tbuckley/cabot-search huggingface dataset:
Abstract 2770: Anti-leukemic response of a NSAID, tolfenamic acid.
Authors: Robert M. Sutphin, Sarah F. Connelly, Chris M. Lee, Umesh T. Sankpal, Don Eslin, Riyaz Basha
Journal: Cancer Research (2013)

Abstract Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug is known to inhibit human cancer cells and mouse tumor growth in some cancer models; however its anti-leukemic response is not yet evaluated. Research from our laboratory and others showed that TA targets specificity protein (Sp) transcription factors which mediate the expression of several genes associated with cancer. We also showed that TA inhibits the expression of survivin, a key member of inhibitor of apoptosis family in several human cancer cells. Recent work from several laboratories revealed a strong association of survivin in leukemia. We hypothesize by targeting Sp proteins and survivin, TA can act as an anti-leukemic agent. The anti-proliferative response of TA was determined using four human leukemia cell lines, Jurkat (acute T-cell leukemia), Nalm-6 (pre-B cell leukemia), Molt-4 (acute lymphoblastic leukemia; T lymphoblast), and Reh (acute lymphoblastic leukemia, non-T; non-B) Cells were treated with increasing (25/50/75/100 μM) concentrations of TA and the cell viability was measured at 24, 48, and 72 h post-treatment using CellTiter-Glo kit. Results show a consistent decrease in cell viability in a dose and time-dependent manner. Confirmatory studies to elucidate the mechanism of action were conducted using selected cell lines, Jurkat and Nalm-6. Apoptosis and cell cycle analysis was performed using flow cytometry. The expression of c-PARP, Sp1, survivin, CDC2, CDC4, Cyclin D3 and pRb was determined by Western blot analysis and the caspases were measured by using Caspse-Glo kit(s). Results showed a significant increase in the apoptotic (annexin V positive) cell population following TA treatment, while cell cycle phase distribution analysis showed G0/G1 arrest. TA-induced cell apoptosis is supported by robust activation of caspases (3/7, 8 and 9), and the expression of c-PARP. TA down-regulated the expression of CDC2, CDC4, Cyclin D3 and pRb that mediate the early phases of cell cycle. In summary, TA modulated the expression of critical candidate genes associated with the early phases of cell cycle with validated efficacy in causing G0/G1 arrest. Western blot results reveal that TA significantly decreases Sp1 and survivin expression. Further work is needed to clarify the role of TA as a novel therapeutic agent for leukemia. Citation Format: Robert M. Sutphin, Sarah F. Connelly, Chris M. Lee, Umesh T. Sankpal, Don Eslin, Riyaz Basha. Anti-leukemic response of a NSAID, tolfenamic acid. [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 2770. doi:10.1158/1538-7445.AM2013-2770
BIVALIRUDIN VERSUS HEPARIN WITH OR WITHOUT GLYCOPROTEIN IIB/IIIA INHIBITORS IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: A META-ANALYSIS OF &gt;40,000 PATIENTS
Authors: Ashish Adrian Correa, Abel Casso Dominguez, Jacqueline Tamis-Holland, Mount Sinai
Journal: Journal of the American College of Cardiology (2016)
Abstract 722: Acquired resistance to vorinostat in acute myeloid leukemia
Authors: Daphné Dupéré-Richer, Hélène Retrouvey, Filippa Pettersson Pettersson, Wilson Miller Miller
Journal: Cancer Research (2011)

