tbuckley/cabot-search huggingface dataset:
Abstract 2582: In vitro effects of 4-OXO-docosahexaenoic ester on cell signaling in molecular subtypes of human breast cancer cell lines.
Authors: Henry J. Thompson, Weiqin Jiang, Zongjian Zhu, John P. Vanden Heuvel, Shantu Amin, Krishne Gowda, Andrea Manni, Karam El-Bayoumy
Journal: Cancer Research (2013)

Abstract In vivo preclinical evidence of a heterogeneous effect of n-3 fatty acids (N3FA) on cell signaling pathways associated with the reduced growth of mammary carcinomas (Cancer Res. 2012 Aug 1;72(15):3795-806) is consistent with the expectation that N3FA will not exert uniform effects on all molecular subtypes of breast cancer. Similarly, available evidence indicates that specific metabolites of N3FA are synthesized by mammalian cells and that they exert metabolite specific biological activities. To begin to unravel the complex relationships among molecular subtype specific cell signaling and effects exerted by specific N3FA metabolites on those pathways, a series of proof-in-concept experiments were conducted using cell lines representing 5 molecular subtypes of human breast cancer (BT-474, MCF-7, SKBR-3, MDA-MB-231, MDA-MB-468) and 4-oxo-docosahexaenoic keto ester (4-oxo-DHA), a putative metabolite of docosahexaneoic acid (DHA) that has superior activity to that of DHA in inducing PPARγ activation in vitro. 4-oxo-DHA induced dose dependent inhibition of cell number accumulation of all molecular subtypes but the dose and time responses varied markedly with MCF-7 cells being the least affected and MDA-MB-468 being inhibited to the greatest extent. Detailed mechanistic studies in BT-474, SKBR-3, and MDAMB-463 revealed subtype specific patterns of cell cycle inhibition and apoptosis induction with apoptosis induction dominating in BT-474 and SKBR-3 and inhibition of cell proliferation and apoptosis induction accounting for growth inhibition of MDA-MB-468. While some molecular subtypes were inhibited by mechanisms involving PPARγ activation, others underwent cell growth inhibition via modulation of multiple regulatory nodes in the mTOR signaling network. Evidence is consistent with differential sensitivity among cell types based on whether they are basal or luminal in origin. The experiments described offer a useful complementary approach to the in vivo experiments needed to resolve the N3FA-breast cancer conundrum. This work was supported by grant KG081632 from the Susan G. Komen Foundation. Citation Format: Henry J. Thompson, Weiqin Jiang, Zongjian Zhu, John P. Vanden Heuvel, Shantu Amin, Krishne Gowda, Andrea Manni, Karam El-Bayoumy. In vitro effects of 4-OXO-docosahexaenoic ester on cell signaling in molecular subtypes of human breast cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2582. doi:10.1158/1538-7445.AM2013-2582
Reply to Bohle and Zoller
Authors: A. Kutup
Journal: Endoscopy (2012)

We appreciate Bohle and Zoller’s well-advised comments on our paper “Endoscopic ultrasound in gastric cancer: does it help management decisions in the era of neoadjuvant treatment?” [1]. Bohle and Zoller express concerns regarding the poor results of N staging. The use of endoscopic ultrasonography (EUS) findings to distinguish between benign and malignant lymph nodes is still controversial, and the accuracy of EUS in staging gastric cancers varies in reports alongside concerns that EUS over-stages nodal invasion because of inflammation around the tumor or in the lymph nodes [2] [3].
Abstract 4037: Downregulation of ZNF516 and INTS1 is related with promoter methylation in cervical uterine cancer cell lines
Authors: Carmen G. Ili, Priscilla Brebi, Alejandra Andana, Pamela Leal, Patricia Garcia, Rafael Guerrero-Preston, Juan C. Roa
Journal: Cancer Research (2012)

