tbuckley/cabot-search huggingface dataset:
Abstract 4803: A novel class of phenylacrylonitrile-based small molecules selectively induce double-strand DNA damage in breast cancer cells
Authors: Jennette A. Sakoff, Jayne Gilbert, Geoff De Iuliis, Adam McCluskey
Journal: Cancer Research (2016)

Abstract We have discovered a class of phenylacrylonitrile-based small molecules that selectively target breast cancer cell lines while having little to no effect on normal breast cancer cells or on cell lines derived from other tumour types including colon, ovarian, lung, skin, prostate and pancreatic carcinomas, neuroblastoma and glioblastoma. Indeed these molecules show more than 200-fold selectivity towards breast cancer cells compared with other tumour types, while maintaining nM potency, as determined by the MTT growth inhibition (GI50) assay with GI50 values of 0.2-2.0μM (72h exposure). Moreover, the sensitive breast cancer cell lines represent tumour types from the four main breast cancer classifications including ER+ luminal A (MCF-7, T47-D and ZR-75-1 cells), ER+ luminal B (BT-474), HER2+ (SKBR-3), and most importantly the Basal (triple negative MDA-MB-468 and BT20) classification which traditionally carries a very poor prognosis. Our novel class of molecules also retain activity in MCF-7/VP16 cells (GI50 0.2μM) which overexpresses the drug resistance ABCC1 gene. Only one breast cancer cell line has shown insensitivity, MDA-MB-231 (Basal triple negative), which unlike all of the other breast cell types has amplifying mutations in KRas and BRaf activity, a genotype found in less than 5% of breast cancer tumours. Furthermore, our novel compounds induce minimal effects on the growth of normal MCF10A breast cells. Analysis of our most sensitive breast cancer cell line (MDA-MB-468) shows a significant increase in gammaH2AX within 12h of exposure to our lead phenylacrylonitrile molecule, indicative of DNA double strand breakage. This response is concomitant with an increase in the phosphorylation of the cell cycle check point activator CHK2. Cell cycle analysis shows an increase in the proportion of cells in the S-phase of the cell cycle within 24h of exposure, concomitant with a decrease in the proportion of cells in the G1-phase, and preceding an increase in the sub-G1 cell death population. The ability to specifically target breast tumours, while having little or no effect on normal breast cells, or other tumour types is a unique finding. Elucidating the mechanism controlling this phenomenon is now the focus of our research efforts. Citation Format: Jennette A. Sakoff, Jayne Gilbert, Geoff De Iuliis, Adam McCluskey. A novel class of phenylacrylonitrile-based small molecules selectively induce double-strand DNA damage in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4803.
Abstract 1875: Identification of LASEP3 as a serological and tissue biomarker and a therapeutic target for lung cancer
Authors: Atsushi Takano, Yusuke Nakamura, Yataro Daigo
Journal: Cancer Research (2016)

Abstract Lung cancer is the leading cause of cancer deaths worldwide. The prognosis of patients with lung cancer remains poor, because of its occult metastasis even at earlier stage of the disease and its resistance to conventional multimodal treatments. Therefore, this study aims to identify novel serum and tissue biomarkers for personalized therapy and/or therapeutic targets for lung cancers through screening and functional analyses of cancer-specific oncoproteins. We used cDNA microarrays for screening genes encoding transmembrane/secretory proteins that are up-regulated in lung cancers, and identified a secreted protein, LASEP3 (lung cancer-associated serum protein 3) as a candidate. Immunohistochemical staining of LASEP3 showed that LASEP3 expression was observed in 198 (54.8%) of 361 NSCLCs (non-small cell lung cancer) that had undergone curative surgery. High level of LASEP3 expression was associated with poor prognosis for NSCLC patients. (P = 0.0183 by log-rank test). Serum LASEP3 levels were higher in NSCLC patients than in healthy volunteers. The proportion of serum LASEP3-positive cases was 160 (61.8%) of 259 NSCLCs (49.4% for stage I-II, 67.4% for stage III-IV), while 6 (5.5%) of 109 healthy volunteers were falsely diagnosed. Moreover, reduction of LASEP3 expression by siRNAs suppressed lung cancer cell proliferation, probably through apoptosis as suggested by flow cytometric analysis and caspase-3 and 7 assays. Furthermore, subsequent microarray analysis of these cancer cells identified several candidate downstream genes of LASEP3 that relate to cell growth and invasion signals. LASEP3 is a possible diagnostic and prognostic biomarker and a therapeutic target for lung cancer. Citation Format: Atsushi Takano, Yusuke Nakamura, Yataro Daigo. Identification of LASEP3 as a serological and tissue biomarker and a therapeutic target for lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1875.
Platelet ADP Receptor P2Y12 Stabilizes Atherosclerosis Plaques by Regulating Alpha Granule Release and Inflammatory Cell Recruitment
Authors: Ding Li, Yanhua Wang, Kemin Wang, Lin Zhang, Weiran Chai, Yueping Sun, Changgeng Ruan, Guo-Qiang Chen, T. Kent Gartner, Junling Liu
Journal: Blood (2010)
Case 20-1968
Authors: Allan L. Friedlich, Jay P. Mohr, Benjamin Castleman
Journal: New England Journal of Medicine (1968)

