tbuckley/cabot-search huggingface dataset:
P3-01-07: A Murine Xenograft Model for the Study of Ciclooxygenase-2 Expression and Function in Human Breast Cancer.
Authors: AR Solano, UD Orlando, J Garona, GV Ripoli, AB Duarte, PM Maloberti, MA Avagnina, DF Alonso, DE Gomez, EJ Podesta
Journal: Cancer Research (2011)

Abstract BACKGROUND: ciclooxygenase-2 (COX-2) has been suggested as a necessary component of the cellular and molecular mechanisms behind breast cancer cell motility and invasion The potential therapeutic benefit of COX-2 inhibitors in a range of cancers is being seen as a great promise however, there have been recent concerns about potential cardiotoxicity. Thus, there is an urgency to develop new inhibitors exhibiting a better risk/benefit ratio. Acyl-CoA synthetase 4 (ACSL4), belongs to a five-member familyof enzymes that esterifies mainly arachidonic acid into acyl-CoA. We have provided first-time evidence demonstrating that, ACSL4 is the key enzyme that regulates the induction of COX-2, the production of prostaglandin E2 (PGE2) and the proliferation and metastatic potential of breast cancer cells. Therefore, the aim of the study was the development of an in vivo model of human breast tumor xenografts for the study of the regulation of COX-2 expression and action. RESULTS: stable transfection of MCF-7 cells with ACSL4 cDNA under the control of tetracycline (MCF-7 Tet-off-ACSL4) resulted in a significant increase in the expression of COX-2. The increment in COX-2 expression registered in MCF-7 Tet-off-ACSL4 cells is accompanied with an increase in the production of PGE2, and the proliferation and metastatic potential of cancer cells. Next, we tested whether the injection of MCF-7 Tet-off/ACSL4 cells into nude mice resulted in tumor development. The results of those experiments demonstrate that MCF-7 Tet-off/ACSL4 cells develop into murine mammary tumors whereas cells transfected with the MCF-7 Tet-off empty vector did not. Interestingly, treatment of nude mice with tetracycline resulted in tumor growth inhibition. The results show that the sole transfection of ACSL4 results in a phenotype change that endows the cells with the capacity to develop into tumors when injected into nude mice. Tumor volume (TV) at day 70 reached 468.4 ± 189.3mm3. Treatment with tetracycline reduced TV to 189.3 ± 65.9mm3 (p&amp;lt;0.05). The growth rate between days 45–70 was 12.30 mm3/day. Tumors were classified as Basal-like subtypes. We have also observed an inhibition of proliferation and migration of MDA-MB-231 cell cultures when exposed to a combination of ACSL4 and COX-2 inhibitors. Interestingly, the compounds assayed markedly reduced cell proliferation and migration at concentrations that are less effective when used alone. These results point to an effect that has the advantage of exposing the cells to lower drug concentrations. CONCLUSION: Based on our results, we hypothesize that ACSL4 and COX-2 could constitute potential therapeutic targets for the control of tumor growth. Our animal model of mammary tumors constitutes a proper platform for the study of those therapies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-07.
The incidence of bacteremia after EUS-FNA and potential interventions
Authors: Na Li, Hongmin Qi, Siyu Sun, Nan Ge, Zhijun Liu
Journal: Endoscopy (2011)

Bacteremia might occur after EUS-FNA. Povidone-iodine solution disinfection by washing gastrointestinal mucosa might reduce the incidence. PPI taken increase the PH valve of the gastric acid might decrease the bacteriostasis of gastric acid, which might increase the incidence.
Peers vote to legislate against smoking in cars with children
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Labour and cross bench peers defeated the UK government by 25 votes on 29 January and passed an amendment to the Children and Families Bill that would ban smoking in cars when a child is present.

Labour proposed the amendment, and there is expected to be a free vote on the measure in the House of Commons in February. Under the plan a breach of the law would carry a £60 (€73; $99) fine.