Abstract Histone deacetylase inhibitors (HDACi) have recently emerged as promising anticancer agents. Some HDACi have advanced into Phase II and III clinical trials, both as a single agent and in combination with cytotoxics for a variety of malignancies. Encouraging results have been obtained in acute myeloid leukemia (AML). However, HDACi target many pathways and the full mechanism responsible for their anti-neoplastic activity is still far from clear. An understanding of the molecular mechanisms underlying resistance to HDACi may help to elucidate their mechanism of action and may be of relevance in an attempt to design more effective combination strategies. The purpose of this study is to understand the molecular alterations associated with resistance to vorinostat (Zolinza®). A vorinostat resistant clone (U937-VR) was derived from the AML cell line U937 using a dose escalation protocol. The vorinostat-resistant cells (U937-VR) are able to grow in 2 µM vorinostat without induction of apoptosis. U937-VR cells are cross-resistant to the cytotoxic effects of other HDACi, as measured by propidium iodide staining and caspase 3/7 activation. Using western blot, we observed that vorinostat exposure increases tubulin acetylation in U937-VR cells while being incapable of inducing histone acetylation. These data demonstrate effective drug import into the cells, an event that is otherwise commonly altered in drug resistant cells. Furthermore, western blotting reveals a drastic difference in the protein level of the histone acetyltransferase CBP (CREB binding protein) between VR-U937 and parental U937 cells, whereas no alterations in the protein levels of the main HDACs targeted by vorinostat is seen. This indicates that the balance between HDAC and HAT activity might be perturbed. Finally, the resistance index (the ratio between the LD50 of resistant and sensitive cells) of different drugs was evaluated by measuring apoptosis using propidium iodide staining. U937 parental and U937-VR cells have equivalent LD50 for the DNA damaging agent cisplatin and for the microtubule stabilizing agent taxol. In contrast, we observed that U937-VR cells exhibit increased sensitivity toward the proteasome inhibitors MG132 and Bortezomib. This increased sensitivity correlates with a higher level of ubiquitinated protein accumulation in U937-VR. Cumulatively, our data suggest that the U937-VR cells are not multidrug resistant and that the apoptotic cascade remains functional. The importance of the alteration in HAT level and the acquired sensitivity to proteasome inhibitor by chronic exposure to HDACi need further investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 722. doi:10.1158/1538-7445.AM2011-722
Emergency transvaginal hybrid natural orifice transluminal endoscopic surgery
Authors: J. Noguera, A. Cuadrado, F. Sánchez-Margallo, C. Dolz, J. Asencio, J. Olea, R. Morales, L. Lozano, J. Vicens
Journal: Endoscopy (2010)

In a clinical series, 10 consecutive female patients with intra-abdominal infections were successfully treated with natural orifice transluminal endoscopic surgery (NOTES) performed transvaginally. The surgery, which consisted of a hybrid NOTES procedure using a transvaginal approach, was performed on an emergency basis by the surgical team on call. The indications for surgery were acute cholecystitis (n = 6), acute appendicitis (n = 2), and pelvic peritonitis (n = 2) with intra-abdominal infection. The procedure was successfully performed in all patients using a dual-channel endoscope and mini-laparoscopy assistance. This is the first clinical series in which NOTES has been performed on an emergency basis to treat intra-abdominal infections. Transvaginal surgery for intra-abdominal infection is a feasible procedure for groups experienced in the elective NOTES approach.
Abstract 25: CBL enhances breast tumor formation by inhibiting tumor suppressive activity of TGF-beta signaling
Authors: Jin Muk Kang, Sujin Park, Staci Jakyong Kim, Seong-Jin Kim
Journal: Cancer Research (2012)

Abstract CBL protein family functions as multifunctional adaptor proteins and E3 ubiquitin ligases that are implicated as regulators of signaling in various cell types. Recent discovery revealed mutations of proto-oncogenic CBL in the linker region and RING finger domain in human acute myeloid neoplasm and these transforming mutations induced carcinogenesis. However, the adaptor function of CBL mediated signaling pathway during tumorigenesis has not been well characterized. Here, we show that CBL highly expresses in breast cancer cells and significantly inhibits TGF-β tumor suppressive activity. Knockdown of CBL expression resulted in the increased expression of TGF-β target genes, SERPINE1 and CDK inhibitors such as p15INK4b and p21Cip1. Furthermore, we demonstrate that CBL is frequently overexpressed in human breast cancer tissues and the loss of CBL decreases a tumorigenic activity of breast cancer cells in vivo. CBL directly binds to Smad3 through its proline-rich motif, thereby preventing Smad3 from interacting with Smad4 and blocking nuclear translocation of Smad3. CBL-b, one of CBL protein family, also interacted with Smad3 and knockdown of both CBL and CBL-b further enhanced TGF-β transcriptional activity. Our findings provide evidence for a previously undescribed mechanism by which oncogenic CBL can block TGF-β tumor suppressor activity. 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 25. doi:1538-7445.AM2012-25
FDG PET Imaging in a Patient With Primary Seminoma of the Prostate
Authors: Kazumasa Hayasaka, Masamichi Koyama, Iwao Fukui
Journal: Clinical Nuclear Medicine (2011)