Presentation of CaseA fifty-seven-year-old woman was admitted to the hospital because of pain in the chest.Two months before admission there was the onset of episodes of dyspnea and left precordial pressure pain that radiated down the inner aspect of the left arm; the distress was precipitated by exertion. Subsequently, she experienced a heavy sensation in the chest after exertion, associated with sweating. She had no palpitation, orthopnea, nocturnal dyspnea or ankle edema, but complained of a dry cough. On examination one month before admission the lungs were clear; the first and second heart sounds were split; no murmur . . .
Abstract 1323: Both programmed cell death protein 1 and programmed death-ligand 1 molecules can be expressed on the cell surface of small-cell lung cancer
Authors: Hiromichi Yamane, Hideko Isozaki, Nobuaki Ochi, Kenichiro Kudo, Yoshihiro Honda, Tomoko Yamagishi, Toshio Kubo, Katsuyuki Kiura, Nagio Takigawa
Journal: Cancer Research (2015)

Abstract Background: Programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) play a major role in suppressing the immune system by forming the PD-1/PD-L1 complex, which transmits an inhibitory signal to reduce T-cell activity. PD-L1 is often expressed in various malignant tumors. On the other hand, PD-1 is generally observed in activated lymphocytes and myeloid-derived dendritic cells. Of the malignant cells, only Jurkat cells (under special conditions) and angioimmunoblastic T-cell lymphoma tissue cells express PD-1 on their surface. Purpose: To clarify whether PD-1/PD-L1 complex participates in the immunotolerance on small-cell lung cancer (SCLC) cells. Materials and methods: We examined the expression levels of PD-1 and PD-L1 on the cell surface of SCLC cell lines using flowcytometry and reverse transcription polymerase chain reaction. Subsequently, the soluble PD-L1 (sPD-L1) concentration was measured using enzyme-linked immunosorbent assay, and the cell growth inhibitory effect of IFN-γ was determined by direct cell counting using a hemocytometer and Trypan blue staining. Results: Among the four SCLC cell lines examined, only SBC-3 cells expressed both PD-1 and PD-L1. The sPD-L1 concentrations in culture medium gradually increased according to cell growth. Although IFN-γ alone inhibited the growth of SBC-3 cells, PD-L1 expression on the cell surface was not induced by IFN-γ. Conclusions: We demonstrated that both PD-1 and PD-L1 molecules are co-expressed on the surface of SCLC cells. Although the biological implications of this remain unclear, we speculate that PD-1 and its ligand on the SCLC cells may participate in the growth inhibition of tumor cells as is reported in cytotoxic T cells. Citation Format: Hiromichi Yamane, Hideko Isozaki, Nobuaki Ochi, Kenichiro Kudo, Yoshihiro Honda, Tomoko Yamagishi, Toshio Kubo, Katsuyuki Kiura, Nagio Takigawa. Both programmed cell death protein 1 and programmed death-ligand 1 molecules can be expressed on the cell surface of small-cell lung cancer. [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 1323. doi:10.1158/1538-7445.AM2015-1323
Interest of Non-Myeloablative Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma: A Multicenter Retrospective Study.
Authors: Steven Le Gouill, Nikolaus Kroeger, Nathalie Dhedin, Arnon Nagler, Krimo Bouabdallah, Ibrahim Yakoub-Agha, Claude-Eric Bulabois, Agnes Buzyn, Bernard Rio, Marie-Pierre Moles, Avichai Shimoni, Thierry Guillaume, Noel Milpied, Lucie Planche, Jean-Luc Harousseau, Mohamad Mohty
Journal: Blood (2008)
Abstract 939: Cell-free DNA associated with extracellular vesicle: Biomarker or bioactivity
Authors: Ganesh V. Shelke, Su Chul Jang, Yanan Yin, Cecilia Lässer, Jan Lötvall
Journal: Cancer Research (2016)