Abstract Introduction: One of the most common neoplasia in developing countries is cervical uterine carcinoma (CC). HPV infection is recognized as the major risk factor for carcinogenesis of cervix. However, not all infected women will develop a cervical cancer. Several studies have proposed DNA methylation as early biomarker in CC. A higher promoter methylation is associated with lower gene expression. Aim: To evaluate the association between DNA methylation and gene expression of ZNF516 and INTS1 in cervical cancer cell lines. Materials and Methods: DNA isolated from 12 normal and 7 cervical cancer tissue samples was enriched by Methylated DNA Immunoprecipitation (MeDIP) and hybridized to Nimblegen 385K CpG Islands plus Promoter arrays (MeDIP-chip). Bioinformatics strategies were used for background correction, array normalization and data analysis of differentially methylated genomic regions by Methylation Specific PCR in a cohort of 221 normal, premalignant, and cervical cancer samples. Relative expression analysis was performed in a normal cervical epithelium cell line (ECT1 E6/E7) and three cervical cancer cell lines (C-4I, SiHa and C-33A) using real time PCR. MSP was also used to examine promoter methylation in normal cervical and cervical cancer cells lines. Results: ZNF516 and INTS1 were differential methylated in the promoter region of normal and cervical cancer samples in the MeDIP-chip discovery project. The methylation frequency was 100% in cervical cancer cell lines. Relative expression of ZNF516 was significantly lower in C-4I and SiHa (p &amp;lt;0.05) in relation with the normal cell line. C-33A showed elevated promoter methylation and a low expression of ZNF516, however, this result was not significant. INTS1 expression was significantly lower in C-33A and SiHa (p &amp;lt;0.05) in relation with the normal cell line. C-4I showed a high promoter methylation and a low expression of INTS1, however, this result was not significant. Conclusions: We have identified ZNF516 and INTS1 as potentials biomarkers for cervical cancer. These genes may be a useful tool for diagnosis and clinical management of cervical cancer. These results need to be confirmed in clinical samples, from an independent laboratory before the gene panel is examined in a Phase II Biomarker Development Trial. Work sponsored by CORFO Project 09CN14-5960 and Postdoctoral Fondecyt Research Project 3120141. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4037. doi:1538-7445.AM2012-4037
Argonaute 2-dependent Regulation of Gene Expression by Single-stranded miRNA Mimics
Authors: Masayuki Matsui, Thazha P Prakash, David R Corey
Journal: Molecular Therapy (2016)

MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development. MicroRNAs (miRNAs) are small noncoding transcripts that regulate gene expression. Aberrant expression of miRNAs can affect development of cancer and other diseases. Synthetic miRNA mimics can modulate gene expression and offer an approach to therapy. Inside cells, mature miRNAs are produced as double-stranded RNAs and miRNA mimics typically retain both strands. This need for two strands has the potential to complicate drug development. Recently, synthetic chemically modified single-stranded silencing RNAs (ss-siRNA) have been shown to function through the RNAi pathway to induce gene silencing in cell culture and animals. Here, we test the hypothesis that single-stranded miRNA (ss-miRNA) can also mimic the function of miRNAs. We show that ss-miRNAs can act as miRNA mimics to silence the expression of target genes. Gene silencing requires expression of argonaute 2 (AGO2) protein and involves recruitment of AGO2 to the target transcripts. Chemically modified ss-miRNAs function effectively inside cells through endogenous RNAi pathways and broaden the options for miRNA-based oligonucleotide drug development.
Abstract P6-02-07: In vitro 3D Model of Breast Tumor Stroma
Authors: H Jaganathan, S Mitra, B Dave, B Godin
Journal: Cancer Research (2012)