Primary seminoma of the prostate is extremely rare. We describe a case of a 35-year-old man who presented with difficulty in urinating. Physical findings were unremarkable, but a rectal examination revealed a slightly hardened prostate with a nodule in the right lobe. Blood parameters were normal; however, blood chemistry revealed slightly elevated lactic dehydrogenase, and microscopic hematuria was evident. Serum prostate acid phosphate, carcinoembryonic antigen, and alpha-fetoprotein values were within normal limits. Both computed tomography and magnetic resonance images revealed a large mass in the prostate gland. A prostatic sarcoma or malignant lymphoma was initially suspected. A systemic survey using 18-fluoro-2-deoxyglucose (F-18 FDG) positron emission tomography revealed focal FDG uptake in the prostate gland. A prostatic biopsy of the mass was histologically diagnosed to reveal an extragonadal seminoma.
THU0543 Constitutive Activation of STAT3 in Rheumatoid Arthritis Correlates with IL-6 Levels
Authors: P. Isomäki, I. Junttila, K.-L. Vidqvist, M. Korpela, O. Silvennoinen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Many cytokines involved in the inflammatory process in rheumatoid arthritis (RA) activate the JAK-STAT pathways. Therapeutic drugs that inhibit these pathways are currently being developed for RA. <h3>Objectives</h3> To investigate whether there are disease-related alterations in the activity of JAK-STAT pathways in RA, we have studied the expression and activation of STAT1 and STAT3 in unstimulated cells, and in response to interferon (IFN)-γ, interleukin (IL)-6 and IL-10 stimulation. <h3>Methods</h3> The expression of STAT1 and STAT3 mRNA in peripheral blood (PB) and synovial fluid (SF) T cells and monocytes were studied from patients with RA and healthy volunteers by reverse transcriptase polymerase chain reaction. Basal and cytokine-induced STAT phosphorylations were analysed in PB T cells and monocytes using multicolour flow cytometric analysis. Cytokine levels were determined by ELISA. <h3>Results</h3> STAT3 mRNA levels were upregulated in both PB and SF T cells and monocytes from RA patients. STAT1 expression was elevated in SF monocytes. The levels of phospho-STAT3 in resting PB T cells and monocytes were significantly higher in patients with RA than in healthy volunteers. IL-6 levels were elevated in RA plasma, and correlated with the degree of STAT3 phosphorylation in CD4<sup>+</sup> T cells and monocytes. The IL-6-mediated STAT3 activation was downregulated in T cells from RA patients. IL-6-induced phosphorylation of STAT3 was decreased in CD4<sup>+</sup> T cells from patients with high plasma IL-6 levels and constitutive STAT3 phosphorylation. <h3>Conclusions</h3> These results suggest that IL-6 induces hyperactivation of STAT3 in circulating immune cells in active RA, and this subsequently desensitizes the IL-6 response in T cells. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3075
A case of terminal ileal prolapse presenting as a polyp
Authors: K. Keshk, J. Turner, J. Green, M. Morgan
Journal: Endoscopy (2013)

A 66-year-old man was referred for a colonoscopy to investigate persistent diarrhea associated with iron deficiency. A large polypoid lesion (2 × 4 cm) was identified at the ileocecal valve ([Fig. 1 a]). Examination with chromoendoscopy (0.4 % indigo carmine dye) demonstrated the appearance of villi ([Fig. 1 b]). The terminal ileum had a normal appearance on intubation ([Fig. 1 c]); however, the lesion had disappeared on withdrawal of the colonoscope back into the cecum ([Fig. 1 d]). Biopsies from the lesion confirmed small-bowel architecture ([Fig. 2]). This endoscopic appearance in conjunction with the biopsy results was consistent with a prolapsing ileum.
Association of<i>Campylobacter pylori</i>on the Gastric Mucosa with Antral Gastritis in Children
Authors: Brendan Drumm, Philip Sherman, Ernest Cutz, Mohamed Karmali
Journal: New England Journal of Medicine (1987)