The Labour peer Philip Hunt told the House of Lords that it was right for parliament to take action to protect children. He said that children …
Abstract 3021: Mechanistic insight into MIG6 phosphorylation-mediated inhibitory effect on active EGFR.
Authors: Kihong Kim, Yi Zhang, Kyusam Choi, Ingu Do, Matthew Meyerson, Jeonghee Cho
Journal: Cancer Research (2013)

Abstract Genomic alteration of Epidermal Growth Factor Receptor (EGFR) plays a crucial role in pathogenesis of various types of cancer. By a systematic quantitative phosphoproteomic approach (iTRAQ), we found that tyrosine phosphorylation occurs within segment 2 of MIG6, a negative feedback regulator of EGFR, in the cells transformed by lung-cancer derived EGFR mutants. We further confirmed this MIG6 phosphorylation is directly induced by activated EGFR by in vitro kinase assay with purified proteins followed by immunoblotting with phospho-specific antibody. Importantly, we also found that MIG6 phosphorylation seems to play a crucial role in its inhibitory role of EGFR activation. While wild-type MIG6 was able to completely inhibit the enzymatic activation of oncogenic mutant EGFR and subsequent cellular transformation, phosphorylation defective MIG6 mutants were unable to exert the same effects. Moreover, consistent with its functional role, we found that phosphorylation defective MIG6 failed to interact with mutant EGFR by co-immunoprecipitation assay, suggesting that the phosphorylation on MIG6 is required for interaction between MIG6 and EGFR. Taken together, we propose a working model that phosphorylation on segment 2 of MIG6 is directly induced by active EGFR, promoting tight interaction of MIG6 segment 2 and EGFR active site and subsequently blocking the enzymatic activity of EGFR. Citation Format: Kihong Kim, Yi Zhang, Kyusam Choi, Ingu Do, Matthew Meyerson, Jeonghee Cho. Mechanistic insight into MIG6 phosphorylation-mediated inhibitory effect on active EGFR. [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 3021. doi:10.1158/1538-7445.AM2013-3021
Spontaneous Regression of Hepatic Pseudotumor Demonstrated By Ga-67 Imaging
Authors: TON-HO YOUNG, YOU-CHEN CHAO, HUNG-SHANG TANG
Journal: Clinical Nuclear Medicine (1998)

A 27-year-old man with a history of primary malignant lymphoma of the spine received radiotherapy and chemotherapy and had a complete remission. Ga-67 scintigraphy performed 8 months after chemotherapy showed intense accumulation in a liver mass. Aspiration biopsy showed that the liver mass was an inflammatory pseudotumor. Repeat Ga-67 scintigraphy 10 months later showed no abnormal uptake. The hepatic pseudotumor showed spontaneous regression.
A Role for Hepatitis C Virus Infection in Type II Cryoglobulinemia
Authors: Vincent Agnello, Raymond T. Chung, Lee M. Kaplan
Journal: New England Journal of Medicine (1992)

Type II cryoglobulinemia is a vasculitis characterized by cryoglobulins consisting of complexes of polyclonal IgG and monoclonal IgM rheumatoid factors, the cause of these immune complexes is unknown, though both the hepatitis B (HBV) and C (HCV) viruses have been suspected.
Abstract 1453: The cannabinoid Win55, 212-2 enhances the response of breast cancer cells to radiation
Authors: Sean M. Emery, Evan T. Sumner, Aron H. Lichtman, David A. Gewirtz
Journal: Cancer Research (2012)