Abstract One in eight women is diagnosed with breast cancer in the United States every year. Despite advancements for early diagnosis and initial treatment of breast cancer, the complexity and multiplicity of biological factors and barriers in tumor microenvironment prevent potent active agents from reaching their targets in cancer cells. There has been a growing body of evidence about the importance of three-dimensional (3D) culture systems in discovery and modeling of biological processes with in vivo relevance. A few examples that have been reported in 3D monocultures include different growth patterns of normal and malignant breast cancer cells in 3D cultures of laminin-rich gels and effect on cell polarity pathways. These effects are not observed in conventional two-dimensional (2D) cultures, showing that cells organized in a 3D matrix can shed light on novel mechanisms in breast cancer biology. Moreover, neither 2D nor 3D monoculture models available today mimic the complexity of clinically observed tumor microenvironment (tumor stroma), which also contains fibroblasts, macrophages and endothelial cells and represents an important physiological barrier for efficient delivery of therapeutics to breast tumors. In this work we propose and investigate an in vitro system mimicking the tumor microenvironment in which relevant cell populations in tumor microenvironment are co-cultured with breast cancer cells*. The system uses the Nano3D® platform based on magnetic levitation. 3D tumor models for breast cancer were designed and optimized by co-culturing SUM159 and MDA-MB-231, triple negative breast cancer cells, with 293T fibroblasts. The cells were co-cultured at different ratios and for a various time periods. Further, to assess the similarity of the in vitro system to the in vivo disease, we tested an an orthotopic model of breast cancer in SCID beige mice. Histological analysis of frozen tissues from in vitro and in vivo studies confirmed that the in vitro 3D system based on the mixture of fibroblasts and cancer cells has structural similarities to the in vivo observed tumor stroma. Engineering an in vitro 3D tumor model that accurately represents the in vivo tumor will further benefit research efforts in breast cancer diagnosis and therapy. *Patent pending – inventors: B. Godin, G. Souza, and B. Dave Acknowledgments: The authors acknowledge a financial support from the Susan G. Komen Postdoctoral Fellowship #PDF12229449. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-02-07.
The Clinical Importance of Coagulase-Positive, Penicillin-Resistant<i>Staphylococcus aureus</i>
Authors: Paul M. Beigelman, Lowell A. Rantz
Journal: New England Journal of Medicine (1950)

PENICILLIN-resistant Staphylococcus aureus has been isolated with increasing frequency since the introduction of this agent in 1941. Rammelkamp and Maxon1 tested 29 strains of Staph. aureus in 1942. All were inhibited by low concentrations of penicillin on initial isolation, but resistant organisms appeared in 4 cases after the administration of the drug. During 1943, Spink and his associates2 reported 12 per cent of 68, and Rantz and Kirby3 26 per cent of 43 strains to be penicillin resistant. Kirby4 recovered similar organisms from 7 patients, none of whom had received penicillin.Gallardo,5 in 1944, tested 85 strains of coagulase-positive Staph. . . .
Abstract 3680: Drug screening for glioblastoma patients
Authors: Pengfei Jiang, Rajesh Mukthavaram, IlaSri Summitt, Ying Chao, Matthew Gallagher, Ryan Kim, Sandra Pastorino, Santosh Kesari
Journal: Cancer Research (2012)

Abstract The modest benefits of chemotherapy for Glioblastoma (GBM) patients’ makes it urgent to find potent drugs or combinations that can inhibitor tumor cell growth and proliferation. We have devised drug screening based on the NIH clinical collection compounds. This collection included 446 compounds that all have history of use in human clinical trials. The positive compounds can be rapidly entered into clinical trials for GBM. After found 22 drugs/compounds that can inhibit U87 cell proliferation and we tested 15 available positive drugs with A172, LN443, U118 cell line. After confirming in established serum-grown cell lines, we tested 8 FDA approved drugs in GBM primary cells with stem cell like features isolated from fresh brain tumor tissue samples and cultured in stem cell media. The various drug responses amongst the different patients’ primary cells suggested that we may be able to personalize drugs to optimize outcomes. In addition, we found that certain combinations of FDA approved drug had significantly enhanced activity against GBM cells in vitro when compared to the same agents used alone. Our work reveals that screening drugs and combinations for GBM patient may have clinical implications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3680. doi:1538-7445.AM2012-3680
Abstract 5084: Treadmill exercise modulates AMP-activated protein kinase and downstream signaling in mammary gland of p53+/−, but not p53+/+ mice
Authors: Karrie E. Wheatley, Leticia M. Nogueira, Susan N. Perkins, Stephen D. Hursting
Journal: Cancer Research (2010)