We investigated the presence of Campylobacter pylori colonization of the gastric mucosa and of histologic evidence of gastritis in a prospective study of 71 consecutive children undergoing upper gastrointestinal tract endoscopy and gastric biopsies because of gastrointestinal symptoms. Two tissue samples from the gastric antrum were obtained from 67 of the 71 children (mean age [±SD], 11.4±3.8 years). One sample was evaluated for evidence of gastritis and stained with silver to detect organisms morphologically resembling campylobacter. The second sample was cultured for C. pylori, and a portion was used to perform a urease-screening test for the presence of C. pylori. Antral gastritis was diagnosed histologically in 18 of 67 patients. C. pylori was identified by both culture and silver staining on the antral mucosa in 7 of 10 patients with unexplained gastritis (primary gastritis) but in none of 8 patients with gastritis associated with an identifiable underlying cause (secondary gastritis). C. pylori was not identified in any of the 49 cases with normal histologic features. The urease-screening test was positive in only three of six patients with a positive culture for C. pylori. Duodenal ulcers were diagnosed by endoscopy in five patients. Each of the five had C. pylori on the antral mucosa, but organisms were not identified on the duodenal mucosa. We conclude that the presence of C. pylori on the antral mucosa is specifically associated with primary antral gastritis and may also be associated with primary duodenal ulceration. (N Engl J Med 1987; 316:1557–61.)
A PHASE 2, MULTI-CENTER, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS AND EXPLORATORY CLINICAL ACTIVITY OF ALN-TTRSC, AN RNAI THERAPEUTIC FOR THE TREATMENT OF PATIENTS WITH TRANSTHYRETIN CARDIAC AMYLOIDOSIS
Authors: Julian David Gillmore, Rodney Falk, Mathew Maurer, Mazen Hanna, Verena Karsten, Craig Penz, Tracy Zimmermann, Jared Gollob, Philip Hawkins
Journal: Journal of the American College of Cardiology (2015)
Phase I/II trial combining the HDAC inhibitor, valproic acid (VPA) and FEC100 (5-fluorouracil, epirubicin and cyclophosphamide) in locally advanced/metastatic breast cancer
Authors: P. N. Munster, D. C. Marchion, M. Schmitt, E. Bicaku, M. Lacevic, S. Minton, W. Carter, A. Daud
Journal: Journal of Clinical Oncology (2007)

1065 Background: Cell culture and xenograft studies suggest a synergistic interaction between histone deacetylase inhibitors (HDACi) and topoisomerase (topo) inhibitors, as well as other DNA targeting agents. Methods: In this phase I/II study, we determined the effects of escalating doses of VPA on the clinical efficacy and tolerability of epirubicin. The phase I part was open to patients will all solid tumors. A limited phase II part at the maximum tolerated dose (MTD) of VPA enrolled 10 breast cancer patients and incorporated the breast cancer regimen FEC100 (5-fluorouracil, epirubicin, cyclophosphamide (600/100/600 mg/m 2 )). VPA was given on days 1–3 prior to epirubicin/FEC100 in 3-week cycles. HDAC expression, histone acetylation and topo II expression were evaluated in pre-and post-VPA peripheral blood mononuclear cells and tumor samples. Results: Fifty-four (44 in phase I and 10 in phase II) patients [median age 55 (39–78)] received VPA (mg/kg/day): 15, 30, 45, 60, 75, 90, 100, 120, 140 and 160. Tumor types included: breast (10+10), melanoma (11), lung (6), sarcoma (2), GYN (2), GI (5) and others (8). Dose-limiting toxicities included somnolence, confusion and febrile neutropenia. No exacerbation of FEC100/epirubicin-related toxicities was observed. Objective responses in the phase I part 9/41 (22%) were seen across different tumor types despite a median number of 3 (0–6) prior regimens with stable disease/minor response in 16/41 (39%). In the breast-specific phase II part, partial responses to date were seen in 4/8 (50%) and stable disease in 2/8 (25%), progression in 1/8 (12.5%), 1/8 (12.5%) patients withdrew consent. All breast cancer patients with a response/stable disease received the maximal number of seven cycles. VPA plasma concentrations correlated with VPA dose. There was a positive correlation between histone acetylation and VPA dose as well as plasma levels in PBMC and further correlated with those in tumors. Conclusion: A sequence-specific combination of VPA and FEC100 in breast cancer is highly active without exacerbation of chemotherapy-induced toxicities. A neoadjuvant phase II trial using VPA (120 mg/kg) -&gt; FEC100 in patients with early stage breast cancer is ongoing. [Table: see text]
An audit of fracture clinic services in a London district general hospital: Are patients being referred according to national guidance?
Authors: J. Balogun-Lynch, C. Jennings, P. Haggis, R. Dimock, Z. Little
Journal: International Journal of Surgery (2015)