Abstract Win55, 212-2 (Win2) is a full efficacy agonist for the endocannabinoid system, which is the target of Δ9-tetrahydrocannabinol (THC), the psychoactive compound in marijuana. Cannabinoids have demonstrated antiproliferative actions in many preclinical cancer models both in vitro and in vivo. The current studies were performed in the MCF-7, MDA-MB-231, or 4T1 breast cancer cell lines. Trypan blue exclusion was utilized as a measure of cell viability. Flow cytometry with propidium iodide was used for cell cycle analysis, while apoptosis and necrosis were assessed by Annexin V/PI staining. Win2, at concentrations of 4, 8 and 12μM, enhanced the antiproliferative effects of ionizing radiation (2, 4 and 8 Gy doses) in MCF-7 cells. The combination of Win2 and IR was also shown to be effective in MDA-MB-231 and 4T1 cells. This interaction was confirmed in vivo in 4T1 cells using 5mg/kg Win2 administered twice weekly in combination with one 10Gy dose of radiation. Win2 (8μM) for 24 hrs and 1 x 2Gy radiation was used for all subsequent experiments (Win/IR). Interestingly, neither THC nor the non-psychoactive cannabinoid, Cannabidiol, enhanced the response to radiation in MCF-7 cells, suggesting a possible drug-class specific effect. A time course study using Win/IR in MCF-7 cells suggested that Win2 and IR each alone induced growth arrest while the combination caused cell death. Cell cycle analysis indicated that at 24 hrs radiation alone (2 Gy) had no significant effect on cell cycle distribution; however, Win2 either alone or in combination with radiation produced a robust G1 accumulation. At 48 hrs, Win2 alone or in combination with radiation caused a significant increase in the subG1 population, implicating necrosis or apoptosis; however Annexin V/ PI staining was not consistent with either mode of cell death. The absence of apoptosis or necrosis lead us to believe that autophagy may be involved; however, the late autophagic inhibitor, Chloroquine (CQ), was unable to alter the effects of Win/IR, suggesting that autophagy is also not playing a primary role. Taken together, the absence of strong evidence for apoptosis, necrosis or autophagy suggests that the subG1 population could reflect necroptosis, and studies are underway to assess this possibility. Although the mechanisms of drug-radiation interaction remain to be defined, it is clear that Win2 does enhance the effects of radiation in breast cancer cells. 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 1453. doi:1538-7445.AM2012-1453
Joint Disorders Frequency and Structural Changes during Anastrozole Adjuvant Treatment in Early Breast Cancer: A Prospective Trial (D5392L00013).
Authors: T. Delozier, A. Daban, V. Dieras, L. Mauriac, J. Gligorov, M. Tubiana-Hulin, F. Goldwasser, K. Briot, C. Roux, A. Amrate, J. Guastalla
Journal: Cancer Research (2009)

Abstract Background:Aromatase inhibitors (AIs) are standard adjuvant endocrine-therapy in postmenopausal women with hormone-sensitive breast cancer. However, main side effects reported are musculoskeletal symptoms. The pathogenic and anatomic features of AI-induced arthralgia have not been clearly defined. The objective of the study was to describe the joint symptoms and structural joint changes in women received adjuvant anastrozoleMethods: Postmenopausal women with hormone receptor positive early breast cancer were enrolled in this open, multicentre trial. Anastrozole was administrated 1mg/day p.o. All of them were naïve of AI and tamoxifen treatment. Patients were followed one year with clinical examination every 3 months, ultrasound (US) examination every 6 months, measurements of inflammation biomarkers and cartilage biomarkers of degradation U-CTX-II (urinary C-terminal crosslinked telopeptide of type II collagen) every 6 months and X-rays at baseline and 12 monthsResults: From June 2006 to December 2007, one hundred and fourteen patients (114) were included and 106, with a median age of 61.5 (49-79) years, were followed-up for 1 year.Overall, 33% of patients were previously treated by chemotherapy, (anthracyclines 97%, taxanes 63 %) and 40.6% were receiving hormone replacement therapy (HRT) at tumour diagnosis. The prevalences of arthralgia were 40.6, 59.1 and 60.6 % at baseline, 6 months and 12 months respectively.Among the 63 (59.4%) patients without arthralgia at baseline, 37 patients presented with arthralgia during treatment (26 between baseline and M6, 11 between M6 and M12) with median time to onset of 4 months.In univariate logistic analysis, significant determinant factors of joint disorders at 12 months were previous osteoarthritis and personal history of arthralgia but not the previous HRT or previous adjuvant chemotherapy with taxanes. In multivariate analysis, none of those factors were significant.Clinical examination by rheumatologist and US examination did not show any significant changes of the number of synovitis and tenosynovitis over 12 months.There were no significant changes of the U-CTX-II levels and of joint damages assessed by radiographs. Inflammation biomarkers did not significantly change over 12 months.Conclusion: This prospective study with a systematic rheumatologist follow up of the patients showed that arthralgia occurs early after the beginning of anastrozole therapy (first 6 months); and suggest that joint disorders were not associated with any cartilage degradation after 1 year of treatment. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 801.
HER2 positive early breast cancers: tumour demographics and trastuzumab therapy in the real-world.
Authors: S Marla, P Roxburgh, P Burton, S Stallard, E Mallon, P Canney, T Cooke
Journal: Cancer Research (2009)