Abstract Extracellular vesicles (EVs) including exosomes transfer bioactive cargo, including proteins and nucleic acids. Recently, EVs associated DNA were shown to be surrogate biomarker present in body fluids harboring various oncogenic mutations. Cell-free, extracellular DNA is reported in cell cultures and many body fluids, but its relative location in relation to EVs and function is not known. Our study demonstrates that DNase sensitive nucleic acids were present on the surface of EV isolates from mast cell lines. Association of EV-DNA was revealed by increase of zeta potential and particle number upon DNase treatment. Additionally, cytoplasmic DNA traces were found in recipient mesenchymal stem cell after EVs treatment. In conclusion, we define that surface association of DNA with EVs that could regulate recipient cellular function. Citation Format: Ganesh V. Shelke, Su Chul Jang, Yanan Yin, Cecilia Lässer, Jan Lötvall. Cell-free DNA associated with extracellular vesicle: Biomarker or bioactivity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 939.
Abstract 1065: Reduced expression of microRNA-200 family associated with aggressiveness and poorer patient outcome of clear cell renal cell carcinomas
Authors: Masahiro Gotoh, Eri Arai, Akio Matsuda, Hiroyuki Fujimoto, Kenji Matsumoto, Yae Kanai
Journal: Cancer Research (2016)

Abstract [Introduction] The aim of this study was to clarify the significance of alterations of microRNA (miRNA) expression during renal carcinogenesis. [Materials and methods] Expression profiles of miRNA were examined using the SurePrint G3 miRNA Expression microarray in paired samples of cancerous tissue (T) and non-cancerous renal cortex tissue (N) from 95 patients with clear cell renal cell carcinomas (RCCs). The expression levels of miRNA and mRNA were quantified by reverse transcription PCR (RT-PCR) using TaqMan system. The MetaCore pathway analysis by GeneGo was performed using miRNAs of which expression levels were significantly altered during renal carcinogenesis. [Results] The expression levels of 39 and 169 miRNAs were increased (T/N&amp;gt; = 2) and reduced (T/N&amp;lt;0.5) in T samples relative to the corresponding N samples, respectively. MetaCore pathway analysis revealed that such expression alterations of the 208 miRNAs were significantly accumulated in four pathways, which included “Development microRNA-dependent inhibition of epithelial-mesenchymal transition (EMT) pathway” (P = 8.695×10−15). The expression levels of any of 5 EMT-related miRNAs, i.e. miR-200a, miR-200c, miR-141, miR-429 and miR-200b, called as miR-200 family, were reduced in 93 (98%) of the examined 95 RCCs. Quantitative RT-PCR analysis verified that the expression levels of miR-200 family were significantly reduced in T samples relative to the corresponding N samples. Additionally, the mRNA expression levels of the ZEB1 and ZEB2 genes, which were downstream targets of miR-200 family, were significantly increased, and their target CDH1 gene expression was further decrease in T samples. The expression levels of miR-200 family in T samples were significantly correlated with clinicopathological parameters reflecting tumor aggressiveness, such as invasive macroscopic configuration, higher histological grade, vascular involvement, renal vein tumor thrombus, invasive growth pattern, tumor necrosis, distant metastasis and higher histological TNM stage. Moreover, the expression levels of miR-200 family were significantly correlated with both of cancer-free and overall survival rates of patients with clear cell RCCs. [Conclusions] These data suggested that reduced expression of miR-200 family may participate in the malignant progression resulting in poorer patient outcome of clear cell RCCs, via regulation of the EMT pathway. Citation Format: Masahiro Gotoh, Eri Arai, Akio Matsuda, Hiroyuki Fujimoto, Kenji Matsumoto, Yae Kanai. Reduced expression of microRNA-200 family associated with aggressiveness and poorer patient outcome of clear cell renal cell carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1065.
PTU-226 Prospective observational cohort study of laparoscopic versus open emergency stoma formation: Abstract PTU-226 Table 1
Authors: C Thomas, S Allan, D Harji, P Coyne, B Griffiths, S Plusa
Journal: Gut (2015)