Abstract Epidemiological data show that exercise is generally protective against breast cancer. Inhibition of mammalian target of rapamyocin (mTOR) through activation of AMP-activated protein kinase (AMPK) has been shown to be responsive to exercise. Decreased activation of ribosomal protein S6, a marker for mTOR inhibition, is associated with decreased growth and proliferation. Recently, this energy-sensing pathway has been shown to be inhibited by increased production of reactive oxygen species (ROS) leading to AMPK activation. ROS levels are maintained by p53-inducible anti-oxidant enzymes. Therefore, we hypothesized that energy sensing pathways that mediate the protective effects of exercise in breast cancer are modulated by p53 gene dosage. To test this hypothesis, we fed ovariectomized mice a high-fat diet (60% kcal) ad libitum for 10 weeks to model post-menopausal obesity. Mice were then randomized to a sedentary or exercise regimen (n=15/group). Exercised mice ran on a variable speed treadmill (5% incline, 20 m/min, 40 min/day, 5 days/week for 22 weeks). Changes in percent body fat were measured every 2 weeks using quantitative magnetic resonance. Immunoblot analysis was performed to measure phosphorylation of AMPK (Thr 172) and ribosomal protein S6 (Ser 240/244) relative to total levels in the mammary fat pad (MFP). Also, qRT-PCR was performed to measure mRNA expression of the p53-inducible anti-oxidant enzyme sestrin 1. At the end of the diet-induced obesity regimen, there was no effect of p53 genotype on percent body fat (54.4 ± 0.7 in p53+/+ versus 55.9 ± 1.1 in p53+/−). After 22 weeks of exercise, the EX mice displayed signficantly less percent body fat than sedentary controls, with no effect of genotype (44.4 ± 0.6 versus 47.8 ± 0.8 % respectively, p&amp;lt;0.05). Immunoblot analysis revealed that in p53+/− mice, but not p53+/+ mice, exercise increased AMPK phosphorylation. This increased AMPK phosphorylation was associated with decreased phosphorylation of ribosomal protein S6, a marker of mTOR pathway activation (n=3/group). The observed increase in AMPK phosphorylation in p53+/− exercised mice relative to sedentary p53+/− was associated with decreased mRNA levels of sestrin 1 (n=4-6/group), indicating that the p53+/− mice may have higher levels of ROS in the MFP. In conclusion, exercise may increase AMPK activation in MFP of p53+/− mice relative to sedentary p53+/− mice through an ROS-mediated mechanism. Current analysis is focused on understanding how exercise affects AMPK activation in the mammary fat pad of MMTV-Wnt-1 transgenic mice heterozygous for p53, and how this impacts mammary tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5084.
P103 Cardiopulmonary Exercise Testing In COPD: Cycle Ergometry or Treadmill Which is Better?
Authors: Mir Shad Ali, S Joshi, Mandeep Singh, AS Sandhya, D Talwar
Journal: Thorax (2012)

