotype was derived from patient-reported outcomes and associations were computed by logistic regression. GWAS used cumulative bleomycin dose and 10 genetic principal components as covariates. Gene set enrichment analysis (GSEA) utilized genes ranked by the most significant GWAS SNP in/within 20 kilobases. A polygenic risk score for CVD derived from four prior independent GWAS (Khera et al. NEJM 2016) was assessed for association with RP. Results: Of 749 patients (median age 38 y, median time since chemotherapy 5 y), 38% reported RP. Bleomycin dose was the most significant predictor of RP (OR 100 mg/m 2 = 1.25, p &lt; 0.0001). Number of years smoking also correlated with RP (OR year = 1.05, p = 0.002). Age and hypertension showed no significant correlation with RP. GSEA revealed several significant pathways (FDR q &lt; 0.1), including “ cellular response to VEGF stimulus” (q = 0.05) and “ cardiac muscle cell action potential” (q = 0.09). We hypothesized that RP may share genetic architecture with CVD. Deriving a polygenic risk score from genome-wide significant SNPs in prior CVD GWAS (n = 4260-22,389), we showed nearly significant case-control differences in CVD polygenic risk score (two-tailed t-test, p = 0.053). RP frequency significantly increased with polygenic risk score quartile (OR = 1.19, p = 0.008). Conclusions: Over one third of TCS report RP, with greater frequency among bleomycin-treated patients and smokers. Implicated genetic pathways include ones established in CVD. Although shared genetic risk between chemotherapy-induced RP and CVD may be possible, further investigation is required. Primary RP has been inconsistently linked with CVD.
RhoA信号伝達阻害は内皮細胞内NO産生を促進し摘出ウサギ腸間膜動脈収縮を抑制する(Inhibition of RhoA signalling enhances NO production in endothelial cells and reduces contractility in the isolated rabbit mesenteric artery)
Authors: Hara K, Higashi Y, Umemura T, Jitsuiki D, Nishioka K, Kimura M, Noma K, Nakagawa K, Ooshima T
Journal: Circulation (2004)
Abstract 1769: The clinical outcome of stage I lung adenocarcinoma patients with or without activating EGFR mutation
Authors: Yueh-Fu Fang
Journal: Cancer Research (2017)

Abstract Purpose: Advanced stage lung adenocarcinoma patients with activating EGFR mutation have better survival result after EGFR tyrosine kinase inhibitor developed. The prevalence of EGFR mutation is high in Asian lung adenocarcinoma patients. The difference of clinical outcome of stage I lung adenocarcinoma patients with or without activating EGFR mutation was unclear. Our aim of study is to evaluate the clinical outcome between wild and mutated stage I lung adenocarcinoma. Patients and Methods: We had 343 Stage I lung adenocarcinoma patients who received surgical resection from January 2010 to April 2014. The preliminary data of EGFR mutation in 167 patients was done. Sanger method of direct PCR, scorpion &amp; ARMS method or ABI allele specific TagMan PCR were used to check the EGFR mutation status of these patients’ samples. The selection of these methods was depended on purity of tumor samples. Results: There were 93 stage IA patients and 74 stage IB patients. Sixty-four (69%) patients had activating EGFR mutations in stage IA patients, and fifty (68%) patients had activating EGFR mutations in stage IB patients. The survival of stage IA and IB were similar in patients with or without EGFR mutations. The patients without mutated EGFR had better progression free survival in IA and IB patients, especially in the IB patients, although the significance did not be reached in small preliminary sample size. Conclusion: The survival was similar in stage IA or IB lung adenocarcinoma with or without EGFR mutations. Patient without EGFR mutation had better progression free survival although there was no statistical significance between patients with or without EGFR mutations. We will collect more patients’ data for analysis. Citation Format: Yueh-Fu Fang. The clinical outcome of stage I lung adenocarcinoma patients with or without activating EGFR mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1769. doi:10.1158/1538-7445.AM2017-1769
Roger W. O'Gara, 1915–1971. An Appreciation
Authors: Harold L. Stewart, M.D.
Journal: JNCI Journal of the National Cancer Institute (1971)

Roger W. O'Gara, 1915–1971. An Appreciation Get access Harold L. Stewart, M.D. Harold L. Stewart, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 46, Issue 6, June 1971, Pages VI–X, https://doi.org/10.1093/jnci/46.6.VI Published: 01 June 1971
Abstract 518: Synergistic effects of dual inhibition of YAP1 and TAZ in non-small cell lung cancer cells
Authors: Elaine Shum, Huijie Liu, Liang Zhu, Roman Perez-Soler, Balazs Halmos, Haiying Cheng
Journal: Cancer Research (2017)

Abstract Background: The Hippo signaling pathway is associated with regulation of cell growth and apoptosis. Downstream effectors of this pathway, YAP and its paralog, TAZ, interact with TEA domain (TEAD) transcription factors leading to cell proliferation and anti-apoptosis. As a result, YAP and TAZ have emerged as attractive anti-cancer therapeutic targets. Several studies, including our previous report, have noted the individual effects of YAP or TAZ ablation; however, consequences of dual inhibition have not yet been investigated in lung cancer. We hypothesize that dual inhibition of YAP and TAZ will lead to more pronounced cytotoxicity than each knockdown alone as a result of diminished compensatory mechanism by the remaining family member. Methods: NSCLC cell lines, such as PC9 and A549, were transfected with individual YAP1, TAZ siRNA or a combination of both siRNAs. Western blotting was performed to determine the levels of YAP1 and TAZ proteins following knockdown. Quantitative RT-PCR was also performed to confirm effective YAP1 and TAZ knockdown. In addition, gene and protein expression of downstream targets, such as CTGF and Cyr61, were assessed. Clonogenic assays were performed to determine cell survival. Results: Successful siRNA-mediated YAP and TAZ ablation were confirmed with Western blot and qRT-PCR. The expression of the Hippo-YAP/TAZ downstream targets, CTGF, Cyr61 and AXL, were also reduced accordingly. Moreover, dual knockdown of YAP and TAZ led to a more pronounced inhibition of cell survival/proliferation than ablation of individual genes alone. In addition, dual inhibition of YAP/TAZ exhibited significantly diminished levels of the mesenchymal markers, vimentin and N-cadherin, and increased levels of the epithelial marker, E-cadherin. EMT has been recognized as an essential process during lung cancer tumor migration and metastasis. Conclusion: Our findings show that dual inhibition of YAP1 and TAZ are synergistic in blocking NSCLC cell survival signaling. Thus, dual inhibition may serve as a better therapeutic strategy in targeting the Hippo pathway than sole YAP1 blockade in the management of NSCLC. Citation Format: Elaine Shum, Huijie Liu, Liang Zhu, Roman Perez-Soler, Balazs Halmos, Haiying Cheng. Synergistic effects of dual inhibition of YAP1 and TAZ in non-small cell lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 518. doi:10.1158/1538-7445.AM2017-518