<h3>Introduction</h3> Emergency general surgery is a huge clinical service, with over a third of admissions secondary to colorectal pathology, including diverticular disease, colorectal malignancy and inflammatory bowel disease. This cohort of patients often requires surgical intervention with the formation of a stoma. There has been a steady rise in the use of laparoscopic surgery (LS) in the emergency colorectal surgery. The aim of this study is to investigate the role of LS in the colorectal emergency requiring a stoma. <h3>Method</h3> A prospective observational cohort study was conducted between March 2013 and June 2014. All adult patients (&gt;18 years old) undergoing an emergency operation as defined by NCEPOD guidelines resulting in the formation of a stoma were included. Data was analysed using SPSS version 22. <h3>Results</h3> A total of 77 patients were identified, with 23 (29.9%) in LS group and 54 (70.1%) in the open surgery (OS) group. Conversion rate was 13%. Forty-two (54.5%) ileostomies and 35 (45.5%) colostomies were constructed. LS was associated with reduced morbidity and median length of stay. <h3>Conclusion</h3> Emergency LS is a feasible and effective option in the colorectal emergency requiring a stoma, with improved clinical outcomes over OS. <h3>Disclosure of interest</h3> None Declared.
Abstract 2181: Chemotherapeutic, chemomodulatory and vascular protective effects of naturally occurring hydroxyphenylalkanes and diarylheptanoids
Authors: Mohammed A. Baghdadi, Eman A. Al-Ghamdi, Abdulmohsin J. Alamoudi, Fahad A. Al-Abbasi, Hany M. El-Bassossy, Ali M. El-Halawany, Ahmed M. Al-Abd
Journal: Cancer Research (2016)

Abstract Hydroxyphenylalkanes and diarylheptanoids possess potential therapeutic values in different patho-physiological conditions such as inflammation, oxidative stress, cardiovascular disorders and malignancy. Doxorubicin is widely used chemotherapeutic agent against several types of neoplastic disorders. In the current study, naturally isolated hydroxyphenylalkane and diarylheptanoid compounds were investigated for their potential chemo-modulatory effects on the top of their potential vascular protective role with doxorubicin. Shogaol and 4-methoxygingerol showed considerable cytotoxic effects against HCT116, HeLa, HepG2 and MCF7 cells with IC50 ranging from 3.1 to 18.7 μM and from 9.1 to 19.4 μM, respectively. Using DPPH free radical scavenging assay, diarylheptanoids were stronger antioxidant than hydroxyphenylalkanes with EC50 ranging from 0.5 to 5.9 μM and from 4.6 to 9.5 μM, respectively. In addition, all tested diarylheptanoids significantly ameliorated CCl4 induced disturbed intracellular GSH/GSSG balance. Gingerol moderately enhanced the cytotoxic profile of doxorubicin against HepG2 and Huh7 cells decreasing their IC50's from 0.52 to 0.37 μM and from 50 to 30 nM, respectively. Combination index of gingerol with doxorubicin (combination at equitoxic ratio of 1/100) was indicative of additive interaction (CI-value were 1.1 and 1.0, respectively). To further investigate the interactive characteristics between doxorubicin and gingerol, cell cycle distribution of HepG2 and Huh7 cells was studied using DNA cytometry after exposure to their single and equitoxic combination. Doxorubicin induced cell accumulation at S-phase and G2/M-phase while, gingerol combination with doxorubicin significantly induced cell cycle arrest at G2/M-phase. To study the potential vascular protective effect of gingerol against doxorubicin induced vascular toxicity, doxorubicin (10 μM for 1h) was incubated with or without different concentrations of 6-gingerol (3, 10 and 30 μM for 1h) on isolated aortic rings and their response to phenylephrine (PE) and acetylcholine (ACh) was examined. Co-incubation of 6-gingerol (30 μM) completely blocked the exaggerated vasoconstriction and impaired vascular relaxation induced by doxorubicin Citation Format: Mohammed A. Baghdadi, Eman A. Al-Ghamdi, Abdulmohsin J. Alamoudi, Fahad A. Al-Abbasi, Hany M. El-Bassossy, Ali M. El-Halawany, Ahmed M. Al-Abd. Chemotherapeutic, chemomodulatory and vascular protective effects of naturally occurring hydroxyphenylalkanes and diarylheptanoids. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2181.
Persistence of cytotoxic T lymphocyte reactivity against donor antigens is a prognostic marker for chronic rejection after liver transplantation.
Authors: van den Arie Berg, de Aalzen Haan, BG Hepkema, E Van Dijk, IJ Klompmaker, SP Lems, EB Haagsma, MJ Slooff, de Louis Leij
Journal: Hepatology (1999)
Abstract 3321: PUMA expression targets αvβ3/Slug+ “stem-like” tumor cells to prevent breast cancer progression independent of subtype
Authors: Qi Sun, Jacqueline Lesperance, Jay S. Desgrosellier
Journal: Cancer Research (2016)