s / International Journal of Surgery 23 (2015) S15eS134 S80 Aim: Informed consent is essential so patients are aware of the benefits and potential risks of surgery. The objective of this audit was to assess whether patients were consented appropriately for total knee replacement (TKR) and total hip replacement (THR). We used “Orthoconsent” which is endorsed by the British Orthopaedic Association as the set standard. Methods: This was a retrospective audit undertaken within a London Teaching Hospital. Data was collected for 10 patients undergoing TKR and 10 patients undergoing THR. Participants were identified from ward lists and all had capacity to give consent. Results: THR consent forms had 71% documented completion of the benefits and occurring risks required to make informed consent. TKR consent forms were completed with 42% accuracy. In many instances, important risks that are specific to these operations were not stated. Conclusion: Inadequate consent can lead to false expectations and may lead to litigation. The use of template consent forms (TCF) may improve consent for TKR and THR by providing the information required to responsibly consent for the operation. Patients can raise concerns before signing the consent form, allowing for “Informed Consent”. We have developed TCFs for use in our hospital and strongly recommend there use nationally. 0115: AN AUDIT OF FRACTURE CLINIC SERVICES IN A LONDON DISTRICT GENERAL HOSPITAL: ARE PATIENTS BEING REFERRED ACCORDING TO NATIONAL GUIDANCE? J. Balogun-Lynch, C. Jennings, P. Haggis, R. Dimock, Z. Little. Northwick
ASSOCIATION OF GLOBAL LONGITUDINAL STRAIN WITH SEVERITY OF NEUROCARDIAC INJURY IN PATIENTS WITH SUBARACHNOID HEMORRHAGE
Authors: Zhi Qi, Masataka Sugahara, Elizabeth A. Crago, Yuefang Chang, Theodore F. Lagattuta, Khalil Yousef, Robert M. Friedlander, Marilyn T. Hravnak, John Gorcsan
Journal: Journal of the American College of Cardiology (2016)
Abstract 4998: NFAT signaling modulates tumor microenvironment.
Authors: Aura Kaunisto, Alex Toker
Journal: Cancer Research (2013)

Abstract Nuclear factor of activated T cells (NFAT) transcription factors regulate several cancer-related processes, such as migration and invasion. We have shown that NFAT is both necessary and sufficient to drive invasive migration of breast carcinoma cells. NFAT target genes that contribute to this phenotype encode cyclo-oxygenase-2, the enzyme required for the production of prostaglandin E2, and autotaxin, which catalyzes the synthesis of lysophosphatidic acid. NFAT also promotes tumor progression downstream of vascular endothelial growth factors and contributes to angiogenesis and lymphangiogenesis, though the underlying molecular mechanisms that control these phenotypes have remained unknown. In our present studies, we have identified novel NFAT target genes whose products are likely to modify tumor microenvironment through paracrine signaling to immune cells. We have generated stable pools of breast cancer cells with inducible lentiviral silencing or overexpression of NFAT and performed quantitative real-time RT-PCR to identify NFAT-responsive genes that code for soluble factors. This approach yielded several novel candidates, including those encoding cytokines and chemokines. The contribution of these NFAT-regulated gene products to tumor-stromal interactions is currently under investigation. Our studies propose a central role for NFAT in modulating tumor microenvironment. Citation Format: Aura Kaunisto, Alex Toker. NFAT signaling modulates tumor microenvironment. [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 4998. doi:10.1158/1538-7445.AM2013-4998
Body Mass Index and Lung Cancer Survival: Results From the Icare Study
Authors: H. Sanikini, G. Clain, M. Sanchez, A.V. Guizard, A.S. Woronoff, B. Tretarre, F. Molinie, P. Delafosse, D. Luce, I. Stücker
Journal: Annals of Oncology (2015)