Abstract Abstract #3159 Background: Various trials have shown substantial benefits of addition of Trastuzumab (Herceptin®) to adjuvant chemotherapy in Early Breast Cancer (EBC). We analysed our breast cancer population to determine the incidence of HER2 positive Early Breast Cancers, the tumour demographics and the number of patients eligible for and receiving trastuzumab therapy in this group.&amp;#x2028; Methods: Data for all patients diagnosed with EBC in 2006 was recorded prospectively in a database. Case notes were consulted where the HER2 positive patients, determined by a combination of IHC and FISH, had not received trastuzumab, to ascertain the reasons.&amp;#x2028; Results: A total of 951 patients were diagnosed with Breast Cancer in 2006. 417 (43.9%) of these were screen-detected cancers.&amp;#x2028; There were 123 (12.9%) HER2 positive newly diagnosed Breast Cancers of whom 117 were EBCs. The HER2 positivity rate in the screen detected cancers (n=417) was 9% and 17% in the symptomatic cancers (n=433).&amp;#x2028; 1. Demographics of the HER2 positive Early Breast Cancer Population:&amp;#x2028; The median age at diagnosis was 61 yrs (range: 30-92).&amp;#x2028; &amp;#x2028; 2. Fifty nine (50.4%) of the HER2 positive EBCs received trastuzumab therapy.&amp;#x2028; &amp;#x2028; Conclusions: The HER2 positivity rate is lower than that previously reported suggestive of changing demographics secondary to a high screen detected cancer population. A third of the HER2 positive tumours are screen detected. The percentage of ER positive, node negative and low grade tumours was higher than anticipated.&amp;#x2028; Only 50% of HER 2 positive EBC patients received trastuzumab therapy. Of those who did not receive trastuzumab, the commonest reason was low risk status or age and co-morbidities precluded chemotherapy.&amp;#x2028; HER 2 positivity alone confers high risk irrespective of pathological stage. Further trials are required to evaluate whether the substantial number of patients who are at present not eligible for trastuzumab therapy might also benefit. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3159.
Abstract 3894: Discovery, synthesis and SAR studies of a novel nonpeptidic reversible proteosome inhibitor with low nano-molar chymotrypsin like activity
Authors: Sevil Ozcan, Aslamuzzaman Kazi, Nan N. Sun, Kenyon Daniel, Wayne C. Guida, Harshani R. Lawrence, Said M. Sebti
Journal: Cancer Research (2012)