Abstract Breast cancer cells bearing similarities to normal mammary stem cells represent some of the most aggressive tumors cells. Here, we show that αvβ3/Slug+ “stem-like” tumor cells are highly vulnerable to cell death induced by PUMA (p53-upregulated modulator of apoptosis). In human breast cancers, we were surprised to find that αvβ3/Slug+ cells represent a unique subset of tumor cells associated with progression that are present in all major histological subtypes. Analysis of “stem-like” cell lines showed that αvβ3 directs an EMT-independent role for Slug in suppressing PUMA expression and promoting tumor cell survival and stemness. In fact, αvβ3 is both necessary and sufficient for PUMA suppression and PUMA knockdown specifically rescued defective colony formation and tumor initiation caused by decreased β3 expression. Inducing PUMA expression with specific therapies selectively ablated αvβ3/Slug+ cells, preventing the formation of new colonies or tumors, with no effect on established disease. These new findings define an unexpected role for αvβ3/Slug-mediated PUMA suppression in driving stemness and suggest that inducing PUMA with specific therapies can selectively target “stem-like” breast cancer cells to prevent aggressive disease. Citation Format: Qi Sun, Jacqueline Lesperance, Jay S. Desgrosellier. PUMA expression targets αvβ3/Slug+ “stem-like” tumor cells to prevent breast cancer progression independent of subtype. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3321.
Comparison between Two Reduced-Intensity Conditioning Regimens Prior to Allogeneic Stem Cell Transplantation: Fludarabine and Melphalan Is Associated with Higher Incidence of Acute Graft-Versus-Host Disease and Non-Relapse Mortality and Lower Incidence of Relapse Than Fludarabine and Busulfan.
Authors: Avichai Shimoni, Izhar Hardan, Noga Shem-Tov, Ronit Yerushalmi, Michal Bar-Natan, Friderikos Tsolakis, Arnon Nagler
Journal: Blood (2006)
An interesting encounter: Did I teach him survival skills and healthcare priorities?
Authors: K. Weerasuriya
Journal: BMJ (1998)

There is a paraplegic—I wonder what the aetiology is—who, seated on the ground with his crutches next to him, asks for donations at the entrance to the supermarket. He is a pleasant man and always has a smile despite his disabilities. As a member of the middle class in an Asian society and a healthcare …
Radiologic Notes in Cardiology
Authors: MURRAY G. BARON
Journal: Circulation (1971)

Obscuration of the superior margin of the aortic knob together with a widening of the mediastinal shadow to the left is a common sign of coarctation of the aorta. It is easily seen on the routine frontal chest film and may be the first detected evidence of the lesion. Although the appearance is not pathognomonic of a coarctation, it certainly indicates the need for further studies.
Abstract 1156: Downregulation of glycine decarboxylase contributes to paclitaxel resistance in ovarian cancer cells
Authors: Jin Young Kim, Sojin Shin, Eunyoung HA, Soondo Cha, Chi-Heum Cho
Journal: Cancer Research (2016)

Abstract Glycine decarboxylase (GLDC) is a metabolic oncogene that links glycine metabolism with tumorigenesis. In humans, GLDC is part of a multienzyme complex that couples the decarboxylation of glycine to the biosynthesis of serine. The role of GLDC in relation to chemoresistance is unclear. We designed this study to determine the role of GLDC in chemoresistance in ovarian cancer cells. First, we found GLDC is downregulated in paclitaxel resistant ovarian cancer cells (OVCAR3/PTX). Prompted by decreased glucose transport in OVCAR3/PTX cells, we transplanted OVCAR3 and OVCAR3/PTX onto the back of the NOD-scid IL2Rgammanull mice and found that the OVCAR3/PTX tumor grew less rapidly than paclitaxel sensitive ovarian cancer cells (OVCAR3). We also found that GLDC is downregulated in OVCAR3/PTX tumor. In vitro study revealed that the inhibitory effect of siGLDC on proliferation was significantly greater in OVCAR3 than in OVCAR3/PTX. We also found that knockdown of GLDC in OVCAR3 cells rendered ovarian cancer cells PTX-resistant. Finally, we determined GLDC expressions in patients with chemosensitive and chemoresistant serous type ovarian cancer and found that GLDC expression was markedly downregulated in chemoresistant cancer patients. These results suggest GLDC is associated with ovarian cancer chemoresistance. Citation Format: Jin Young Kim, Sojin Shin, Eunyoung HA, Soondo Cha, Chi-Heum Cho. Downregulation of glycine decarboxylase contributes to paclitaxel resistance in ovarian cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1156.