<h3>Introduction/Objectives</h3> Traditionally Cycle Ergometry is used for CPET to assess functional exercise capacity in COPD. However, walking is closely related to daily functional needs of COPD patients. The aim of this study was to evaluate the efficacy and tolerance of Naughton’s treadmill protocol over Cycle Ergometry in COPD patients during maximal CPET. <h3>Result</h3> All patients were able to complete the treadmill protocol in CPET, while on the Cycle Ergometry test it was symptom limited. The mean age was 58.0 + 10.1 years with mean FEV1% of 56.11+ 26.2%. VE, HR, VE/VCO2, VE/VO2, VD/VT and PETCO2 at the end of the exercise during treadmill and Cycle Ergometry were not statistically different. Hence all variables e.g. VO2 peak, VO2% predicted, duration of exercise and VO2 at LT were comparable. The VO2 Peak during treadmill was significantly higher during treadmill as compared to Cycle Ergometry (1347.5+308 ml/min vs. 1089.9+277.9 ml/min respectively; p=0.013). The duration of exercise was also significantly more during treadmill as compared to cycle ergometer (12.6+3.8 min. vs. 8.3+3.12 min. respectively p=0.002; p=0.68) although there was no significant difference in VO2 at LT (41.3 + 14.1% during treadmill vs. 33.4 + 10.6% during cycle ergometry; p-value- 0.087). <h3>Conclusion</h3> Patients performing CPET on treadmill as compared to Cycle Ergometry showed increase exercise capacity. Hence in Indian COPD subjects treadmill CPET may be better for functional assessment.
OP0060 Underinvestigated Mechanisms of Chronic Pain in Knee Osteoarthritis
Authors: E. Turovskaya, L. Alekseeva, E. Filatova
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In recent studies was shown that chronic pain in knee osteoarthritis (OA) has multicomponent mechanism. Besides degenerative changes of the knee, neuroplastic changes of CNS play a leading role in sustaining pain in chronic status. <h3>Objectives</h3> To evaluate the role of CNS in pathogenesis of chronic pain syndrome in knee osteoarthritis (OA). <h3>Methods</h3> 62 women (middle age 59±5) OA with chronic knee pain (duration more than 3 months)passed through WOMAC, X-ray and US of the knee. Duration of knee symptoms, and pain intensity were taken into consideration. Neurological examination with detailed analysis of pain sensitivity, as well as qualitative analysis of neuropathic transcripts with the help of neuropathic pain scales (Paindetect and DN4) were performed. We used the prevalence of anxiety and depressive disorders in population with OA, examined the interrelationships between severity of pain and emotional disturbances by Hospital Anxiety and Depression scale. <h3>Results</h3> According to the results of DN4 32% (n=20) pt with OA had DN4 score≥4 - neuropatic components of pain compared with 68% (n=42) who had only nociceptive mechanism of pain. Neurologic examination revealed 56%, (n=35) with referred hyperalgesia (not only knee localization (primary hyperalgesia) but also hip and shank localization) and 44%, (n=27) had primary hyperalgesia. No other somatosensory defects were found. The presence of referred hyperalgesia correlated with higher pain intensity (VAS), poor WOMAC and significantly associated with higher level of depression, poor quality of life.No significant differences between groups were seen in age, body index, duration of knee OA and level of structural changes. <h3>Conclusions</h3> Chronic OA is a mixture of pain mechanisms: nociceptive and dysfunctional pain. The presence of signs of NP and referred hyperalgesia, that spreads beyond impacted joint, may be qualified as clinical features of central sensitization.The degree of spreading sensitization is correlated with the level of clinical pain and does not correlate with structural changes. The central sensitization of pain neurons of spinal chord take place in sustaining chronic pain and demonstrates the important role of these dysfunctional changes of CNS of chronic pain mechanisms in knee osteoarthritis (OA). So rational treatment should also target structures of central nervous system. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3801
Abstract 3306: Traditional Chinese Medicine (TCM) enhances efficacy and reduces toxicity of tumor-targeting <i>S. typhimurium</i> A1-R in a syngeneic breast cancer metastatic mouse model.
Authors: Yong Zhang, Nan Zhang, Shibing Su, Robert M. Hoffman, Ming Zhao
Journal: Cancer Research (2013)

Abstract We have previously developed a bacterial cancer therapy strategy using the genetically-engineered strain, Salmonella typhimurium A1-R (A1-R). A1-R has been shown to be effective against metastatic human prostate, breast, and pancreatic cancer cell lines as well as osteosarcoma, fibrosarcoma, and glioma cell lines in nude mouse models. In the current study, we have evaluated Traditional Chinese Medicine (TCM) (Huang Zi, Mai Men Dong, Mu Dan Pi, Sheng Di Huang) in combination with A1-R bacterial therapy in a syngeneic orthotropic model of 4T1 mouse breast cancer. TCM treatment improved the host's ability to clear bacteria from the liver and spleen and prevent body weight loss after bacterial infection. Fur discoloration and reduced activity was also observed in mice treated with A1-R only, but ameliorated when bacterial treatment was combined with TCM. The combination of TCM and A1-R enabled S. typhimurium to be safely administered at a dose of 1×107 CFU once a week i.v. for a long period of time in immunocompetent mice. Efficacy and survival were increased by combination treatment compared to monotherapy with A1-R (1 × 107CFU) . The results of the present study suggest that TCM potentiates A1-R cancer therapy. Citation Format: Yong Zhang, Nan Zhang, Shibing Su, Robert M. Hoffman, Ming Zhao. Traditional Chinese Medicine (TCM) enhances efficacy and reduces toxicity of tumor-targeting S. typhimurium A1-R in a syngeneic breast cancer metastatic mouse model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3306. doi:10.1158/1538-7445.AM2013-3306