Abstract The development of proteosome inhibitors for CT-L activity has been the subject of considerable interest in the treatment of cancer due to its critical role in maintaining homeostasis and hence its key position in many cellular processes. Proteosome inhibitors are classified as reversible or irreversible inhibitors according to their chemical structure and their mechanism of inhibition. Irreversible inhibitors possess a chemically reactive group, such as aldehydes, boronic acids, epoxy ketones that react with catalytic Thr1-O covalently, where as reversible inhibitors inhibit proteosome non-covalently via H-bond interactions (electrostatic and/or van der Waals). Bortezomib, a peptide boronic acid analog, is the first clinically approved proteosome inhibitor and is found to be an irreversible or slow reversible inhibitor that forms covalent bond with the N-terminal nucleophilic Thr1 in the β5 subunit of the proteasome. Reversible proteosome inhibitors (peptidic molecules) reported to date inhibit the proteosome non-covalently. Similar to Bortezomib, MLN9708 is a modified dipeptidyl boronic acid, which hydroylses immediately in plasma to MLN2238, is a potent, reversible and specific inhibitor of the chymotrypsin-like subunit of the proteasome. Small molecules as reversible proteosome inhibitors are less extensively investigated. In this study, we present the discovery of PI-184, non-peptidic small molecule with a pyridine and oxadiazole pharmacore as a reversible, potent and a novel proteasome inhibitor. Structure Activity relationship (SAR) guided synthesis of analogs around PI-184 led to the discovery of highly potent compounds with in-vivo chymotrypsin-like inhibitory activity. Here we present the detailed SAR, in-vitro and in-vivo proteasome activity of PI-184 class of compounds as potential anti-cancer agents. 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 3894. doi:1538-7445.AM2012-3894
Abstract 4080: 5-Azacitydine augments the anti-glioma efficacy of Herpes-based oncolytic virotherapy
Authors: Kazuo Okemoto, Benjamin P. Wagner, Amy M. Haseley, Richard L. Price, Balveen Kaur, Antonio E. Chiocca
Journal: Cancer Research (2012)

Abstract Oncolytic virotherapy (OV) using modified Herpes simplex virus (HSV) type 1, is currently being evaluated for safety and efficacy in numerous phase I-III clinical trials. However, the host innate immune response and a compromised ability to counter cellular defense responses in order to sustain efficient viral replication in tumor cells is still a major obstacle to efficacious virotherapy. Sodium valporate (VPA) is a simple branched-chain fatty acid FDA-approved medication used in treating epilepsy. We previously demonstrated that pretreatment of cultured glioma cells with VPA significantly increases OV replication. However, the mechanism underlying VPA mediated increased virus replication has not been fully elucidated. Understanding the mechanism of this effect can lead to the development of better pharmacologic sensitizers for OV therapy. We found that activation of STAT3 and inhibition of DNA methylation are involved in VPA's ability to enhance virus replication. Furthermore, we demonstrated that the combination of a DNA methylation inhibitor, 5-Azacitydine (5-Aza), at a 1-2 uM concentration coupled with IL-6-mediated (10ng/mL) STAT3 activation effectively enhanced OV replication 125 fold when compared with OV alone. This combination was comparable to what was previously observed when VPA alone was utilized to increase OV replication. The combination also showed increased anti-glioma activity (ED50 of 5-Aza: 2 uM; with IL-6, 0.3 uM) when compared to only VPA treatment. Given these in vitro results, we are currently performing experiments in mice assessing the effect of 5-Aza pretreatment on enhancing OV therapy of gliomas. Oncolytic HSV in combination with the DNA methylation inhibitor, 5-Aza, and activation of STAT3 represents a promising strategy for treating human gliomas. 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 4080. doi:1538-7445.AM2012-4080
Diastolic Function With 16-Phase Gated Myocardial Perfusion SPECT
Authors: Noel M. Bennett, Salima Qamruddin, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2014)

Diastolic dysfunction is commonly associated with heart failure with preserved systolic function. Diastolic abnormality includes progressively impaired left ventricle (LV) relaxation, followed by pseudonormal mitral inflow pattern with Valsalva enhancement, and finally restrictive LV filling. Diastolic dysfunction may lead to left atrial dilatation with consequent atrial fibrillation. Gated myocardial perfusion SPECT evaluates systolic function with LV volumes and ejection fraction, but its ability to identify diastolic dysfunction is not typically considered. We correlate 16-phase gated SPECT time-volume curves with echo Doppler early/late diastolic flow ratios for diastolic dysfunction.
TCT-231 Investigation of Fractional Flow Reserve Correlation with Direct Anatomical Parameters Using a Percutaneous Model of Coronary Artery Stenosis
Authors: Nicolas Foin, Sayan Sen, Ricardo Petraco, Ryo Torii, Sukhjinder Nijjer, Yun X. Xu, Vikram Mehta, Jamil Mayet, Alun Hughes, Darrel Francis, Carlo Di Mario, Rob Krams, Justin Davies
Journal: Journal of the American College of Cardiology (2012)